Science.gov

Sample records for administration human tissue

  1. Administrative Aspects of Human Experimentation.

    ERIC Educational Resources Information Center

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. Trade in human tissue products.

    PubMed

    Tonti-Filippini, Nicholas; Zeps, Nikolajs

    2011-03-01

    Trade in human tissue in Australia is prohibited by state law, and in ethical guidelines by the National Health and Medical Research Council: National statement on ethical conduct in human research; Organ and tissue donation by living donors: guidelines for ethical practice for health professionals. However, trade in human tissue products is a common practice especially for: reconstructive orthopaedic or plastic surgery; novel human tissue products such as a replacement trachea created by using human mesenchymal stem cells; biomedical research using cell lines, DNA and protein provided through biobanks. Cost pressures on these have forced consideration of commercial models to sustain their operations. Both the existing and novel activities require a robust framework to enable commercial uses of human tissue products while maintaining community acceptability of such practices, but to date no such framework exists. In this article, we propose a model ethical framework for ethical governance which identifies specific ethical issues such as: privacy; unique value of a person's tissue; commodification of the body; equity and benefit to the community; perverse incentives; and "attenuation" as a potentially useful concept to help deal with the broad range of subjective views relevant to whether it is acceptable to commercialise certain human tissue products. PMID:21382003

  9. [Brown fat tissue in humans].

    PubMed

    Medvedev, L N; Elsukova, E I

    2002-01-01

    Brown adipose tissue (BAT) is universally present in mammals. Thermal production in such tissue is physiologically important for maintaining temperature homeostasis and regulation of body mass in small-size homoiotherms. At present it is clearly established that unlike other large mammals, brown adipose in man and primates is retained throughout the whole postnatal othogenesis. Therefore, BAT appears as a possible effector of pharmacogenetic protection from human excessive adiposis. Systematic reserach of various functioning aspects of this unique organ of mammals were started abroad as early as 1960-es, and are actively developing at present. Domestic research of energy circulation physiology and of thermoregulation developed mostly outside the brown adipose tissue. Therefore, the principal objective of this publication is to draw attention of experimental and clinical researches to an intriguing aspect of the issue of energy circulation in humans--the issue of brown adipose functioning. PMID:12004574

  10. Pathways to the Humanities in Educational Administration.

    ERIC Educational Resources Information Center

    Popper, Samuel H.

    Based on the author's own experience as a professor of educational administration, this monograph is an argument for establishing a link between the humanities and instruction in school administration. Part I discusses the instrumental value of the humanities in administrative preparation and recounts the limitations of past attempts by the…

  11. 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

  12. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect

    Tamura, Akitoshi Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  13. Transcriptomic Identification of ADH1B as a Novel Candidate Gene for Obesity and Insulin Resistance in Human Adipose Tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES)

    PubMed Central

    Winnier, Deidre A.; Fourcaudot, Marcel; Norton, Luke; Abdul-Ghani, Muhammad A.; Hu, Shirley L.; Farook, Vidya S.; Coletta, Dawn K.; Kumar, Satish; Puppala, Sobha; Chittoor, Geetha; Dyer, Thomas D.; Arya, Rector; Carless, Melanie; Lehman, Donna M.; Curran, Joanne E.; Cromack, Douglas T.; Tripathy, Devjit; Blangero, John; Duggirala, Ravindranath; Göring, Harald H. H.; DeFronzo, Ralph A.; Jenkinson, Christopher P.

    2015-01-01

    Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10-9), BMI (5.4 x 10-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits. PMID:25830378

  14. Transcriptomic identification of ADH1B as a novel candidate gene for obesity and insulin resistance in human adipose tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES).

    PubMed

    Winnier, Deidre A; Fourcaudot, Marcel; Norton, Luke; Abdul-Ghani, Muhammad A; Hu, Shirley L; Farook, Vidya S; Coletta, Dawn K; Kumar, Satish; Puppala, Sobha; Chittoor, Geetha; Dyer, Thomas D; Arya, Rector; Carless, Melanie; Lehman, Donna M; Curran, Joanne E; Cromack, Douglas T; Tripathy, Devjit; Blangero, John; Duggirala, Ravindranath; Göring, Harald H H; DeFronzo, Ralph A; Jenkinson, Christopher P

    2015-01-01

    Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10(-4)) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10(-60)) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10(-9)), BMI (5.4 x 10(-6)), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits. PMID:25830378

  15. 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...

  16. 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...

  17. Peripheral neuropathy following administration of nerve tissue antirabies vaccine.

    PubMed

    Arega, D; Zenebe, G

    1999-10-01

    In 1997, two patients were admitted to Tikur Anbessa Hospital with complaints of ascending paralysis in all extremities following administration of sheep brain tissue anti-rabies vaccine following a rabies exposure. The paralysis had started after 14 daily subcutaneous injections of the Fermi type nerve tissue vaccine. After an eight week stay in the hospital with supportive care and physiotherapy, the patients showed remarkable improvement. They received a booster dose of vaccine while in the hospital, with no deterioration in their neurological status and were discharged. PMID:11961878

  18. Somatostatin in rat tissues is depleted by cysteamine administration

    SciTech Connect

    Szabo, S.; Reichlin, S.

    1981-12-01

    Administration of cysteamine (mercaptoethylamine) induces in rats severe perforating duodenal ulcers. Because the ulcerogenic properties of cysteamine are markedly reduced by treatment with somatostatin, we considered the possibility that cysteamine-induced duodenal ulcer might be mediated by depletion of tissue somatostatin, and thereby of its paracrine influences on gastrin and gastric acid secretion. To test this hypothesis, we measured the concentration of immunoreactive somatostatin (IR-somatostatin) in stomach and duodenal mucosa at intervals after administration of a single ulcerogenic dose (30 mg/kg by stomach tube). IR-somatostatin in these tissues fell rapidly to reach a minimum at 4 h (stomach 31%, duodenum 60% of control respectively). IR-somatostatin in hypothalamus and pancreas decreased gradually to a minimum at 7 h. Another duodenal ulcerogen, propionitrile (10 mg/100 g bw, s.c.) which is more toxic than cysteamine, and several stressful procedures including ether anesthesia, restraint and s.c. formalin did not lower stomach or duodenal IR-somatostatin. Gut, pancreas and hypothalamic VIP levels were not influenced by cysteamine. These findings suggest that cysteamine is a relatively specific depletor of tissue somatostatin. Because blood levels of somatostatin fell, and only trivial amounts of the peptide were found in the stomach lumen after cysteamine administration, it appears likely that this agent acts at the cellular level to cause breakdown of preformed somatostatin and/or to acutely reduce its synthesis.

  19. α-Klotho Expression in Human Tissues

    PubMed Central

    Lim, Kenneth; Groen, Arnoud; Molostvov, Guerman; Lu, Tzongshi; Lilley, Kathryn S.; Snead, David; James, Sean; Wilkinson, Ian B.; Ting, Stephen

    2015-01-01

    Context: α-Klotho has emerged as a powerful regulator of the aging process. To date, the expression profile of α-Klotho in human tissues is unknown, and its existence in some human tissue types is subject to much controversy. Objective: This is the first study to characterize systemwide tissue expression of transmembrane α-Klotho in humans. We have employed next-generation targeted proteomic analysis using parallel reaction monitoring in parallel with conventional antibody-based methods to determine the expression and spatial distribution of human α-Klotho expression in health. Results: The distribution of α-Klotho in human tissues from various organ systems, including arterial, epithelial, endocrine, reproductive, and neuronal tissues, was first identified by immunohistochemistry. Kidney tissues showed strong α-Klotho expression, whereas liver did not reveal a detectable signal. These results were next confirmed by Western blotting of both whole tissues and primary cells. To validate our antibody-based results, α-Klotho-expressing tissues were subjected to parallel reaction monitoring mass spectrometry (data deposited at ProteomeXchange, PXD002775) identifying peptides specific for the full-length, transmembrane α-Klotho isoform. Conclusions: The data presented confirm α-Klotho expression in the kidney tubule and in the artery and provide evidence of α-Klotho expression across organ systems and cell types that has not previously been described in humans. PMID:26280509

  20. Use of human tissue explants to study human infectious agents

    PubMed Central

    Grivel, Jean-Charles; Margolis, Leonid

    2012-01-01

    The study of human cell–cell and cell–pathogen interactions that occur in the context of complex tissue cytoarchitecture is critical for deciphering the mechanisms of many normal and pathogenic processes. This protocol describes methods for culturing and infecting explants of human tissues to study the pathogenesis of human infectious agents and their local interactions. The protocol relies on the use of fresh human tissues dissected into small blocks or biopsies that are cultured at the liquid–air interface on collagen rafts. These tissue blocks retain their cytoarchitecture and support productive infection of various pathogens without exogenous stimulation. Experimental details for setting up cultures of human tonsils, lymph nodes and cervicovaginal and rectosigmoid tissues, including protocols for their infection with HIV-1 and other pathogens, are described here. Using this protocol, culture and infections can be set up in 3–6 h and be maintained for 2–3 weeks, depending on the tissue used. PMID:19197269

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Three Dimension Filamentous Human Cardiac Tissue Model

    PubMed Central

    Ma, Zhen; Koo, Sangmo; Finnegan, Micaela A.; Loskill, Peter; Huebsch, Nathaniel; Marks, Natalie C.; Conklin, Bruce R.; Grigoropoulos, Costas P.; Healy, Kevin E.

    2013-01-01

    A human in vitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an in vitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity. PMID:24268663

  7. 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.

  8. Effect of intrapulmonary tetrahydrocannabinol administration in humans.

    PubMed

    Zuurman, L; Roy, C; Schoemaker, R C; Hazekamp, A; den Hartigh, J; Bender, J C M E; Verpoorte, R; Pinquier, J L; Cohen, A F; van Gerven, J M A

    2008-09-01

    This randomised, double-blind, placebo-controlled, cross-over study was designed to identify which pharmacodynamic parameters most accurately quantify the effects of delta-9-Tetrahydrocannabinol (THC), the predominantly psychoactive component of cannabis. In addition, we investigated the acceptability and usefulness of a novel mode of intrapulmonary THC administration using a Volcano vaporizer and pure THC instead of cannabis. Rising doses of THC (2, 4, 6 and 8 mg) or vehicle were administered with 90 minutes intervals to twelve healthy males using a Volcano vaporizer. Very low between-subject variability was observed in THC plasma concentrations, characterising the Volcano vaporizer as a suitable method for the administration of THC. Heart rate showed a sharp increase and rapid decline after each THC administration (8 mg: 19.4 bpm: 95% CI 13.2, 25.5). By contrast, dose dependent effects of body sway (8 mg: 108.5%: 95% CI 72.2%, 152.4%) and different subjective parameters did not return to baseline between doses (Visual Analogue Scales of 'alertness' (8 mg: -33.6 mm: 95% CI -41.6, -25.7), 'feeling high' (8 mg: 1.09 U: 95% CI 0.85, 1.33), 'external perception' (8 mg: 0.62 U: 95% CI 0.37, 0.86)). PK/PD-modeling of heart rate displayed a relatively short equilibration half-life of 7.68 min. CNS parameters showed equilibration half-lives ranging between 39.4 - 84.2 min. Some EEG-frequency bands, and pupil size showed small changes following the highest dose of THC. No changes were seen in saccadic eye movements, smooth pursuit and adaptive tracking performance. These results may be applicable in the development of novel cannabinoid agonists and antagonists, and in studies of the pharmacology and physiology of cannabinoid systems in humans. PMID:18515447

  9. Engineering tissue from human embryonic stem cells

    PubMed Central

    Metallo, CM; Azarin, SM; Ji, L; De Pablo, JJ; Palecek, SP

    2008-01-01

    Abstract Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here, we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome. PMID:18194458

  10. Alpha-dispersion in human tissue

    NASA Astrophysics Data System (ADS)

    Grimnes, Sverre; Martinsen, Ørjan G.

    2010-04-01

    Beta dispersion is found in living tissue in the kilohertz - megahertz range and is caused by the cellular structure of biological materials with low frequency properties caused by cell membranes. Alpha dispersion is found in the hertz range and the causes are not so well known. Alpha dispersions are the first to disappear when tissue dies. Tissue data have often been based upon excised specimen from animals and are therefore not necessarily representative for human tissue alpha dispersions. Here we present data obtained with non-invasive skin surface electrodes for different segments of the living human body. We found alpha dispersions in all cases; the ankle-wrist results had the smallest. Large alpha dispersions were found where the distance between the electrodes and muscle masses was small, e.g. on the calf. Further studies on electrode technique and reciprocity, electrode positioning, statistical variations, gender, age and bodily constitutions are necessary in order to reveal more about the alpha dispersion, its appearance and disappearance.

  11. Pathways to the Humanities in School Administration. Third Edition.

    ERIC Educational Resources Information Center

    Popper, Samuel H.

    Based on the author's experience as a professor of educational administration, this monograph is an argument for establishing a link between the humanities and instruction in school administration. Part 1 discusses the instrumental value of the humanities in administrative preparation and recounts the limitations of past attempts by the University…

  12. 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.

  13. Finite Element Modeling of Human Placental Tissue

    PubMed Central

    Yu, Mao; Manoogian, Sarah; Duma, Stefan M.; Stitzel, Joel D.

    2009-01-01

    Motor vehicle crashes account for a large portion of placental abruption and fetal losses. To better understand the material properties of the human placenta, a Finite Element (FE) model of human placenta tissue was created and verified using data from uniaxial tension tests. Sixty-four tensile tests at three different strain rates of 7% strain/s, 70% strain/s, and 700% strain/s from six whole human placentas were used for model development. Nominal stresses were calculated by dividing forces at the grips by the original cross-sectional area. Nominal strains were calculated by dividing cross-head displacement by the original gauge length. A detailed methodology for interpreting experimental data for application to material model development is presented. A model of the tension coupon was created in LS-DYNA and stretched in the same manner as the uniaxial tension tests. The behavior of the material was optimized to the uniaxial tension test using a multi-island genetic algorithm. The results demonstrate good correlation between experiments and the model, with an average difference of 2% between the optimized FE and experimental first principal stress at the termination state. The material parameters found in this study can be utilized in FE models of placental tissues for behavior under dynamic loading. PMID:20184849

  14. Tissue distribution of berberine and its metabolites after oral administration in rats.

    PubMed

    Tan, Xiang-Shan; Ma, Jing-Yi; Feng, Ru; Ma, Chao; Chen, Wen-Jing; Sun, Yu-Peng; Fu, Jie; Huang, Min; He, Chi-Yu; Shou, Jia-Wen; He, Wen-Yi; Wang, Yan; Jiang, Jian-Dong

    2013-01-01

    Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic. PMID:24205048

  15. 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

  16. Hippocampus and epilepsy: Findings from human tissues.

    PubMed

    Huberfeld, G; Blauwblomme, T; Miles, R

    2015-03-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several focal epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including temporal lobe epilepsies with hippocampal sclerosis, cortical dysplasias, epilepsies associated with tumors and developmental malformations. Slices of tissue from patients 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 the 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 and consequently suppressing interictal

  17. Transformational Leadership: Overview of a Human Resources Administrative Practice.

    ERIC Educational Resources Information Center

    Evans, Thomas J.

    Increasingly, educational leaders have adopted human-resource approaches in school administration. The approach has facilitated the development of transformational leadership. This paper explores in detail the nature of leadership associated with a human-resources approach toward educational administration. The paper describes the theoretical…

  18. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    PubMed Central

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  19. Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils

    PubMed Central

    Zimmermann, N.; McBride, M. L.; Yamada, Y.; Hudson, S. A.; Jones, C.; Cromie, K. D.; Crocker, P. R.; Rothenberg, M. E.; Bochner, B. S.

    2009-01-01

    Background Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that bind sialic acid and mostly contain immunoreceptor tyrosine-based inhibitory motifs, suggesting that these molecules possess inhibitory functions. We have recently identified Siglec-8 as an eosinophil-prominent Siglec, and cross-linking of Siglec-8 on human eosinophils induces apoptosis. In this article, we address the in vivo consequences of Siglec engagement. We and others have identified mouse Siglec-F as the closest functional paralog of human Siglec-8, based on shared ligand-binding and expression pattern. We therefore hypothesized that Siglec-F engagement would affect levels and viability of eosinophils in vivo. Methods Wild type and hypereosinophilic mice were administered Siglec-F antibody and levels of eosinophils in peripheral blood and tissue were measured. Eosinophil apoptosis (in vivo and in vitro) was determined by binding of Annexin-V. Results Studies in IL-5 transgenic mice, displaying hypereosinophilia, show that administration of a single dose of Siglec-F antibody results in rapid reductions in quantum of eosinophils in the blood. This decrease was accompanied by reductions in tissue eosinophils. Quantum of eosinophils in blood was decreased using two separate antibodies, as well as in other mouse models (wild type mice and in a mouse model of chronic eosinophilic leukemia). Mechanistic studies demonstrated that Siglec-F antibody administration induced apoptosis of eosinophils in vivo and in vitro. Conclusion These data demonstrate that activation of innate immune receptors, like Siglec-F, can significantly reduce mouse eosinophil viability. As such, targeting Siglec-8/F may be a therapeutic approach for eosinophilic disorders. PMID:18699932

  20. Human Resource Administration in Catholic School Systems.

    ERIC Educational Resources Information Center

    Dobzanski, Joan L.

    2000-01-01

    Describes a comprehensive human resource program, the purpose of which is to enhance the quality of Catholic education for all students. Defines the assumptions on which the formation and implementation of human resource programs for Catholic schools are based. Highlights the role and responsibilities of Catholic school system leaders. (VWC)

  1. Proteomics. Tissue-based map of the human proteome.

    PubMed

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M; Lindskog, Cecilia; Oksvold, Per; Mardinoglu, Adil; Sivertsson, Åsa; Kampf, Caroline; Sjöstedt, Evelina; Asplund, Anna; Olsson, IngMarie; Edlund, Karolina; Lundberg, Emma; Navani, Sanjay; Szigyarto, Cristina Al-Khalili; Odeberg, Jacob; Djureinovic, Dijana; Takanen, Jenny Ottosson; Hober, Sophia; Alm, Tove; Edqvist, Per-Henrik; Berling, Holger; Tegel, Hanna; Mulder, Jan; Rockberg, Johan; Nilsson, Peter; Schwenk, Jochen M; Hamsten, Marica; von Feilitzen, Kalle; Forsberg, Mattias; Persson, Lukas; Johansson, Fredric; Zwahlen, Martin; von Heijne, Gunnar; Nielsen, Jens; Pontén, Fredrik

    2015-01-23

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. PMID:25613900

  2. Human Factors in Library Administration. Revised Edition.

    ERIC Educational Resources Information Center

    Barnhard, Neil

    Intended for the beginning or inexperienced supervisor, this continuing education course syllabus presents basic information on the development of human relations skills, particularly in the areas of leadership, communication, conflict, and motivation. Role playing situations set in various types of medical libraries are also outlined to provide…

  3. Imaging the Human Body: Micro- and Nanostructure of Human Tissues

    NASA Astrophysics Data System (ADS)

    Schulz, Georg; Deyhle, Hans; Müller, Bert

    Computed tomography based on X-rays is known to provide the best spatial resolution of all clinical three-dimensional imaging facilities and currently reaches a fraction of a millimeter. Better spatial and density resolution is obtained by means of micro computed tomography well established in the field of materials science. It is also very supportive imaging human tissues down to the level of individual cells (Lareida et al. J. Microsc. 234:95, 2009). The article demonstrates the power of micro computed tomography for imaging parts of the human body such as teeth, inner ear, cerebellum, tumors, and urethral tissue with conventional X-ray sources and synchrotron radiation facilities in absorption and phase contrast modes. The second part of the chapter relies on scanning X-ray scattering of tooth slices (Müller et al. Eur. J. Clin. Nanomed. 3:30, 2010) to uncover the presence of nanostructures including their anisotropy and orientation. This imaging technique gives unrivalled insights for medical experts, which will have a major influence on fields such as dental and incontinence treatments.

  4. Oromucosal Administration of Interferon to Humans

    PubMed Central

    Beilharz, Manfred W.; Cummins, Martin J.; Bennett, Alayne L.; Cummins, Joseph M.

    2010-01-01

    The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNα therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.

  5. Gene Electrotransfer in 3D Reconstructed Human Dermal Tissue.

    PubMed

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

    2016-01-01

    Gene electrotransfer into the skin is of particular interest for the development of medical applications including DNA vaccination, cancer treatment, wound healing or treatment of local skin disorders. However, such clinical applications are currently limited due to poor understanding of the mechanisms governing DNA electrotransfer within human tissue. Nowadays, most studies are carried out in rodent models but rodent skin varies from human skin in terms of cell composition and architecture. We used a tissue-engineering approach to study gene electrotransfer mechanisms in a human tissue context. Primary human dermal fibroblasts were cultured according to the self-assembly method to produce 3D reconstructed human dermal tissue. In this study, we showed that cells of the reconstructed cutaneous tissue were efficiently electropermeabilized by applying millisecond electric pulses, without affecting their viability. A reporter gene was successfully electrotransferred into this human tissue and gene expression was detected for up to 48h. Interestingly, the transfected cells were solely located on the upper surface of the tissue, where they were in close contact with plasmid DNA solution. Furthermore, we report evidences that electrotransfection success depends on plasmid mobility within tissue- rich in collagens, but not on cell proliferation status. In conclusion, in addition to proposing a reliable alternative to animal experiments, tissue engineering produces valid biological tool for the in vitro study of gene electrotransfer mechanisms in human tissue. PMID:27029947

  6. Brief report: investigation into recalled human tissue for transplantation--United States, 2005-2006.

    PubMed

    2006-05-26

    On September 29, 2005, a human tissue-processing company discovered inaccuracies in donor records forwarded from a tissue-recovery firm and notified the Food and Drug Administration (FDA). An FDA investigation determined that the recovery firm, Biomedical Tissue Services, Ltd. (BTS) (Fort Lee, New Jersey), recovered tissues from human donors who might not have met donor eligibility requirements and who were not screened properly for certain infectious diseases. In October 2005, BTS and the five processors that had received the tissues, working with FDA, issued a recall for all tissues recovered by BTS. The continuing FDA investigation determined that information for some donors (e.g., cause, place, or time of death) was not consistent with death certificate data obtained from the states where the deaths occurred. The investigation also determined that BTS had failed to recover tissues in a manner that would prevent contamination or cross-contamination and failed to control environmental conditions adequately during tissue recovery. These failures were violations of the Current Good Tissue Practice Rules (effective May 25, 2005), which require manufacturers to recover, process, store, label, package, and distribute human cells, tissue, and cellular and tissue-based products (HCT/Ps) to prevent introduction, transmission, or spread of communicable diseases. In January 2006, FDA ordered BTS to cease manufacturing and to retain all HCT/Ps. PMID:16723969

  7. Transplantation of a tissue-engineered human vascularized cardiac muscle.

    PubMed

    Lesman, Ayelet; Habib, Manhal; Caspi, Oren; Gepstein, Amira; Arbel, Gil; Levenberg, Shulamit; Gepstein, Lior

    2010-01-01

    Myocardial regeneration strategies have been hampered by the lack of sources for human cardiomyocytes (CMs) and by the significant donor cell loss following transplantation. We assessed the ability of a three-dimensional tissue-engineered human vascularized cardiac muscle to engraft in the in vivo rat heart and to promote functional vascularization. Human embryonic stem cell-derived CMs alone or with human endothelial cells (human umbilical vein endothelial cells) and embryonic fibroblasts (triculture constructs) were seeded onto biodegradable porous scaffolds. The resulting tissue constructs were transplanted to the in vivo rat heart and formed cardiac tissue grafts. Immunostaining studies for human-specific CD31 and alpha-smooth muscle actin demonstrated the formation of both donor (human) and host (rat)-derived vasculature within the engrafted triculture tissue constructs. Intraventricular injection of fluorescent microspheres or lectin resulted in their incorporation by human-derived vessels, confirming their functional integration with host coronary vasculature. Finally, the number of blood vessels was significantly greater in the triculture tissue constructs (60.3 +/- 8/mm(3), p < 0.05) when compared with scaffolds containing only CMs (39.0 +/- 14.4/mm(3)). In conclusion, a tissue-engineered human vascularized cardiac muscle can be established ex vivo and transplanted in vivo to form stable grafts. By utilizing a multicellular preparation we were able to increase biograft vascularization and to show that the preexisting human vessels can become functional and contribute to tissue perfusion. PMID:19642856

  8. Fluorescence Lifetimes of Normal and Carcinomatous Human Nasopharyngeal Tissues

    NASA Astrophysics Data System (ADS)

    Chen, M.; Li, H.; Li, B.; Chen, R.; Zheng, G.; Song, C.

    2016-03-01

    Time-resolved fluorescence spectra of normal and carcinomatous in vitro human nasopharyngeal tissues are compared. By fitting the time-resolved emission with exponential decays, mean lifetimes were obtained. There were marked differences between the lifetimes of the carcinomatous and the normal tissues. Thus, early diagnosis of nasopharyngeal carcinoma is possible. In general, comprehensive information from human tissue autofluorescence can be acquired via both time-resolved and steady-state fluorescence spectra.

  9. The human transcriptome across tissues and individuals

    PubMed Central

    Melé, Marta; Ferreira, Pedro G.; Reverter, Ferran; DeLuca, David S.; Monlong, Jean; Sammeth, Michael; Young, Taylor R.; Goldmann, Jakob M; Pervouchine, Dmitri D.; Sullivan, Timothy J.; Johnson, Rory; Segrè, Ayellet V.; Djebali, Sarah; Niarchou, Anastasia; Wright, Fred A.; Lappalainen, Tuuli; Calvo, Miquel; Getz, Gad; Dermitzakis, Emmanouil T.; Ardlie, Kristin G.; Guigó, Roderic

    2015-01-01

    Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes. PMID:25954002

  10. Pharmacokinetics of Telithromycin in Plasma and Soft Tissues after Single-Dose Administration to Healthy Volunteers

    PubMed Central

    Gattringer, Rainer; Urbauer, Eleonora; Traunmüller, Friederike; Zeitlinger, Markus; Dehghanyar, Pejman; Zeleny, Petra; Graninger, Wolfgang; Müller, Markus; Joukhadar, Christian

    2004-01-01

    By use of microdialysis we assessed the concentrations of telithromycin in muscle and adipose tissue to test its ability to penetrate soft tissues. The ratios of the area under the concentration-versus-time curve from 0 to 24 h to the MIC indicated that free concentrations of telithromycin in tissue and plasma might be effective against Streptococcus pyogenes but not against staphylococci and human and animal bite pathogens. PMID:15561839

  11. Predicting DNA methylation level across human tissues

    PubMed Central

    Ma, Baoshan; Wilker, Elissa H.; Willis-Owen, Saffron A. G.; Byun, Hyang-Min; Wong, Kenny C. C.; Motta, Valeria; Baccarelli, Andrea A.; Schwartz, Joel; Cookson, William O. C. M.; Khabbaz, Kamal; Mittleman, Murray A.; Moffatt, Miriam F.; Liang, Liming

    2014-01-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  12. Predicting DNA methylation level across human tissues.

    PubMed

    Ma, Baoshan; Wilker, Elissa H; Willis-Owen, Saffron A G; Byun, Hyang-Min; Wong, Kenny C C; Motta, Valeria; Baccarelli, Andrea A; Schwartz, Joel; Cookson, William O C M; Khabbaz, Kamal; Mittleman, Murray A; Moffatt, Miriam F; Liang, Liming

    2014-04-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R(2) increases from 0.38 (original R(2) between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  13. 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.

  14. Analysis of human breast tissues with Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Gang; Zhang, Lin; Liu, Jianhong; Yu, Fan; Sun, Shizhong

    2006-01-01

    Raman microspectroscopy was used to study normal, benign and malignant human breast tissues. The Raman spectrum of normal breast tissue recorded with 514.5 nm line of Ar + laser excitation contains features attributed to carotenoids and lipids. The CH II bending mode near 1447 cm -1 in normal tissue shifts up to 1454 cm -1 in diseased tissues (benign and malignant). The band near 1660 cm -1 in normal tissue is narrow and sharp; whereas the band is broaden in the diseased tissues. In the region of C-H stretching mode, the 2902-/2860-cm -1 intensity ratio shows differences among normal, benign and malignant breast tissues. The ratio is the smallest in carcinoma tissue. The observed spectra differences may be used to probe breast lesion. The results show that Raman spectroscopic technique may have clinical applications.

  15. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    EPA Science Inventory

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE
    AFTER ACUTE ORAL ADMINISTRATION

    Michael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  16. Identification of progesterone receptor in human subcutaneous adipose tissue.

    PubMed

    O'Brien, S N; Welter, B H; Mantzke, K A; Price, T M

    1998-02-01

    Sex steroids are postulated to play a role in adipose tissue regulation and distribution, because the amount and location of adipose tissue changes during puberty and menopause. Because of the nature of adipose tissue, receptors for the female sex steroids have been difficult to demonstrate. To date, estrogen receptor messenger RNA and protein have been identified in human subcutaneous adipose tissue, but the presence of progesterone receptor (PR) has not been reported. In this study, we demonstrate PR message by Northern blot analysis in RNA isolated from the abdominal subcutaneous adipose tissue of premenopausal women. These preliminary studies revealed that PR messenger RNA levels are higher in the stromal-vascular fraction as opposed to the adipocyte fraction. Western blot analysis demonstrates both PR protein isoforms (human PR-A and human PR-B) in human subcutaneous adipose tissue. Using an enzyme-linked immunosorbent assay, total PR could be quantitated. These studies substantiate that sex steroid receptors are present in human adipose tissue, thereby providing a direct route for regulation of adipose tissue by female sex steroids. PMID:9467566

  17. 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

    2016-05-01

    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). PMID:26921406

  18. Distribution of miRNA expression across human tissues

    PubMed Central

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

    2016-01-01

    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). PMID:26921406

  19. 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.

  20. 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.

  1. National Human Adipose Tissue Survey (Nhats)

    EPA Science Inventory

    Background:

    The U.S. Environmental Protection Agency (EPA)'s National Human Monitoring Program (NHMP), established by the U.S. Public Health Service in 1967, used an exposure-based approach to assess human exposure to toxic substances. Its primary component was the Natio...

  2. Bovine Leukemia Virus DNA in Human Breast Tissue

    PubMed Central

    Shen, Hua Min; Jensen, Hanne M.; Choi, K. Yeon; Sun, Dejun; Nuovo, Gerard

    2014-01-01

    Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease. PMID:24750974

  3. 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...

  4. Tissue-based imaging model of human trabecular meshwork.

    PubMed

    Chu, Edward R; Gonzalez, Jose M; Tan, James C H

    2014-01-01

    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

  5. Tissue distribution of amiodarone and desethylamiodarone in rats after multiple intraperitoneal administration of various amiodarone dosages.

    PubMed

    Plomp, T A; Wiersinga, W M; Maes, R A

    1985-01-01

    Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was studied after repeated intraperitoneal administration of the drug. Tissue and serum concentrations of amiodarone and desethylamiodarone were determined by high-performance liquid chromatography. The levels of amiodarone and desethylamiodarone in serum and tissues obtained after repeated intraperitoneal application of doses varying from 25 mg to 200 mg/kg show that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent and both drugs are preferentially distributed in decreasing order in adipose tissue, lung, liver, kidney and thyroid gland. The penetration of the drug and its metabolite into brain was poor and with all the applied dosages brain levels were considerably lower than the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were substantially lower than the corresponding amiodarone concentrations and varied from 1 to 48% (mean 15%) depending on the dosage used and the kind of tissue. The amiodarone tissue/serum concentration ratios were exceptionally high in adipose tissue (1,000-4,000) and moderate to high in the other tissues except brain (5-90), and indicate an extensive distribution of the drug with fat as a reservoir with a large storage capacity. The levels of amiodarone and desethylamiodarone, obtained with 50 mg/kg and 100 mg/kg dosages, showed in function of time clearly an increase in serum and tissues. The observed amiodarone tissue/serum ratios in function of time revealed no further significant increase (p less than or equal to 0.05) after 3 injections over a 6-day period, indicating the attainment of "steady-state".(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4039141

  6. 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. PMID:26609415

  7. 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

  8. 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.

  9. 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. PMID:25788148

  10. Metabolism of human insulin after subcutaneous administration: A possible means to uncover insulin misuse.

    PubMed

    Thomas, Andreas; Brinkkötter, Paul; Schänzer, Wilhelm; Thevis, Mario

    2015-10-15

    The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases. In vitro experiments with skin tissue lysates (S9 fraction and microsomes), different biological fluids (urine, serum, plasma) and recombinant human insulin were performed and the deriving metabolites were characterized by liquid chromatography coupled to high resolution mass spectrometry (HRMS). Afterwards, authentic blood samples of patients suffering from diabetes mellitus and a control group of healthy humans were analysed. Therefore, a method using protein precipitation, ultrafiltration and antibody-coated magnetic beads for purification with subsequent separation by nano-scale liquid chromatography coupled a Q Exactive mass spectrometer was applied. Several metabolites of insulin with C-terminally truncated sequences of the B-chain (and A-chain in minor extent) were identified within this study. Here, the DesB30 human insulin represents the major metabolite in all experiments. This metabolite is frequently found in urine samples due to degradation processes and, thus, disqualifies this matrix for the intended purposes. In contrast, blood samples do commonly not contain DesB30 insulin, which was corroborated by data obtained from the control group. In post-administration blood samples, minute but distinct amounts (approx. 50 pg mL(-1)) of DesB30 insulin were found and suggest the use of this analyte as potential marker for subcutaneous human insulin administration, supporting the attempts to

  11. Tissue distribution of cloxacillin after intramammary administration in the isolated perfused bovine udder

    PubMed Central

    2010-01-01

    Background Various intramammary suspensions containing cloxacillin benzathine are registered for use in cattle as antibiotics for intramammary use at drying off. To ensure antibacterial efficacy, the glandular tissue concentration of an antimicrobial agent must be sufficient. Since the possibilities to measure concentrations in the different areas of the glandular tissue in vivo are very limited, it was the aim of the present study to examine the distribution of cloxacillin in vitro using the isolated perfused bovine udder. Methods Mammary glands taken at slaughter from healthy lactating cows were perfused in vitro with warmed and gassed Tyrode solution. 600 mg cloxacillin benzathine were administered as Orbenin Extra Dry Cow by the intramammary route to six front and rear quarters each. Samples of glandular tissue - at different distances from and vertical to the teat right up to the udder base - were gathered from the treated quarters after 6 h. Perfusate was also sampled before and hourly after treatment for 6 h. The cloxacillin content of the tissue samples and perfusate samples was analysed by high performance liquid chromatography. Results The concentration of cloxacillin in the glandular tissue of front quarters measured 6 h after administration tended to decrease with increasing vertical distance from the teat. The decrease pattern of the concentration was not quite clear in rear quarters. A considerable variation in the tissue concentrations of cloxacillin was obvious, which reflects in vivo conditions. The concentrations measured in the perfusate samples were below the limit of quantification at all time points, indicating limited absorption of the antibiotic from the glandular tissue. Conclusion After intramammary administration of the dry off product containing cloxacillin benzathine concentrations of more than 0.5 μg/g (MIC) were reached in all regions of the front and rear quarters. PMID:20925913

  12. Changes in Metallothionein Level in Rat Hepatic Tissue after Administration of Natural Mouldy Wheat

    PubMed Central

    Vasatkova, Anna; Krizova, Sarka; Adam, Vojtech; Zeman, Ladislav; Kizek, Rene

    2009-01-01

    Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. This work was aimed at investigation of influence of mouldy wheat contaminated by pathogenic fungi producing mycotoxins on metallothionein levels in hepatic tissue of rats. The rats were administrating feed mixtures with different contents of vitamins or naturally mouldy wheat for 28 days. It was found that the wheat contained deoxynivalenol (80 ± 5 μg per kg of mouldy wheat), zearalenone (56 ± 3 μg/kg), T2-toxin (20 ± 2 μg/kg) and aflatoxins as a sum of B1, B2, G1 and G2 (3.9 ± 0.2 μg/kg). Rats were fed diets containing 0, 33, 66 and 100% naturally moulded wheat. Control group 0, 33, 66 and 100% contained vitamins according to Nutrient Requirements of Rats (NRC). Other four groups (control group with vitamins, vit33, vit66 and vit100%) were fed on the same levels of mouldy wheat, also vitamins at levels 100% higher than the previous mixtures. We determined weight, feed conversion and performed dissection to observe pathological processes. Changes between control group and experimental groups exposed to influence of mouldy wheat and experimental groups supplemented by higher concentration of vitamins and mouldy wheat were not observed. Livers were sampled and did not demonstrate significant changes in morphology compared to control either. In the following experiments the levels of metallothionein as a marker of oxidative stress was determined. We observed a quite surprising trend in metallothionein levels in animals supplemented with increased concentration of vitamins. Its level enhanced with increasing content of mouldy wheat. It was possible to determine a statistically significant decline (p<0.05) between control group and groups of animals fed with 33, 66 and 100% mouldy wheat. It is likely that some mycotoxins presented in mouldy wheat are able to block the mechanism of metallothionein synthesis. PMID:19399242

  13. 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

    ... 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 culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  14. 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

    ... 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 culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  15. 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

    ... 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 culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  16. 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

    ... 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 culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  17. 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

    ... 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 culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  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. Predicting tissue-specific enhancers in the human genome

    PubMed Central

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

    2007-01-01

    Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multicellular complexity; yet the genetic code of vertebrate gene regulation remains poorly understood. In an attempt to elucidate this code, we synergistically combined genome-wide gene-expression profiling, vertebrate genome comparisons, and transcription factor binding-site analysis to define sequence signatures characteristic of candidate tissue-specific enhancers in the human genome. We applied this strategy to microarray-based gene expression profiles from 79 human tissues and identified 7187 candidate enhancers that defined their flanking gene expression, the majority of which were located outside of known promoters. We cross-validated this method for its ability to de novo predict tissue-specific gene expression and confirmed its reliability in 57 of the 79 available human tissues, with an average precision in enhancer recognition ranging from 32% to 63% and a sensitivity of 47%. We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to ∼328,000 human–mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision. These results indicate the power of combining complementary genomic data sets as an initial computational foray into a global view of tissue-specific gene regulation in vertebrates. PMID:17210927

  20. Investigation of endocrine and immunological response in fat tissue to hyperbaric oxygen administration in rats.

    PubMed

    Şen, H; Erbağ, G; Ovali, M A; Öztopuz, R Ö; Uzun, M

    2016-01-01

    Though HBO treatment is becoming more common, the mechanism of action is not fully known. The positive effects of HBO administration on the inflammatory response is thought to be a possible basic mechanism. As a result, we aimed to research whether endocrine and immunological response of fat tissue changes in rats given HBO treatment model. This research was carried out on Wistar albino rats, they were treated with hyperbaric oxygen therapy. Their fatty tissue were taken from the abdomen, gene expression of the cytokines and adipokines were analyzed with Real time PCR method. When the gene expression of hormones and cytokines by fat tissue was examined, the leptin, visfatin, TNF-α, IL-1β and IL-10 levels in the HBO treatment group were statistically significantly increased compared to the control group (p=0.0313, p=0.0156, p=0.0156, p=0.0156, p=0.0313). In conclusion, in our study we identified that HBO administration affected the endochrinological functions of fat tissue. PMID:27188864

  1. Tissue toxicity following the vaginal administration of nanosilver particles in rabbits.

    PubMed

    Chen, Dandan; Yang, Zhaopeng

    2015-12-01

    Nanosilver particles are used in various clinical settings because of their antibacterial properties. However, their safety evaluation when used for gynaecological disorders has not been established. Nanosilver particles were administrated in the vagina of New Zealand rabbits, and the pathological appearance of the surrounding tissue was examined by hematoxylin-eosin staining and transmission electron microscopy (TEM) after 1 and 3 days of treatment. The nanosilver content was assessed by plasma mass spectrometry, and the presence of particles in the hepatic portal vein blood was assessed by TEM. The results of our study show that the vaginal administration of nanosilver particles caused ultrastructural changes to the vaginal mucosa, urethra and rectum, with accumulation of particles in all tissues. These results demonstrate a new migration route of nanosilver particles following vaginal administration. They also demonstrate, for the first time, that the vaginal administration of nanosilver particles can enter the blood circulation system by examining the hepatic portal vein blood under the TEM which is the most direct visualized evidence. PMID:26816649

  2. Tissue toxicity following the vaginal administration of nanosilver particles in rabbits

    PubMed Central

    Chen, Dandan; Yang, Zhaopeng

    2015-01-01

    Nanosilver particles are used in various clinical settings because of their antibacterial properties. However, their safety evaluation when used for gynaecological disorders has not been established. Nanosilver particles were administrated in the vagina of New Zealand rabbits, and the pathological appearance of the surrounding tissue was examined by hematoxylin–eosin staining and transmission electron microscopy (TEM) after 1 and 3 days of treatment. The nanosilver content was assessed by plasma mass spectrometry, and the presence of particles in the hepatic portal vein blood was assessed by TEM. The results of our study show that the vaginal administration of nanosilver particles caused ultrastructural changes to the vaginal mucosa, urethra and rectum, with accumulation of particles in all tissues. These results demonstrate a new migration route of nanosilver particles following vaginal administration. They also demonstrate, for the first time, that the vaginal administration of nanosilver particles can enter the blood circulation system by examining the hepatic portal vein blood under the TEM which is the most direct visualized evidence. PMID:26816649

  3. Polybrominated diphenyl ethers: human tissue levels and toxicology.

    PubMed

    Gill, Udai; Chu, Ih; Ryan, John J; Feeley, Mark

    2004-01-01

    PBDEs are being released to the environment in wastes from their production facilities, degradation, or leaching and volatilization from products that contain PBDEs during the product's useful life. Brominated diphenyl ether congeners BDE-47, -99, and -153 are ubiquitous in the environment and are regarded as the most dominant congeners present in wildlife and humans. The tetra- to hexa-BDE are most likely the congeners to which humans are exposed through food consumption. Knowledge of PBDE uptake, metabolism, elimination, and enzyme induction is restricted largely to rodents (rats and mice) in vitro and in vivo. Feeding studies have shown that excretion of higher brominated BDEs is much greater than lower brominated BDEs. Penta-BDE is more toxic than octa- and deca-BDE following oral administration (oral LD50 in rats, 0.5-5 g/kg). In rodents, repeated exposure to PBDEs results in thyroid hormone disruption, developmental neurotoxicity, some changes of fetal development, and hepatotoxic effects. The observed chronic NOELs depend upon the technical mixture type (i.e., deca-, octa-, or penta- and their congener composition), animal species, and study protocol. Values range from 0.6 to 100 mg/kg in rats and from I to 100 mg/kg in mice. PBDEs are neither mutagenic nor genotoxic. Immunotoxicity in mice is observed following exposure to BDE-47 at 18 mg/kg/d, where splenocyte number decreased. Mice exposed neonatally to a single oral dose of BDE-47(10.5 mg/kg) or BDE-99 (12 mg/kg) on Pnd10 (period of rapid brain growth and development) show permanent impairment of spontaneous motor behavior when reaching adulthood. BDE-99 also induced adverse effects on learning and memory functions of mice. The estimated daily intake based on food consumption for PBDEs ranges from 44 to 51 ng/d, with fish contributing almost one-half. The BDE-99 body burden from a human milk survey can be estimated at 0.64 microg/kg, well below the experimental body burden of 0.4 mg/kg BDE-99 associated

  4. Expression of tmp21 in normal adult human tissues

    PubMed Central

    Xie, Jian; Yang, Yuan; Li, Jianbo; Hou, Jing; Xia, Kun; Song, Weihong; Liu, Shengchun

    2014-01-01

    TMP21, known as p23 protein, is one important member of the p24 protein families. The degradation of TMP21 is mediated by the ubiquitin-proteasome pathway, as with the other presenilin-associated γ-secretase complex members. NFAT plays a very important role in regulation of human TMP21 gene expression. Compared with the function of TMP21, the studies about the distribution of this protein in human tissues are limited. We collected 19 normal adult human tissues from a healthy adult man died in a traffic accident and did examination of all the tissues collected for ICH, western blot and RT-PCR. It was shown that the expression of TMP21 is at high levels in heart, liver, lung, kidney and adrenal gland; moderate levels in brain, pancreas, prostate gland, testicle, small intestine, colon, stomach, gall bladder, thyroid gland and trachea; low levels in skeletal muscle, skin and lymphonodus. TMP21 is widely existed in normal adult human tissues. The current study provided for the first time a comprehensive expression of TMP21 in normal adult human tissues. It will benefit on helping in the design and interpretation of future studies focused on expounding the function of TMP21. PMID:25356171

  5. 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.

  6. Ceftiofur derivates in serum and endometrial tissue after intramuscular administration in healthy mares.

    PubMed

    Witte, T S; Bergwerff, A A; Scherpenisse, P; Drillich, M; Heuwieser, W

    2010-08-01

    Endometritis is one of the major problems in the horse breeding industry. The use of antibiotics for treatment of endometritis in the mare is recommended as best practice. The intrauterine application of antibiotics, however, has been under discussion over the last years because of concerns about its efficacy. The systemic use of antibiotics has been considered more effective because of its better distribution within the uterus. The objective of the present study was to determine the concentration of ceftiofur derivates in serum and endometrial tissue after intramuscular administration. Specifically, the authors tested the hypothesis that ceftiofur concentrations in serum and endometrial tissue remain above the minimum inhibitory concentration (MIC) for common uterine pathogens for 24 h. Nine mares in estrus received a single dose of 2.2 mg/kg ceftiofur hydrochloride intramuscular per kg of body weight. Blood samples and endometrial tissue were obtained immediately before treatment (-1 h) and 2 h and 24 h after treatment. Endometrial tissue was collected with a Kevorkian biopsy punch. Additional blood samples were collected 4 h and 10 h after treatment from the jugular veins. For determination of ceftiofur derivates in serum and endometrial tissue a high performance liquid chromatography (HPLC) assay was used. Results in serum and uterine tissue revealed greatest concentration of ceftiofur at 2 h and lowest concentrations at 24 h after treatment. Concentrations of ceftiofur at 2 and 24 h after treatment were significantly greater in serum than in endometrial tissue, but remained above the reported MIC for Streptococcus equi zooepidemicus and Escherichia coli in both serum and endometrial tissue until 24 h after treatment. PMID:20494421

  7. 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.

  8. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  9. Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration.

    PubMed

    Coetzee, J F; Mosher, R A; Griffith, G R; Gehring, R; Anderson, D E; KuKanich, B; Miesner, M

    2015-12-01

    The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297-392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC-MS-MS methods. The mean (± SD) Cmax , Cmin , and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam-treated calves will have low residue concentrations by 21 days after repeated oral administration. PMID:25708937

  10. Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

    PubMed Central

    Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; De Paepe, Monique E.; Gruppuso, Philip A.; Sanders, Jennifer A.

    2014-01-01

    Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology. PMID:25193996

  11. Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis.

    PubMed

    Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; De Paepe, Monique E; Gruppuso, Philip A; Sanders, Jennifer A

    2014-12-01

    Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology. PMID:25193996

  12. 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.

  13. Integrative analysis of haplotype-resolved epigenomes across human tissues.

    PubMed

    Leung, Danny; Jung, Inkyung; Rajagopal, Nisha; Schmitt, Anthony; Selvaraj, Siddarth; Lee, Ah Young; Yen, Chia-An; Lin, Shin; Lin, Yiing; Qiu, Yunjiang; Xie, Wei; Yue, Feng; Hariharan, Manoj; Ray, Pradipta; Kuan, Samantha; Edsall, Lee; Yang, Hongbo; Chi, Neil C; Zhang, Michael Q; Ecker, Joseph R; Ren, Bing

    2015-02-19

    Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich data sets described here will enhance our understanding of the mechanisms by which cis-regulatory elements control gene expression programs. PMID:25693566

  14. Integrative analysis of haplotype-resolved epigenomes across human tissues

    PubMed Central

    Schmitt, Anthony; Selvaraj, Siddarth; Lee, Ah Young; Yen, Chia-An; Lin, Shin; Lin, Yiing; Qiu, Yunjiang; Xie, Wei; Yue, Feng; Hariharan, Manoj; Ray, Pradipta; Kuan, Samantha; Edsall, Lee; Yang, Hongbo; Chi, Neil C.; Zhang, Michael Q.; Ecker, Joseph R.; Ren, Bing

    2015-01-01

    Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here, for the first time, we delineate allelic chromatin modifications and transcriptomes amongst a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy1. The resulting masses of haplotype-resolved epigenomic maps reveal extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich datasets described here will enhance our understanding of the mechanisms of how cis-regulatory elements control gene expression programs. PMID:25693566

  15. Solubility of Freon 22 in human blood and lung tissue

    SciTech Connect

    Varene, N.; Choukroun, M.L.; Marthan, R.; Varene, P.

    1989-05-01

    The solubility of Freon 22 in human blood and lung tissue was determined using the chromatographic method of Wagner et al. In normal human blood, the mean Bunsen coefficient of solubility (alpha B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased with hematocrit (Hct) according to the equation alpha B = 0.274 Hct + 0.691. Tissue homogenates were prepared from macroscopically normal lung pieces obtained at thoracotomy from eight patients undergoing resection for lung carcinoma. The Bunsen solubility coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed and unwashed lung, respectively. These values can be used in the determination of both cardiac output and pulmonary tissue volume in humans by use of the rebreathing technique.

  16. Comparison of tissue and plasma levels of ibuprofen after oral and topical administration.

    PubMed

    Dominkus, M; Nicolakis, M; Kotz, R; Wilkinson, F E; Kaiser, R R; Chlud, K

    1996-12-01

    The penetration and absorption of ibuprofen (CAS 15687-27-1) from a topical gel and oral tablets were tested in an open study, performed in 17 patients with degenerative knee disorders requiring an operation. Patients administered the topical test preparation (ibugel, 3 x 375 mg ibuprofen daily) or the standard oral preparation (2 x 600 mg ibuprofen daily) for 3 days prior to the operation. Samples of blood, synovial fluid, muscle, fasciae and subcutis were obtained during the operation (15 h after the last administration) and analysed for ibuprofen content using a validated HPLC method. Different absorption profiles were observed for topical and oral administration. Oral administration led to higher concentrations in the plasma, synovial fluid and fasciae, while higher levels in the muscle and subcutis were found after topical administration. After topical application, the concentrations in the fasciae, muscle and subcutis were significantly higher than those in the blood plasma and synovial fluid (p < 0.05). Very low levels of ibuprofen were observed in the subcutis after oral administration. This can be explained by the different pathways. This study demonstrated that concentrations of ibuprofen in the various biological samples were still within therapeutically effective levels 15 h after topical or oral administration. By use of an oral comparison group, it has been possible to show that the concentrations in times directly under the site of topical application lie in the same order of magnitude as those found after preoral treatment. Therapy of intra-articular inflammatory and degenerative joint diseases requires oral administration of non-steroidal anti-inflammatory drugs (NSAIDs). However, based on the results of this study, topical therapy with NSAIDs can be recommended for soft tissue rheumatism and periarticular insertion tendinopathia. PMID:9006788

  17. Gastroenterology-urology devices; classification of tissue culture media for human ex vivo tissue and cell culture processing applications. Final rule.

    PubMed

    2001-05-16

    The Food and Drug Administration (FDA) is classifying tissue culture media for human ex vivo tissue and cell culture processing applications into class II (special controls). The special control that will apply to this device is a guidance document entitled "Class II Special Controls Guidance Document: issue Culture Media for Human Ex Vivo Tissue and Cell Culture Processing Applications; Final Guidance for Industry and FDA Reviewers." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997. The agency is classifying these devices into class II (special controls) in order to provide a reasonable assurance of the safety and effectiveness of the devices. PMID:11721690

  18. Fluorescence Spectroscopy of Human Nonmalignant and Malignant Cells and Tissues.

    NASA Astrophysics Data System (ADS)

    Glassman, Wenling Sha

    This thesis explores steady state and time resolved fluorescence spectroscopy from human malignant and non -malignant cells and tissues. The focus of these studies are the analysis of the excitation spectra, emission spectra, and decay time based on the contribution from several key intrinsic fluorophors: NAD(P)H, flavins, tryptophan, elastin and collagen that exist in different amounts in the human tissues and cells. The comparison between the spectra from malignant and non-malignant cells and tissues gives information on the changes that occur from non-malignancy to malignancy in the cells and tissues. The spectra of tissues and cells are also compared to help in understanding what fluorophors are responsible for fluorescence spectral differences between the malignant and non-malignant tissues and cells. The results in this thesis show that the spectral differences between the normal and cancerous tissues and cells exist in various wavelength ranges. The experimental data from GYN tissues have shown with over 95% of the sensitivity and specificity to separate malignant from non-malignant tissues using 300nm excitation. The 340nm band, which is mostly in response to intrinsic fluorophor (amino acid tryptophan), from malignant tissues were relatively higher then that from the non-malignant tissues. This might have been caused by the higher concentration of free tryptophan in the malignant tumor when compared to that of the normal tissue. This has been found in medical clinical study. The experimental data in this thesis also show that the fluorescence intensities around 450nm-460nm, which are mostly due to the intrinsic fluorophor coenzyme NADH, from both malignant cells in vitro and tissues in vitro are relatively higher than from non-malignant cells in vitro and tissues in vitro. These findings are reinforced by the faster decay time of the NADH fluorescence from normal cells in vitro than from neoplasm cells in vitro. Thus, the NADH in the mitochondria might be

  19. 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

    2015-11-01

    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. PMID:26414679

  20. 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..., recall, and destruction of human tissue. (a) Upon a finding that human tissue may be in violation of the... dispose of the tissue in any manner except to recall and/or destroy the tissue consistent with...

  1. 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..., recall, and destruction of human tissue. (a) Upon a finding that human tissue may be in violation of the... dispose of the tissue in any manner except to recall and/or destroy the tissue consistent with...

  2. 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..., recall, and destruction of human tissue. (a) Upon a finding that human tissue may be in violation of the... dispose of the tissue in any manner except to recall and/or destroy the tissue consistent with...

  3. 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. PMID:8884541

  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. Thermogenic potential and physiological relevance of human epicardial adipose tissue

    PubMed Central

    Chechi, K; Richard, D

    2015-01-01

    Epicardial adipose tissue is a unique fat depot around the heart that shares a close anatomic proximity and vascular supply with the myocardium and coronary arteries. Its accumulation around the heart, measured using various imaging modalities, has been associated with the onset and progression of coronary artery disease in humans. Epicardial adipose tissue is also the only fat depot around the heart that is known to express uncoupling protein 1 at both mRNA and protein levels in the detectable range. Recent advances have further indicated that human epicardial fat exhibits beige fat-like features. Here we provide an overview of the physiological and pathophysiological relevance of human epicardial fat, and further discuss whether its thermogenic properties can serve as a target for the therapeutic management of coronary heart disease in humans. PMID:27152172

  6. Tissue dosimetry, metabolism and excretion of pentavalent and trivalent dimethylated arsenic in mice after oral administration

    SciTech Connect

    Hughes, Michael F. Devesa, Vicenta; Adair, Blakely M.; Conklin, Sean D.; Creed, John T.; Styblo, Miroslav; Kenyon, Elaina M.; Thomas, David J.

    2008-02-15

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were administered [{sup 14}C]-DMA(V) (0.6 or 60 mg As/kg) and sacrificed serially over 24 h. Tissues and excreta were collected for analysis of radioactivity. Other mice were administered unlabeled DMA(V) (0.6 or 60 mg As/kg) or dimethylarsinous acid (DMA(III)) (0.6 mg As/kg) and sacrificed at 2 or 24 h. Tissues (2 h) and urine (24 h) were collected and analyzed for arsenicals. Absorption, distribution and excretion of [{sup 14}C]-DMA(V) were rapid, as radioactivity was detected in tissues and urine at 0.25 h. For low dose DMA(V) mice, there was a greater fractional absorption of DMA(V) and significantly greater tissue concentrations of radioactivity at several time points. Radioactivity distributed greatest to the liver (1-2% of dose) and declined to less than 0.05% in all tissues examined at 24 h. Urinary excretion of radioactivity was significantly greater in the 0.6 mg As/kg DMA(V) group. Conversely, fecal excretion of radioactivity was significantly greater in the high dose group. Urinary metabolites of DMA(V) included DMA(III), trimethylarsine oxide (TMAO), dimethylthioarsinic acid and trimethylarsine sulfide. Urinary metabolites of DMA(III) included TMAO, dimethylthioarsinic acid and trimethylarsine sulfide. DMA(V) was also excreted by DMA(III)-treated mice, showing its sensitivity to oxidation. TMAO was detected in tissues of the high dose DMA(V) group. The low acute toxicity of DMA(V) in the mouse appears to be due in part to its minimal retention and rapid elimination.

  7. 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

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

    PubMed

    Sanger, G J; Broad, J; Kung, V; Knowles, C H

    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. PMID:22946540

  9. Analysis of the phosphofructokinase subunits and isoenzymes in human tissues.

    PubMed Central

    Dunaway, G A; Kasten, T P; Sebo, T; Trapp, R

    1988-01-01

    The 6-phosphofructo-1-kinase (PFK) subunits and isoenzymes were studied in human muscle, heart, brain, liver, platelets, fibroblasts, erythrocytes, placenta and umbilical cord. In each tissue, the subunit types in the native isoenzymes were characterized by immunological titration with subunit-specific antibodies and by column chromatography on QAE (quaternary aminoethyl)-Sephadex. Further, the subunits of the partially purified native isoenzymes were resolved by SDS/polyacrylamide-gel electrophoresis, identified by immunoblotting, and quantified by scanning gel densitometry of silver-stained gels and immunoblots. Depending on the type of tissue, one to three subunits were detected. The Mr values of the L, M and C subunits regardless of tissue were 76,700 +/- 1400, 82,500 +/- 1640 and 86,500 +/- 1620. Of the tissues studied, only the muscle PFK isoenzymes exhibited one subunit, which was the M-type subunit. Of the other tissues studied, the PFK isoenzymes contained various amounts of all three subunits. Considering the properties of the native PFK isoenzymes, it is clear that, in human tissues, they are not simply various combinations of two or three homotetrameric isoenzymes, but complex mixtures of homotetramers and heterotetramers. The kinetic/regulatory properties of the various isoenzyme pools were found to be dependent on subunit composition. Images Fig. 1. PMID:2970843

  10. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    PubMed

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). PMID:24254959

  11. 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.

  12. Does Intravenous Administration of Recombinant Tissue Plasminogen Activator for Ischemic Stroke can Cause Inferior Myocardial Infarction?

    PubMed Central

    Almasi, Mostafa; Razmeh, Saeed; Habibi, Amir Hassan; Rezaee, Amir Hassan

    2016-01-01

    Recombinant tissue plasminogen activator (rTPA) is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI) is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved. PMID:27441068

  13. 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

  14. 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.

  15. 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.

  16. Renal nursing and the Human Tissue Act 2004.

    PubMed

    Robertson, Abbe; Noble, Helen

    The Human Tissue Act of 2004 was introduced in the UK on 1 September 2006. It replaced all Acts that previously governed the procurement and utilization of tissues, cells and organs. It has promoted changes in requirements predominantly in transplantation settings. Past research has highlighted a shortage of organs for transplantation, particularly in renal donation. The new act hopes to remedy this so that future renal transplantations will occur more frequently, therefore improving choice and quality of life for patients with end stage renal disease. For UK renal nurses, the implementation of the Human Tissue Act 2004 presents challenges requiring adaptations of prior learning with new nursing roles. Recommendations can be made to help during the change process. Kurt Lewin's model of change provides a foundation for the understanding and recognition of change processes that occur in the implementation of individual and organizational change. PMID:17851366

  17. The implications of the Human Tissue Act 2004 for dentistry.

    PubMed

    Forsyth, Laura; Woof, Marcus

    2006-12-23

    Partly as a consequence of the inquiries into the events at the Bristol Royal Infirmary and the Royal Liverpool Children's Hospital (Alder Hey), the Government recently enacted the Human Tissue Act 2004. The main provisions of the Act came into force on 1 September 2006 and have potential implications for dentists. PMID:17183410

  18. Plant-Derived Human Collagen Scaffolds for Skin Tissue Engineering

    PubMed Central

    Willard, James J.; Drexler, Jason W.; Das, Amitava; Roy, Sashwati; Shilo, Shani; Shoseyov, Oded

    2013-01-01

    Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues, such as bovine hide. Risks associated with the use of these materials include hypersensitivity and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity, but possess the risk of disease transmission. Methods engineering recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin (ES), PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. The processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than the bovine material. Interleukin-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of ES. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission. PMID:23298216

  19. Plant-derived human collagen scaffolds for skin tissue engineering.

    PubMed

    Willard, James J; Drexler, Jason W; Das, Amitava; Roy, Sashwati; Shilo, Shani; Shoseyov, Oded; Powell, Heather M

    2013-07-01

    Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues, such as bovine hide. Risks associated with the use of these materials include hypersensitivity and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity, but possess the risk of disease transmission. Methods engineering recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin (ES), PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. The processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than the bovine material. Interleukin-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of ES. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission. PMID:23298216

  20. More insights into a human adipose tissue GPAT activity assay

    PubMed Central

    Morgan-Bathke, Maria; Chen, Liang; Oberschneider, Elisabeth; Harteneck, Debra; Jensen, Michael D

    2016-01-01

    ABSTRACT Adipose tissue fatty acid storage varies according to sex, adipose tissue depot and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We recently published findings based on the glycerol 3-phosphate acyltransferase (GPAT) enzyme activity assay we optimized for use with human adipose tissue. These findings include a decrease in total GPAT and GPAT1 as a function of adipocyte size in both omental and subcutaneous adipose tissue and a strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots and between these storage factors and palmitate storage rates into TAG. The aim of this commentary is to expand upon the data from our recent publication. We describe here additional details on the optimization of the GPAT enzyme activity assay, a correlation between DGAT and percentage palmitate in the diacylglycerol fraction, and sex differences in fatty acid storage factors and storage rates into TAG at high palmitate concentrations. PMID:27144101

  1. Optical spectroscopy for quantitative sensing in human pancreatic tissues

    NASA Astrophysics Data System (ADS)

    Wilson, Robert H.; Chandra, Malavika; Lloyd, William; Chen, Leng-Chun; Scheiman, James; Simeone, Diane; McKenna, Barbara; Mycek, Mary-Ann

    2011-07-01

    Pancreatic adenocarcinoma has a five-year survival rate of only 6%, largely because current diagnostic methods cannot reliably detect the disease in its early stages. Reflectance and fluorescence spectroscopies have the potential to provide quantitative, minimally-invasive means of distinguishing pancreatic adenocarcinoma from normal pancreatic tissue and chronic pancreatitis. The first collection of wavelength-resolved reflectance and fluorescence spectra and time-resolved fluorescence decay curves from human pancreatic tissues was acquired with clinically-compatible instrumentation. Mathematical models of reflectance and fluorescence extracted parameters related to tissue morphology and biochemistry that were statistically significant for distinguishing between pancreatic tissue types. These results suggest that optical spectroscopy has the potential to detect pancreatic disease in a clinical setting.

  2. Method for characterizing viscoelasticity of human gluteal tissue.

    PubMed

    Then, C; Vogl, T J; Silber, G

    2012-04-30

    Characterizing compressive transient large deformation properties of biological tissue is becoming increasingly important in impact biomechanics and rehabilitation engineering, which includes devices interfacing with the human body and virtual surgical guidance simulation. Individual mechanical in vivo behaviour, specifically of human gluteal adipose and passive skeletal muscle tissue compressed with finite strain, has, however, been sparsely characterised. Employing a combined experimental and numerical approach, a method is presented to investigate the time-dependent properties of in vivo gluteal adipose and passive skeletal muscle tissue. Specifically, displacement-controlled ramp-and-hold indentation relaxation tests were performed and documented with magnetic resonance imaging. A time domain quasi-linear viscoelasticity (QLV) formulation with Prony series valid for finite strains was used in conjunction with a hyperelastic model formulation for soft tissue constitutive model parameter identification and calibration of the relaxation test data. A finite element model of the indentation region was employed. Strong non-linear elastic but linear viscoelastic tissue material behaviour at finite strains was apparent for both adipose and passive skeletal muscle mechanical properties with orthogonal skin and transversal muscle fibre loading. Using a force-equilibrium assumption, the employed material model was well suited to fit the experimental data and derive viscoelastic model parameters by inverse finite element parameter estimation. An individual characterisation of in vivo gluteal adipose and muscle tissue could thus be established. Initial shear moduli were calculated from the long-term parameters for human gluteal skin/fat: G(∞,S/F)=1850 Pa and for cross-fibre gluteal muscle tissue: G(∞,M)=881 Pa. Instantaneous shear moduli were found at the employed ramp speed: G(0,S/F)=1920 Pa and G(0,M)=1032 Pa. PMID:22360834

  3. Thymoquinone ameliorates testicular tissue inflammation induced by chronic administration of oral sodium nitrite.

    PubMed

    Alyoussef, A; Al-Gayyar, M M H

    2016-06-01

    Although sodium nitrite has been widely used as food preservative, building bases of scientific evidence about nitrite continues to oppose the general safety in human health. Moreover, thymoquinone (TQ) has therapeutic potential as antioxidant, anti-inflammatory, antibacterial and anticancer. Therefore, we investigated the effects of both sodium nitrite and TQ on testicular tissues of rats. Forty adult male Sprague Dawley rats were used. They received either 80 mg kg(-1) sodium nitrite or 50 mg kg(-1) TQ daily for twelve weeks. Serum testosterone was measured. Testis were weighed and the testicular tissue homogenates were used for measurements of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL10, caspase-3, caspase-8 and caspase-9. Sodium nitrite resulted in significant reduction in serum testosterone concentration and elevation in testis weight and Gonado-Somatic Index. We found significant reduction in testicular tissues levels of IL-4 and IL-10 associated with elevated levels of TNF-α, IL-1β, IL-6, caspase-3, caspase-8 and caspase-9. In conclusion, chronic oral sodium nitrite induced changes in the weight of rat testis accompanied by elevation in the testicular tissue level of oxidative stress markers and inflammatory cytokines. TQ attenuated sodium nitrite-induced testicular tissue damage through blocking oxidative stress, restoration of normal inflammatory cytokines balance and blocking of apoptosis. PMID:26260072

  4. 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.

  5. 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

  6. Gene expression in human ovarian tissue after xenografting.

    PubMed

    Van Langendonckt, A; Romeu, L; Ambroise, J; Amorim, C; Bearzatto, B; Gala, J L; Donnez, J; Dolmans, M M

    2014-06-01

    Cryobanking and transplantation of ovarian tissue is a promising approach to restore fertility in cancer patients. However, ischemic stress following avascular ovarian cortex grafting is known to induce stromal tissue fibrosis and alterations in follicular development. The aim of the study was to analyze the impact of freeze-thawing and grafting procedures on gene expression in human ovarian tissue. Frozen-thawed ovarian tissue from 14 patients was xenografted for 7 days to nude mice and one ungrafted fragment was used as a control. Immediately after recovery, grafts were processed for RNA extraction and histological analysis. Their expression profile was screened by whole-genome oligonucleotide array (n = 4) and validated by reverse-transcriptase polymerase chain analysis (n = 10). After data filtering, the Limma package was used to build a linear regression model for each gene and to compute its fold change between tissues on Days 0 and 7. After adjusting the P-value by the Sidak method, 84 of the transcripts were significantly altered after 7 days of grafting, including matrix metalloproteinase-9 and -14 and angiogenic factors such as placental growth factor and C-X-C chemokine receptor type 4 (CXCR4). Major biological processes were related to tissue remodeling, including secretory processes, cellular adhesion and response to chemical and hormonal stimuli. Angiopoietin signaling, the interleukin-8 pathway and peroxisome proliferator-activated receptor activation were shown to be differentially regulated. On Day 7, overexpression was confirmed by PCR for interleukin-8, transforming growth factor-beta 1, matrix metalloproteinase-14 and CXCR4, compared with ungrafted controls. In conclusion, new as well as known genes involved in tissue restructuring and angiogenesis were identified and found to play a key role during the first days after human ovarian tissue transplantation. This will facilitate the development of strategies to optimize grafting techniques. PMID

  7. Modeling network correlations in cortical tissue from juvenile human epileptics

    NASA Astrophysics Data System (ADS)

    Hobbs, Jonathan Paul

    Models of neural tissue can make predictions about a real neural network, but these predictions rely on the data to determine parameters. Hence, the model is only as good as the data. I collected in vitro data removed from juvenile humans with refractory epilepsy, and found human-specific spatial and temporal dynamics that are not found in rats. I will first describe the general characteristics of the human data in comparison with rat data, and my attempts to model these differences with three popular models of neural networks: branching, pair-wise maximum entropy, and a forest fire model. I will describe three key discoveries from this exploration: first, spatial dynamics are more easily satisfied than temporal in both the rat and human tissue, second temporal correlations are not captured by the branching or the maximum entropy model, and thirdly, strong temporal correlations can be accounted for with the addition of a parameter in the forest fire model. Finally I will suggest new questions that this research has revealed about human tissue, and models of neural networks.

  8. Reprogramming of the human intestinal epigenome by surgical tissue transposition

    PubMed Central

    Lay, Fides D.; Triche, Timothy J.; Tsai, Yvonne C.; Su, Sheng-Fang; Martin, Sue Ellen; Daneshmand, Siamak; Skinner, Eila C.; Liang, Gangning; Chihara, Yoshitomo; Jones, Peter A.

    2014-01-01

    Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre- and post-neobladder construction using the Infinium HumanMethylation450 BeadChip. Our study is the first to quantify the effect of environmental cues on the human epigenome and show that the local tissue environment directly modulates DNA methylation patterns in normal differentiated cells in vivo. In the neobladder, the intestinal epithelial cells lose their tissue-specific epigenetic landscape in a time-dependent manner following the tissue’s exposure to a bladder environment. We find that de novo methylation of many intestine-specific enhancers occurs at the rate of 0.41% per month (P < 0.01, Pearson = 0.71), while demethylation of primarily non-intestine-specific transcribed regions occurs at the rate of −0.37% per month (P < 0.01, Pearson = −0.57). The dynamic resetting of the DNA methylome in the neobladder not only implicates local environmental cues in the shaping and maintenance of the epigenome but also illustrates an unexpected cross-talk between the epigenome and the cellular environment. PMID:24515120

  9. 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

  10. Profiling RNA editing in human tissues: towards the inosinome Atlas

    PubMed Central

    Picardi, Ernesto; Manzari, Caterina; Mastropasqua, Francesca; Aiello, Italia; D’Erchia, Anna Maria; Pesole, Graziano

    2015-01-01

    Adenine to Inosine RNA editing is a widespread co- and post-transcriptional mechanism mediated by ADAR enzymes acting on double stranded RNA. It has a plethora of biological effects, appears to be particularly pervasive in humans with respect to other mammals, and is implicated in a number of diverse human pathologies. Here we present the first human inosinome atlas comprising 3,041,422 A-to-I events identified in six tissues from three healthy individuals. Matched directional total-RNA-Seq and whole genome sequence datasets were generated and analysed within a dedicated computational framework, also capable of detecting hyper-edited reads. Inosinome profiles are tissue specific and edited gene sets consistently show enrichment of genes involved in neurological disorders and cancer. Overall frequency of editing also varies, but is strongly correlated with ADAR expression levels. The inosinome database is available at: http://srv00.ibbe.cnr.it/editing/. PMID:26449202

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

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

    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.

  12. Biorepository standards and protocols for collecting, processing, and storing human tissues.

    PubMed

    Troyer, Dean

    2008-01-01

    Recent advances in high-throughput assays for gene expression (genomics), proteins (proteomics), and metabolites (metabolomics) have engendered a parallel need for well-annotated human biological samples. Samples from both diseased and unaffected normal tissues are often required. Biorepositories consist of a specimen bank linked to a database of information. Assuring chain of custody and annotation of samples with relevant clinical information is required. The value of samples to end users is generally commensurate with the quality and extent of relevant clinical data included with the samples. Procurement of tissues is often done with parallel pre- and/or post-treatment venipuncture to obtain blood and tissue samples from the same subject. Biorepositories must also process, preserve, and distribute samples to end users. Like traditional libraries, biorepositories are meant to be used, and they are most useful when the needs of end users (researchers) are considered in the planning and development process. Ethics review and an awareness of regulatory requirements for storage, transport, and distribution are required. In the USA, Institutional Review Boards are the local regulatory entities that review protocols for banking of human biological tissues. Governmental and professional agencies and organizations provide some guidelines for standard operating procedures. The Food and Drug Administration (FDA), the Centers For Disease Control (CDC), and professional organizations such as the American Association of Tissue Banks (AATB), the American Association of Blood Banks, The International Red Cross, International Society for Biological Repositories (ISBER) and other organizations provide guidelines for biorepositories and banking of human tissues (see Table 1). To date, these guidelines are directed largely toward procurement, banking, and distribution of human tissues for therapeutic uses. In the international setting, the World Health Organization provides ethical

  13. Tissue factor expression during human and mouse development.

    PubMed Central

    Luther, T.; Flössel, C.; Mackman, N.; Bierhaus, A.; Kasper, M.; Albrecht, S.; Sage, E. H.; Iruela-Arispe, L.; Grossmann, H.; Ströhlein, A.; Zhang, Y.; Nawroth, P. P.; Carmeliet, P.; Loskutoff, D. J.; Müller, M.

    1996-01-01

    In the adult organism the cellular distribution of tissue factor (TF) expression corresponds to biological boundary layers forming a hemostatic barrier ready to activate blood coagulation after tissue injury. Whether TF expression might also play a role in development is unknown. To determine the significance of TF in ontogenesis, we examined the pattern of TF expression in mouse development and compared it with the distribution of TF in human post-implantation embryos and fetuses of corresponding gestational age. At early embryonic periods of murine (6.5 and 7.5 pc) and human (stage 5) development, there was strong expression of TF in both ectodermal and entodermal cells. In situ hybridization and immunohistochemistry demonstrated that TF mRNA and protein were expressed widely in epithelial areas with high levels of morphogenic activity during organogenesis. Staining for TF was seen during ontogenetic development in tissues such as epidermis, myocardium, bronchial epithelium, and hepatocytes, which express TF in the adult organism. Surprisingly, during renal development and in adults, expression of TF differed between humans and mice. In humans, maturing stage glomeruli were stained for TF whereas in mice, TF was absent from glomeruli but was present in the epithelia of tubular segments. In neuroepithelial cells, there was a substantial expression of TF. Moreover, there was robust TF expression in tissues such as skeletal muscle and pancreas, which do not express it in the adult. In contrast, expression of the physiological ligand for TF, factor VII, was not detectable during early stages of human embryogenesis using immunohistochemistry. The temporal and spatial pattern of TF expression during murine and human development supports the contention that TF serves as an important morphogenic factor during embryogenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8686734

  14. 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. PMID:25748681

  15. The human tri-peptide GHK and tissue remodeling.

    PubMed

    Pickart, Loren

    2008-01-01

    Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling. PMID:18644225

  16. Near-infrared laser speckle imaging of human breast tissue

    NASA Astrophysics Data System (ADS)

    Bean, Robert Speer

    Current methods of breast cancer diagnostics (self-exam, clinical exam, x-ray mammography) fail to diagnose a significant number of cases while still in readily operable stages. This is especially true in younger women, where fibrotic tissue reduces the efficacy of x-ray mammography. Near infrared (NIR) laser photons pass diffusively through human tissue, creating a speckle pattern in a detector after transmission. The high and low intensity variations of the speckle have the appearance of random noise, but are not. The speckle pattern will have an intensity distribution that is informative about the scattering and absorption properties of the tissue that is imaged. Adaptations to the Los Alamos National Laboratory MCNP code are described that allow simulation of NIR laser transport through human tissue. A HeNe laser was used to create laser intensity patterns via transmission through homogeneous and non-homogeneous tissue phantoms. The Kolmogorov-Smirnov test was used to compare the cumulative distribution functions of the laser intensity patterns, and identify the presence of a non-homogeneity. Laser speckle techniques offer the ability to image tumors with few (<3) millimeter resolution without ionizing radiation dose.

  17. 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.

  18. Thyroxine monodeiodination in normal human kidney tissue in vitro.

    PubMed

    Boye, N

    1986-08-01

    The present study deals with thyroxine monodeiodination in normal human kidney. To allow for comparison with previous reports, the present methods are similar to those used by others in rat tissue studies. The microsomal cell fraction of normal human kidney tissue was obtained by differential ultracentrifugation. The microsomes were incubated under various conditions and the deiodination products assayed with radioimmunoassay. A type I 5'-monodeiodinase was demonstrated, pH optimum around 6.5. Competitive inhibition was observed of T3 generation from T4 by rT3 with a Km of 3.0 microM and a Ki of 4 microM. Vmax was 26.1 pmol/min/mg protein. Likewise rT3 was generated from added T4, but it was rapidly degraded, while T3 was relatively stable as is the case in rat tissue preparations. Propylthiouracil inhibited 5'-deiodination in a dose dependent fashion with complete abolishment of deiodination at propylthiouracil concentration of 10(-4) M. Ipodate inhibited the reaction with complete inhibition at 10(-2) M. The data demonstrate that a human kidney particulate cell-fraction contained considerable amounts of T4 deiodinases, very similar to the type I deiodinase of various rat tissue, although the handling of rT3 and the inhibitory action of this iodothyronine on T4 to T3 conversion seem to be slightly different in the two species. PMID:3751464

  19. The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration.

    PubMed

    Bankvall, Maria; Östberg, Anna-Karin; Jontell, Mats; Wold, Agnes; Östman, Sofia

    2016-09-01

    The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. PMID:27288650

  20. The effects of long-term leptin administration on morphometrical changes of mice testicular tissue

    PubMed Central

    Esmaili-Nejad, Mohammad-Reza; Babaei, Homayoon; Kheirandish, Reza

    2015-01-01

    Objective(s): Leptin is a novel and interesting hormone for anyone trying to lose weight, but its effects on male gonad structure in longitudinal study is unknown. The present study was designed to explore morphometrical changes of mouse testicular tissue after long-term administration of leptin. Materials and Methods: Thirty healthy mature male mice were randomly assigned to either control (n=15) or treatment (n=15) groups. Leptin was intraperitoneally injected to the treatment group (0.1 µg/100 µl of physiological saline) once a day for 30 consecutive days, and control animals received normal saline with the same volume and route. Five mice from each experimental group were sacrificed at 15, 30 and 60 days after the beginning of treatments. Left testes were removed, weighted and then fixed in 10% buffered formalin, and stained with hematoxylin and eosine for morphometrical assays. Results: Except for sertoli cell nucleus diameter, which was affected from 30th day, evaluation of other morphometrical parameters such as Johnsen’s score, meiotic index, spermatogenesis, epithelial height, seminiferous tubules diameter and spermatogonial nucleus diameter revealed significant decrease from 15th day after leptin administration compare to those of the control group (P<0.05). Thus, meiotic index and spermatogonial cell nucleus diameter were two parameters that were further disturbed on 30th day compare to the day 15 (3.09±0.03 vs. 3.23±0.03, P=0.006 and 5.50±0.09 vs. 6.08±0.14, P=0.007, respectively). Conclusion: Our results showed that long-term administration of leptin could disturb testicular tissue structure and delay spermatogenesis process. PMID:26877846

  1. Epithelial cell cultures from normal and cancerous human tissues.

    PubMed

    Owens, R B; Smith, H S; Nelson-Rees, W A; Springer, E L

    1976-04-01

    Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal. PMID:176412

  2. Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide

    PubMed Central

    Toombs, Christopher F; Insko, Michael A; Wintner, Edward A; Deckwerth, Thomas L; Usansky, Helen; Jamil, Khurram; Goldstein, Brahm; Cooreman, Michael; Szabo, Csaba

    2010-01-01

    INTRODUCTION Hydrogen sulphide (H2S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H2S to the tissues. In the current study, we have measured H2S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. METHODS We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H2S concentrations using a custom-made device based on a sulphide gas detector (Interscan). RESULTS Administration of IK-1001, a parenteral formulation of Na2S (0.005–0.20 mg kg−1, i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1–5 min following administration of IK-1001 at 0.10 mg kg−1 dose and higher. In all subjects, basal exhaled H2S was observed to be higher than the ambient concentration of H2S gas in room air, indicative of on-going endogenous H2S production in human subjects. Upon intravenous administration of Na2S, a rapid elevation of exhaled H2S concentrations was observed. The amount of exhaled H2S rapidly decreased after discontinuation of the infusion of Na2S. CONCLUSION Exhaled H2S represents a detectable route of elimination after parenteral administration of Na2S. PMID:20565454

  3. Tissue and serum concentrations of amikacin after intramuscular and intrauterine administration to mares in estrus.

    PubMed Central

    Orsini, J A; Park, M I; Spencer, P A

    1996-01-01

    Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 and 4 h postinfusion on the 1st treatment day. Amikacin was found to penetrate the endometrium after intramuscular injection; however, the levels attained were not as high as those achieved following intrauterine infusion. Based on the tissue and serum concentrations of amikacin, an intrauterine infusion at a dose of 4.4 mg/kg BW/d would appear to be an appropriate therapeutic regimen for the treatment of gram-negative endometritis. PMID:8681283

  4. Analysis and distribution of esculetin in plasma and tissues of rats after oral administration.

    PubMed

    Kim, Ji-Sun; Ha, Tae-Youl; Ahn, Jiyun; Kim, Suna

    2014-12-01

    In this study, we developed a method to quantify esculetin (6,7-dihydroxycoumarin) in plasma and tissues using HPLC coupled with ultraviolet detection and measured the level of esculetin in rat plasma after oral administration. The calibration curve for esculetin was linear in the range of 4.8 ng/mL to 476.2 ng/mL, with a correlation coefficient (r(2)) of 0.996, a limit of detection value of 33.2 ng/mL, and a limit of quantification value of 100.6 ng/mL. Recovery rates for the 95.2 ng/mL and 190.5 ng/mL samples were 95.2% and 100.3%, within-runs and 104.8% and 101.0% between-runs, respectively. The relative standard deviation was less than 7% for both runs. In the pharmacokinetic analysis, the peak plasma esculetin level was reached 5 min after administration (Cmax=173.3 ng/mL; T1/2=45 min; AUC0 ~180 min=5,167.5 ng · min/mL). At 180 min post-administration (i.e., after euthanasia), esculetin was only detectable in the liver (30.87±11.33 ng/g) and the kidney (20.29±7.02 ng/g). PMID:25580397

  5. Monitoring changes in tissue optical properties following interstitial photothermal therapy of ex vivo human prostate tissue

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; He, Jie; Veilleux, Israel; Trachtenberg, John; Wilson, Brian C.

    2013-03-01

    We are developing a method of monitoring treatment progression of interstitial photothermal therapy of focal prostate cancer using transrectal diffuse optical tomography (TRDOT) combined with transrectal 3D ultrasound (3D-TRUS). Measurements of prostate tissue optical properties were made on ex vivo human prostate samples prior to and post coagulation. Interstitial photothermal treatments were delivered to the ex vivo samples and monitored using an interstitial probe near the treatment fiber. After treatment, bulk optical properties were measured on native and coagulated zones of tissue. Changes in optical properties across the boundary between native and coagulated tissues were spatially mapped using a small diffuse reflectance probe. The optical property estimates and spatial information obtained using each method was compared.

  6. 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.

  7. Fallout sup 3 H in human tissue at Akita, Japan

    SciTech Connect

    Hisamatsu, S.; Takizawa, Y.; Itoh, M.; Ueno, K.; Katsumata, T.; Sakanoue, M. )

    1989-10-01

    The {sup 3}H concentration in Japanese human tissue samples is reported in this paper. Four brain, 10 liver, and nine lung samples from 11 cases were collected from Akita Prefecture in northern Japan from January to July 1986. The median of free-water {sup 3}H concentration was similar in these tissues and agreed well with the concentrations in the diet, including tap water. The median specific activity ratio of tissue-bound {sup 3}H to free-water {sup 3}H was 1.1 and was slightly lower than that in the diet. The specific activity ratio was also lower than that reported in the United States and significantly lower than in Italy.

  8. Pharmacokinetics and tissue distribution of spinosin after intravenous administration in rats.

    PubMed

    Li, Yu-Juan; Dai, Yue-Han; Yu, Ye-Ling; Li, Yan; Deng, Yu-Lin

    2007-08-01

    Spinosin is the major effective single constituent in the traditional Chinese herb Semen Ziziphi Spinosae, which is used for sedation and hypnosis. For the further use of spinosin in treating insomnia, the pharmacokinetics and tissue distribution of spinosin after intravenous administration to rats was investigated. An HPLC method with an ODS column (250 mm x 4.6 mm, i.d.) and a mobile phase of acetonitrile-water-acetic acid (23:77:1) was used for the determination of spinosin in the plasma and tissues of rats. Vanillin was used as an internal standard, and spinosin was detected at 334 nm. The calibration curve of spinosin in plasma showed good linearity over the concentration range of 1-300 microg/ml, and the quantitation of limit of plasma was 1 microg/ml. The linear range of concentrations of spinosin in the heart, spleen, stomach, lung, testis, brain, and intestine was 0.1-40 microg/ml and the quantitation limit was 0.1 microg/ml. The linear range of concentrations of spinosin in the liver and kidney was 1-150 microg/ml, and the quantitation limit was 1 microg/ml. The correlation coefficients of all calibration curves were between 0.9939 and 0.9980. The intra and interrun precision for all samples was less than < or =11.0%. The time-concentration curve of spinosin after the intravenous administration of a single dose of 20 mg/kg to rats corresponded to the two-compartment model. The main pharmacokinetic parameters T(0.5alpha), T(0.5beta), CLs, AUC(0-T), and V(c) were 6.66 min, 51.5 min, 1.42 l.min(-1), 2.83 mg.min.ml(-1), and 14.0 l.kg(-1), respectively. At 20 min, a concentration peak occurred in liver and brain tissues. The highest level of spinosin occurred in the liver, followed by the spleen and kidney. The lowest level of spinosin appeared in the testis, followed by the brain. Spinosin was not detected in smooth and skeletal muscle. After intravenous administration, the drug was distributed extensively and transferred quickly in rats in vivo. PMID

  9. 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. PMID:25817474

  10. Levels of chlordane, oxychlordane, and nonachlor in human adipose tissues

    SciTech Connect

    Hirai, Yukio; Tomokuni, Katsumaro )

    1991-08-01

    Chlordane was used as a termiticide for more than twenty years in Japan. Chlordane is stable in the environment such as sediment and its bioaccumulation in some species of bacteria, freshwater invertebrates, and marine fish is large. Many researches were done to elucidate the levels of chlordane and/or its metabolite oxychlordane in human adipose tissues. A comprehensive review concerning chlordane was recently provided by USEPA. On the other hand, Japan authorities banned the use of chlordane in September 1986. In the last paper, the authors reported that both water and sediment of the rivers around Saga city were slightly contaminated with chlordane. In the present study, they investigated the levels of chlordane, oxychlordane and nonachlor in human adipose tissues.

  11. 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

  12. Expression of the endocannabinoid receptors in human fascial tissue.

    PubMed

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

  13. Intranasal administration of oxytocin increases human aggressive behavior.

    PubMed

    Ne'eman, R; Perach-Barzilay, N; Fischer-Shofty, M; Atias, A; Shamay-Tsoory, S G

    2016-04-01

    Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naïve to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. PMID:26862988

  14. Effects of temperature on fluorescence in human tissue

    NASA Astrophysics Data System (ADS)

    Masters, D. B.; Walsh, Alex; Welch, A. J.; Mahadevan-Jansen, Anita

    2010-02-01

    The fluorescence properties of human tissue are known to be temperature dependent. The most apparent effect of this dependence is the inverse relationship between fluorescence and temperature. In this study, we used fluorescence and diffuse-reflectance spectroscopy to investigate the effects of temperature on fluorescence, thermal coagulation, and tissue optical properties. Human tissue from the breast and abdomen were examined in vitro, and human skin was examined in vivo using a fluorescence and diffuse-reflectance system to observe the effects of temperature on fluorescence and optical properties. Fluorescence measurements were carried out using a pulsed nitrogen laser at 337 nm for excitation and a thermal camera for temperature measurements. Thermal variation of the specimens was provided by a phosphate buffered saline solution for the in vitro experiments and an ice pack and heat lamp for the in vivo experiments. In vitro temperatures varied from 0°C to 70°C and in vivo temperatures varied from 15°C to 40°C. Optical property measurements and Monte Carlo simulations were carried out on the in vitro samples for different levels of thermal exposure. Results of both the in vivo and in vitro experiments indicate that optical properties of human tissue change at high temperatures, primarily due to increased scattering. In addition, certain internal processes may have contributed to a decrease in fluorescence with increasing temperature. Some of these effects were found to be reversible before a certain temperature threshold, while some effects of coagulation on fluorescence and optical properties were not reversible.

  15. Cervical Tissue Engineering Using Silk Scaffolds and Human Cervical Cells

    PubMed Central

    Sanchez, Cristina C.; Rice, William L.; Socrate, Simona; Kaplan, David L.

    2010-01-01

    Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p < 0.05), sulfated glycosaminoglycan synthesis (p < 0.05), and mechanical stiffness (p < 0.05). Serum concentration did not affect measured variables. Relevant human tissue-engineered cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

  16. Cervical tissue engineering using silk scaffolds and human cervical cells.

    PubMed

    House, Michael; Sanchez, Cristina C; Rice, William L; Socrate, Simona; Kaplan, David L

    2010-06-01

    Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p < 0.05), sulfated glycosaminoglycan synthesis (p < 0.05), and mechanical stiffness (p < 0.05). Serum concentration did not affect measured variables. Relevant human tissue-engineered cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

  17. The formation of immunoglobulins by human tissues in vitro

    PubMed Central

    Van Furth, R.; Schuit, Henrica R. E.; Hijmans, W.

    1966-01-01

    The formation of immunoglobulins by human tissues was studied by three techniques: (1) Autoradiography of the immunoelectrophoretic pattern of culture fluids of tissue fragments or cell suspensions in a medium with radio-active amino acids; (2) immunofluorescent staining of the tissue sections or cell suspensions, before incubation, with antisera specific for one immunoglobulin; and (3) histological and cytological study of the samples. The paper gives a detailed description of the techniques applied and evaluates the specificity of the immunological methods used. Various control experiments were performed: Incubation of dead tissues or normal serum in the radioactive culture medium excluded the adsorption of [14C]amino acids on to immunoglobulins. Cultures of tissue fragments in the presence of puromycin showed an inhibition of the synthesis of [14C]immunoglobulins. Autoradiography of a `fingerprint' of radioactive IgG demonstrated radioactive amino acids present in different peptides of the synthesized molecule. From these control experiments it can be concluded that the labelling of the immunoglobulins is based on the incorporation of [14C]amino acids during incubation in vitro. The specificity of the immunofluorescent staining was evaluated by immunodiffusion of the antisera and conjugates, by blocking procedures and by specific staining of bone-marrow samples from patients with various immunoglobulin abnormalities. ImagesFIG. 3FIG. 4FIG. 5 PMID:4161984

  18. DNA methylation age of human tissues and cell types

    PubMed Central

    2013-01-01

    Background It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. Results I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. Conclusions I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research. PMID:24138928

  19. Streamlined bioreactor-based production of human cartilage tissues.

    PubMed

    Tonnarelli, B; Santoro, R; Adelaide Asnaghi, M; Wendt, D

    2016-01-01

    Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines. PMID:27232665

  20. Insulin is ubiquitous in extrapancreatic tissues of rats and humans.

    PubMed Central

    Rosenzweig, J L; Havrankova, J; Lesniak, M A; Brownstein, M; Roth, J

    1980-01-01

    Insulin has been detected, at levels higher than those in plasma, in a broad range of extrapancreatic tissues in both rats and humans. Rat liver insulin was shown to be indistinguishable from genuine insulin by radioimmunoassay, Sephadex chromatography, bioassay, and antibody neutralization. Liver insulin (like brain insulin) was unchanged in ob/ob mice, in rats treated with streptozotocin, or in fasted rats, despite marked alterations in pancreatic secretion of insulin and in liver content of insulin receptors. Insulin was found in cultured human IM-9 lymphocytes and cultured fibroblasts at concentrations greater than 100 times the levels in the media. IM-9 lymphocyte insulin also was shown to be indistinguishable from genuine insulin, by the same criteria used for liver insulin. The insulin concentration in cultured human cells was unaffected by depletion of insulin from the culture medium or by addition of beef insulin to the medium. The data suggest that a part, if not all, of the extrapancreatic tissue insulin is independent of plasma insulin and may be synthesized by the tissues themselves. PMID:6987656

  1. Disposition of hop prenylflavonoids in human breast tissue

    PubMed Central

    Bolca, Selin; Li, Jinghu; Nikolic, Dejan; Roche, Nathalie; Blondeel, Phillip; Possemiers, Sam; De Keukeleire, Denis; Bracke, Marc; Heyerick, Arne; van Breemen, Richard B.; Depypere, Herman

    2013-01-01

    Hop-derived products may contain xanthohumol (XN), isoxanthohumol (IX), and the potent phytoestrogen 8-prenylnaringenin (8-PN). To evaluate the potential health effects of these prenylflavonoids on breast tissue, their concentration, nature of metabolites, and biodistribution were assessed and compared to 17β-estradiol (E2) exposure. In this dietary intervention study, women were randomly allocated to hop (n=11; 2.04 mg XN, 1.20 mg IX, and 0.1 mg 8-PN per supplement) or control (n=10). After a run-in of ≥4d, 3 supplements were taken daily during 5d preceding an aesthetic breast reduction. Blood and breast biopsies were analyzed using HPLC-ESI-MS/MS. Upon hop administration, XN and IX concentrations ranged between 0.72–17.65 nmol/L and 3.30–31.50 nmol/L, and between 0.26– 5.14 pmol/g and 1.16–83.67 pmol/g in hydrolyzed serum and breast tissue, respectively. 8-PN however, was only detected in samples of moderate and strong 8-PN producers (0.43–7.06 nmol/L and 0.78–4.83 pmol/g). Phase I metabolism appeared to be minor (~10%), whereas extensive glucuronidation was observed (>90%). Total prenylflavonoids showed a breast adipose/glandular tissue distribution of 38/62 and their derived E2-equivalents were negligible compared to E2 in adipose (384.6±118.8 fmol/g, P=0.009) and glandular (241.6±93.1 fmol/g, P<0.001) tissue, respectively. Consequently, low doses of prenylflavonoids are unlikely to elicit estrogenic responses in breast tissue. PMID:20486208

  2. Disposition of hop prenylflavonoids in human breast tissue.

    PubMed

    Bolca, Selin; Li, Jinghu; Nikolic, Dejan; Roche, Nathalie; Blondeel, Phillip; Possemiers, Sam; De Keukeleire, Denis; Bracke, Marc; Heyerick, Arne; van Breemen, Richard B; Depypere, Herman

    2010-07-01

    Hop-derived products may contain xanthohumol (XN), isoxanthohumol (IX), and the potent phytoestrogen 8-prenylnaringenin (8-PN). To evaluate the potential health effects of these prenylflavonoids on breast tissue, their concentration, nature of metabolites, and biodistribution were assessed and compared with 17beta-estradiol (E(2)) exposure. In this dietary intervention study, women were randomly allocated to hop (n=11; 2.04 mg XN, 1.20 mg IX, and 0.1 mg 8-PN per supplement) or control (n=10). After a run-in of >or=4 days, three supplements were taken daily for 5 days preceding an aesthetic breast reduction. Blood and breast biopsies were analyzed using HPLC-ESI-MS/MS. Upon hop administration, XN and IX concentrations ranged between 0.72 and 17.65 nmol/L and 3.30 and 31.50 nmol/L, and between 0.26 and 5.14 pmol/g and 1.16 and 83.67 pmol/g in hydrolyzed serum and breast tissue, respectively. 8-PN however, was only detected in samples of moderate and strong 8-PN producers (0.43-7.06 nmol/L and 0.78-4.83 pmol/g). Phase I metabolism appeared to be minor (approximately 10%), whereas extensive glucuronidation was observed (> 90%). Total prenylflavonoids showed a breast adipose/glandular tissue distribution of 38/62 and their derived E(2)-equivalents were negligible compared with E(2) in adipose (384.6+/-118.8 fmol/g, p=0.009) and glandular (241.6+/-93.1 fmol/g, p<0.001) tissue, respectively. Consequently, low doses of prenylflavonoids are unlikely to elicit estrogenic responses in breast tissue. PMID:20486208

  3. Elastic, Permeability and Swelling Properties of Human Intervertebral Disc Tissues: A Benchmark for Tissue engineering

    PubMed Central

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

    2014-01-01

    SUMMARY 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 matrix was higher in the CEP (390 kPa) compared to the NP (100 kPA) or AF (30 kPa). The permeability was very different across tissues regions, with the AF permeability (80 E−4 mm4/Ns) higher than the NP and CEP (6-7 E−16 m4/Ns). Additionally, a normalized time-constant (3000 sec) 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

  4. Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.

    PubMed

    Golasik, Magdalena; Herman, Małgorzata; Olbert, Magdalena; Librowski, Tadeusz; Szklarzewicz, Janusz; Piekoszewski, Wojciech

    2016-04-15

    Titanium is widely used both in food and cosmetics, as well as in surgery and industry. Contrary to most studies, the present work focused on the determination of the toxicokinetic parameters of titanium in ionic form, as well as on its tissue biodistribution in rats. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver. The present study contributes to the knowledge of the toxicokinetics of titanium in ionic form, which may be especially useful when assessing the health risks of long-term exposure to titanium alloy implants in patients. PMID:26892718

  5. 3D Extracellular Matrix from Sectioned Human Tissues

    PubMed Central

    Campbell, Catherine B; Cukierman, Edna; Artym, Vira V

    2014-01-01

    corneal endothelial cell lines produce an ECM mimicking an in vivo subendothelium, and the EHS tumor cell line produces a matrix that can be extracted to produce Matrigel, which simulates basement membrane molecular complexity including laminin, collagen IV and nidogen (Beacham, et al., 2007; Friedl and Brocker, 2000). To simulate a physiological environment even more closely, 3D matrices derived from mouse tissue slices from which cells were extracted have reportedly provided successful ECM replicas for studying in vivo cellular behavior (Cukierman, et al., 2001). Because of the important roles of the extracellular microenvironment on normal and tumor cells, we have developed protocols to produce cell-free (decellularized) 3D matrices from cryostat sections of normal and tumor human tissues. These extracted matrices can be used as a 3D tissue culture environment to analyze effects of various 3D matrices on normal and tumor cell responses and behavior. Using human pancreas and breast tissue samples, we have successfully prepared cell-free 3D ECM models, used them as cell culture substrates for a human breast cancer cell line, MDA-MB-231, and then performed immunofluorescence staining to characterize intracellular structures. A frequently observed difference between normal and tumor tissue-derived ECM environments involves the amount of deposited fibrillar collagen (Provenzano, 2008). Tumor tissues from both breast and pancreas often contain substantially more collagen than normal adjacent tissue, and this protocol preserves this difference in cell-free 3D matrices from these tissues (Vidi, et al., 2013). This 3D culture system we describe using cell-free 3D matrix provides an approach to studying cellular behavior and migratory mechanisms associated with cancer. The basic protocol describes methods for successfully extracting cells and cellular debris from human tissue cryostat sections to obtain a clean, cell-free 3D ECM for plating cell lines (Figure 1). Cellular

  6. Intravenous Administration of Human ES-derived Neural Precursor Cells Attenuates Cuprizone-induced CNS Demyelination

    PubMed Central

    Crocker, Stephen J.; Bajpai, Ruchi; Moore, Craig S.; Frausto, Ricardo F.; Brown, Graham D.; Pagarigan, Roberto R.; Whitton, J. Lindsay; Terskikh, Alexey V.

    2011-01-01

    Aims Previous studies have demonstrated the therapeutic potential for human embryonic stem cell-derived neural precursor cells (hES-NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. Methods C57Bl/6 mice were fed cuprizone (0.2%) for two weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional two weeks of dietary cuprizone treatment, CNS tissues were analyzed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). Results Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, GFAP. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice. Conclusions These findings indicated that systemically-administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and (c) the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells. PMID:21276029

  7. 78 FR 42381 - Administrative Detention of Drugs Intended for Human or Animal Use

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... regulations for the administrative detention of drugs (78 FR 21085). The docket was intended to ensure that... July 15, 2013 Part IV Department of Health and Human Services Food and Drug Administration 21 CFR Parts... / Proposed Rules#0;#0; ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts...

  8. Characterization of Leukocyte Formin FMNL1 Expression in Human Tissues.

    PubMed

    Gardberg, Maria; Heuser, Vanina D; Iljin, Kristiina; Kampf, Caroline; Uhlen, Mathias; Carpén, Olli

    2014-04-01

    Formins are cytoskeleton regulating proteins characterized by a common FH2 structural domain. As key players in the assembly of actin filaments, formins direct dynamic cytoskeletal processes that influence cell shape, movement and adhesion. The large number of formin genes, fifteen in the human, suggests distinct tasks and expression patterns for individual family members, in addition to overlapping functions. Several formins have been associated with invasive cell properties in experimental models, linking them to cancer biology. One example is FMNL1, which is considered to be a leukocyte formin and is known to be overexpressed in lymphomas. Studies on FMNL1 and many other formins have been hampered by a lack of research tools, especially antibodies suitable for staining paraffin-embedded formalin-fixed tissues. Here we characterize, using bioinformatics tools and a validated antibody, the expression pattern of FMNL1 in human tissues and study its subcellular distribution. Our results indicate that FMNL1 expression is not restricted to hematopoietic tissues and that neoexpression of FMNL1 can be seen in epithelial cancer. PMID:24700756

  9. Characterization of Leukocyte Formin FMNL1 Expression in Human Tissues

    PubMed Central

    Heuser, Vanina D.; Iljin, Kristiina; Kampf, Caroline; Uhlen, Mathias; Carpén, Olli

    2014-01-01

    Formins are cytoskeleton regulating proteins characterized by a common FH2 structural domain. As key players in the assembly of actin filaments, formins direct dynamic cytoskeletal processes that influence cell shape, movement and adhesion. The large number of formin genes, fifteen in the human, suggests distinct tasks and expression patterns for individual family members, in addition to overlapping functions. Several formins have been associated with invasive cell properties in experimental models, linking them to cancer biology. One example is FMNL1, which is considered to be a leukocyte formin and is known to be overexpressed in lymphomas. Studies on FMNL1 and many other formins have been hampered by a lack of research tools, especially antibodies suitable for staining paraffin-embedded formalin-fixed tissues. Here we characterize, using bioinformatics tools and a validated antibody, the expression pattern of FMNL1 in human tissues and study its subcellular distribution. Our results indicate that FMNL1 expression is not restricted to hematopoietic tissues and that neoexpression of FMNL1 can be seen in epithelial cancer. PMID:24700756

  10. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  11. Comparison of the transcriptional landscapes between human and mouse tissues.

    PubMed

    Lin, Shin; Lin, Yiing; Nery, Joseph R; Urich, Mark A; Breschi, Alessandra; Davis, Carrie A; Dobin, Alexander; Zaleski, Christopher; Beer, Michael A; Chapman, William C; Gingeras, Thomas R; Ecker, Joseph R; Snyder, Michael P

    2014-12-01

    Although the similarities between humans and mice are typically highlighted, morphologically and genetically, there are many differences. To better understand these two species on a molecular level, we performed a comparison of the expression profiles of 15 tissues by deep RNA sequencing and examined the similarities and differences in the transcriptome for both protein-coding and -noncoding transcripts. Although commonalities are evident in the expression of tissue-specific genes between the two species, the expression for many sets of genes was found to be more similar in different tissues within the same species than between species. These findings were further corroborated by associated epigenetic histone mark analyses. We also find that many noncoding transcripts are expressed at a low level and are not detectable at appreciable levels across individuals. Moreover, the majority lack obvious sequence homologs between species, even when we restrict our attention to those which are most highly reproducible across biological replicates. Overall, our results indicate that there is considerable RNA expression diversity between humans and mice, well beyond what was described previously, likely reflecting the fundamental physiological differences between these two organisms. PMID:25413365

  12. Comparison of the transcriptional landscapes between human and mouse tissues

    PubMed Central

    Lin, Shin; Lin, Yiing; Nery, Joseph R.; Urich, Mark A.; Breschi, Alessandra; Davis, Carrie A.; Dobin, Alexander; Zaleski, Christopher; Beer, Michael A.; Chapman, William C.; Gingeras, Thomas R.; Ecker, Joseph R.; Snyder, Michael P.

    2014-01-01

    Although the similarities between humans and mice are typically highlighted, morphologically and genetically, there are many differences. To better understand these two species on a molecular level, we performed a comparison of the expression profiles of 15 tissues by deep RNA sequencing and examined the similarities and differences in the transcriptome for both protein-coding and -noncoding transcripts. Although commonalities are evident in the expression of tissue-specific genes between the two species, the expression for many sets of genes was found to be more similar in different tissues within the same species than between species. These findings were further corroborated by associated epigenetic histone mark analyses. We also find that many noncoding transcripts are expressed at a low level and are not detectable at appreciable levels across individuals. Moreover, the majority lack obvious sequence homologs between species, even when we restrict our attention to those which are most highly reproducible across biological replicates. Overall, our results indicate that there is considerable RNA expression diversity between humans and mice, well beyond what was described previously, likely reflecting the fundamental physiological differences between these two organisms. PMID:25413365

  13. Dynamic biaxial tissue properties of the human cadaver aorta.

    PubMed

    Shah, Chirag S; Hardy, Warren N; Mason, Matthew J; Yang, King H; Van Ee, Chris A; Morgan, Richard; Digges, Kennerly

    2006-11-01

    This study focuses on the biaxial mechanical properties of planar aorta tissue at strain rates likely to be experienced during automotive crashes. It also examines the structural response of the whole aorta to longitudinal tension. Twenty-six tissue-level tests were conducted using twelve thoracic aortas harvested from human cadavers. Cruciate samples were excised from the ascending, peri-isthmic, and descending regions. The samples were subjected to equibiaxial stretch at two nominal speed levels using a new biaxial tissue-testing device. Inertia-compensated loads were measured to facilitate calculation of true stress. High-speed videography and regional correlation analysis were used to track ink dots marked on the center of each sample to obtain strain. In a series of component-level tests, the response of the intact thoracic aorta to longitudinal stretch was obtained using seven aorta specimens. The aorta fails within the peri-isthmic region. The aorta fails in the transverse direction, and the intima fails before the media or adventitia. The aorta tissue exhibits nonlinear behavior. The aorta as complete structure can transect completely from 92 N axial load and 0.221 axial strain. Complete transection can be accompanied by intimal tears. These results have application to finite element modeling and the better understanding of traumatic rupture of the aorta. PMID:17311166

  14. 78 FR 26639 - Proposed Collection; 60-Day Comment Request: Financial Sustainability of Human Tissue Biobanking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-07

    ... Sustainability of Human Tissue Biobanking (NCI) Summary: In compliance with the requirement of Section 3506(c)(2...: Financial Sustainability of Human Tissue Biobanking, 0925-NEW, National Cancer Institute (NCI),...

  15. 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. PMID:25830209

  16. Dynamic DNA methylation across diverse human cell lines and tissues

    PubMed Central

    Varley, Katherine E.; Gertz, Jason; Bowling, Kevin M.; Parker, Stephanie L.; Reddy, Timothy E.; Pauli-Behn, Florencia; Cross, Marie K.; Williams, Brian A.; Stamatoyannopoulos, John A.; Crawford, Gregory E.; Absher, Devin M.; Wold, Barbara J.; Myers, Richard M.

    2013-01-01

    As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease. PMID:23325432

  17. Human Engineered Heart Tissue: Analysis of Contractile Force.

    PubMed

    Mannhardt, Ingra; Breckwoldt, Kaja; Letuffe-Brenière, David; Schaaf, Sebastian; Schulz, Herbert; Neuber, Christiane; Benzin, Anika; Werner, Tessa; Eder, Alexandra; Schulze, Thomas; Klampe, Birgit; Christ, Torsten; Hirt, Marc N; Huebner, Norbert; Moretti, Alessandra; Eschenhagen, Thomas; Hansen, Arne

    2016-07-12

    Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). This study describes the generation of 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM and their physiological and pharmacological properties. CM were differentiated from hiPSC by a growth factor-based three-stage protocol. EHTs were generated and analyzed histologically and functionally. HiPSC-CM in EHTs showed well-developed sarcomeric organization and alignment, and frequent mitochondria. Systematic contractility analysis (26 concentration-response curves) reveals that EHTs replicated canonical response to physiological and pharmacological regulators of inotropy, membrane- and calcium-clock mediators of pacemaking, modulators of ion-channel currents, and proarrhythmic compounds with unprecedented precision. The analysis demonstrates a high degree of similarity between hiPSC-CM in EHT format and native human heart tissue, indicating that human EHTs are useful for preclinical drug testing and disease modeling. PMID:27211213

  18. Expression of interleukin-17RC protein in normal human tissues

    PubMed Central

    Ge, Dongxia; You, Zongbing

    2008-01-01

    Background Interleukin-17 (IL-17) cytokines and receptors play an important role in many autoimmune and inflammatory diseases. IL-17 receptors IL-17RA and IL-17RC have been found to form a heterodimer for mediating the signals of IL-17A and IL-17F cytokines. While the function and signaling pathway of IL-17RA has been revealed, IL-17RC has not been well characterized. The function and signaling pathway of IL-17RC remain largely unknown. The purpose of the present study was to systematically examine IL-17RC protein expression in 53 human tissues. Results IL-17RC expression in 51 normal human tissues and two benign tumors (i.e., lymphangioma and parathyroid adenoma) on the tissue microarrays was determined by immunohistochemical staining, using two polyclonal antibodies against IL-17RC. IL-17RC protein was expressed in many cell types including the myocardial cells, vascular and lymphatic endothelial cells, glandular cells (of the adrenal, parathyroid, pituitary, thyroid, pancreas, parotid salivary, and subepidermal glands), epithelial cells (of the esophagus, stomach, intestine, anus, renal tubule, breast, cervix, Fallopian tube, epididymis, seminal vesicle, prostate, gallbladder, bronchus, lung, and skin), oocytes in the ovary, Sertoli cells in the testis, motor neurons in the spinal cord, autonomic ganglia and nerves in the intestine, skeletal muscle cells, adipocytes, articular chondrocytes, and synovial cells. High levels of IL-17RC protein expression were observed in most vascular and lymphatic endothelium and squamous epithelium. The epithelium of the breast, cervix, Fallopian tube, kidney, bladder and bronchus also expressed high levels of IL-17RC, so did the glandular cells in the adrenal cortex, parotid salivary and subepidermal glands. In contrast, IL-17RC protein was not detectable in the smooth muscle cells, fibroblasts, antral mucosa of the stomach, mucosa of the colon, endometrium of the uterus, neurons of the brain, hepatocytes, or lymphocytes

  19. Direct measurement of the permeability of human cervical tissue.

    PubMed

    Fernandez, Michael; Vink, Joy; Yoshida, Kyoko; Wapner, Ronald; Myers, Kristin M

    2013-02-01

    The mechanical integrity of the uterine cervix is critical for a pregnancy to successfully reach full term. It must be strong to retain the fetus throughout gestation and then undergo a remodeling and softening process before labor for delivery of the fetus. It is believed that cervical insufficiency (CI), a condition in pregnancy resulting in preterm birth (PTB), is related to a cervix with compromised mechanical strength which cannot resist deformation caused by external forces generated by the growing fetus. Such PTBs are responsible for infant developmental problems and in severe cases infant mortality. To understand the etiologies of CI, our overall research goal is to investigate the mechanical behavior of the cervix. Permeability is a mechanical property of hydrated collagenous tissues that dictates the time-dependent response of the tissue to mechanical loading. The goal of this study was to design a novel soft tissue permeability testing device and to present direct hydraulic permeability measurements of excised nonpregnant (NP) and pregnant (PG) human cervical tissue from women with different obstetric histories. Results of hydraulic permeability testing indicate repeatability for specimens from single patients, with an order of magnitude separating the NP and PG group means (2.1 ± 1.4×10(-14) and 3.2 ± 4.8×10(-13)m(4)/N[middle dot]s, respectively), and large variability within the NP and PG sample groups. Differences were found between samples with similar obstetric histories, supporting the view that medical history may not be a good predictor of permeability (and therefore mechanical behavior) and highlighting the need for patient-specific measurements of cervical mechanical properties. The permeability measurements from this study will be used in future work to model the constitutive material behavior of cervical tissue and to develop in vivo diagnostic tools to stage the progression of labor. PMID:23445069

  20. Identification of Tissue-Specific Protein-Coding and Noncoding Transcripts across 14 Human Tissues Using RNA-seq

    PubMed Central

    Zhu, Jinhang; Chen, Geng; Zhu, Sibo; Li, Suqing; Wen, Zhuo; Bin Li; Zheng, Yuanting; Shi, Leming

    2016-01-01

    Many diseases and adverse drug reactions exhibit tissue specificity. To better understand the tissue-specific expression characteristics of transcripts in different human tissues, we deeply sequenced RNA samples from 14 different human tissues. After filtering many lowly expressed transcripts, 24,729 protein-coding transcripts and 1,653 noncoding transcripts were identified. By analyzing highly expressed tissue-specific protein-coding transcripts (TSCTs) and noncoding transcripts (TSNTs), we found that testis expressed the highest numbers of TSCTs and TSNTs. Brain, monocytes, ovary, and heart expressed more TSCTs than the rest tissues, whereas brain, placenta, heart, and monocytes expressed more TSNTs than other tissues. Co-expression network constructed based on the TSCTs and TSNTs showed that each hub TSNT was co-expressed with several TSCTs, allowing functional annotation of TSNTs. Important biological processes and KEGG pathways highly related to the specific functions or diseases of each tissue were enriched with the corresponding TSCTs. These TSCTs and TSNTs may participate in the tissue-specific physiological or pathological processes. Our study provided a unique data set and systematic analysis of expression characteristics and functions of both TSCTs and TSNTs based on 14 distinct human tissues, and could facilitate future investigation of the mechanisms behind tissue-specific diseases and adverse drug reactions. PMID:27329541

  1. Identification of Tissue-Specific Protein-Coding and Noncoding Transcripts across 14 Human Tissues Using RNA-seq.

    PubMed

    Zhu, Jinhang; Chen, Geng; Zhu, Sibo; Li, Suqing; Wen, Zhuo; Bin Li; Zheng, Yuanting; Shi, Leming

    2016-01-01

    Many diseases and adverse drug reactions exhibit tissue specificity. To better understand the tissue-specific expression characteristics of transcripts in different human tissues, we deeply sequenced RNA samples from 14 different human tissues. After filtering many lowly expressed transcripts, 24,729 protein-coding transcripts and 1,653 noncoding transcripts were identified. By analyzing highly expressed tissue-specific protein-coding transcripts (TSCTs) and noncoding transcripts (TSNTs), we found that testis expressed the highest numbers of TSCTs and TSNTs. Brain, monocytes, ovary, and heart expressed more TSCTs than the rest tissues, whereas brain, placenta, heart, and monocytes expressed more TSNTs than other tissues. Co-expression network constructed based on the TSCTs and TSNTs showed that each hub TSNT was co-expressed with several TSCTs, allowing functional annotation of TSNTs. Important biological processes and KEGG pathways highly related to the specific functions or diseases of each tissue were enriched with the corresponding TSCTs. These TSCTs and TSNTs may participate in the tissue-specific physiological or pathological processes. Our study provided a unique data set and systematic analysis of expression characteristics and functions of both TSCTs and TSNTs based on 14 distinct human tissues, and could facilitate future investigation of the mechanisms behind tissue-specific diseases and adverse drug reactions. PMID:27329541

  2. The effect of Setarud (IMODTM) on angiogenesis in transplanted human ovarian tissue to nude mice

    PubMed Central

    Hormozi, Maryam; Talebi, Saeed; Khorram Khorshid, Hamid Reza; Zarnani, Amir-Hassan; Kamali, Koorosh; Jeddi-Tehrani, Mahmood; Soltangoraee, Haleh; Akhondi, Mohammad Mehdi

    2015-01-01

    Background: One of the promising methods in fertility preservation among women with cancer is cryopreservation of ovarian cortex but there are many drawbacks such as apoptosis and considerable reduction of follicular density in the transplanted ovary. One solution to reduce ischemic damage is enhancing angiogenesis after transplantation of ovarian cortex tissue. Objective: The aim of this study was to investigate the effect of Setarud, on angiogenesis in transplanted human ovarian tissue. Materials and Methods: In this case control study, twenty four nude mice were implanted subcutaneously, with human ovarian tissues, from four women. The mice were randomly divided into two groups (n=12): the experimental group was treated with Setarud, while control group received only vehicle. Each group was divided into three subgroups (n=4) based on the graft recovery days post transplantation (PT). The transplanted fragments were removed on days 2, 7, and 30 PT and the expression of Angiopoietin-1, Angiopoietin-2, and Vascular endothelial growth factor at both gene and protein levels and vascular density were studied in the grafted ovarian tissues. Results: On the 2nd and 7th day PT, the level of Angiopoietin-1 gene expression in case group was significantly lower than that in control group, while the opposite results were obtained for Angiopoietin-2 and Vascular endothelial growth factor. These results were also confirmed at the protein level. The density of vessels in Setarud group elevated significantly on day 7 PT compared to pre-treatment state. Conclusion: Our results showed that administration of Setarud may stimulates angiogenesis in transplanted human ovarian tissues, although further researches are needed before a clear judgment is made. PMID:26644788

  3. 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

  4. Marketing of human organs and tissues is justified and necessary.

    PubMed

    Kevorkian, J

    1989-01-01

    The bioethical guidelines now banning commerce in human body parts to be used for transplantation manifest unrealistic and arbitrary inflexibility which perpetuates and worsens the deficit in organ supply. Instead of relying on traditionally revered but now outmoded and even irrelevant bioethical maxims, formulators of the guidelines should have concentrated on a more meaningful situational adaptation to contemporary real-life circumstances. Many unexpectedly relevant and important nuances of concepts such as property, ownership, and altruism must now be taken into account. Hypothetical examples explore the morality of a universal ban by fiat and the associated problems of organ supply and demand, of cost and affordability, and of fair equity. It is difficult to justify purely altruistic organ donation today, when the health care professions and industries are frantically pursuing commercial profits. It is concluded that the ban should be scrapped in favor of a well-organized, open, and legally regulated commercial market for human organs and tissues. PMID:2495395

  5. Brominated dioxins and dibenzofurans in human adipose tissue. Final report

    SciTech Connect

    Cramer, P.H.; Stanley, J.S.; Bauer, K.; Ayling, R.E.; Thornburg, K.R.

    1990-04-11

    The report describes the analytical efforts for the determination of polybrominated dioxins (PBDDs) and furans (PBDFs) in human adipose tissues. Data on the precision and accuracy of the method for three tetra- through hexabrominated dioxins and three tetra- through hexabrominated furans (specific 2,3,7,8-substituted isomers) were generated from the analysis of 5 unspiked and 10 spiked (5 replicates at 2 spike levels) adipose tissue samples that were included with the analysis of the FY 1987 samples. In addition, data are presented on the results of the analysis of 48 composite samples for the six specific PBDD and PBDF compounds. The targeted 2,3,7,8-substituted PBDDs and PBDFs were not detected in any of the samples except those prepared as spiked QC materials. The detection limits calculated for the tetrabromo congeners in the samples ranged from 0.46 to 8.9 pg/g (lipid basis). The detection limits for the higher brominated congeners were typically greater than that observed for the tetrabrominated compounds. There is some evidence for the presence of other brominated compounds in the adipose tissue samples. Specifically, responses were noted that correspond to the qualitative criteria for polybrominated diphenyl ethers (hexa through octabromo).

  6. 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.

  7. The significance of using pooled human serum in human articular cartilage tissue engineering.

    PubMed

    Azmi, B; Aminuddin, B S; Sharaf, I; Samsudin, O C; Munirah, S; Chua, K H; Ruszymah, B H I

    2004-05-01

    Animal serum is commonly used in chondrocytes culture expansion to promote cell proliferation and shorten the time lag before new tissue reconstruction is possible. However, animal serum is not suitable for regeneration of clinical tissue because it has potential risk of viral and prion related disease transmission particularly mad cow disease and foreign protein contamination that can stimulate immune reaction leading to graft rejection. In this context, human serum as homologous supplement has a greater potential as growth promoting agents for human chondrocytes culture. PMID:15468795

  8. TISSUE DISTRIBUTION OF INORGANIC ARSENIC (AS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV)

    EPA Science Inventory

    TISSUE DISTRIBUTION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV). E M Kenyon1, L M Del Razo2, and M F Hughes1. 1NHEERL, ORD, US EPA, RTP, NC, USA; 2CINVESTAV-IPN, Mexico City, Mexico.

    The relationship o...

  9. Human cells, tissues, and cellular and tissue-based products; establishment registration and listing. Interim final rule; opportunity for public comment.

    PubMed

    2004-01-27

    The Food and Drug Administration (FDA) is issuing an interim final rule to except human dura mater and human heart valve allografts, currently subject to application or notification requirements under the Federal Food, Drug, and Cosmetic Act (the act), from the scope of the definition of "human cells, tissues, or cellular or tissue-based products (HCT/P's)" subject to the registration and listing requirements contained in 21 CFR part 1271. That definition became effective on January 21, 2004. FDA is taking this action to assure that these products, which are currently subject to the act and therefore regulated under the current good manufacturing practice regulations set out in the quality system regulations in 21 CFR part 820 are not released from the scope of those regulations before a more comprehensive regulatory framework applicable to HCT/P's, including donor suitability requirements, good tissue practice regulations, and appropriate enforcement provisions, is fully in place. When that comprehensive framework is in place, FDA intends that human dura mater and human heart valves will be subject to it. FDA intends to revoke this interim final rule at that time. PMID:14968801

  10. Brown adipose tissue thermogenesis does not explain the intra-administration hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide to rats.

    PubMed

    Al-Noori, Salwa; Ramsay, Douglas S; Cimpan, Andreas; Maltzer, Zoe; Zou, Jessie; Kaiyala, Karl J

    2016-08-01

    Initial administration of ≥60% nitrous oxide (N2O) to rats promotes hypothermia primarily by increasing whole-body heat loss. We hypothesized that the drug promotes heat loss via the tail and might initially inhibit thermogenesis via brown adipose tissue (BAT), major organs of thermoregulation in rodents. Following repeated administrations, N2O inhalation evokes hyperthermia underlain by increased whole-body heat production. We hypothesized that elevated BAT thermogenesis plays a role in this thermoregulatory sign reversal. Using dual probe telemetric temperature implants and infrared (IR) thermography, we assessed the effects of nine repeated 60% N2O administrations compared to control (con) administrations on core temperature, BAT temperature, lumbar back temperature and tail temperature. Telemetric core temperature, telemetric BAT temperature, and IR BAT temperature were reduced significantly during initial 60% N2O inhalation (p≤0.001 compared to con). IR thermography revealed that acute N2O administration unexpectedly reduced tail temperature (p=0.0001) and also inhibited IR lumbar temperature (p<0.0001). In the 9th session, N2O inhalation significantly increased telemetric core temperature (p=0.007) indicative of a hyperthermic sign reversal, yet compared to control administrations, telemetric BAT temperature (p=0.86), IR BAT temperature (p=0.85) and tail temperature (p=0.47) did not differ significantly. Thus, an initial administration of 60% N2O at 21°C may promote hypothermia via reduced BAT thermogenesis accompanied by tail vasoconstriction as a compensatory mechanism to limit body heat loss. Following repeated N2O administrations rats exhibit a hyperthermic core temperature but a normalized BAT temperature, suggesting induction of a hyperthermia-promoting thermogenic adaptation of unknown origin. PMID:27503733

  11. CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing

    PubMed Central

    Clark, Andrew J.; Wiley, Devin T.; Zuckerman, Jonathan E.; Webster, Paul; Chao, Joseph; Lin, James; Yen, Yun; Davis, Mark E.

    2016-01-01

    Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24–48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors. PMID:27001839

  12. Congratulations or Condolences? The Role of Human Capital in the Cultivation of a University Administrator

    ERIC Educational Resources Information Center

    McDowell, John; Singell, Larry D., Jr.; Stater, Mark

    2009-01-01

    Administrative skill is essential to organizational effectiveness. Yet, few studies examine how human capital investments over a career affect selection into administration. We use panel data for economists to estimate the probability of choosing administration over a pure academic track. The results show that, while research-specific human…

  13. Clenbuterol Distribution and Residues in Goat Tissues After the Repeated Administration of a Growth-Promoting Dose.

    PubMed

    Zhao, Zhen; Yao, Ting; Qin, Yuchang; Yang, Xiaowei; Li, Jun; Li, Junguo; Gu, Xu

    2015-01-01

    This study was conducted to investigate the deposition and depletion process of clenbuterol (CL) in goat tissues, plasma and urine after the repeated administration of a growth-promoting dose. The experiment was conducted in 24 goats (21 treated and 3 controls). Treated animals were administered orally in a dose of 16 µg/kg body mass once daily for 21 consecutive days and randomly sacrificed on days 0.25, 1, 3, 7, 14, 21 and 28 of the withdrawal period. CL in goat tissues was extracted with organic solvents and determined using liquid chromatography tandem mass spectrometry. The depletion rates of tissue differed significantly. The highest concentrations of CL in all tissues are detected on day 0.25 of treatment discontinuation. After administration had been discontinued for 28 days, CL still residues in all tissues, especially, in whole eye, where the concentrations reach 363.29 ± 31.60 μg/kg. These findings confirmed that the whole eye, which are rich in pigment, showed a much higher concentration than any other studied tissue during the withdrawal period. PMID:25910488

  14. Disulphide bond assignment in human tissue inhibitor of metalloproteinases (TIMP).

    PubMed Central

    Williamson, R A; Marston, F A; Angal, S; Koklitis, P; Panico, M; Morris, H R; Carne, A F; Smith, B J; Harris, T J; Freedman, R B

    1990-01-01

    Disulphide bonds in human recombinant tissue inhibitor of metalloproteinases (TIMP) were assigned by resolving proteolytic digests of TIMP on reverse-phase h.p.l.c. and sequencing those peaks judged to contain disulphide bonds by virtue of a change in retention time on reduction. This procedure allowed the direct assignment of Cys-145-Cys-166 and the isolation of two other peptides containing two disulphide bonds each. Further peptide cleavage in conjunction with fast-atom-bombardment m.s. analysis permitted the assignments Cys-1-Cys-70, Cys-3-Cys-99, Cys-13-Cys-124 and Cys-127-Cys-174 from these peptides. The sixth bond Cys-132-Cys-137 was assigned by inference, as the native protein has no detectable free thiol groups. Images Fig. 1. PMID:2163605

  15. Second harmonic generation imaging of dermal collagen component in human keloid tissue

    NASA Astrophysics Data System (ADS)

    Yu, H. B.; Chen, S.; Zhu, X. Q.; Yang, H. Q.; Chen, J. X.

    2011-01-01

    In this paper, we report second harmonic generation (SHG) imaging of human keloid tissue. High resolution SHG images of collagen component were obtained in the superficial, medial and deep dermis of human keloid tissue, respectively. Our results show that this method has a capability to observe the structure of collagen component in human keloid tissue, which will help to better understand the formation process of human keloid scar at the molecular level.

  16. Relevance Revisited: Curriculum Development in the Humanities. No. II: Administrative Strategies for Curriculum Change.

    ERIC Educational Resources Information Center

    Mondale, Clarence C., Ed.

    Papers presented in advance of a workshop on "administrative strategies" for curricular change in the humanities and brief summaries of discussions taking place at the workshop are provided. Background papers include: "Curricular Change and the Humanities," by Edward A. Lindell; "Developing Administrative Strategies for Curricular Change," by…

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

    PubMed Central

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

    2013-01-01

    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. PMID:23653480

  18. Endogenous ways to stimulate brown adipose tissue in humans.

    PubMed

    Broeders, Evie; Bouvy, Nicole D; van Marken Lichtenbelt, Wouter D

    2015-03-01

    Obesity is the result of disequilibrium between energy intake and energy expenditure (EE). Successful long-term weight loss is difficult to achieve with current strategies for the correction of this caloric imbalance. Non-shivering thermogenesis (NST) in brown adipose tissue (BAT) is a possible therapeutic target for the prevention and treatment of obesity and associated metabolic diseases. In recent years, more knowledge about the function and stimulation of bat has been obtained. The sympathetic nervous system (SNS) is currently seen as the main effector for brown fat function. Also, interplay between the thyroid axis and SNS plays an important role in BAT thermogenesis. Almost daily new pathways for the induction of BAT thermogenesis and 'browning' of white adipose tissue (WAT) are identified. Especially the activation of BAT via endogenous pathways has received strong scientific attention. Here we will discuss the relevance of several pathways in activating BAT and their implications for the treatment of obesity. In this review we will focus on the discussion of the most promising endocrine and paracrine pathways to stimulate BAT, by factors and pathways that naturally occur in the human body. PMID:24521443

  19. 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.

  20. 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.

  1. Hexabrachion proteins in embryonic chicken tissues and human tumors.

    PubMed

    Erickson, H P; Taylor, H C

    1987-09-01

    Cell cultures of chicken embryo and human fibroblasts produce a large extracellular matrix molecule with a six-armed structure that we called a hexabrachion (Erickson, H. P., and J. L. Iglesias, 1984, Nature (Lond.), 311:267-269. In the present work we have determined that the myotendinous (M1) antigen described by M. Chiquet and D. M. Fambrough in chicken tissues (1984, J. Cell Biol., 98:1926-1936), and the glioma mesenchymal extracellular matrix protein described by Bourdon et al. in human tumors (Bourdon, M. A., C. J. Wikstrand, H. Furthmayr, T. J. Matthews, and D. D. Bigner, 1983, Cancer Res. 43:2796-2805) have the structure of hexabrachions. We also demonstrate that the M1 antigen is present in embryonic brain, where it was previously reported absent, and have purified hexabrachions from brain homogenates. The recently described cytotactin (Grumet, M., S. Hoffman, K. L. Crossin, and G. M. Edelman, 1985, Proc. Natl. Acad. Sci. USA, 82:8075-8079) now appears to be identical to the chicken hexabrachion protein. In a search for functional roles, we looked for a possible cell attachment activity. A strong, fibronectin-like attachment activity was present in (NH4)2SO4 precipitates of cell supernatant and sedimented with hexabrachions in glycerol gradients. Hexabrachions purified by antibody adsorption, however, had lost this activity, suggesting that it was due to a separate factor associated with hexabrachions in the gradient fractions. The combined information in the several, previously unrelated studies suggests that hexabrachions may play a role in organizing localized regions of extracellular matrix. The protein is prominently expressed at specific times and locations during embryonic development, is retained in certain adult tissues, and is reexpressed in a variety of tumors. PMID:3654758

  2. 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

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

    PubMed

    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

  4. Caprine Abscess Model of Tulathromycin Concentrations in Interstitial Fluid from Tissue Chambers Inoculated with Corynebacterium pseudotuberculosis following Subcutaneous or Intrachamber Administration

    PubMed Central

    Fajt, V. R.; Lawhon, S. D.; Adams, L. G.; Tell, L. A.; Bissett, W. T.

    2013-01-01

    Corynebacterium pseudotuberculosis causes chronic, suppurative, abscessing conditions in livestock and humans. We used an in vivo model to evaluate antimicrobial efficacy for focal abscesses caused by C. pseudotuberculosis. Tissue chambers were surgically implanted in the subcutaneous tissues of the right and left paralumbar fossa of 12 goats to serve as a model for isolated, focal abscesses. For each goat, one tissue chamber was inoculated with C. pseudotuberculosis, while the contralateral chamber served as an uninoculated control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg of body weight subcutaneously, while the other six received the same dose by injection directly into the inoculated chambers. Our objective was to compare the effects and tulathromycin concentrations in interstitial fluid (IF) samples collected from C. pseudotuberculosis-infected and control chambers following subcutaneous or intrachamber injection of tulathromycin. In addition, the effects of tulathromycin on the quantity of C. pseudotuberculosis reisolated from inoculated chambers were assessed over time. Tulathromycin IF concentrations from C. pseudotuberculosis-infected and control tissue chambers were similar to those in plasma following subcutaneous administration. Following intrachamber administration, tulathromycin IF concentrations in infected chambers were continuously above the MIC for the C. pseudotuberculosis isolate for 15 days. There were no significant differences for plasma area under the curve and elimination half-lives between subcutaneous and intrachamber administration. Six of the 12 infected chambers had no growth of C. pseudotuberculosis 15 days postadministration. Results of this study indicate that tulathromycin may be beneficial in the treatment of focal infections such as those caused by C. pseudotuberculosis. PMID:24100501

  5. Human Resources Administration in Education: A Management Approach. Sixth Edition.

    ERIC Educational Resources Information Center

    Rebore, Ronald W.

    This book reflects the changing aspects of school human-resources management. Current concerns include the impact of new laws related to disabilities, civil rights, family and medical leave, and the testing of school bus drivers for alcohol and controlled substances. Also examined are human resources' responsibilities to military reservists and…

  6. Human Methadone Self-Administration and the Generalized Matching Law

    ERIC Educational Resources Information Center

    Spiga, Ralph; Maxwell, R. Stockton; Meisch, Richard A.; Grabowski, John

    2005-01-01

    The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited…

  7. Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares.

    PubMed

    Papich, M G; Van Camp, S D; Cole, J A; Whitacre, M D

    2002-10-01

    Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria. PMID:12423224

  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. The landscape of genomic imprinting across diverse adult human tissues.

    PubMed

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K; Rivas, Manuel A; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S; Kukurba, Kim R; Zhang, Rui; Eng, Celeste; Torgerson, Dara G; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R; Burchard, Esteban G; Seibold, Max A; MacArthur, Daniel G; Montgomery, Stephen B; Zaitlen, Noah A; Lappalainen, Tuuli

    2015-07-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  10. The landscape of genomic imprinting across diverse adult human tissues

    PubMed Central

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

    2015-01-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  11. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    PubMed

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability. PMID:17652829

  12. Viability of human composite tissue model for experimental study of burns.

    PubMed

    Qu, Miao; Kruse, Stephan; Pitsch, Heinz; Pallua, Norbert; Nourbakhsh, Mahtab

    2016-08-01

    Experimental studies of burns are primarily performed with animal models that have important anatomical and physiological differences relative to human systems. The aim of this study was to develop a human experimental burn model using composite tissue obtained from bariatric surgery. We established a new protocol to maintain viable sections of human cutaneous and subcutaneous (sub/cutaneous) tissue in vitro. Under the conditions selected, multiparametric flow cytometry and histological analysis confirmed the viability and integrity of the human sub/cutaneous tissue for at least 5 days. Furthermore, we utilized a precision McKenna burner to inflict burns on the human tissue model under well-defined thermal conditions in vitro. Our data showed a localized, temporally restricted polarization of the resident macrophages in the subcutaneous human tissue in response to specific thermal forces. Therefore, our model provides a useful alternative to animal studies for further detailed investigations of human responses to injuries and treatments. PMID:27585227

  13. 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. PMID:12872770

  14. Characterizing and Diminishing Autofluorescence in Formalin-fixed Paraffin-embedded Human Respiratory Tissue.

    PubMed

    Davis, A Sally; Richter, Anke; Becker, Steven; Moyer, Jenna E; Sandouk, Aline; Skinner, Jeff; Taubenberger, Jeffery K

    2014-04-10

    Tissue autofluorescence frequently hampers visualization of immunofluorescent markers in formalin-fixed paraffin-embedded respiratory tissues. We assessed nine treatments reported to have efficacy in reducing autofluorescence in other tissue types. The three most efficacious were Eriochrome black T, Sudan black B and sodium borohydride, as measured using white light laser confocal Λ(2) (multi-lambda) analysis. We also assessed the impact of steam antigen retrieval and serum application on human tracheal tissue autofluorescence. Functionally fitting this Λ(2) data to 2-dimensional Gaussian surfaces revealed that steam antigen retrieval and serum application contribute minimally to autofluorescence and that the three treatments are disparately efficacious. Together, these studies provide a set of guidelines for diminishing autofluorescence in formalin-fixed paraffin-embedded human respiratory tissue. Additionally, these characterization techniques are transferable to similar questions in other tissue types, as demonstrated on frozen human liver tissue and paraffin-embedded mouse lung tissue fixed in different fixatives. PMID:24722432

  15. Tissue concentrations of coenzyme Q10 in the rat following its oral and intraperitoneal administration.

    PubMed

    Reahal, S; Wrigglesworth, J

    1992-01-01

    Daily oral or ip administration of coenzyme Q10 to rats for time periods of 2 to 10 weeks leads to its accumulation in liver, concentrating in the soluble fraction of the liver cells. No uptake of coenzyme Q10 can be detected in the heart or kidney. Intraperitoneal administration also results in the accumulation of coenzyme Q10 in the spleen. It is concluded that the normal endogenous levels of quinone in the rat heart and kidney cannot be supplemented over the long term by administration of exogenous quinone. PMID:1355718

  16. Pharmacokinetics and metabolism of benzene in Zymbal gland and other key target tissues after oral administration in rats.

    PubMed Central

    Low, L K; Meeks, J R; Norris, K J; Mehlman, M A; Mackerer, C R

    1989-01-01

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, and mammary gland of Sprague-Dawley rats following chronic oral administration of benzene. The cause for the specificity of such lesions remains unclear, but it is possible that tissue-specific metabolism or pharmacokinetics of benzene is responsible. Metabolism and pharmacokinetic studies were carried out in our laboratory with 14C-benzene at oral doses of 0.15 to 500 mg/kg to ascertain tissue retention, metabolite profile, and elimination kinetics in target and nontarget organs and in blood. Findings from those studies indicate the following: a) the Zymbal gland is not a sink or a site of accumulation for benzene or its metabolites even after a single high dose (500 mg/kg) or after repeated oral administration; b) the metabolite profile is quantitatively different in target tissues (e.g., Zymbal gland, nasal cavity), nontarget tissues and blood; and (c) pharmacokinetic studies show that the elimination of radioactivity from the Zymbal gland is biphasic. PMID:2792043

  17. Pharmacokinetics and metabolism of benzene in Zymbal gland and other key target tissues after oral administration in rats.

    PubMed

    Low, L K; Meeks, J R; Norris, K J; Mehlman, M A; Mackerer, C R

    1989-07-01

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, and mammary gland of Sprague-Dawley rats following chronic oral administration of benzene. The cause for the specificity of such lesions remains unclear, but it is possible that tissue-specific metabolism or pharmacokinetics of benzene is responsible. Metabolism and pharmacokinetic studies were carried out in our laboratory with 14C-benzene at oral doses of 0.15 to 500 mg/kg to ascertain tissue retention, metabolite profile, and elimination kinetics in target and nontarget organs and in blood. Findings from those studies indicate the following: a) the Zymbal gland is not a sink or a site of accumulation for benzene or its metabolites even after a single high dose (500 mg/kg) or after repeated oral administration; b) the metabolite profile is quantitatively different in target tissues (e.g., Zymbal gland, nasal cavity), nontarget tissues and blood; and (c) pharmacokinetic studies show that the elimination of radioactivity from the Zymbal gland is biphasic. PMID:2792043

  18. 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. PMID:19996631

  19. Wave Dispersion and Attenuation on Human Femur Tissue

    PubMed Central

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

    2014-01-01

    Cortical bone is a highly heterogeneous material at the microscale and has one of the most complex structures among materials. Application of elastic wave techniques to this material is thus very challenging. In such media the initial excitation energy goes into the formation of elastic waves of different modes. Due to “dispersion”, these modes tend to separate according to the velocities of the frequency components. This work demonstrates elastic wave measurements on human femur specimens. The aim of the study is to measure parameters like wave velocity, dispersion and attenuation by using broadband acoustic emission sensors. First, four sensors were placed at small intervals on the surface of the bone to record the response after pencil lead break excitations. Next, the results were compared to measurements on a bulk steel block which does not exhibit heterogeneity at the same wave lengths. It can be concluded 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. Of particular interest are waveform parameters like the duration, rise time and average frequency, since in the next stage of research the bone specimens will be fractured with concurrent monitoring of acoustic emission. PMID:25196011

  20. Evaluation of immunohistochemical staining for glucagon in human pancreatic tissue

    PubMed Central

    Gurlo, Tatyana; Butle, Peter C.; Butler, Alexandra E.

    2016-01-01

    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 PMID:27182095

  1. Strategies for improving the physiological relevance of human engineered tissues

    PubMed Central

    Abbott, Rosalyn D; Kaplan, David L

    2015-01-01

    This review examines important robust methods for sustained, steady state, in vitro culture. To achieve ‘physiologically relevant’ tissues in vitro additional complexity must be introduced to provide suitable transport, cell signaling, and matrix support for cells in 3D environments to achieve stable readouts of tissue function. Most tissue engineering systems draw conclusions on tissue functions such as responses to toxins, nutrition or drugs based on short term outcomes with in vitro cultures (2–14 days). However, short term cultures limit insight with physiological relevance, as the cells and tissues have not reached a steady state. PMID:25937289

  2. Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve

    PubMed Central

    Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng

    2016-01-01

    RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474

  3. Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve.

    PubMed

    Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng

    2016-01-01

    RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474

  4. Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues1

    PubMed Central

    Spade, Daniel J.; McDonnell, Elizabeth V.; Heger, Nicholas E.; Sanders, Jennifer A.; Saffarini, Camelia M.; Gruppuso, Philip A.; De Paepe, Monique E.; Boekelheide, Kim

    2015-01-01

    Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development. PMID:25477288

  5. Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

    EPA Science Inventory

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

  6. Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells

    PubMed Central

    Parsons, Xuejun H; Teng, Yang D; Moore, Dennis A; Snyder, Evan Y

    2011-01-01

    Human embryonic stem cells (hESCs) are genetically stable with unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of a large supply of disease-targeted human somatic cells that are restricted to the lineage in need of repair. There is a large healthcare need to develop hESC-based therapeutic solutions to provide optimal regeneration and reconstruction treatment options for the damaged or lost tissue or organ that have been lacking. In spite of controversy surrounding the ownership of hESCs, the number of patent applications related to hESCs is growing rapidly. This review gives an overview of different patent applications on technologies of derivation, maintenance, differentiation, and manipulation of hESCs for therapies. Many of the published patent applications have been based on previously established methods in the animal systems and multi-lineage inclination of pluripotent cells through spontaneous germ-layer differentiation. Innovative human stem cell technologies that are safe and effective for human tissue and organ regeneration in the clinical setting remain to be developed. Our overall view on the current patent situation of hESC technologies suggests a trend towards hESC patent filings on novel therapeutic strategies of direct control and modulation of hESC pluripotent fate, particularly in a 3-dimensional context, when deriving clinically-relevant lineages for regenerative therapies. PMID:23355961

  7. Human Resources Administration: A School-Based Perspective. Second Edition.

    ERIC Educational Resources Information Center

    Smith, Richard E.

    Many human-resource functions previously belonging to the central office are now the responsibility of school principals. Twelve chapters provide practical information about performing these functions. The first chapter provides an overview for the book. It briefly discusses the major topics and provides an overall framework for the more detailed…

  8. Human Resources Administration: A School-Based Perspective. Fourth Edition

    ERIC Educational Resources Information Center

    Smith, Richard

    2009-01-01

    Enhanced and updated, this Fourth Edition of Richard E. Smith's highly successful text examines the growing role of the principal in planning, hiring, staff development, supervision, and other human resource functions. The Fourth Edition includes new sections on ethics, induction, and the role of the mentor teacher. This edition also introduces…

  9. [Tissue engineering and construction of human skin in vitro].

    PubMed

    Arvelo, Francisco

    2007-09-01

    Tissue engineering is the new science that has come to make possible the growth of new organ tissue from small fragments of healthy tissue, thus partially or totally restoring the lost functions of ill tissues or organs, as shown by the achievements made with the culture of skin, cornea or cartilage. Thus far, this new science is able to ensure the recovery of lost functions and, doubtlessly, in a near future will be capable of developing tissues and organs not unlike natural ones. In our laboratory we have began the development of tissue engineering techniques for the successful construction of in vitro skin with the aim at mid term of producing cornea and cartilage. In a first clinical trial, these techniques were applied in the treatment of chronic skin lesions and the advantages and reach of these new tools were demonstrated for the effective solution of problems with would otherwise not be easily solved through the use of conventional treatments. PMID:17853796

  10. NMDA receptors are expressed in human ovarian cancer tissues and human ovarian cancer cell lines.

    PubMed

    North, William G; Liu, Fuli; Tian, Ruiyang; Abbasi, Hamza; Akerman, Bonnie

    2015-01-01

    We have earlier demonstrated that breast cancer and small-cell lung cancer express functional NMDA receptors that can be targeted to promote cancer cell death. Human ovarian cancer tissues and human ovarian cancer cell lines (SKOV3, A2008, and A2780) have now been shown to also express NMDA-receptor subunit 1 (GluN1) and subunit 2B (GluN2B). Seventeen ovarian cancers in two arrays were screened by immunohistochemistry using polyclonal antibodies that recognize an extracellular moiety on GluN1 and on GluN2B. These specimens comprised malignant tissue with pathology diagnoses of serous papillary cystadenocarcinoma, endometrioid adenocarcinoma, and clear-cell carcinoma. Additionally, archival tissues defined as ovarian adenocarcinoma from ten patients treated at this institute were also evaluated. All of the cancerous tissues demonstrated positive staining patterns with the NMDA-receptor antibodies, while no staining was found for tumor-adjacent normal tissues or sections of normal ovarian tissue. Human ovarian adenocarcinoma cell lines (A2008, A2780, SKOV3) were demonstrated to express GluN1 by Western blotting, but displayed different levels of expression. Through immunocytochemistry utilizing GluN1 antibodies and imaging using a confocal microscope, we were able to demonstrate that GluN1 protein is expressed on the surface of these cells. In addition to these findings, GluN2B protein was demonstrated to be expressed using polyclonal antibodies against this protein. Treatment of all ovarian cell lines with antibodies against GluN1 was found to result in decreased cell viability (P<0.001), with decreases to 10%-25% that of untreated cells. Treatment of control HEK293 cells with various dilutions of GluN1 antibodies had no effect on cell viability. The GluN1 antagonist MK-801 (dizocilpine maleate) and the GluN2B antagonist ifenprodil, like antibodies, dramatically decreased the viability of A2780 ovarian tumor cells (P<0.01). Treatment of A2780 tumor xenografts with

  11. NMDA receptors are expressed in human ovarian cancer tissues and human ovarian cancer cell lines

    PubMed Central

    North, William G; Liu, Fuli; Tian, Ruiyang; Abbasi, Hamza; Akerman, Bonnie

    2015-01-01

    We have earlier demonstrated that breast cancer and small-cell lung cancer express functional NMDA receptors that can be targeted to promote cancer cell death. Human ovarian cancer tissues and human ovarian cancer cell lines (SKOV3, A2008, and A2780) have now been shown to also express NMDA-receptor subunit 1 (GluN1) and subunit 2B (GluN2B). Seventeen ovarian cancers in two arrays were screened by immunohistochemistry using polyclonal antibodies that recognize an extracellular moiety on GluN1 and on GluN2B. These specimens comprised malignant tissue with pathology diagnoses of serous papillary cystadenocarcinoma, endometrioid adenocarcinoma, and clear-cell carcinoma. Additionally, archival tissues defined as ovarian adenocarcinoma from ten patients treated at this institute were also evaluated. All of the cancerous tissues demonstrated positive staining patterns with the NMDA-receptor antibodies, while no staining was found for tumor-adjacent normal tissues or sections of normal ovarian tissue. Human ovarian adenocarcinoma cell lines (A2008, A2780, SKOV3) were demonstrated to express GluN1 by Western blotting, but displayed different levels of expression. Through immunocytochemistry utilizing GluN1 antibodies and imaging using a confocal microscope, we were able to demonstrate that GluN1 protein is expressed on the surface of these cells. In addition to these findings, GluN2B protein was demonstrated to be expressed using polyclonal antibodies against this protein. Treatment of all ovarian cell lines with antibodies against GluN1 was found to result in decreased cell viability (P<0.001), with decreases to 10%–25% that of untreated cells. Treatment of control HEK293 cells with various dilutions of GluN1 antibodies had no effect on cell viability. The GluN1 antagonist MK-801 (dizocilpine maleate) and the GluN2B antagonist ifenprodil, like antibodies, dramatically decreased the viability of A2780 ovarian tumor cells (P<0.01). Treatment of A2780 tumor xenografts with

  12. Tissue Specificity of Human Angiotensin I-Converting Enzyme

    PubMed Central

    Kryukova, Olga V.; Tikhomirova, Victoria E.; Golukhova, Elena Z.; Evdokimov, Valery V.; Kalantarov, Gavreel F.; Trakht, Ilya N.; Schwartz, David E.; Dull, Randal O.; Gusakov, Alexander V.; Uporov, Igor V.; Kost, Olga A.; Danilov, Sergei M.

    2015-01-01

    Background Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood. Methods/Principal Findings We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests. Conclusions Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs. PMID:26600189

  13. Human temporal lobe epilepsy analyses by tissue proteomics.

    PubMed

    Mériaux, Céline; Franck, Julien; Park, Dan Bi; Quanico, Jusal; Kim, Young Hye; Chung, Chun Kee; Park, Young Mok; Steinbusch, Harry; Salzet, Michel; Fournier, Isabelle

    2014-06-01

    Although there are many types of epilepsy, temporal lobe epilepsy (TLE) is probably in humans the most common and most often studied. TLE represents 40% of the total epilepsy form of the disease and is difficult to treat. Despite a wealth of descriptive data obtained from the disease history of patients, the EEG recording, imaging techniques, and histological studies, the epileptogenic process remains poorly understood. However, it is unlikely that a single factor or a single mechanism can cause many changes associated with this neuropathological phenomenon. MALDI mass spectrometry imaging (MSI) coupled to protein identification, because of its ability to study a wide range of molecules, appears to be suitable for the preparation of molecular profiles in TLE. Seven neuropeptides have been have been identified in Dental gyrus regions of the hippocampus in relation with TLE pathology. Shot-gun studies taking into account gender influence have been performed. Tissue microextraction from control (10) toward 10 TLE patients have been analyzed after trypsin digestion followed by separation on nanoLC coupled to LTQ orbitrap. From the shot-gun analyses, results confirmed the presence of specific neuropeptides precursors and receptors in TLE patients as well as proteins involved in axons regeneration including neurotrophins, ECM proteins, cell surface proteins, membrane proteins, G-proteins, cytoskeleton proteins and tumor suppressors. Among the tumor suppressors identified, the Leucine-rich glioma inactivated 1 (LGI1) protein was found. LGI1 gene recently been demonstrated being implicated in heritability of TLE. We have also demonstrate the presence a complete profile of tumor suppressors in TLE patients, 7 have been identified. Refining this analysis taken into account the gender influence in both control and in TLE reflected the presence of specific proteins between male and female and thus mechanisms in pathology development could be completely different. PMID:24449190

  14. Combined administration of N-acetylcysteine and monoisoamyl DMSA on tissue oxidative stress during arsenic chelation therapy.

    PubMed

    Kannan, Gurusamy M; Flora, Swaran J S

    2006-04-01

    The present study deals with the therapeutic potential of combined administration of N-acetylcysteine (NAC) along with monoisoamyl DMSA (MiADMSA) against chronic arsenic poisoning in guinea pigs. Animal were exposed to 50 ppm arsenic in drinking water for 8 mo and subsequently treated for 5 consecutive days with 100 mg/kg NAC (orally) and MiADMSA (intraperitoneally), individually or in combination (50 mg/kg each). Arsenic exposure produced a significant depletion of blood delta- aminolevulinic acid dehydrate (ALAD) activity, increased the blood zinc protoporphyrin (ZPP) level, and reduced blood and liver glutathione (GSH) levels in guinea pigs. Hepatic oxidized glutathione (GSSG) and thiobarbituric acid reactive substance (TBARS) levels showed a marked increase, whereas hepatic alkaline phosphatase (ALP) activity decreased and acid phosphatase (ACP) activity increased on arsenic exposure. Significant depletion of liver transaminase activities on arsenic exposure suggests organ injury. Administration of MiADMSA, alone and in combination with NAC after arsenic exposure, was able to significantly enhance hepatic GSH and to reduce GSSG and TBARS levels compared to the arsenic control. Biochemical variables indicative of liver injury generally remained insensitive to any of these treatments. The recoveries in parameters indicative of oxidative stress were more marked in guinea pigs treated with combined administration of NAC and MiADMSA than monotherapy. Interestingly, there was a more pronounced depletion of arsenic from blood and tissues after combined treatment with NAC plus MiADMSA than MiADMSA. Blood and tissues copper, zinc, iron, and calcium concentrations showed a significant increase after arsenic exposure, which showed improvement, particularly after combined administration of MiADMSA and NAC. Based on these data, a proposal can be made that greater effectiveness in chelation treatment against chronic arsenic poisoning (i.e., turnover in the oxidative stress

  15. Raising the standard: changes to the Australian Code of Good Manufacturing Practice (cGMP) for human blood and blood components, human tissues and human cellular therapy products.

    PubMed

    Wright, Craig; Velickovic, Zlatibor; Brown, Ross; Larsen, Stephen; Macpherson, Janet L; Gibson, John; Rasko, John E J

    2014-04-01

    In Australia, manufacture of blood, tissues and biologicals must comply with the federal laws and meet the requirements of the Therapeutic Goods Administration (TGA) Manufacturing Principles as outlined in the current Code of Good Manufacturing Practice (cGMP). The Therapeutic Goods Order (TGO) No. 88 was announced concurrently with the new cGMP, as a new standard for therapeutic goods. This order constitutes a minimum standard for human blood, tissues and cellular therapeutic goods aimed at minimising the risk of infectious disease transmission. The order sets out specific requirements relating to donor selection, donor testing and minimisation of infectious disease transmission from collection and manufacture of these products. The Therapeutic Goods Manufacturing Principles Determination No. 1 of 2013 references the human blood and blood components, human tissues and human cellular therapy products 2013 (2013 cGMP). The name change for the 2013 cGMP has allowed a broadening of the scope of products to include human cellular therapy products. It is difficult to directly compare versions of the code as deletion of some clauses has not changed the requirements to be met, as they are found elsewhere amongst the various guidelines provided. Many sections that were specific for blood and blood components are now less prescriptive and apply to a wider range of cellular therapies, but the general overall intent remains the same. Use of 'should' throughout the document instead of 'must' allows flexibility for alternative processes, but these systems will still require justification by relevant logical argument and validation data to be acceptable to TGA. The cGMP has seemingly evolved so that specific issues identified at audit over the last decade have now been formalised in the new version. There is a notable risk management approach applied to most areas that refer to process justification and decision making. These requirements commenced on 31 May 2013 and a 12 month

  16. TISSUE DOSIMETRY, METABOLISM AND EXCRETION OF PENTAVALENT AND TRIVALENT DIMETHYLATED ARSENIC IN MICE AFTER ORAL ADMINISTRATION

    EPA Science Inventory

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were...

  17. Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust

    PubMed Central

    2011-01-01

    Background Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries. Discussion To a considerable extent, the failure to adequately engage host communities, the opacity of informed consent, and the lack of fair benefit-sharing have played a significant role in eroding trust. These ethical considerations are central to biomedical research in low to middle income countries and failure to attend to them can inadvertently contribute to exploitation and erode trust. A 'tissue trust' may be a plausible means for enabling access to human tissues for research in a manner that is responsive to the ethical challenges considered. Summary Preventing exploitation and restoring trust while simultaneously promoting global health research calls for innovative approaches to human tissues research. A tissue trust can reduce the risk of exploitation and promote host capacity as a key benefit. PMID:21266076

  18. 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. PMID:26535413

  19. 2D Representation of Transcriptomes by t-SNE Exposes Relatedness between Human Tissues

    PubMed Central

    Taskesen, Erdogan; Reinders, Marcel J. T.

    2016-01-01

    The GTEx Consortium reported that hierarchical clustering of RNA profiles from 25 unique tissue types among 1641 individuals accurately distinguished the tissue types, but a multidimensional scaling failed to generate a 2D projection of the data that separates tissue-subtypes. In this study we show that a projection by t-Distributed Stochastic Neighbor Embedding is in line with the cluster analysis which allows a more detailed examination and visualization of human tissue relationships. PMID:26906061

  20. Sharing and Specificity of Co-expression Networks across 35 Human Tissues

    PubMed Central

    Pierson, Emma; Koller, Daphne; Battle, Alexis; Mostafavi, Sara

    2015-01-01

    To understand the regulation of tissue-specific gene expression, the GTEx Consortium generated RNA-seq expression data for more than thirty distinct human tissues. This data provides an opportunity for deriving shared and tissue specific gene regulatory networks on the basis of co-expression between genes. However, a small number of samples are available for a majority of the tissues, and therefore statistical inference of networks in this setting is highly underpowered. To address this problem, we infer tissue-specific gene co-expression networks for 35 tissues in the GTEx dataset using a novel algorithm, GNAT, that uses a hierarchy of tissues to share data between related tissues. We show that this transfer learning approach increases the accuracy with which networks are learned. Analysis of these networks reveals that tissue-specific transcription factors are hubs that preferentially connect to genes with tissue specific functions. Additionally, we observe that genes with tissue-specific functions lie at the peripheries of our networks. We identify numerous modules enriched for Gene Ontology functions, and show that modules conserved across tissues are especially likely to have functions common to all tissues, while modules that are upregulated in a particular tissue are often instrumental to tissue-specific function. Finally, we provide a web tool, available at mostafavilab.stat.ubc.ca/GNAT, which allows exploration of gene function and regulation in a tissue-specific manner. PMID:25970446

  1. 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.

  2. Transplantation of electively aborted human fetal tissue: physicians' attitudes.

    PubMed Central

    Mullen, M A; Williams, J I; Lowy, F H

    1994-01-01

    OBJECTIVE: To provide empirical data on the attitudes of Ontario family physicians and gynecologists toward the use of electively aborted fetal tissue for transplantation (FTT). DESIGN: Cross-sectional survey. SETTING: Ontario. PARTICIPANTS: Random samples of 300 physicians from the membership list of the College of Family Physicians of Canada and 300 from the membership list of the Society of Obstetricians and Gynaecologists of Canada; 248 family physicians and 186 gynecologists responded, for an overall response rate of 72%. OUTCOME MEASURES: Physicians' attitudes toward incentives to collect fetal tissue at abortion, patient-management issues, consent issues and potential conflicts in the supply and demand of fetal tissue. RESULTS: Of those surveyed 75% agreed that there should be no incentives to collect fetal tissue at abortion, 90% believed that decisions to abort must be separate from decisions to donate fetal tissue, 94% agreed that an option to donate fetal tissue should be discussed only after a firm decision to abort has been made, and 88% stated that the demand for fetal tissue should not hinder the availability of new abortion technology such as the abortifacient pill (RU 486). CONCLUSIONS: Results suggest that there is general approval for FTT. Apparent variations between responses to global statements and to practice-oriented statements suggest strategies for effective Canadian public policy regarding FTT. PMID:8039086

  3. 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.

  4. Transcending the Limitations of the Social Sciences: Insight, Understanding, and the Humanities in Educational Administration.

    ERIC Educational Resources Information Center

    Ryan, James

    1994-01-01

    Considers the role of the humanities in the study and practice of educational administration, offering significant insights into the human condition and the philosophical and moral aspects of education. Discusses the limitations of the subject-object dualism underpinning traditional social science. Explains how Slipperjack's "Honor the Sun,"…

  5. Tissue deposition and residue depletion of melamine in fattening pigs following oral administration.

    PubMed

    Wang, Wei; Chen, Hong; Yu, Bing; Mao, Xiangbing; Chen, Daiwen

    2014-01-01

    The adulteration of animal feed as well as milk products with melamine has led to concerns about the ability to establish appropriate withdrawal intervals to ensure food safety. Two experiments were conducted in this study. The first was to investigate the deposition and depletion of melamine in blood and tissues of pigs exposed to adulterated feed with high doses of melamine. A total of 500 or 1000 mg kg(-1) melamine was added to the diet for fattening pigs (initial BW = ±60.24 kg). Melamine residues were detected in tissues (brain, duodenum, liver, heart, muscle and kidney) by LC-MS/MS. Dose-dependent effects were found between melamine residual concentration and its dose in feed. Five days after the withdrawal of melamine from the diets, the residue concentration in tissues fell below 2.5 mg kg(-1). In the second experiment, blood samples were taken at different time points from fattening pigs (BW = 100 kg) fed with adulterated feed with 1000 mg kg(-1) of melamine for 42 days. Results from the pharmacokinetics analysis showed that it would take 83 h for the melamine level in plasma depleting to the safe level of 50 ng ml(-1) after an expose of 1000 mg kg(-1) melamine contaminated feed for 42 days. PMID:24397789

  6. 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. PMID:27211566

  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. 31P magnetic resonance phospholipid profiles of neoplastic human breast tissues.

    PubMed Central

    Merchant, T. E.; Meneses, P.; Gierke, L. W.; Den Otter, W.; Glonek, T.

    1991-01-01

    Phospholipids from malignant, benign and noninvolved human breast tissues were extracted by chloroform-methanol (2:1) and analysed by 31P MR spectroscopy at 202.4 MHz. Thirteen phospholipids were identified as constituents of the profiles obtained among the 55 tissue specimens analysed. Observed patterns in phospholipid tissues profiles were distinct, allowing qualitative characterisation of the three tissue groups. Multivariate analysis of lysophosphatidylcholine (LPC) and an uncharacterised phospholipid were shown to be independently significant in predicting benign tissue histology as either fibrocystic disease or fibroadenoma in 92% of cases. Univariate analysis of relative mole-percentage of phosphorus concentrations of individual phospholipids using the Scheffé comparison procedure revealed that in malignant tissues, phosphatidylethanolamine was significantly elevated compared to benign (+ 32%) and noninvolved tissues (+ 22%). Phosphatidylinositol (+ 33%) and phosphatidylcholine plasmalogen (PC plas) (+ 25%) were increased in malignant compared to benign and LPC was decreased (-44%) in malignant compared to noninvolved. LPC was significantly depressed (-39%) in benign tissue compared to normal. Phospholipid indices computed to further characterise the three tissue groups showed PC plas/PC elevated in malignant tissue compared to benign and PE plas/PE depressed in malignant tissue compared to noninvolved. These findings support previous investigations reporting that the alkyl-phospholipid analogues of phosphatidylcholine are released by malignant tissues and that levels of ethanolamine are elevated in malignant tissues. Indices describing the choline-containing phospholipids showed that these lipids are depressed significantly in malignant tissue relative to healthy tissue. PMID:2039694

  9. Continuous wave terahertz reflection imaging of human colorectal tissue

    NASA Astrophysics Data System (ADS)

    Doradla, Pallavi; Alavi, Karim; Joseph, Cecil S.; Giles, Robert H.

    2013-03-01

    Continuous wave terahertz (THz) imaging has the potential to offer a safe, non-ionizing, and nondestructive medical imaging modality for delineating colorectal cancer. Fresh excisions of normal colon tissue were obtained from surgeries performed at the University of Massachusetts Medical School, Worcester. Reflection measurements of thick sections of colorectal tissues, mounted in an aluminum sample holder, were obtained for both fresh and formalin fixed tissues. The two-dimensional reflection images were acquired by using an optically pumped far-infrared molecular gas laser operating at 584 GHz with liquid Helium cooled silicon bolometer detector. Using polarizers in the experiment both co-polarized and cross-polarized remittance form the samples was collected. Analysis of the images showed the importance of understanding the effects of formalin fixation while determining reflectance level of tissue response. The resulting co- and cross-polarized images of both normal and formalin fixed tissues showed uniform terahertz response over the entire sample area. Initial measurements indicated a co-polarized reflectance of 16%, and a cross-polarized reflectance of 0.55% from fresh excisions of normal colonic tissues.

  10. Effects of simulated microgravity on human brain nervous tissue.

    PubMed

    Wang, Xianghan; Du, Jianxin; Wang, Demei; Zeng, Fan; Wei, Yukui; Wang, Fuli; Feng, Chengcheng; Li, Nuomin; Dai, Rongji; Deng, Yulin; Quan, Zhenzhen; Qing, Hong

    2016-08-01

    During spaceflight, the negative effects of space microgravity on astronauts are becoming more and more prominent, and especially, of which on the nervous system is urgently to be solved. For this purpose tissue blocks and primary cells of nervous tissues obtained from glioma of patients were cultivated after culturing for about 7days, explanted tissues and cells were then randomly divided into two groups, one for static culture (control group, C), and the other for rotary processing for 1day, 3days, 5days, 7days and 14days (experiment group, E). Figures captured by inverted microscope revealed that, with short time rotating for 1day or 3days, morphology changes of tissue blocks were not obvious. When the rotary time was extended to 7days or 14days, it was found that cell somas is significantly larger and the ability of adhesion is declined in comparison with that in control group. Additionally, the arrangement of cells migrated from explanted tissues was disorganized, and the migration distance became shorter. In immunofluorescence analysis, β-tubulin filaments in control group appeared to organize into bundles. While in experiment group, β-tubulin was highly disorganized. In conclusion, simulated microgravity treatment for a week affected the morphology of nervous tissue, and caused highly disorganized distribution of cytoskeleton and the increase of cell apoptosis. These morphological changes might be one of the causes of apoptosis induced by simulated microgravity. PMID:27268042

  11. 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)

  12. Antibiotic concentration in human wound fluid after intravenous administration.

    PubMed Central

    Bagley, D H; Mac Lowry, J; Beazley, R M; Gorschboth, C; Ketcham, A S

    1978-01-01

    Since the wound is the most common focus of infection in the surgical patient, adequate levels of antibiotic within the wound ar essential. This study examines the concentrations of antibiotic achieved in human wounds. Fluid was collected at timed intervals on the first postoperative day from the wounds of 56 patients receiving antibiotics after regional lymph node dissection. Antibiotic concentration was determined by bioassay. Six antibiotics were studied: cephalothin, cefazolin, cephapirin, oxacillin, ampicillin and clindamycin. The cephalosporins and penicillins showed similar patterns of appearance in the wound fluid. The peak level occurred early (1--1 1/2 hours) with subsequent slow decrease. Clindamycin produced nearly constant levels in wound fluid. The concentration of each antibiotic in wound fluid surpassed the serum levels after 2.5 hours. At the dosages studied each antibiotic produced wound fluid concentrations greater than the MIC for most susceptible organisms. Higher doses provided higher wound fluid levels. The rate of appearance and the levels achieved should be considered in the choice of antibiotics in the surgical subject. Images Fig. 1. PMID:686888

  13. Pharmacokinetics of cefadroxil after oral administration in humans.

    PubMed

    La Rosa, F; Ripa, S; Prenna, M; Ghezzi, A; Pfeffer, M

    1982-02-01

    The human oral pharmacokinetics of cefadroxil were studied in parallel at doses of 250, 500, and 1,000 mg in three groups of 10 healthy young male volunteers. Renal excretion of intact cefadroxil, accounted for 82, 79, and 77% of the above doses. Mean peak serum levels were dose linear: 9, 18, and 35 microgram/ml at 250, 500, and 1,000 mg, respectively. However, overall pharmacokinetics were linear only in the 250- to 500-mg dose range; apparent serum clearances were 10 liters/h, and true renal clearances were 9 and 8 liters/h at 250 and 500 mg. At 1,000 mg, apparent serum clearance dropped to about 7 liters/h, true renal clearance, dropped to 6 liters/h, and the area under the curve increased disproportionately. At 250 and 500 mg, mean half-life was about 1.2 h; at 1,000 mg, however, it was 1.6h. The nonlinear decrease in clearance could be related to saturation of active renal tubular secretion of cefadroxil between the 500- and 1,000-mg doses. Previous results indicating that cefadroxil has greater persistence than other oral cephalosporins such as cephalexin, cephradine, cefaclor were confirmed. PMID:7073267

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

    PubMed

    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. PMID:26926869

  15. 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. PMID:21447075

  16. 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.

  17. Cryobanking of human ovarian tissue: Do women still want their tissue stored beyond 5 years?

    PubMed

    Macklon, Kirsten Tryde; Ernst, Erik; Andersen, Anders Nyboe; Andersen, Claus Yding

    2014-10-01

    Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond an initial 5-year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate was 95%. Sixteen of the patients (17%) stated that they wanted disposal of their tissue; the main reason was completion of family (63%). The mean age of those requesting disposal was 36.6 years, whereas those still wanting their tissue stored were significantly younger, with a mean age of 33.0 years (P < 0.008). In conclusion, most women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family. PMID:25129692

  18. [Binding capability of lidamycin apoprotein to human breast cancer detected by tissue microarrays].

    PubMed

    Cai, Lin; Gao, Rui-Juan; Guo, Xiao-Zhong; Li, Yi; Zhen, Yong-Su

    2010-05-01

    This study is to investigate the binding capability of lidamycin apoprotein (LDP), an enediyne-associated apoprotein of the chromoprotein antitumor antibiotic family, to human breast cancer and normal tissues, the correlation of LDP binding capability to human breast cancer tissues and the expression of tumor therapeutic targets such as VEGF and HER2. In this study, the binding capability of LDP to human breast cancer tissues was detected with tissue microarray. The correlation study of LDP binding capability to human breast tumor tissues and relevant therapeutic targets was performed on breast cancer tissue microarrays. Immunocytochemical examination was used to detect the binding capability of LDP to human breast carcinoma MCF-7 cells. As a result, tissue microarray showed that LDP staining of 73.2% (30/41) of breast cancer tissues was positive, whereas that of 48.3% (15/31) of the adjacent normal breast specimens was positive. The difference between the tumor and normal samples was significant (Chi2 = 4.63, P < 0.05). LDP immunoreactivity in breast cancer correlated significantly with the overexpression of VEGF and HER2 (P < 0.001 and < 0.01, r = 0.389 and 0.287, respectively). Determined with confocal immunofluorescent analysis, LDP showed the binding capability to mammary carcinoma MCF-7 cells. It is demonstrated that LDP can bind to human breast cancer tissues and there is significant difference between the breast cancer tissues and the corresponding normal tissues. Notably, the binding reactivity shows positive correlation with the expression of VEGF and HER2 in breast carcinoma tissues. The results imply that LDP may have a potential use as targeting drug carrier in the research and development of new anticancer therapeutics. This study may provide reference for drug combination of LDM and other therapeutic agents. PMID:20931759

  19. Organotin speciation and tissue distribution in rat dams, fetuses, and neonates following oral administration of tributyltin chloride.

    PubMed

    Cooke, Gerard M; Forsyth, Don S; Bondy, Genevieve S; Tachon, Romain; Tague, Brett; Coady, Laurie

    2008-01-01

    Tributyltin (TBT) is a biocide that contaminates human foodstuffs, especially shellfish. TBT is an endocrine disrupter, producing imposex in several marine gastropods. Previous studies showed that oral dosing of rat dams with TBT chloride leads to abnormal fetal and postnatal development. In this study, the tissue distribution and speciation of organotins in tissues were examined in dams, fetuses, and neonates following dosing of rat dams commencing on gestational day (GD) 8 by oral gavage with TBT in olive oil at 0, 0.25, 2.5, or 10 mg/kg body weight (BW)/d. Dams' body weights were significantly reduced by the 10-mg/kg BW/d TBT treatment. At GD20, there were no significant effects of any TBT treatment on pup weights, litter size, sex ratio, or tissue weights. However, at postnatal day (PND) 6 and 12, neonatal pup weights were reduced by the 10-mg/kg BW/d TBT treatment but tissue weights were unaffected, except for the liver weight of female pups, which was reduced by the 10-mg/kg BW/d TBT treatment. Tissues harvested on GD20 and PND6 and PND12 were extracted for determination of organotins by gas chromatography-atomic emission detection (GC-AED). In most tissues, TBT and its metabolite dibutyltin (DBT) were evident but monobutyltin (MBT) was rarely measured above the detection limit. The livers and brains of fetuses contained TBT and DBT at levels that were approximately 50% of the equivalent tissues in the dams. Furthermore, these tissues appeared to preferentially absorb/retain organotins, since the concentrations were greater than were found for the total loading in whole pups. The placenta also contained relatively large quantities of TBT and DBT. Postnatally, the TBT levels in pups decreased markedly, a probable consequence of the extremely low levels of organotins in rat milk. However, DBT levels in pups livers and brains were maintained, probably due to metabolism of TBT to DBT. Similarly, while dams' spleens contained significant quantities of organotins

  20. Controlled Systemic Delivery by Polymeric Implants Enhances Tissue and Plasma Curcumin Levels Compared with Oral Administration

    PubMed Central

    Bansal, Shyam S.; Kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Gupta, Ramesh C.

    2012-01-01

    Curcumin possess potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ~2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ~3.3 ng/ml on day 1 which dropped to ~0.2 ng/ml after 3 months whereas only 0.2–0.3 ng/ml concentration was observed from 4–12 days with diet and was undetected subsequently. Almost 10 fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1±7.3 vs 2.7±0.8 ng/g) and were higher even after 90 days (7.7±3.8 vs 2.2±0.8 ng/g). Although, curcumin levels were similar in liver from both the routes (~25–30 ng/g from day 1–4 and ~10–15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ~28 fold lower doses. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain. PMID:22227368

  1. Magnetic thermal ablation using ferrofluids: influence of administration mode on biological effect in different porcine tissues.

    PubMed

    Bruners, Philipp; Hodenius, Michael; Baumann, Martin; Oversohl, Jessica; Günther, Rolf W; Schmitz-Rode, Thomas; Mahnken, Andreas H

    2008-01-01

    The purpose of this study was to compare the effects of magnetic thermal ablation in different porcine tissues using either a singular injection or a continuous infusion of superparamagnetic iron oxide nanoparticles. In the first setting samples of three ferrofluids containing different amounts of iron (1:171, 2:192, and 3:214 mg/ml) were singularly interstitially injected into specimens of porcine liver, kidney, and muscle (n = 5). Then the specimens were exposed to an alternating magnetic field (2.86 kA/m, 190 kHz) generated by a circular coil for 5 min. In the second experimental setup ferrofluid samples were continuously interstitially infused into the tissue specimens during the exposure to the magnetic field. To measure the temperature increase two fiber-optic temperature probes with a fixed distance of 0.5 cm were inserted into the specimens along the puncture tract of the injection needle and the temperature was measured every 15 s. Finally, the specimens were dissected, the diameters of the created thermal lesions were measured, and the volumes were calculated and compared. Compared to continuous infusion, a single injection of ferrofluids resulted in smaller coagulation volumes in all tissues. Significant differences regarding coagulation volume were found in kidney and muscle specimens. The continuous infusion technique led to more elliptically shaped coagulation volumes due to larger diameters along the puncture tract. Our data show the feasibility of magnetic thermal ablation using either a single interstitial injection or continuous infusion for therapy of lesions in muscle, kidney, and liver. Continuous infusion of ferrofluids results in larger zones of necrosis compared to a single injection technique. PMID:18592306

  2. Magnetic Thermal Ablation Using Ferrofluids: Influence of Administration Mode on Biological Effect in Different Porcine Tissues

    SciTech Connect

    Bruners, Philipp Hodenius, Michael Baumann, Martin Oversohl, Jessica; Guenther, Rolf W.; Schmitz-Rode, Thomas Mahnken, Andreas H.

    2008-11-15

    The purpose of this study was to compare the effects of magnetic thermal ablation in different porcine tissues using either a singular injection or a continuous infusion of superparamagnetic iron oxide nanoparticles. In the first setting samples of three ferrofluids containing different amounts of iron (1:171, 2:192, and 3:214 mg/ml) were singularly interstitially injected into specimens of porcine liver, kidney, and muscle (n = 5). Then the specimens were exposed to an alternating magnetic field (2.86 kA/m, 190 kHz) generated by a circular coil for 5 min. In the second experimental setup ferrofluid samples were continuously interstitially infused into the tissue specimens during the exposure to the magnetic field. To measure the temperature increase two fiber-optic temperature probes with a fixed distance of 0.5 cm were inserted into the specimens along the puncture tract of the injection needle and the temperature was measured every 15 s. Finally, the specimens were dissected, the diameters of the created thermal lesions were measured, and the volumes were calculated and compared. Compared to continuous infusion, a single injection of ferrofluids resulted in smaller coagulation volumes in all tissues. Significant differences regarding coagulation volume were found in kidney and muscle specimens. The continuous infusion technique led to more elliptically shaped coagulation volumes due to larger diameters along the puncture tract. Our data show the feasibility of magnetic thermal ablation using either a single interstitial injection or continuous infusion for therapy of lesions in muscle, kidney, and liver. Continuous infusion of ferrofluids results in larger zones of necrosis compared to a single injection technique.

  3. Intranasal Neuropeptide Administration To Target the Human Brain in Health and Disease.

    PubMed

    Spetter, Maartje S; Hallschmid, Manfred

    2015-08-01

    Central nervous system control of metabolic function relies on the input of endocrine messengers from the periphery, including the pancreatic hormone insulin and the adipokine leptin. This concept primarily derives from experiments in animals where substances can be directly applied to the brain. A feasible approach to study the impact of peptidergic messengers on brain function in humans is the intranasal (IN) route of administration, which bypasses the blood-brain barrier and delivers neuropeptides to the brain compartment, but induces considerably less, if any, peripheral uptake than other administration modes. Experimental IN insulin administration has been extensively used to delineate the role of brain insulin signaling in the control of energy homeostasis, but also cognitive function in healthy humans. Clinical pilot studies have found beneficial effects of IN insulin in patients with memory deficits, suggesting that the IN delivery of this and other peptides bears some promise for new, selectively brain-targeted pharmaceutical approaches in the treatment of metabolic and cognitive disorders. More recently, experiments relying on the IN delivery of the hypothalamic hormone oxytocin, which is primarily known for its involvement in psychosocial processes, have provided evidence that oxytocin influences metabolic control in humans. The IN administration of leptin has been successfully tested in animal models but remains to be investigated in the human setting. We briefly summarize the literature on the IN administration of insulin, leptin, and oxytocin, with a particular focus on metabolic effects, and address limitations and perspectives of IN neuropeptide administration. PMID:25880274

  4. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells

    PubMed Central

    Wang, Limin; Ott, Lindsey; Seshareddy, Kiran; Weiss, Mark L; Detamore, Michael S

    2011-01-01

    Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue engineering and regenerative medicine, yet with so many sources of MSCs, what are the primary criteria for selecting leading candidates? Ideally, the cells will be multipotent, inexpensive, lack donor site morbidity, donor materials should be readily available in large numbers, immunocompatible, politically benign and expandable in vitro for several passages. Bone marrow MSCs do not meet all of these criteria and neither do embryonic stem cells. However, a promising new cell source is emerging in tissue engineering that appears to meet these criteria: MSCs derived from Wharton’s jelly of umbilical cord MSCs. Exposed to appropriate conditions, umbilical cord MSCs can differentiate in vitro along several cell lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal, pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have demonstrated in vivo differentiation ability and promising immunocompatibility with host organs/tissues, even in xenotransplantation. In this article, we address their cellular characteristics, multipotent differentiation ability and potential for tissue engineering with an emphasis on musculoskeletal tissue engineering. PMID:21175290

  5. Genome-wide prediction and analysis of human tissue-selective genes using microarray expression data

    PubMed Central

    2013-01-01

    Background Understanding how genes are expressed specifically in particular tissues is a fundamental question in developmental biology. Many tissue-specific genes are involved in the pathogenesis of complex human diseases. However, experimental identification of tissue-specific genes is time consuming and difficult. The accurate predictions of tissue-specific gene targets could provide useful information for biomarker development and drug target identification. Results In this study, we have developed a machine learning approach for predicting the human tissue-specific genes using microarray expression data. The lists of known tissue-specific genes for different tissues were collected from UniProt database, and the expression data retrieved from the previously compiled dataset according to the lists were used for input vector encoding. Random Forests (RFs) and Support Vector Machines (SVMs) were used to construct accurate classifiers. The RF classifiers were found to outperform SVM models for tissue-specific gene prediction. The results suggest that the candidate genes for brain or liver specific expression can provide valuable information for further experimental studies. Our approach was also applied for identifying tissue-selective gene targets for different types of tissues. Conclusions A machine learning approach has been developed for accurately identifying the candidate genes for tissue specific/selective expression. The approach provides an efficient way to select some interesting genes for developing new biomedical markers and improve our knowledge of tissue-specific expression. PMID:23369200

  6. Tissue transglutaminase is involved in mechanical load-induced osteogenic differentiation of human ligamentum flavum cells.

    PubMed

    Chao, Yuan-Hung; Huang, Shih-Yung; Yang, Ruei-Cheng; Sun, Jui-Sheng

    2016-07-01

    Mechanical load-induced osteogenic differentiation might be the key cellular event in the calcification and ossification of ligamentum flavum. The aim of this study was to investigate the influence of tissue transglutaminase (TGM2) on mechanical load-induced osteogenesis of ligamentum flavum cells. Human ligamentum flavum cells were obtained from 12 patients undergoing lumbar spine surgery. Osteogenic phenotypes of ligamentum flavum cells, such as alkaline phosphatase (ALP), Alizarin red-S stain, and gene expression of osteogenic makers were evaluated following the administration of mechanical load and BMP-2 treatment. The expression of TGM2 was evaluated by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) analysis. Our results showed that mechanical load in combination with BMP-2 enhanced calcium deposition and ALP activity. Mechanical load significantly increased ALP and OC gene expression on day 3, whereas BMP-2 significantly increased ALP, OPN, and Runx2 on day 7. Mechanical load significantly induced TGM2 gene expression and enzyme activity in human ligamentum flavum cells. Exogenous TGM2 increased ALP and OC gene expression; while, inhibited TG activity significantly attenuated mechanical load-induced and TGM2-induced ALP activity. In summary, mechanical load-induced TGM2 expression and enzyme activity is involved in the progression of the calcification of ligamentum flavum. PMID:27115725

  7. 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

  8. Pharmacokinetic study on pradofloxacin in the dog – Comparison of serum analysis, ultrafiltration and tissue sampling after oral administration

    PubMed Central

    2013-01-01

    Background Pradofloxacin, a newly developed 8-cyano-fluoroquinolone, show enhanced activity against Gram-positive organisms and anaerobes to treat canine and feline bacterial infections. The purpose of this cross-over study was to measure the unbound drug concentration of pradofloxacin in the interstitial fluid (ISF) using ultrafiltration and to compare the kinetics of pradofloxacin in serum, ISF and tissue using enrofloxacin as reference. Results After oral administration of enrofloxacin (5 mg/kg) and pradofloxacin (3 mg/kg and 6 mg/kg, respectively), serum collection and ultrafiltration in regular intervals over a period of 24 h were performed, followed by tissue sampling at the end of the third dosing protocol (pradofloxacin 6 mg/kg). Peak concentrations of pradofloxacin (3 mg/kg) were 1.55±0.31 μg/ml in the ISF and 1.85±0.23 μg/ml in serum and for pradofloxacin (6 mg/kg) 2.71±0.81 μg/kg in the ISF and 2.77±0.64 μg/kg in serum; both without a statistical difference between ISF and serum. Comparison between all sampling approaches showed no consistent pattern of statistical differences. Conclusions Despite some technical shortcomings the ultrafiltration approach appears to be the most sensitive sampling technique to estimate pharmacokinetic values of pradofloxacin at the infection site. Pharmacokinetics – Pradofloxacin – Ultrafiltration – Dog – Oral Administration. PMID:23410255

  9. Hyperacute Carotid Stent Thrombosis During Emergent Revascularization Treated with Intraarterial Eptifibatide After Systemic Administration of Recombinant Tissue Plasminogen Activator

    PubMed Central

    Sorkin, Grant C; Dumont, Travis M.; Mokin, Maxim; Eller, Jorge L.; Natarajan, Sabareesh K.; Levy, Elad I.; Siddiqui, Adnan H.

    2015-01-01

    A 57-year-old woman with National Institutes of Health Stroke Scale (NIHSS) score of 26 was found to have an acute left carotid occlusion with tandem left M1 thrombus within 1.5 hours of symptom onset. After no neurologic improvement following standard-dose intravenous (IV) recombinant tissue plasminogen activator (rtPA), emergent neuroendovascular revascularization with carotid stenting and intracranial thrombectomy were performed under conscious sedation. Thrombolysis in myocardial infarction (TIMI)-3 flow restoration and symptom resolution were achieved postprocedure; however, complete carotid stent thrombosis was noted on final angiographic runs (25 minutes later), correlating with neurologic decline. Rapid administration of an intraarterial (IA) bolus dose of eptifibatide resulted in TIMI-3 flow restoration, with neurologic improvement. The patient was discharged three days postrevascularization on dual antiplatelet therapy with an NIHSS score of 1. Intraarterial (IA) eptifibatide can be an effective option for acute stent occlusion during emergent neuroendovascular revascularization after IV rtPA administration. ABBREVIATIONS CLEAR Combined approach to lysis utilizing eptifibatide and RtPA CT computed tomographic Fr French GP glycoprotein IA intraarterial ICA internal carotid artery IV intravenous MCA middle cerebral artery NIHSS National Institutes of Health Stroke Scale rtPA recombinant tissue plasminogen activator TIMI thrombolysis in myocardial infarction PMID:26301032

  10. 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.

  11. Human tissues for research purposes: a conference in the House of Lords.

    PubMed

    Clotworthy, Margaret

    2011-11-01

    The challenges to using human tissues in research are many and varied. However, there is little consensus on how concerns raised by researchers should be addressed, and who should be responsible for ensuring that patients continue to benefit from medical research carried out using human tissues which have been ethically donated or collected after surgery, or where organs donated for transplant are unsuitable for this purpose. A conference in the House of Lords sought to bring together stakeholders from all areas of human tissue research to discuss the problems experienced, share solutions, and form a Working Party to carry the conference momentum forward into action in the near future. PMID:20012896

  12. Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts.

    PubMed

    Jiang, Wenkai; Lv, Haipeng; Wang, Haijing; Wang, Diya; Sun, Shukai; Jia, Qian; Wang, Peina; Song, Bing; Ni, Longxing

    2015-08-01

    The NLRP3/caspase-1 inflammasome pathway plays an important role in cellular immune defence against bacterial infection; however, its function in human dental pulp tissue and human dental pulp fibroblasts remains poorly understood. We demonstrate that NLRP3 protein expression occurs to a greater extent in pulp tissue with irreversible pulpitis than in normal pulp tissue and in tissue with reversible pulpitis. Caspase-1 is present in its active (cleaved) form only in pulp tissue with irreversible pulpitis. NLRP3 and caspase-1 are expressed in the odontoblast layers in normal human dental pulp tissue, whereas in inflamed pulp tissue, the odontoblast layers are disrupted and dental pulp cells are positive for NLRP3 and caspase-1. Additionally, we investigate the role of the NLRP3/caspase-1 inflammasome pathway in human dental pulp fibroblasts and show that ATP activates the P2X7 receptor on the cell membrane triggering K(+) efflux and inducing the gradual recruitment of the membrane pore pannexin-1. Extracellular lipopolysaccharide is able to penetrate the cytosol and activate NLRP3. Furthermore, the low intracellular K(+) concentration in the cytosol triggers reactive oxygen species generation, which also induces the NLRP3 inflammasome. Thus, the NLRP3/caspase-1 pathway has a biological role in the innate immune response mounted by human dental pulp fibroblasts. PMID:25684031

  13. Understanding multicellular function and disease with human tissue-specific networks

    PubMed Central

    Greene, Casey S.; Krishnan, Arjun; Wong, Aaron K.; Ricciotti, Emanuela; Zelaya, Rene A.; Himmelstein, Daniel S.; Zhang, Ran; Hartmann, Boris M.; Zaslavsky, Elena; Sealfon, Stuart C.; Chasman, Daniel I.; FitzGerald, Garret A.; Dolinski, Kara; Grosser, Tilo; Troyanskaya, Olga G.

    2016-01-01

    Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell types developed using a data-driven Bayesian methodology that integrates thousands of diverse experiments spanning tissue and disease states. Tissue-specific networks predict lineage-specific responses to perturbation, reveal genes’ changing functional roles across tissues, and illuminate disease-disease relationships. We introduce NetWAS, which combines genes with nominally significant GWAS p-values and tissue-specific networks to identify disease-gene associations more accurately than GWAS alone. Our webserver, GIANT, provides an interface to human tissue networks through multi-gene queries, network visualization, analysis tools including NetWAS, and downloadable networks. GIANT enables systematic exploration of the landscape of interacting genes that shape specialized cellular functions across more than one hundred human tissues and cell types. PMID:25915600

  14. Busulfan administration produces sublethal effects on somatic tissues and inhibits gametogenesis in Senegalese sole juveniles.

    PubMed

    Pacchiarini, T; Olague, E; Sarasquete, C; Cabrita, E

    2014-05-01

    Busulfan, a cytotoxic alkylating agent used for treatment of chronic myeloid leukemia has effects in mammalian germ cells. In fish species, the use of this compound is of special interest in intra and interspecies germ cell transplants. To determine the effects of busulfan in fish a previous range finding experiment was designed. Survival and growth rate of 150-days after hatching (150DAH) Senegalese sole (Solea senegalensis) juveniles was determined. In a second experiment, the effects of a sublethal busulfan dose in fish germ cell depletion and in somatic tissues were analysed. Sublethal effects of several busulfan treatments (B10-10 days after injection, B20-20 days after injection, B20÷-20 days after injection with double injection) were determined in somatic and gonadal tissues. Alterations were registered through histopathological techniques, TUNEL (cell apoptosis) and quantified at molecular level (Q-PCR analyses) using the vasa mRNAs (Ssvasa1-2 and Ssvasa3-4 mRNAs) as molecular markers for germinal cells in Senegalese sole juveniles. Several sublethal effects were observed with 40 mg kg⁻¹ busulfan, a non-lethal dose, such as: pyknosis in liver, increase of melanomacrophage centres and blood stagnation in spleen and interruption of gonadal development. Females were more affected by busulfan treatments than males in terms of germ cell disruption, since a significant decrease in the expression of both Ssvasa1-2 and Ssvasa3-4 markers was found in the gonad of treated females rather than males. At 10 days post-treatment (B10), females already presented a decrease in germ cell proliferation, as confirmed by Q-PCR. Ssvasa expression proved to be a reliable tool for the direct evaluation of the effects of busulfan on Senegalese sole gonadal development, proving that busulfan can be a suitable treatment for causing transient sterility in recipient gonads for germ cell transplantation. PMID:24371034

  15. NMR Spectroscopy of Human Eye Tissues: A New Insight into Ocular Biochemistry

    PubMed Central

    Kryczka, Tomasz; Wylęgała, Edward; Dobrowolski, Dariusz; Midelfart, Anna

    2014-01-01

    Background. The human eye is a complex organ whose anatomy and functions has been described very well to date. Unfortunately, the knowledge of the biochemistry and metabolic properties of eye tissues varies. Our objective was to reveal the biochemical differences between main tissue components of human eyes. Methods. Corneas, irises, ciliary bodies, lenses, and retinas were obtained from cadaver globes 0-1/2 hours postmortem of 6 male donors (age: 44–61 years). The metabolic profile of tissues was investigated with HR MAS 1H NMR spectroscopy. Results. A total of 29 metabolites were assigned in the NMR spectra of the eye tissues. Significant differences between tissues were revealed in contents of the most distant eye-tissues, while irises and ciliary bodies showed minimal biochemical differences. ATP, acetate, choline, glutamate, lactate, myoinositol, and taurine were identified as the primary biochemical compounds responsible for differentiation of the eye tissues. Conclusions. In this study we showed for the first time the results of the analysis of the main human eye tissues with NMR spectroscopy. The biochemical contents of the selected tissues seemed to correspond to their primary anatomical and functional attributes, the way of the delivery of the nutrients, and the location of the tissues in the eye. PMID:25525621

  16. Distinct microRNA Expression Profiles in Mouse Renal Cortical Tissue after 177Lu-octreotate Administration

    PubMed Central

    Schüler, Emil; Parris, Toshima Z.; Helou, Khalil; Forssell-Aronsson, Eva

    2014-01-01

    Aim The aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers. Methods Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples. Results In total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively). No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways. Conclusion In conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration. PMID:25386939

  17. Histologic evaluation of fresh human ovarian tissue before cryopreservation.

    PubMed

    Azem, Foad; Hasson, Joseph; Ben-Yosef, Dalit; Kossoy, Nadia; Cohen, Tanya; Almog, Beni; Amit, Ami; Lessing, Joseph B; Lifschitz-Mercer, Batriz

    2010-01-01

    Transplantation of cryopreserved tissue from patients with cancer may carry the risk of reactivation or redissemination of micrometastases. This prospective study was conducted to evaluate the potential involvement of micrometastases in ovarian tissue in cancer patients. Ovarian biopsies were collected from patients who underwent ovarian tissue cryopreservation, in our IVF unit before chemotherapy between 2000 and 2008. Indications for cryopreservation included breast cancer (n=13), osteosarcoma (n=13), hematologic malignancies (n=13), uterine cervix carcinoma (n=2), endometrial carcinoma (n=1), colon cancer (n=1), and brain medulloblastoma (n=1). The samples were stained with hematoxylin and eosin, and examined histologically. Immunoperoxidase broad-spectrum cytokeratin staining was also performed on specimens from breast cancer patients. There were 44 patients (age range 5-40 yr) who yielded 40 specimens. No gross pathologic involvement was observed, and the histologic examination revealed normal histology with no evidence of metastases. Our findings showed that for the purpose of considering ovarian tissue cryopreservation in cancer patients, the likelihood of microscopic metastases within ovaries of normal appearance is apparently very low. Clarification of the actual risk of ovarian involvement and any subsequent risk of micrometastases and tumor reimplantation requires further investigation. PMID:19952943

  18. 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.

  19. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

    PubMed Central

    2012-01-01

    The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies. PMID:22971420

  20. A critical review of human endotoxin administration as an experimental paradigm of depression

    PubMed Central

    DellaGioia, Nicole; Hannestad, Jonas

    2009-01-01

    The syndrome called depression may represent the common final pathway at which different aetiopathogenic processes converge. One such atiopathogenic process is innate immune system activation. Some depressed patients increased levels of inflammatory cytokines and other immunologic abnormalities. It is not known whether immune system activation contributes to the pathogenesis of depressive symptoms. Supporting this possibility is the observation that in both rodents and humans, exogenous immune stimuli such as endotoxin can produce symptoms that resemble depression. A new approach to depression research would be to use immune stimuli to elicit depressive symptoms in humans. Here we review each of the symptoms elicited in humans by endotoxin administration, and compare this model to two other immune depression paradigms: interferon-alpha treatment and typhoid vaccine administration, to assess to what degree endotoxin administration represents a valid model of immune depression. We also review corresponding behavioral changes in rodents and the potential molecular pathways through which immune system activation produces each symptom. PMID:19666048

  1. Microhardness of human cancellous bone tissue in progressive hip osteoarthritis.

    PubMed

    Tomanik, Magdalena; Nikodem, Anna; Filipiak, Jarosław

    2016-12-01

    Bone tissue is a biological system in which the dynamic processes of, among others, bone formation or internal reconstruction will determine the spatial structure of the tissue and its mechanical properties. The appearance of a factor disturbing the balance between biological processes, e.g. a disease, will cause changes in the spatial structure of bones, thus affecting its mechanical properties. One of the bone diseases most common in an increasingly ageing population is osteoarthritis, also referred to as degenerative joint disease. It is estimated that in 2050 about 1300 million people will show symptoms of OA. The appearance of a pathological stimulus disturbs the balance of the processes of degradation and synthesis of articular cartilage, chondrocytes and the extracellular matrix, and the subchondral bone layer. As osteoarthritis progresses, study of the epiphysis reveals increasingly widespread changes of the articular surface and the internal structure of bone tissue. In this paper, the authors point out the differences in the mechanical properties of cancellous bone tissue forming the proximal epiphysis of the femoral bone during the progressive stages of OA. In order to determine microproperties of bone trabeculae, specimens from different stages of the disease (N=9) were subjected to microindentation testing, which made it possible to determine the material properties of bone tissue, such as microhardness HV and Young׳s modulus E. In addition, mechanical tests were supplemented with Raman spectroscopy, which determine the degree of bone mineralization, and measurements of structural properties based on analysis using microCT. The conducted tests were used to establish both quantitative and quantitative description of changes in the structural and mechanical properties connected with reorganization of trabeculae making up the bone in the various stages of osteoarthritis. The proposed description will supplement existing knowledge in the literature about

  2. Construction and analyses of human large-scale tissue specific networks.

    PubMed

    Liu, Wei; Wang, Jianying; Wang, Tengjiao; Xie, Hongwei

    2014-01-01

    Construction and analyses of tissue specific networks is crucial to unveil the function and organizational structure of biological systems. As a direct method to detect protein dynamics, human proteome-wide expression data provide an valuable resource to investigate the tissue specificity of proteins and interactions. By integrating protein expression data with large-scale interaction network, we constructed 30 tissue/cell specific networks in human and analyzed their properties and functions. Rather than the tissue specificity of proteins, we mainly focused on the tissue specificity of interactions to distill tissue specific networks. Through comparing our tissue specific networks with those inferred from gene expression data, we found our networks have larger scales and higher reliability. Furthermore, we investigated the similar extent of multiple tissue specific networks, which proved that tissues with similar functions tend to contain more common interactions. Finally, we found that the tissue specific networks differed from the static network in multiple topological properties. The proteins in tissue specific networks are interacting looser and the hubs play more important roles than those in the static network. PMID:25513809

  3. Self-Administration of Cannabinoids by Experimental Animals and Human Marijuana Smokers

    PubMed Central

    Justinova, Zuzana; Goldberg, Steven R.; Heishman, Stephen J.; Tanda, Gianluigi

    2009-01-01

    Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drug-naïve squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans. PMID:15932767

  4. 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

  5. Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue.

    PubMed

    Kamble, Prasad G; Pereira, Maria J; Sidibeh, Cherno O; Amini, Sam; Sundbom, Magnus; Börjesson, Joey Lau; Eriksson, Jan W

    2016-05-15

    The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males. Subcutaneous adipose tissue from both genders treated with recombinant human lipocalin 2 showed a reduction in protein levels of GLUT1 and GLUT4 and in glucose uptake in isolated adipocytes. In subcutaneous adipose tissue, lipocalin 2 increased IL-6 gene expression whereas expression of PPARγ and adiponectin was reduced. Our findings suggest that lipocalin 2 can contribute to insulin resistance in human adipose tissue. In pre-menopausal females, it may partly mediate adverse metabolic effects exerted by glucocorticoid excess. PMID:26973291

  6. Tissue resident regulatory T cells: novel therapeutic targets for human disease

    PubMed Central

    Zhou, Xiaohui; Tang, Jiayou; Cao, Hao; Fan, Huimin; Li, Bin

    2015-01-01

    Over the past decade, the ability of regulatory T cells (Tregs) to suppress multiple types of immune cells has received tremendous attention. Mounting evidence has revealed that tissue resident Tregs control non-immunological processes of their target tissues and contribute to a plethora of human diseases. The identification of novel tissue-specific Tregs has highlighted their heterogeneity and complexity. This review summarizes the recent findings for visceral adipose tissue CD4+Foxp3+ regulatory T cells (VAT Tregs), muscle Tregs, bone Tregs and skin memory Tregs, with a focus on their unique functions in local tissues. This interpretation of the roles of tissue-specific Tregs and of their involvement in disease progression provides new insight into the discovery of potential therapeutic targets of human diseases. PMID:25891216

  7. 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.

  8. Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects

    PubMed Central

    de Jonge, Evert; Friederich, Philip W.; Vlasuk, George P.; Rote, William E.; Vroom, Margaretha B.; Levi, Marcel; van der Poll, Tom

    2003-01-01

    The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa. PMID:12738659

  9. Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues

    PubMed Central

    Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

    2014-01-01

    In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus–pituitary–thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3′,5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. PMID:24692290

  10. Production of tissue microarrays, immunohistochemistry staining and digitalization within the human protein atlas.

    PubMed

    Kampf, Caroline; Olsson, Ingmarie; Ryberg, Urban; Sjöstedt, Evelina; Pontén, Fredrik

    2012-01-01

    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

  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. PMID:26830089

  12. Cryobanking of human ovarian tissue for anti-cancer treatment: comparison of vitrification and conventional freezing.

    PubMed

    Isachenko, Vladimir; Isachenko, Evgenia; Weiss, Juergen M; Todorov, Plamen; Kreienberg, Rolf

    2009-01-01

    The first case of cryopreservation of human ovarian tissue with good survival of follicles after warming was described in 1996. Childbirth after cryopreservation of ovarian tissue is now a reality. Cryopreservation of ovarian tissue can be performed using one of two methods: conventional ("slow") freezing and cryopreservation by direct plunging into liquid nitrogen (so called vitrification or "rapid" freezing). Comparative investigations of vitrification and conventional freezing performed on mammalian ovarian tissue are limited, and authors present different conclusions. The higher effectiveness of vitrification in comparison with conventional freezing for human oocytes and embryos was shown, whereas data on human ovarian tissue are limited. The aim of different studies was to compare the safety and effectiveness of conventional freezing and vitrification of human ovarian tissue. Below we shortly summarize the results of some investigations with different conclusions. The discussion on the post-warming quality of follicles as well as on the problems of microbial contamination of cells in liquid nitrogen at vitrification is presented. In our opinion, for cryopreservation of human ovarian tissue, conventional freezing is more promising than vitrification. PMID:20309501

  13. 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.

  14. General solutions to poroviscoelastic model of hydrocephalic human brain tissue.

    PubMed

    Mehrabian, Amin; Abousleiman, Younane

    2011-12-21

    Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly associated with complexities in cerebrospinal fluid (CSF) circulation in brain. In this paper, hydrocephalus and shunting surgery which is used in its treatment are modeled. Brain tissues are considered to follow a poroviscoelastic constitutive model in order to address the effects of time dependence of mechanical properties of soft tissues and fluid flow hydraulics. Our solution draws from Biot's theory of poroelasticity, generalized to account for viscoelastic effects through the correspondence principle. Geometrically, the brain is conceived to be spherically symmetric, where the ventricles are assumed to be a hollow concentric space filled with cerebrospinal fluid. A generalized Kelvin model is considered for the rheological properties of brain tissues. The solution presented is useful in the analysis of the disorder of hydrocephalus as well as the treatment associated with it, namely, ventriclostomy surgery. The sensitivity of the solution to various factors such as aqueduct blockage level and trabeculae stiffness is thoroughly analyzed using numerical examples. Results indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However, only severe occlusion of the aqueduct can cause a significant increase in the ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular pressure to the normal level. However, sensitivity analysis on the shunt's fluid deliverability parameter has shown that inappropriate design or selection of design shunt may cause under-drainage or over-drainage of the ventricles. Excessive drainage of CSF may increase the normal tensile stress on trabeculae. It can cause rupture of superior cerebral veins or damage to trabeculae or even brain tissues which in turn may lead to subdural hematoma, a common side-effect of the surgery. These Post

  15. Correlating optical coherence elastography based strain measurements with collagen content of the human ovarian tissue

    PubMed Central

    Nandy, Sreyankar; Salehi, Hassan S.; Wang, Tianheng; Wang, Xiaohong; Sanders, Melinda; Kueck, Angela; Brewer, Molly; Zhu, Quing

    2015-01-01

    In this manuscript, the initial feasibility of a catheter based phase stabilized swept source optical coherence tomography (OCT) system was studied for characterization of the strain inside different human ovarian tissue groups. The ovarian tissue samples were periodically compressed with 500 Hz square wave signal along the axial direction between the surface of an unfocused transducer and a glass cover slide. The displacement and corresponding strain were calculated during loading from different locations for each tissue sample. A total of 27 ex vivo ovaries from 16 patients were investigated. Statistically significant difference (p < 0.001) was observed between the average displacement and strain of the normal and malignant tissue groups. A sensitivity of 93.2% and a specificity of 83% were achieved using 25 microstrain (με) as the threshold. The collagen content of the tissues was quantified from the Sirius Red stained histological sections. The average collagen area fraction (CAF) obtained from the tissue groups were found to have a strong negative correlation (R = −0.75, p < 0.0001) with the amount of strain inside the tissue. This indicates much softer and degenerated tissue structure for the malignant ovaries as compared to the dense, collagen rich structure of the normal ovarian tissue. The initial results indicate that the swept source OCT system can be useful for estimating the elasticity of the human ovarian tissue. PMID:26504631

  16. Correlating optical coherence elastography based strain measurements with collagen content of the human ovarian tissue.

    PubMed

    Nandy, Sreyankar; Salehi, Hassan S; Wang, Tianheng; Wang, Xiaohong; Sanders, Melinda; Kueck, Angela; Brewer, Molly; Zhu, Quing

    2015-10-01

    In this manuscript, the initial feasibility of a catheter based phase stabilized swept source optical coherence tomography (OCT) system was studied for characterization of the strain inside different human ovarian tissue groups. The ovarian tissue samples were periodically compressed with 500 Hz square wave signal along the axial direction between the surface of an unfocused transducer and a glass cover slide. The displacement and corresponding strain were calculated during loading from different locations for each tissue sample. A total of 27 ex vivo ovaries from 16 patients were investigated. Statistically significant difference (p < 0.001) was observed between the average displacement and strain of the normal and malignant tissue groups. A sensitivity of 93.2% and a specificity of 83% were achieved using 25 microstrain (με) as the threshold. The collagen content of the tissues was quantified from the Sirius Red stained histological sections. The average collagen area fraction (CAF) obtained from the tissue groups were found to have a strong negative correlation (R = -0.75, p < 0.0001) with the amount of strain inside the tissue. This indicates much softer and degenerated tissue structure for the malignant ovaries as compared to the dense, collagen rich structure of the normal ovarian tissue. The initial results indicate that the swept source OCT system can be useful for estimating the elasticity of the human ovarian tissue. PMID:26504631

  17. Nifedipine and phenytoin induce matrix synthesis, but not proliferation, in intact human gingival connective tissue ex vivo.

    PubMed

    Kim, Shawna S; Michelsons, Sarah; Creber, Kendal; Rieder, Michael J; Hamilton, Douglas W

    2015-12-01

    Drug-induced gingival enlargement (DIGE) is a fibrotic condition that can be caused by the antihypertensive drug nifedipine and the anti-seizure drug phenytoin, but the molecular etiology of this type of fibrosis is not well understood and the role of confounding factors such as inflammation remains to be fully investigated. The aim of this study was to develop an ex vivo gingival explant system to allow investigation of the effects of nifedipine and phenytoin alone on human gingival tissue. Comparisons were made to the histology of human DIGE tissue retrieved from individuals with DIGE. Increased collagen, fibronectin, and proliferating fibroblasts were evident, but myofibroblasts were not detected in DIGE samples caused by nifedipine and phenytoin. In healthy gingiva cultured in nifedipine or phenytoin-containing media, the number of cells positive for p-SMAD2/3 increased, concomitant with increased CCN2 and periostin immunoreactivity compared to untreated explants. Collagen content assessed through hydroxyproline assays was significantly higher in tissues cultured with either drug compared to control tissues, which was confirmed histologically. Matrix fibronectin levels were also qualitatively greater in tissues treated with either drug. No significant differences in proliferating cells were observed between any of the conditions. Our study demonstrates that nifedipine and phenytoin activate canonical transforming growth factor-beta signaling, CCN2 and periostin expression, as well as increase collagen density, but do not influence cell proliferation or induce myofibroblast differentiation. We conclude that in the absence of confounding variables, nifedipine and phenytoin alter matrix homeostasis in gingival tissue explants ex vivo, and drug administration is a significant factor influencing ECM accumulation in gingival enlargement. PMID:26296421

  18. Pharmacokinetics and tissue residues of moroxydine hydrochloride in gibel carp, Carassius gibelio after oral administration.

    PubMed

    Liu, W; Xu, J; Zhou, Y; Chen, J; Ma, J; Zeng, L

    2016-08-01

    The pharmacokinetics and tissue residues of moroxydine hydrochloride were studied in gibel carp at water temperature of 15 and 25 °C. Samples (blood, skin, muscle, liver, and kidney) were collected over 10 days after the treatment and analyzed by high-performance liquid chromatography with an ultraviolet detector. The results indicated that the influence of water temperature on the metabolism of the drug was significant. The plasma concentration-time data of moroxydine hydrochloride conformed to single-compartment open model at the two water temperatures. There were higher absorption rate (t1/2ka ) and longer elimination half-lives (t1/2ke ) at 15 °C (4.29 and 15.87 h, respectively) compared with those at 25 °C (3.02 and 4.22 h, respectively). The maximum plasma concentration (Cmax ) and the time-point of maximum plasma concentration (Tp ) were 2.98 μg/mL and 10.35 h at 15 °C and 3.12 μg/mL and 4.03 h at 25 °C, respectively. The distribution volume (Vd /F) of moroxydine hydrochloride was estimated to be 4.55 L/kg at 15 °C and 2.89 L/kg at 25 °C. The total body clearance (CLb ) of moroxydine hydrochloride was determined to be 0.25 and 0.49 L/(h·kg) at 15 °C and 25 °C, respectively; the areas under the concentration-time curve were 75.89 μg·h/mL at 15 °C and 42.33 μg·h/mL at 25 °C. The depletion of moroxydine hydrochloride in gibel carp was slower with a longer half-life period, especially at lower water temperature that was tested. PMID:26763124

  19. Regional Variation in Tissue Composition and Biomechanical Properties of Postmenopausal Ovine and Human Vagina

    PubMed Central

    Ulrich, Daniela; Edwards, Sharon L.; Letouzey, Vincent; Su, Kai; White, Jacinta F.; Rosamilia, Anna; Gargett, Caroline E.; Werkmeister, Jerome A.

    2014-01-01

    Objective There are increasing numbers of reports describing human vaginal tissue composition in women with and without pelvic organ prolapse with conflicting results. The aim of this study was to compare ovine and human posterior vaginal tissue in terms of histological and biochemical tissue composition and to assess passive biomechanical properties of ovine vagina to further characterise this animal model for pelvic organ prolapse research. Study Design Vaginal tissue was collected from ovariectomised sheep (n = 6) and from postmenopausal women (n = 7) from the proximal, middle and distal thirds. Tissue histology was analyzed using Masson's Trichrome staining; total collagen was quantified by hydroxyproline assays, collagen III/I+III ratios by delayed reduction SDS PAGE, glycosaminoglycans by dimethylmethylene blue assay, and elastic tissue associated proteins (ETAP) by amino acid analysis. Young's modulus, maximum stress/strain, and permanent strain following cyclic loading were determined in ovine vagina. Results Both sheep and human vaginal tissue showed comparable tissue composition. Ovine vaginal tissue showed significantly higher total collagen and glycosaminoglycan values (p<0.05) nearest the cervix. No significant differences were found along the length of the human vagina for collagen, GAG or ETAP content. The proximal region was the stiffest (Young's modulus, p<0.05), strongest (maximum stress, p<0.05) compared to distal region, and most elastic (permanent strain). Conclusion Sheep tissue composition and mechanical properties showed regional differences along the postmenopausal vaginal wall not apparent in human vagina, although the absolute content of proteins were similar. Knowledge of this baseline variation in the composition and mechanical properties of the vaginal wall will assist future studies using sheep as a model for vaginal surgery. PMID:25148261

  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. Quantifying psoralen in tissues by fluorescence: dosimetry for psoralen administration followed by ultraviolet A irradiation (PUVA) to block restenosis

    NASA Astrophysics Data System (ADS)

    Jacques, Steven L.; Buckley, Lisa A.; Prahl, Scott A.; Gregory, Kenton W.

    1994-07-01

    PUVA therapy may prove effective in preventing restenosis of vessels following balloon angioplasty to open vessels narrowed by atherosclerosis. The technique relies on the ability of PUVA (psoralen administration followed by ultraviolet A irradiation) to cause crosslinks and monoadducts that prevent cellular proliferation without causing cell death. Such PUVA treatment has been successful in controlling cutaneous cell proliferation of psoriasis. The efficacy of PUVA treatment depends on the drug concentration and the light dose. The amount of light delivered is easily modified to adapt to variations in the drug concentration if the drug levels in the vessel wall are known. This paper demonstrates the feasibility of assaying psoralen levels in tissues and in serum samples using psoralen fluorescence as an indictor.

  2. 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. PMID:26035010

  3. 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.

  4. Mineral density volume gradients in normal and diseased human tissues

    DOE PAGESBeta

    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-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

  5. 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

  6. Mineral density volume gradients in normal and diseased human tissues.

    PubMed

    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: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/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

  7. The response of human tissues to carbon reinforced epoxy resin.

    PubMed

    Howard, C B; Tayton, K J; Gibbs, A

    1985-08-01

    The tissue surrounding carbon fibre reinforced epoxy resin plates applied to forearm and tibial fractures was biopsied in 32 patients at the time the plates were removed. The reaction was minimal and was compared with that in a control group of 16 similar patients in whom stainless steel plates were used. No significant histological differences were found. A series of experiments on rats, in which the histology was studied from 2 to 78 weeks, also showed that there was very little reaction to carbon fibre reinforced plastic. PMID:4030870

  8. The state of human bone tissue during space flight

    NASA Astrophysics Data System (ADS)

    Oganov, V. S.; Rakhmanov, A. S.; Novikov, V. E.; Zatsepin, S. T.; Rodionova, S. S.; Cann, Ch.

    The results of studying the bone tissue of cosmonauts after the flights (4-8 month) have been compared to the data of investigating the healthy individuals during head-down tilt (HDT, 370 days). Noninvasive methods (computer tomography, gammaphoton absorptiometry) revealed a decrease in the vertebral spongy mineral density or a increase of this parameter by a similar magnitude versus the individual preflight values in some cosmonauts. During studies of clinical cases of osteoporosis it was shown that the vertebral mineral density ratios and presence or absence of vertebral compression fractures in different age groups are nonequal.

  9. [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. PMID:24855737

  10. The human tissue transglutaminase gene maps on chromosome 20q12 by in situ fluorescence hybridization

    SciTech Connect

    Gentile, V.; Davies, P.J.A. ); Baldini, A. )

    1994-03-15

    A cDNA encoding for the human tissue transglutaminase gene has been used to identify the chromosomal localization of the corresponding structural gene. The precise chromosomal and subregional localizations have been established by using in situ fluorescence mapping with a recombinant [lambda]-Zap phage containing the full cDNA coding sequence. The study showed that the human tissue transglutaminase gene is localized on chromosome 20 and, more precisely, within the band 20q12. To date, this is the third member of the transglutaminase gene family to be mapped. Human factor XIIIa (plasma transglutaminase), human keratinocyte transglutaminase (type I), and human tissue transglutaminase (type II) genes, although codifying for homologous enzymes, are localized on three different chromosomes. 16 refs., 1 fig.

  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. Evidence for existence in human tissues of monomers for plastics and rubber manufacture.

    PubMed

    Wolff, M S

    1976-10-01

    Although exposure to many industrially important monomers is controlled by law, few of these reactive chemicals have been determined in human tissues. Analogy with other fat-soluble organic substances strongly implies that these monomers may be retained in tissue, subject to the usual physiological constraints of metabolism, solubility and volatility. The storage of DDT and PCBs is discussed, as well as tetrachloro-ethylene (PCE) and trichloroethylene (TCE), which are chemically similar to many industrially used monomers. Styrene in blood and breath and its metabolites in urine have been studied in humans. Styrene and vinyl chloride have been measured in fat tissue of polymerization workers. PMID:829070

  13. Human Papillomavirus Vaccine Administration Among Medicaid Providers Who Consistently Recommended Vaccination

    PubMed Central

    Malo, Teri L.; Staras, Stephanie A. S.; Bynum, Shalanda A.; Giuliano, Anna R.; Shenkman, Elizabeth A.; Vadaparampil, Susan T.

    2014-01-01

    We examined factors potentially related to providers’ self-reported human papillomavirus vaccine administration to female Medicaid enrollees among providers who consistently recommended vaccination. Some pronounced variability was observed in characteristics among providers who consistently administered vaccination, including provider age, race, and Vaccines for Children enrollment; patient/parent vaccine refusal; patient race/ethnicity; and patient volume. PMID:24335743

  14. The Work of the School Principal in the Area of Human Resources Administration in Arizona.

    ERIC Educational Resources Information Center

    Norton, M. Scott

    1999-01-01

    One hundred Arizona elementary and secondary principals were asked to detail their responsibilities in human-resource administration; 74 responded. Specifically, staff selection, staff assignment, and organizational climate received responses above the 90% level, followed by staff development, staff evaluation, and staff orientation--all basic…

  15. 76 FR 25538 - Criteria Used To Order Administrative Detention of Food for Human or Animal Consumption

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-05

    ... detention of food for human or animal consumption under the Bioterrorism Act (68 FR 25242 at 25250). The... rule) in the Federal Register of May 9, 2003 (68 FR 25242), proposing procedures for the administrative detention of an article of food. In the Federal Register of June 4, 2004 (69 FR 31660), the Agency...

  16. Human papillomavirus vaccine administration among Medicaid providers who consistently recommended vaccination.

    PubMed

    Malo, Teri L; Staras, Stephanie A S; Bynum, Shalanda A; Giuliano, Anna R; Shenkman, Elizabeth A; Vadaparampil, Susan T

    2014-01-01

    We examined factors potentially related to providers' self-reported human papillomavirus vaccine administration to female Medicaid enrollees among providers who consistently recommended vaccination. Some pronounced variability was observed in characteristics among providers who consistently administered vaccination, including provider age, race, and Vaccines for Children enrollment; patient/parent vaccine refusal; patient race/ethnicity; and patient volume. PMID:24335743

  17. Randomised Trials or the Test of Time? The Story of Human Albumin Administration.

    ERIC Educational Resources Information Center

    Roberts, Ian

    2000-01-01

    Conducted a systematic review of randomized controlled trials of the administration of human albumin in critically ill patients. Findings raised serious concerns about the safety of an intervention that has been widely used in health care around the world. Findings illustrate the importance of systematic reviews in health care and other areas of…

  18. 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

  19. Administrative Coordination in Non-Profit Human Service Delivery Networks: The Role of Competition and Trust

    PubMed Central

    Bunger, Alicia C.

    2014-01-01

    Non-profit human service organizations operating within the same regional network are often faced with dual pressure to compete as well as coordinate administrative operations (by sharing funding, staff or space) to enhance efficiency. Emerging evidence has demonstrated that competing organizations coordinate, despite the risks. Trust, or perceived trustworthiness between two organizations may mitigate the negative influence of competition on coordination, however there have been few explicit tests of this hypothesis among non-profit organizations. Drawing on quantitative data collected from a network of 36 non-profit children’s behavioral health organizations, this paper empirically tests how competition and perceived trustworthiness interact to influence administrative coordination. Results support the hypothesis that trustworthiness moderates the influence of competition on administrative coordination. Findings suggest that as competing non-profit leaders build trust, the more their agencies coordinate their administrative functions. This study highlights the importance of leaders’ perceptions for organizational strategy. PMID:25349468

  20. 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

  1. Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis.

    PubMed

    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

  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-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells.

    PubMed

    Dash, Biraja C; Levi, Karen; Schwan, Jonas; Luo, Jiesi; Bartulos, Oscar; Wu, Hongwei; Qiu, Caihong; Yi, Ting; Ren, Yongming; Campbell, Stuart; Rolle, Marsha W; Qyang, Yibing

    2016-07-12

    There is an urgent need for an efficient approach to obtain a large-scale and renewable source of functional human vascular smooth muscle cells (VSMCs) to establish robust, patient-specific tissue model systems for studying the pathogenesis of vascular disease, and for developing novel therapeutic interventions. Here, we have derived a large quantity of highly enriched functional VSMCs from human induced pluripotent stem cells (hiPSC-VSMCs). Furthermore, we have engineered 3D tissue rings from hiPSC-VSMCs using a facile one-step cellular self-assembly approach. The tissue rings are mechanically robust and can be used for vascular tissue engineering and disease modeling of supravalvular aortic stenosis syndrome. Our method may serve as a model system, extendable to study other vascular proliferative diseases for drug screening. Thus, this report describes an exciting platform technology with broad utility for manufacturing cell-based tissues and materials for various biomedical applications. PMID:27411102

  4. Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue

    PubMed Central

    Pelekanos, Rebecca A.; Sardesai, Varda S.; Futrega, Kathryn; Lott, William B.; Kuhn, Michael; Doran, Michael R.

    2016-01-01

    Mesenchymal stem/stromal cells (MSC) are promising candidates for use in cell-based therapies. In most cases, therapeutic response appears to be cell-dose dependent. Human term placenta is rich in MSC and is a physically large tissue that is generally discarded following birth. Placenta is an ideal starting material for the large-scale manufacture of multiple cell doses of allogeneic MSC. The placenta is a fetomaternal organ from which either fetal or maternal tissue can be isolated. This article describes the placental anatomy and procedure to dissect apart the decidua (maternal), chorionic villi (fetal), and chorionic plate (fetal) tissue. The protocol then outlines how to isolate MSC from each dissected tissue region, and provides representative analysis of expanded MSC derived from the respective tissue types. These methods are intended for pre-clinical MSC isolation, but have also been adapted for clinical manufacture of placental MSC for human therapeutic use. PMID:27340821

  5. Distribution of tissue plasminogen activator in human and monkey eyes. An immunohistochemical study.

    PubMed

    Tripathi, B J; Geanon, J D; Tripathi, R C

    1987-11-01

    The authors examined various structures of human and rhesus monkey eyes for the presence of tissue plasminogen activator (t-PA) by using the peroxidase-antiperoxidase immunohistochemical technique with a monoclonal antibody specific for human t-PA. Positive staining for t-PA was observed both intracellularly and in the extracellular matrix of many tissues in both species. The tissues which stained intensely for t-PA included the corneal endothelium, corneal epithelium, trabecular meshwork, lens epithelium, peripheral vitreous, uveal tract, inner retina, and all vascular endothelia. The apparent minor difference in staining intensity between human and monkey eyes may be related to the time-dependent degradation of t-PA, to variations in the tissue content of t-PA, or to the difference in animal species. The discussion includes a consideration of the fibrinolytic activity of t-PA and of its emerging role in the destructive remodeling of the extracellular matrix in various ocular structures. PMID:3120076

  6. A Novel Human Adipocyte-derived Basement Membrane for Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Damm, Aaron

    Tissue engineering strategies have traditionally focused on the use of synthetic polymers as support scaffolds for cell growth. Recently, strategies have shifted towards a natural biologically derived scaffold, with the main focus on decellularized organs. Here, we report the development and engineering of a scaffold naturally secreted by human preadipocytes during differentiation. During this differentiation process, the preadipocytes remodel the extracellular matrix by releasing new extracellular proteins. Finally, we investigated the viability of the new basement membrane as a scaffold for tissue engineering using human pancreatic islets, and as a scaffold for soft tissue repair. After identifying the original scaffold material, we sought to improve the yield of material, treating the cell as a bioreactor, through various nutritional and cytokine stimuli. The results suggest that adipocytes can be used as bioreactors to produce a designer-specified engineered human extracellular matrix scaffold for specific tissue engineering applications.

  7. 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.

  8. History of Diffuse Optical Spectroscopy of Human Tissue

    NASA Astrophysics Data System (ADS)

    Huppert, Theodore J.

    Diffuse optical spectroscopy is a noninvasive method that uses low levels of near-infrared light to measure blood oxygenation in the brain. Over the last 35 years, the number of diffuse optical studies and the range of clinical and research applications have grown steadily. Compared to other neuroimaging methods to measure cerebral blood oxygenation, such as magnetic resonance imaging or positron emission tomography, diffuse optical imaging (DOI) is more cost effective and often uses small portable instrumentation. Wireless and bedside optical systems are currently produced commercially. The portability of these instruments has extended the use of optical methods into several unique applications including brain imaging in infants and children, studies of the brain during ambulatory tasks such as walking or balance, and interoperative brain assessments. This chapter will introduce the history and basic principles of DOI including discussion of the factors contributing to the optical properties of tissue, instrumentation, and an overview of applications of the technology.

  9. Adult human adipose tissue contains several types of multipotent cells.

    PubMed

    Tallone, Tiziano; Realini, Claudio; Böhmler, Andreas; Kornfeld, Christopher; Vassalli, Giuseppe; Moccetti, Tiziano; Bardelli, Silvana; Soldati, Gianni

    2011-04-01

    Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria. PMID:21327755

  10. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

    PubMed

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Cimpean, Anca Maria; Nica, Cristian; Raica, Marius

    2016-06-01

    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

  11. 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

  12. 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...

  13. [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. PMID:2445007

  14. Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection

    PubMed Central

    2013-01-01

    Background Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections. Materials and methods Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated. Results The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury. Conclusions HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model. PMID:23458564

  15. Hydrolysis kinetics of propylene glycol monomethyl ether acetate in rats in vivo and in rat and human tissues in vitro.

    PubMed

    Domoradzki, J Y; Brzak, K A; Thornton, C M

    2003-09-01

    The kinetic equivalency of propylene glycol monomethyl ether (PGME), derived from propylene glycol monomethyl ether acetate (PGMEA), as well as the parent compound (PGME) following intravenous administration to Fischer 344 rats was evaluated. In addition, in vitro hydrolysis rates of PGMEA in blood and liver tissue from rats and humans were determined. The blood kinetics were determined following iv administration to rats of PGME and PGMEA of low [10 and 14.7 mg/kg body weight (bw)] or high (100 and 147 mg/kg) equimolar dosages of PGME and PGMEA, respectively. The blood time courses of PGME elimination for both dosages of both compounds were identical. Half-lives of PGMEA elimination following iv administration of 14.7 or 147 mg PGMEA/kg bw were calculated to be 1.6 and 2.3 min, respectively. Rat and human in vitro hydrolysis rates of PGMEA were determined by incubation of 5 or 50 microg PGMEA/ml in whole blood or liver homogenate. The rate of loss of PGMEA was more rapid in rat blood than in human blood, with hydrolysis half-lives of 36 and 34 min in human blood and 16 and 15 min in rat blood for the 5 and 50 microg/ml concentrations of PGMEA, respectively. In contrast the rate of loss of PGMEA in human and rat liver homogenate incubations was similar, 27-30 min and 34 min, respectively. These data demonstrate the rapid hydrolysis of PGMEA in vivo to its parent glycol ether, PGME and that, once hydrolyzed, the kinetics for PGME derived from PGMEA are identical to that for PGME. This study supports the use of the toxicological database on PGME as a surrogate for PGMEA. PMID:12857936

  16. 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. PMID:27535251

  17. 2009 pandemic H1N1 influenza virus replicates in human lung tissues

    PubMed Central

    Zhang, Jinxia; Zhang, Zengfeng; Fan, Xiaohui; Liu, Yuansheng; Wang, Jia; Zheng, Zuoyi; Chen, Rirong; Wang, Pui; Song, Wenjun; Chen, Honglin; Guan, Yi

    2009-01-01

    Replication activity of 2009 pandemic H1N1 influenza virus in human lung cells was evaluated in this study. Twenty-two surgically removed human lung tissue samples were infected ex vivo with pandemic H1N1, A/California/04/2009, seasonal human H1N1 virus, A/ST/92/2009, or a highly pathogenic H5N1 virus, A/Vietnam/1194/04. Examination of nucleoprotein (NP) protein expression and vRNA replication in infected human lung tissues showed that while CA/04 replication varied between tissue samples, overall, it replicated more efficiently than seasonal H1N1 but less efficiently than H5N1 virus. Double immunostaining for viral antigens and cellular markers indicated that CA/04 replicates in type II alveolar epithelial cells. PMID:20370480

  18. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices.

    PubMed

    Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

    2014-10-15

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out

  19. The Effects of Exogenous Administration of Human Coagulation Factors Following Pig-to-Baboon Liver Xenotransplantation.

    PubMed

    Navarro-Alvarez, N; Shah, J A; Zhu, A; Ligocka, J; Yeh, H; Elias, N; Rosales, I; Colvin, R; Cosimi, A B; Markmann, J F; Hertl, M; Sachs, D H; Vagefi, P A

    2016-06-01

    We sought to determine the effects of exogenous administration of human coagulation factors following pig-to-baboon liver xenotransplantation (LXT) using GalT-KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor VIIa (1 µg/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large-vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor VIIa. Further studies are warranted because this regimen may allow for prolonged survival following LXT. PMID:26613235

  20. Species-specific metastasis of human tumor cells in the severe combined immunodeficiency mouse engrafted with human tissue.

    PubMed Central

    Shtivelman, E; Namikawa, R

    1995-01-01

    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 gamma-irradiation or to interleukin 1 alpha. 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. Images Fig. 1 Fig. 2 Fig. 3 PMID:7753860

  1. 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.

  2. Stromal vascular progenitors in adult human adipose tissue

    PubMed Central

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Pfeifer, Melanie E.; Meyer, E. Michael; Péault, Bruno; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    Background The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem cells (ADSC) remains elusive, owing in part to the complex organization of stromal cells surrounding the small vessels, and the rapidity with which adipose stromal vascular cells adopt a mesenchymal phenotype in vitro. Methods Immunohistostaining of intact adipose tissue was used to identify 3 markers (CD31, CD34, CD146) which together unambiguously discriminate histologically distinct inner and outer rings of vessel-associated stromal cells, as well as capillary and small vessel endothelial cells. These markers were used in multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90, CD117) to further characterize stromal vascular fraction (SVF) subpopulations. Two mesenchymal and two endothelial populations were isolated by high speed flow cytometric sorting, expanded in short term culture and tested for adipogenesis. Results The inner layer of stromal cells in contact with small vessel endothelium (pericytes) was CD146+/α-SMA+/CD90±/CD34−/CD31−; the outer adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA-ASC) was CD146−/α-SMA−/CD90+/CD34+/CD31−. Capillary endothelial cells were CD31+/CD34+/CD90+ (endothelial progenitor), while small vessel endothelium was CD31+/CD34−/CD90− (endothelial mature). Flow cytometry confirmed these expression patterns and revealed a CD146+/CD90+/CD34+/CD31− pericyte subset that may be transitional between pericytes and SA-ASC. Pericytes had the most potent adipogenic potential, followed by the more numerous SA-ASC. Endothelial populations had significantly reduced adipogenic potential compared to unsorted expanded SVF cells. Conclusions In adipose tissue perivascular stromal cells are organized in two discrete layers, the innermost consisting of CD146+/CD34− pericytes, and the outermost of CD146−/CD34+ SA-ASC, both of which have adipogenic potential in culture. A CD146+/CD

  3. Subpedicle connective tissue graft versus guided tissue regeneration with bioabsorbable membrane in the treatment of human gingival recession defects.

    PubMed

    Trombelli, L; Scabbia, A; Tatakis, D N; Calura, G

    1998-11-01

    The purpose of the present clinical study was to evaluate the effect of guided tissue regeneration (GTR) in comparison to subpedicle connective tissue graft (SCTG) in the treatment of gingival recession defects. A total of 12 patients, each contributing a pair of Miller's Class I or II buccal gingival recessions, was treated. According to a randomization list, one defect in each patient received a polyglycolide/lactide bioabsorbable membrane, while the paired defect received a SCTG. Treatment effect was evaluated 6 months postsurgery. Clinical recordings included full-mouth and defect-specific oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). Mean RD significantly decreased from 3.1 mm presurgery to 1.5 mm at 6 months postsurgery for the GTR group (48% root coverage), and from 3.0 mm to 0.5 mm for the SCTG group (81% root coverage). RD reduction and root coverage were significantly greater in SCTG group compared to GTR group. Mean CAL gain amounted to 1.7 mm for the GTR group, and 2.3 mm in the SCTG group. No significant differences in PD changes were observed within and between groups. KT increased significantly from presurgery for both treatment groups, however gingival augmentation was significantly greater in the SCTG group compared to GTR group. Results indicate that: 1) treatment of human gingival recession defects by means of both GTR and SCTG procedures results in clinically and statistically significant improvement of the soft tissue conditions of the defect; and 2) treatment outcome was significantly better following SCTG compared to GTR in terms of recession depth reduction, root coverage, and keratinized tissue increase. PMID:9848537

  4. Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

    PubMed Central

    2012-01-01

    Background Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. Methods Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. Results Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. Conclusions Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue. PMID:22974251

  5. 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

  6. Formalizing an electronic institution for the distribution of human tissues.

    PubMed

    Vázquez-Salceda, J; Padget, J A; Cortés, U; López-Navidad, A; Caballero, F

    2003-03-01

    The use of multi-agent systems (MAS) in health-care domains is increasing. Such agent-mediated medical systems can manage complex tasks and have the potential to adapt gracefully to unexpected events. However, in these kinds of systems the issues of privacy, security and trust are particularly sensitive in relation to matters such as agents' access to patient records, what is acceptable behaviour for an agent in a particular role and the development of trust both between (heterogeneous) agents and between users and agents. To address these issues we propose a formal normative framework, deriving from and developing the notion of an electronic institution. Such institutions provide a framework to define and police norms that guide, control and regulate the behaviour of the heterogeneous agents that participate in the institution. These norms define the acceptable actions that each agent may perform depending on the role or roles it is playing, and clearly specifies the data it may access and/or modify in playing those roles. In this paper, we present the formalization of Carrel, a virtual organization for the procurement of organs and tissues for transplantation purposes, as an electronic institution using the ISLANDER institution specification language as formalizing languages. We demonstrate aspects of the formalization of such an institution, example fragments in the language used for the textual specification, and how such formalization can be used as a blueprint in the implementation of the final agent architecture, through techniques such as skeleton generation. PMID:12667738

  7. Luminescence lifetime determination for oxygen imaging in human tissue

    NASA Astrophysics Data System (ADS)

    Lochmann, C.; Häupl, T.; Beuthan, J.

    2008-02-01

    Imaging and monitoring of biochemical parameters in vitro and in vivo have become the goal of many investigations in medical physics. The main imaging technique used is laser-induced luminescence due to its cost effectiveness and diversity of applications [1]. One key parameter in medical investigations, for instance to control photodynamic therapy, is the molecular oxygen concentration. The use of optical methods provides possible means of measuring molecular oxygen. The basis of such a method is the measurement of the luminescence lifetime of a dye which is quenched by molecular oxygen. The molecular oxygen concentration can be monitored two-dimensionally by pixel-wise determination of the luminescence lifetime with a CCD-camera. An oxygen imaging system based on this principle was built and tested with a commercially available oxygen sensitive sol gel-layer. The embedded ruthenium complex is quenched by molecular oxygen and because of the oxygen permeability of the layer; it is suitable for oxygen measurements. The characteristics and dependence on the pH-value and temperature of the luminescence lifetime of the layer were examined in preparation for measurements on tissue to exclude cross-correlation of other quenching processes.

  8. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche1

    PubMed Central

    Templeton, Zach S.; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V.; Tamaresis, John S.; Bachmann, Michael H.; Lee, Kitty; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.

    2015-01-01

    BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. PMID:26696367

  9. Human Circulating and Tissue-Resident CD56bright Natural Killer Cell Populations

    PubMed Central

    Melsen, Janine E.; Lugthart, Gertjan; Lankester, Arjan C.; Schilham, Marco W.

    2016-01-01

    Two human natural killer (NK) cell subsets are usually distinguished, displaying the CD56dimCD16+ and the CD56brightCD16−/+ phenotype. This distinction is based on NK cells present in blood, where the CD56dim NK cells predominate. However, CD56bright NK cells outnumber CD56dim NK cells in the human body due to the fact that they are predominant in peripheral and lymphoid tissues. Interestingly, within the total CD56bright NK cell compartment, a major phenotypical and functional diversity is observed, as demonstrated by the discovery of tissue-resident CD56bright NK cells in the uterus, liver, and lymphoid tissues. Uterus-resident CD56bright NK cells express CD49a while the liver- and lymphoid tissue-resident CD56bright NK cells are characterized by co-expression of CD69 and CXCR6. Tissue-resident CD56bright NK cells have a low natural cytotoxicity and produce little interferon-γ upon monokine stimulation. Their distribution and specific phenotype suggest that the tissue-resident CD56bright NK cells exert tissue-specific functions. In this review, we examine the CD56bright NK cell diversity by discussing the distribution, phenotype, and function of circulating and tissue-resident CD56bright NK cells. In addition, we address the ongoing debate concerning the developmental relationship between circulating CD56bright and CD56dim NK cells and speculate on the position of tissue-resident CD56bright NK cells. We conclude that distinguishing tissue-resident CD56bright NK cells from circulating CD56bright NK cells is a prerequisite for the better understanding of the specific role of CD56bright NK cells in the complex process of human immune regulation. PMID:27446091

  10. Hydrolysis of somatostatin by human tissue kallikrein after the amino acid pair phe-Phe.

    PubMed Central

    Pimenta, D C; Juliano, M A; Juliano, L

    1997-01-01

    Somatostatin-(1-14) was hydrolysed by human tissue kallikrein at the Phe7-Trp8 bond, after a Phe-Phe pair of amino acids, with similar kinetic parameters to those described for human high- and low-molecular-mass kininogens. Substance P and human insulin, which also contain a Phe-Phe pair in their sequences, were both resistant. More details of this hydrolytic specificity of human tissue kallikrein were obtained by synthesizing and assaying internally quenched fluorescent peptides containing the sequence of somatostatin-(1-14), as well as the reactive-centre loop of human kallikrein-binding protein (kallistatin). We also observed that human tissue kallikrein hydrolysed growth hormone-releasing hormone at the Arg11-Lys12 bond, although this peptide contains in its structure a pair of leucines (Leu22-Leu23), in contrast with the Phe-Phe pair in somatostatin. We have also demonstrated the susceptibility to human tissue kallikrein of some chromogenic peptide s with the general structure of X-Phe-Phe-p-nitroanilide and D-Pro-Phe-Phe-4-methylcoumaryl-7-amide. PMID:9355730

  11. Decellularization of human stromal refractive lenticules for corneal tissue engineering.

    PubMed

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  12. Decellularization of human stromal refractive lenticules for corneal tissue engineering

    PubMed Central

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M.; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S.

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  13. A convex optimization approach for identification of human tissue-specific interactomes

    PubMed Central

    Mohammadi, Shahin; Grama, Ananth

    2016-01-01

    Motivation: Analysis of organism-specific interactomes has yielded novel insights into cellular function and coordination, understanding of pathology, and identification of markers and drug targets. Genes, however, can exhibit varying levels of cell type specificity in their expression, and their coordinated expression manifests in tissue-specific function and pathology. Tissue-specific/tissue-selective interaction mechanisms have significant applications in drug discovery, as they are more likely to reveal drug targets. Furthermore, tissue-specific transcription factors (tsTFs) are significantly implicated in human disease, including cancers. Finally, disease genes and protein complexes have the tendency to be differentially expressed in tissues in which defects cause pathology. These observations motivate the construction of refined tissue-specific interactomes from organism-specific interactomes. Results: We present a novel technique for constructing human tissue-specific interactomes. Using a variety of validation tests (Edge Set Enrichment Analysis, Gene Ontology Enrichment, Disease-Gene Subnetwork Compactness), we show that our proposed approach significantly outperforms state-of-the-art techniques. Finally, using case studies of Alzheimer’s and Parkinson’s diseases, we show that tissue-specific interactomes derived from our study can be used to construct pathways implicated in pathology and demonstrate the use of these pathways in identifying novel targets. Availability and implementation: http://www.cs.purdue.edu/homes/mohammas/projects/ActPro.html Contact: mohammadi@purdue.edu PMID:27307623

  14. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity.

    PubMed

    Kang, Hyun-Wook; Lee, Sang Jin; Ko, In Kap; Kengla, Carlos; Yoo, James J; Atala, Anthony

    2016-03-01

    A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs. PMID:26878319

  15. Fluid and Thermal Dynamics of Cryogen Sprays Impinging on a Human Tissue Phantom

    PubMed Central

    Franco, Walfre; Vu, Henry; Jia, Wangcun; Nelson, J. Stuart; Aguilar, Guillermo

    2009-01-01

    Cryogen spray cooling (CSC) protects the epidermis from unintended heating during cutaneous laser surgery. The present work investigated the time-dependent flow characteristics of cryogen sprays and correspondent thermal dynamics at the surface of a human tissue phantom. First, a numerical analysis was carried out to evaluate an epoxy block substrate as a human tissue phantom. Next, the velocity and diameter of cryogen droplets were measured simultaneously and correlated with surface temperature of the human tissue phantom during CSC. Finally, velocity and diameter measurements were used to compute the spray number, mass, and kinetic energy fluxes, and temperature measurements were used to compute the surface heat flux. Numerical modeling showed that the thermal response of our phantom was qualitatively similar to that of human stratum corneum and epidermis; quantitatively, thermal responses differed. A simple transformation to map the temperature response of the phantom to that of tissue was derived. Despite the relatively short spurt durations (10 ms, 30 ms, and 50 ms), cryogen delivery is mostly a steady state process with initial and final fluid transients mainly due to the valve dynamics. Thermal transients (16 ms) are longer than fluid transients (4 ms) due to the low thermal diffusivity of human tissues; steady states are comparable in duration (≈10 ms, 30 ms, and 50 ms) although there is an inherent thermal delay (≈12 ms). Steady state temperatures are the lowest surface temperatures experienced by the substrate, independent of spurt duration; hence, longer spurt durations result in larger exposures of the tissue surface to the same lower, steady state temperature as in shorter spurts. Temperatures in human tissue during CSC for the spray system and parameters used herein are estimated to be ≈−19°C at the stratum corneum surface and >0°C across the epidermis. PMID:19045512

  16. Inosculation and perfusion of pre-vascularized tissue patches containing aligned human microvessels after myocardial infarction.

    PubMed

    Riemenschneider, Sonja B; Mattia, Donald J; Wendel, Jacqueline S; Schaefer, Jeremy A; Ye, Lei; Guzman, Pilar A; Tranquillo, Robert T

    2016-08-01

    A major goal of tissue engineering is the creation of pre-vascularized tissues that have a high density of organized microvessels that can be rapidly perfused following implantation. This is especially critical for highly metabolic tissues like myocardium, where a thick myocardial engineered tissue would require rapid perfusion within the first several days to survive transplantation. In the present work, tissue patches containing human microvessels that were either randomly oriented or aligned were placed acutely on rat hearts post-infarction and for each case it was determined whether rapid inosculation could occur and perfusion of the patch could be maintained for 6 days in an infarct environment. Patches containing self-assembled microvessels were formed by co-entrapment of human blood outgrowth endothelial cells and human pericytes in fibrin gel. Cell-induced gel contraction was mechanically-constrained resulting in samples with high densities of microvessels that were either randomly oriented (with 420 ± 140 lumens/mm(2)) or uniaxially aligned (with 940 ± 240 lumens/mm(2)) at the time of implantation. These patches were sutured onto the epicardial surface of the hearts of athymic rats following permanent ligation of the left anterior descending artery. In both aligned and randomly oriented microvessel patches, inosculation occurred and perfusion of the transplanted human microvessels was maintained, proving the in vivo vascularization potential of these engineered tissues. No difference was found in the number of human microvessels that were perfused in the randomly oriented (111 ± 75 perfused lumens/mm(2)) and aligned (173 ± 97 perfused lumens/mm(2)) patches. Our results demonstrate that tissue patches containing a high density of either aligned or randomly oriented human pre-formed microvessels achieve rapid perfusion in the myocardial infarct environment - a necessary first-step toward the creation of a thick, perfusable heart patch. PMID

  17. Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals.

    PubMed

    Washietl, Stefan; Kellis, Manolis; Garber, Manuel

    2014-04-01

    Long intergenic noncoding RNAs (lincRNAs) play diverse regulatory roles in human development and disease, but little is known about their evolutionary history and constraint. Here, we characterize human lincRNA expression patterns in nine tissues across six mammalian species and multiple individuals. Of the 1898 human lincRNAs expressed in these tissues, we find orthologous transcripts for 80% in chimpanzee, 63% in rhesus, 39% in cow, 38% in mouse, and 35% in rat. Mammalian-expressed lincRNAs show remarkably strong conservation of tissue specificity, suggesting that it is selectively maintained. In contrast, abundant splice-site turnover suggests that exact splice sites are not critical. Relative to evolutionarily young lincRNAs, mammalian-expressed lincRNAs show higher primary sequence conservation in their promoters and exons, increased proximity to protein-coding genes enriched for tissue-specific functions, fewer repeat elements, and more frequent single-exon transcripts. Remarkably, we find that ∼20% of human lincRNAs are not expressed beyond chimpanzee and are undetectable even in rhesus. These hominid-specific lincRNAs are more tissue specific, enriched for testis, and faster evolving within the human lineage. PMID:24429298

  18. Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics.

    PubMed

    Manohara, S R; Hanagodimath, S M; Gerward, L

    2011-01-01

    Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Z(eff). These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues. With the proper knowledge of buildup factors of human organs and tissues, energy absorption in the human body can be carefully controlled. The present results will help in estimating safe dose levels for radiotherapy patients and also useful in diagnostics and dosimetry. The tissue-equivalent materials for skeletal muscle, adipose tissue, cortical bone, and lung tissue are also discussed. It is observed that water and MS20 are good tissue equivalent materials for skeletal muscle in the extended energy range. PMID:22089011

  19. HIV binding, penetration, and primary infection in human cervicovaginal tissue

    PubMed Central

    Maher, Diane; Wu, Xiaoyun; Schacker, Timothy; Horbul, Julie; Southern, Peter

    2005-01-01

    We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3–4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against β1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract. PMID:16061810

  20. [Obtention of human skin sheets by means of tissue engineering].

    PubMed

    Arvelo, Francisco; Pérez, Pedro; Cotte, Carlos

    2004-01-01

    The aim of this "in vitro" study was to develop a new system for keratinocyte culture on a dermal equivalent that enables treatment of different skin injuries. The keratinocyte where obtained from primary cell cultures derived from skin biopsies, seeded over a fibrin matrix enhanced with live human fibroblast. Cells growing over the dermal equivalent, rapidly confluences and a stratified epithelium was obtained within 20-25 days culture. Detachment of composite culture from flask is a simple and quick procedure with no need for chemical or enzyme treatments. The method described provides a number of advantages which include the large expansion of keratinocyte from the primary cell cultures without the need of a feeder layer, the availability of plasma from blood banks, and the versatile and safe manipulation of composite obtained "in vitro". All these facts allow to assure that this system could result very efficient for the treatment of all type of skin injuries. PMID:15916167

  1. [Plasma and tissue concentrations of biphenylacetic acid following 1 week oral fenbufen medication and topical administration of Felbinac gel on the knee joint].

    PubMed

    Bolten, W; Salzmann, G; Goldmann, R; Miehlke, K

    1989-01-01

    In an randomised study 30 patients were treated during one week before undergoing an elective surgery of the knee joint with 1 or 2 g respectively of 3% Felbinac gel (biphenylacetic acid gel) or oral 300 mg Fenbufen thrice daily. Biphenylacetic acid (BPAA) is the therapeutically active metabolite of the non-steroid anti-inflammatory drug Fenbufen. Plasma concentrations were measured before, during therapy and at the time of the operation. During the surgery of the knee joint specimens of synovial fluid and -membrane, of cartilage, muscle and tendons as well as of the skin and the subcutaneous fatty tissue were obtained and the BPAA concentrations measured. There was a large variance of the obtained values in all groups. It seems that mainly methodical problems are responsible for this. At the time of surgery, the plasma concentrations following oral administration were with 10,080 ng/ml 20 to 50 times higher than those after topical administration. The tissue concentrations reached 1/8 to 1/2 of the plasma concentrations. The relation of tissue concentrations to plasma concentrations of BPAA was smaller in patients treated with oral administration than in patients treated with topical administration. Therefore a partial direct penetration of Felbinac into the deeper tissue compartments can be assumed. There was no significant difference in plasma-, synovial- or tissue concentrations between the two groups treated with the topical administration. The tissue concentrations were 1 to 2 orders of magnitude lower than those after oral administration. Only in the skin the concentrations were with 9160 respectively 3830 ng/g higher than those obtained after oral application (2110 ng/g). PMID:2696292

  2. Estimation of absorbed cadmium in tissues of male and female albino rats through different routes of administration.

    PubMed

    Nwokocha, C R; Nwokocha, M I; Owu, D U; Edidjana, E; Nwogbo, N; Ekpo, U; Ufearo, C S

    2011-06-01

    The resultant effects of cadmium exposure are seen in almost all the systems of the body, however, this study is designed to quantify its accumulation in tissues of animals exposed to cadmium. The rats were divided into two distinct groups of males and females, which were then divided into three groups, each for the monitoring of exposure. Group 1 served as control male and female and received normal rat chow and tap water. Group 2 males and females were treated with 5 mg/kg body weight of cadmium chloride (Cd) intraperitoneally for eight days while Group 3 males and females rats received 100 ppm of Cd in drinking water for 18 days. The concentrations of cadmium were analyzed in tissues (lung, stomach, kidney, heart, spleen, blood) by AAS. There were significant (P<0.05) increase in Cd (ppm) accumulation in males compared with females lungs (2.253 ± 1.47 vs 0.317 ± 0.001), stomach (0.187 ± 0.094 vs 0.045 ± 0.032) and blood (0.070 ± 0.001 vs 0.001±0.001) when Cd was administered intraperitoneally. Following oral administration, there were significant (P<0.05) difference in Cd (ppm) content between males and females (kidney (0.506 ± 0.074 vs 0.748 ± 0.147), stomach (0.045 ± 0.020 vs 0.001± 0.001) and blood (1.126 ± 0.001 vs 0.114 ± 0.001). Our results suggest that Cd accumulation in the various organs was sex and route of exposure-dependent in rats. PMID:22314995

  3. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  4. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  5. Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice.

    PubMed

    Fan, Yao-Yun; Avery, Lindsay B; Wang, Mengmeng; O'Hara, Denise M; Leung, Sheldon; Neubert, Hendrik

    2016-07-01

    The neonatal Fc receptor (FcRn) is a homeostatic receptor responsible for prolonging immunoglobulin G (IgG) half-life by protecting it from lysosomal degradation and recycling it to systemic circulation. Tissue-specific FcRn expression is a critical parameter in physiologically-based pharmacokinetic (PBPK) modeling for translational pharmacokinetics of Fc-containing biotherapeutics. Using online peptide immuno-affinity chromatography coupled with high resolution mass spectrometry, we established a quantitative FcRn tissue protein expression profile in human FcRn (hFcRn) transgenic mice, Tg32 homozygous and hemizygous strains. The concentration of hFcRn across 14 tissues ranged from 3.5 to 111.2 pmole per gram of tissue. Our hFcRn quantification data from Tg32 mice will enable a more refined PBPK model to improve the accuracy of human PK predictions for Fc-containing biotherapeutics. PMID:27104806

  6. Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model.

    PubMed

    Allahtavakoli, Mohammad; Amin, Fatemeh; Esmaeeli-Nadimi, Ali; Shamsizadeh, Ali; Kazemi-Arababadi, Mohammad; Kennedy, Derek

    2015-11-01

    Delayed treatment of stroke with recombinant tissue plasminogen activator (r-tPA) induces overexpression of matrix metalloproteinase 9 (MMP-9) which leads to breakdown of the blood-brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r-tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA-treated (500 mg/kg; 5 hr after stroke) rats, r-tPA-treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r-tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP-9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r-tPA-treated animals, AA alone (p < 0.001) or in combination with r-tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r-tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP-9 (p < 0.05 versus control; p < 0.01 versus r-tPA) and brain oedema (p < 0.001) when compared to either the control or the r-tPA-treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r-tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r-tPA in stroke therapy. PMID:25899606

  7. Thorium-232 in human tissues: Metabolic parameters and radiation doses

    SciTech Connect

    Stehney, A.F.

    1994-09-01

    Higher than environmental levels of {sup 232}Th have been found in autopsy samples of lungs and other organs from four former employees of a Th refinery. Working periods of the subjects ranged from 3 to 24 years, and times from end of work to death ranged from 6 to 31 years. Concentrations of {sup 232}Th in these samples and in tissues from two cases of non-occupational exposure were examined for compatibility with dosimetric models in Publication 30 of the International Commission on Radiological Protection (ICPP 1979a). The concentrations of {sup 232}Th in the lungs of the Th workers relative to the concentrations in bone or liver were much higher than calculated from the model for class Y aerosols of Th and the exposure histories of the subjects, and concentrations in the pulmonary lymph nodes were much lower than calculated for three of the Th workers and both non-occupational cases. Least-squares fits to the measured concentrations showed that the biological half-times of Th in liver, spleen, and kidneys are similar to the half-time in bone instead of the factor of 10 less suggested in Publication 30, and the fractions translocated from body fluids were found to be about 0.03, 0.02, and 0.005, respectively, when the fraction to bone was held at the suggested value of 0.7. Fitted values of the respiratory parameters differed significantly between cases and the differences were ascribable to aerosol differences. Average inhalation rates calculated for individual Th workers ranged from 50 to 110 Bq {sup 232}Th y{sup {minus}1}, and dose equivalents as high as 9.3 Sv to the lungs, 2.0 Sv to bone surfaces, and 1.1 Sv effective dose equivalent were calculated from the inhalation rates and fitted values of the metabolic parameters. The radiation doses were about the same when calculated from parameter values fitted with an assumed translocation fraction of 0.2 from body fluids to bone instead of 0.7.

  8. Effects of vasopressin administration on diuresis of water immersion in normal humans

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

    1981-01-01

    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  9. Autofluorescence multiphoton microscopy for visualization of tissue morphology and cellular dynamics in murine and human airways

    PubMed Central

    Kretschmer, Sarah; Pieper, Mario; Hüttmann, Gereon; Bölke, Torsten; Wollenberg, Barbara; Marsh, Leigh M; Garn, Holger; König, Peter

    2016-01-01

    The basic understanding of inflammatory airway diseases greatly benefits from imaging the cellular dynamics of immune cells. Current imaging approaches focus on labeling specific cells to follow their dynamics but fail to visualize the surrounding tissue. To overcome this problem, we evaluated autofluorescence multiphoton microscopy for following the motion and interaction of cells in the airways in the context of tissue morphology. Freshly isolated murine tracheae from healthy mice and mice with experimental allergic airway inflammation were examined by autofluorescence multiphoton microscopy. In addition, fluorescently labeled ovalbumin and fluorophore-labeled antibodies were applied to visualize antigen uptake and to identify specific cell populations, respectively. The trachea in living mice was imaged to verify that the ex vivo preparation reflects the in vivo situation. Autofluorescence multiphoton microscopy was also tested to examine human tissue from patients in short-term tissue culture. Using autofluorescence, the epithelium, underlying cells, and fibers of the connective tissue, as well as blood vessels, were identified in isolated tracheae. Similar structures were visualized in living mice and in the human airway tissue. In explanted murine airways, mobile cells were localized within the tissue and we could follow their migration, interactions between individual cells, and their phagocytic activity. During allergic airway inflammation, increased number of eosinophil and neutrophil granulocytes were detected that moved within the connective tissue and immediately below the epithelium without damaging the epithelial cells or connective tissues. Contacts between granulocytes were transient lasting 3 min on average. Unexpectedly, prolonged interactions between granulocytes and antigen-uptaking cells were observed lasting for an average of 13 min. Our results indicate that autofluorescence-based imaging can detect previously unknown immune cell

  10. Autofluorescence multiphoton microscopy for visualization of tissue morphology and cellular dynamics in murine and human airways.

    PubMed

    Kretschmer, Sarah; Pieper, Mario; Hüttmann, Gereon; Bölke, Torsten; Wollenberg, Barbara; Marsh, Leigh M; Garn, Holger; König, Peter

    2016-08-01

    The basic understanding of inflammatory airway diseases greatly benefits from imaging the cellular dynamics of immune cells. Current imaging approaches focus on labeling specific cells to follow their dynamics but fail to visualize the surrounding tissue. To overcome this problem, we evaluated autofluorescence multiphoton microscopy for following the motion and interaction of cells in the airways in the context of tissue morphology. Freshly isolated murine tracheae from healthy mice and mice with experimental allergic airway inflammation were examined by autofluorescence multiphoton microscopy. In addition, fluorescently labeled ovalbumin and fluorophore-labeled antibodies were applied to visualize antigen uptake and to identify specific cell populations, respectively. The trachea in living mice was imaged to verify that the ex vivo preparation reflects the in vivo situation. Autofluorescence multiphoton microscopy was also tested to examine human tissue from patients in short-term tissue culture. Using autofluorescence, the epithelium, underlying cells, and fibers of the connective tissue, as well as blood vessels, were identified in isolated tracheae. Similar structures were visualized in living mice and in the human airway tissue. In explanted murine airways, mobile cells were localized within the tissue and we could follow their migration, interactions between individual cells, and their phagocytic activity. During allergic airway inflammation, increased number of eosinophil and neutrophil granulocytes were detected that moved within the connective tissue and immediately below the epithelium without damaging the epithelial cells or connective tissues. Contacts between granulocytes were transient lasting 3 min on average. Unexpectedly, prolonged interactions between granulocytes and antigen-uptaking cells were observed lasting for an average of 13 min. Our results indicate that autofluorescence-based imaging can detect previously unknown immune cell

  11. Divergent viral presentation among human tumors and adjacent normal tissues.

    PubMed

    Cao, Song; Wendl, Michael C; Wyczalkowski, Matthew A; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J; Gay, Hiram; Chen, Ken; Rader, Janet S; Dipersio, John F; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  12. Tissue culture system for infection with human hepatitis delta virus.

    PubMed Central

    Sureau, C; Jacob, J R; Eichberg, J W; Lanford, R E

    1991-01-01

    An in vitro culture system was developed for assaying the infectivity of the human hepatitis delta virus (HDV). Hepatocytes were isolated from chimpanzee liver and grown in a serum-free medium. Cells were shown to be infectible by HDV and to remain susceptible to infection for at least 3 weeks in culture, as evidenced by the appearance of RNA species characteristic of HDV replication as early as 6 days postinfection. When repeated experiments were carried out on cells derived from an animal free of hepatitis B virus (HBV), HDV infection occurred in a consistent fashion but there was no indication of infection with the HBV that was present in the inoculum. Despite numerous attempts with different sources of HBV inocula free of HDV, there was no evidence that indicated susceptibility of these cells to HBV infection. This observation may indicate that HBV and HDV use different modes of entry into hepatocytes. When cells derived from an HBV-infected animal were exposed to HDV, synthesis and release of progeny HDV particles were obtained in addition to HBV replication and production of Dane particles. Although not infectible with HBV, primary cultures of chimpanzee hepatocytes are capable of supporting part of the life cycle of HBV and the entire life cycle of HDV. Images PMID:2041075

  13. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  14. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    PubMed Central

    Bjork, James M.; Gilman, Jodi M.

    2014-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

  15. Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans

    PubMed Central

    Ceperuelo-Mallafré, Victòria; Ejarque, Miriam; Serena, Carolina; Duran, Xavier; Montori-Grau, Marta; Rodríguez, Miguel Angel; Yanes, Oscar; Núñez-Roa, Catalina; Roche, Kelly; Puthanveetil, Prasanth; Garrido-Sánchez, Lourdes; Saez, Enrique; Tinahones, Francisco J.; Garcia-Roves, Pablo M.; Gómez-Foix, Anna Ma; Saltiel, Alan R.; Vendrell, Joan; Fernández-Veledo, Sonia

    2015-01-01

    Objective Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance. Methods We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts. Results We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated

  16. Tissue-Specific Cultured Human Pericytes: Perivascular Cells from Smooth Muscle Tissue Have Restricted Mesodermal Differentiation Ability.

    PubMed

    Pierantozzi, Enrico; Vezzani, Bianca; Badin, Margherita; Curina, Carlo; Severi, Filiberto Maria; Petraglia, Felice; Randazzo, Davide; Rossi, Daniela; Sorrentino, Vincenzo

    2016-05-01

    Microvascular pericytes (PCs) are considered the adult counterpart of the embryonic mesoangioblasts, which represent a multipotent cell population that resides in the dorsal aorta of the developing embryo. Although PCs have been isolated from several adult organs and tissues, it is still controversial whether PCs from different tissues exhibit distinct differentiation potentials. To address this point, we investigated the differentiation potentials of isogenic human cultured PCs isolated from skeletal (sk-hPCs) and smooth muscle tissues (sm-hPCs). We found that both sk-hPCs and sm-hPCs expressed known pericytic markers and did not express endothelial, hematopoietic, and myogenic markers. Both sk-hPCs and sm-hPCs were able to differentiate into smooth muscle cells. In contrast, sk-hPCs, but not sm-hPCs, differentiated in skeletal muscle cells and osteocytes. Given the reported ability of the Notch pathway to regulate skeletal muscle and osteogenic differentiation, sk-hPCs and sm-hPCs were treated with N-[N-(3,5- difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a known inhibitor of Notch signaling. DAPT treatment, as assessed by histological and molecular analysis, enhanced myogenic differentiation and abolished osteogenic potential of sk-hPCs. In contrast, DAPT treatment did not affect either myogenic or osteogenic differentiation of sm-hPCs. In summary, these results indicate that, despite being isolated from the same anatomical niche, cultured PCs from skeletal muscle and smooth muscle tissues display distinct differentiation abilities. PMID:26956507

  17. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways.

    PubMed

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  18. The sensitivity of massively parallel sequencing for detecting candidate infectious agents associated with human tissue.

    PubMed

    Moore, Richard A; Warren, René L; Freeman, J Douglas; Gustavsen, Julia A; Chénard, Caroline; Friedman, Jan M; Suttle, Curtis A; Zhao, Yongjun; Holt, Robert A

    2011-01-01

    Massively parallel sequencing technology now provides the opportunity to sample the transcriptome of a given tissue comprehensively. Transcripts at only a few copies per cell are readily detectable, allowing the discovery of low abundance viral and bacterial transcripts in human tissue samples. Here we describe an approach for mining large sequence data sets for the presence of microbial sequences. Further, we demonstrate the sensitivity of this approach by sequencing human RNA-seq libraries spiked with decreasing amounts of an RNA-virus. At a modest depth of sequencing, viral transcripts can be detected at frequencies less than 1 in 1,000,000. With current sequencing platforms approaching outputs of one billion reads per run, this is a highly sensitive method for detecting putative infectious agents associated with human tissues. PMID:21603639

  19. Proteomic Analysis of Human Brown Adipose Tissue Reveals Utilization of Coupled and Uncoupled Energy Expenditure Pathways

    PubMed Central

    Müller, Sebastian; Balaz, Miroslav; Stefanicka, Patrik; Varga, Lukas; Amri, Ez-Zoubir; Ukropec, Jozef; Wollscheid, Bernd; Wolfrum, Christian

    2016-01-01

    Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity. In addition to uncoupling protein 1 (UCP1), the main functional effector for uncoupled respiration, we also detected the mitochondrial creatine kinases (CKMT1A/B, CKMT2), as effective modulators of ATP synthase coupled respiration, to be exclusively expressed in BAT. The abundant expression and utilization of both energy expenditure pathways in parallel highlights the complex functional involvement of BAT in human physiology. PMID:27418403

  20. Advanced Imaging and Tissue Engineering of the Human Limbal Epithelial Stem Cell Niche

    PubMed Central

    Massie, Isobel; Dziasko, Marc; Kureshi, Alvena; Levis, Hannah J.; Morgan, Louise; Neale, Michael; Sheth, Radhika; Tovell, Victoria E.; Vernon, Amanda J.; Funderburgh, James L.; Daniels, Julie T.

    2015-01-01

    The limbal epithelial stem cell niche provides a unique, physically protective environment in which limbal epithelial stem cells reside in close proximity with accessory cell types and their secreted factors. The use of advanced imaging techniques is described to visualize the niche in three dimensions in native human corneal tissue. In addition, a protocol is provided for the isolation and culture of three different cell types, including human limbal epithelial stem cells from the limbal niche of human donor tissue. Finally, the process of incorporating these cells within plastic compressed collagen constructs to form a tissue-engineered corneal limbus is described and how immunohistochemical techniques may be applied to characterize cell phenotype therein. PMID:25388395

  1. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    PubMed

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  2. "The state of the heart": Recent advances in engineering human cardiac tissue from pluripotent stem cells.

    PubMed

    Sirabella, Dario; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2015-08-01

    The pressing need for effective cell therapy for the heart has led to the investigation of suitable cell sources for tissue replacement. In recent years, human pluripotent stem cell research expanded tremendously, in particular since the derivation of human-induced pluripotent stem cells. In parallel, bioengineering technologies have led to novel approaches for in vitro cell culture. The combination of these two fields holds potential for in vitro generation of high-fidelity heart tissue, both for basic research and for therapeutic applications. However, this new multidisciplinary science is still at an early stage. Many questions need to be answered and improvements need to be made before clinical applications become a reality. Here we discuss the current status of human stem cell differentiation into cardiomyocytes and the combined use of bioengineering approaches for cardiac tissue formation and maturation in developmental studies, disease modeling, drug testing, and regenerative medicine. PMID:26069271

  3. A Single Intraduodenal Administration of Human Adenovirus 40 Vaccine Effectively Prevents Anaphylactic Shock

    PubMed Central

    Yamasaki, Satoshi; Miura, Yoshiaki; Davydova, Julia; Vickers, Selwyn M.

    2013-01-01

    Vaccine administration into the intestine is known to induce mucosal tolerance most efficiently. Therefore, developing a delivery system that targets the intestinal mucosa is expected to improve the efficiency of immunosuppression. Human enteric adenovirus serotype 40 (Ad40)-based vectors have the advantage of targeting intestinal mucosa, making them prime candidates as mucosal vaccine carriers for immunosuppression. Here, after both oral and intraduodenal administrations, the vector distribution of replication-defective recombinant Ad40 vectors (rAd40) was significantly higher than that of a conventional Ad vector based on human adenovirus 5 (Ad5) in ilea containing Peyer's patches. Single intraduodenal administration of rAd40 induced antigen-specific mucosal immunoreaction mediated by intestinal mucosal and systemic immunity. In ovalbumin-induced allergy mouse models, this approach inhibited antigen-specific delayed-type hypersensitivity reactions, diarrhea occurrence, and systemic anaphylaxis. Thus, a single intraduodenal administration of rAd40 provides a potent method of inducing allergen-specific mucosal tolerance and a new allergen-specific immunotherapy for overcoming problems with current therapies against life-threatening allergic reactions, including anaphylaxis. PMID:23885027

  4. Representing Organization Theory with a Human Face: The Search for a Human and Humane Understanding of Administration.

    ERIC Educational Resources Information Center

    Greenfield, Thomas B.

    The study of educational administration should continue its trend toward a qualitative interpretation of reality and abandon the positivistic, scientific approach of the last 25 years. Herbert Simon's work in 1945 set the field upon the path of accepting the assumptions of positivistic thought as the limits of scientific inquiry in administration,…

  5. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    PubMed Central

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  6. An experimental model of tool mark striations by a serrated blade in human soft tissues.

    PubMed

    Jacques, Rebekah; Kogon, Stanley; Shkrum, Michael

    2014-03-01

    Tool mark analysis is a method of matching a weapon with the injury it caused. In a homicidal stabbing using a serrated knife, a stab wound that involves a cartilage may leave striations from the serration points on the blade edge. Assessing tissue striations is a means of identifying the weapon as having a serrated blade. This prospective study examines the possibility that similar striations may be produced in human soft tissues. Using tissues taken at the time of hospital-consented autopsies, stab wound tracks were assessed in a variety of human tissues (aorta, skin, liver, kidney, and cardiac and skeletal muscle). Stab wounds were produced postmortem with similar serrated and smooth-edged blades. The walls of the stab wounds were exposed, documented by photography and cast with dental impression material. Striations were identified by naked-eye examination in the skin and aorta. Photodocumentation of fresh tissue was best achieved in the aorta. Striations were not identified in wound tracks produced by the smooth-edged blade. Three blinded forensic pathologists were assessed for their ability to detect striations in photographs of wound tracks and had substantial interobserver agreement (κ = 0.76) identifying striations. This study demonstrates that tool mark striations can be present in some noncartilaginous human tissues. PMID:24457587

  7. Measuring the compressive viscoelastic mechanical properties of human cervical tissue using indentation.

    PubMed

    Yao, Wang; Yoshida, Kyoko; Fernandez, Michael; Vink, Joy; Wapner, Ronald J; Ananth, Cande V; Oyen, Michelle L; Myers, Kristin M

    2014-06-01

    The human cervix is an important mechanical barrier in pregnancy which must withstand the compressive and tensile forces generated from the growing fetus. Premature cervical shortening resulting from premature cervical remodeling and alterations of cervical material properties are known to increase a woman׳s risk of preterm birth (PTB). To understand the mechanical role of the cervix during pregnancy and to potentially develop indentation techniques for in vivo diagnostics to identify women who are at risk for premature cervical remodeling and thus preterm birth, we developed a spherical indentation technique to measure the time-dependent material properties of human cervical tissue taken from patients undergoing hysterectomy. In this study we present an inverse finite element analysis (IFEA) that optimizes material parameters of a viscoelastic material model to fit the stress-relaxation response of excised tissue slices to spherical indentation. Here we detail our IFEA methodology, report compressive viscoelastic material parameters for cervical tissue slices from nonpregnant (NP) and pregnant (PG) hysterectomy patients, and report slice-by-slice data for whole cervical tissue specimens. The material parameters reported here for human cervical tissue can be used to model the compressive time-dependent behavior of the tissue within a small strain regime of 25%. PMID:24548950

  8. Tissue-specific expression of human arylsulfatase-C isozymes and steroid sulfatase.

    PubMed Central

    Munroe, D G; Chang, P L

    1987-01-01

    Steroid sulfatase (STS; E.C.3.1.6.2), which acts on 3-hydroxysteroid sulfates, and arylsulfatase-C (ARC; E.C.3.1.6.1), assayed with aromatic artificial substrates, are both membrane-bound, microsomal enzymes with alkaline pH optima. Although they copurify during preparation and their gene loci are mapped to the short arm of the human X chromosome where they appear to have escaped from X inactivation, it has not been settled whether STS and ARC are the same enzyme or not. Recent work from our laboratory has shown that ARC exists in two electrophoretically distinct forms in human fibroblasts. We now report that these two forms--the faster migrating (F) and more slowly migrating (S)--occur in human tissues. Each of 11 human tissue types from 10 subjects showed a consistent pattern of ARC isozymes. Thyroid, heart, spleen, skeletal muscle, and adrenal tissue mainly had the S form. In contrast, kidney, liver, and pancreas tissue had mainly the F form, while gonadal, lung, and intestinal tissue had both the S and the F forms. The question of escape of their gene locus from X-chromosome inactivation was examined by comparing the specific activities of ARC and STS in male-derived vis-à-vis female-derived tissues. The majority of the tissues did not show any significant difference in these activities between the sexes, the exceptions being heart muscle, gonadal, and kidney tissue. None showed the 1:2 ratio between male- and female-derived tissues expected of a locus that had escaped X inactivation. The question of identity between ARC and STS was examined by comparing the ratios of their activities in these tissue types: if the enzymes were identical, the ratios of their activities should have remained constant across the different tissue types. It was thus shown that ARC activity varied by as much as 100-fold, depending on the ARC isozymic pattern of the tissue. STS, measured as estrone sulfatase and dehydroepiandrosterone sulfatase, did not show similar variations. This

  9. Tissue-specific hypomethylation of the human c-K-ras gene.

    PubMed Central

    Metter, J; Cho, C

    1989-01-01

    Methylation of the c-K-ras gene was examined in a wide variety of human tissues using the methylation sensitive restriction endonuclease HpaII. All tissues showed hypomethylation in the region of exon zero. Specific hypomethylation of a particular HpaII site in the second intron was observed in gastrointestinal and tracheobronchial epithelial cell DNAs. Specific hypomethylation was also observed in a cluster of HpaII sites within the first intron in sperm, endometrium and placenta DNAs. These regions were predominantly methylated in a wide variety of other tissues, including fetal gut. The possible implications are discussed. Images PMID:2476726

  10. Comparison of organochlorine residues in human adipose tissue autopsy samples from two Ontario municipalities

    SciTech Connect

    Williams, D.T.; LeBel, G.L.; Junkins, E.

    1984-01-01

    Human adipose tissue samples obtained during autopsies in a Canadian Great Lakes community, Kingston, Ontario, and a second community, Ottawa, Ontario, were analyzed for organochlorine pesticides, polychlorobiphenyls, chlorobenzenes, and chlorophenols. Significantly different levels of Dichlorodiphenyl-dichlorethane, mirex, hexachlorobenzene, and 2,3,4,6-tetrachlorophenol were found in Kingston adipose tissues compared to Ottawa tissues. Residue levels of oxychlordane, mirex, and polychlorinated biphenyls were significantly different in Kingston males versus Kingston females. The means and ranges of residue levels were contrasted with those reported in previous Canadian surveys.

  11. Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model.

    PubMed

    Weber, Benedikt; Dijkman, Petra E; Scherman, Jacques; Sanders, Bart; Emmert, Maximilian Y; Grünenfelder, Jürg; Verbeek, Renier; Bracher, Mona; Black, Melanie; Franz, Thomas; Kortsmit, Jeroen; Modregger, Peter; Peter, Silvia; Stampanoni, Marco; Robert, Jérôme; Kehl, Debora; van Doeselaar, Marina; Schweiger, Martin; Brokopp, Chad E; Wälchli, Thomas; Falk, Volkmar; Zilla, Peter; Driessen-Mol, Anita; Baaijens, Frank P T; Hoerstrup, Simon P

    2013-10-01

    Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs. PMID:23810254

  12. The fractional viscoelastic response of human breast tissue cells

    NASA Astrophysics Data System (ADS)

    Carmichael, B.; Babahosseini, H.; Mahmoodi, S. N.; Agah, M.

    2015-07-01

    The mechanical response of a living cell is notoriously complicated. The complex, heterogeneous characteristics of cellular structure introduce difficulties that simple linear models of viscoelasticity cannot overcome, particularly at deep indentation depths. Herein, a nano-scale stress-relaxation analysis performed with an atomic force microscope reveals that isolated human breast cells do not exhibit simple exponential relaxation capable of being modeled by the standard linear solid (SLS) model. Therefore, this work proposes the application of the fractional Zener (FZ) model of viscoelasticity to extract mechanical parameters from the entire relaxation response, improving upon existing physical techniques to probe isolated cells. The FZ model introduces a new parameter that describes the fractional time-derivative dependence of the response. The results show an exceptional increase in conformance to the experimental data compared to that predicted by the SLS model, and the order of the fractional derivative (α) is remarkably homogeneous across the populations, with a median value of 0.48 ± 0.06 for the malignant population and 0.51 ± 0.07 for the benign. The cells’ responses exhibit power-law behavior and complexity not associated with simple relaxation (SLS, α = 1) that supports the application of a fractional model. The distributions of some of the FZ parameters also preserve the distinction between the malignant and benign sample populations seen from the linear model and previous results while including the contribution of fast-relaxation behavior. The resulting viscosity, measured by a composite relaxation time, exhibits considerably less dispersion due to residual error than the distribution generated by the linear model and therefore serves as a more powerful marker for cell differentiation.

  13. Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B.

    PubMed

    Digby, J E; Chen, J; Tang, J Y; Lehnert, H; Matthews, R N; Randeva, H S

    2006-10-01

    Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression was detected in subcutaneous (s.c.) and omental adipose tissue and in isolated adipocytes. Protein for OX1R and OX2R was also detected in whole adipose tissue sections and lysates. Treatment with orexin-A, and orexin-B (100 nM, 24 h) resulted in a significant increase in peroxisome proliferator-activated receptors gamma-2 mRNA expression in s.c. adipose tissue (P < 0.05). Hormone sensitive lipase mRNA was significantly reduced in omental adipose tissue with orexin-A and orexin-B treatment (P < 0.05). Glycerol release from omental adipose tissue was also significantly reduced with orexin-A treatment (P < 0.05). These findings demonstrate for the first time the presence of functional orexin receptors in human adipose tissue and suggest a role for orexins in adipose tissue metabolism and adipogenesis. PMID:17065396

  14. Influence of trace elements in human tissue in low-energy photon brachytherapy dosimetry

    NASA Astrophysics Data System (ADS)

    White, Shane A.; Landry, Guillaume; van Gils, Francis; Verhaegen, Frank; Reniers, Brigitte

    2012-06-01

    The aim of this paper is to determine the dosimetric impact of trace elements in human tissues for low-energy photon sources used in brachytherapy. Monte Carlo dose calculations were used to investigate the dosimetric effect of trace elements present in normal or cancerous human tissues. The effect of individual traces (atomic number Z = 11-30) was studied in soft tissue irradiated by low-energy brachytherapy sources. Three other tissue types (prostate, adipose and mammary gland) were also simulated with varying trace concentrations to quantify the contribution of each trace to the dose distribution. The dose differences between cancerous and healthy prostate tissues were calculated in single- and multi-source geometries. The presence of traces in a tissue produces a difference in the dose distribution that is dependent on Z and the concentration of the trace. Low-Z traces (Na) have a negligible effect (<0.3%) in all tissues, while higher Z (K) had a larger effect (>3%). There is a potentially significant difference in the dose distribution between cancerous and healthy prostate tissues (4%) and even larger if compared to the trace-free composition (15%) in both single- and multi-sourced geometries. Trace elements have a non-negligible (up to 8% in prostate D90) effect on the dose in tissues irradiated with low-energy photon sources. This study underlines the need for further investigation into accurate determination of the trace composition of tissues associated with low-energy brachytherapy. Alternatively, trace elements could be incorporated as a source of uncertainty in dose calculations. This work was part of an invited presentation at the ‘International Workshop on Recent Advances in Monte Carlo Techniques for Radiation Therapy’, held in Montreal, June 8-10, 2011.

  15. Regulation of homocysteine metabolism and methylation in human and mouse tissues

    PubMed Central

    Chen, Natalie C.; Yang, Fan; Capecci, Louis M.; Gu, Ziyu; Schafer, Andrew I.; Durante, William; Yang, Xiao-Feng; Wang, Hong

    2010-01-01

    Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine β-synthase, cystathionine-γ-lyase, paraxonase 1, 5,10-methylenetetrahydrofolate reductase, betaine:homocysteine methyltransferase, methionine adenosyltransferase, phosphatidylethanolamine N-methyltransferases and glycine N-methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl-tRNA synthase, 5-methyltetrahydrofolate:Hcy methyltransferase, S-adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone-lysine N-methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation.—Chen, N. C., Yang, F., Capecci, L. M., Gu, Z., Schafer, A. I., Durante, W., Yang, X.-F., Wang, H. Regulation of homocysteine metabolism and methylation in human and mouse tissues. PMID:20305127

  16. The appropriateness of swab cultures for the release of human allograft tissue.

    PubMed

    Ronholdt, Chad J; Bogdansky, Simon

    2005-08-01

    Surgeries utilizing human allograft tissues have increased dramatically in recent years. With this increase has come a greater reliance on the use of swab culturing to assess allograft tissues for microbial contamination prior to distribution. In contrast to the typical industrial microbiological uses for swabs, the tissue banking industry has relied on swab cultures as a sterility release method for allograft tissues. It has been reported in the literature that swabs have limitations, both in sensitivity and reproducibility, so their suitability as a final sterility release method was evaluated in this study. Two different swab-culturing systems were evaluated (COPAN, EZ Culturette) using human allograft tissues spiked with low levels of multiple bacterial and fungal microorganisms. The average microbial recoveries for all challenge microorganisms for each tissue type and each swab system were calculated. Percent recoveries for each challenge microorganism were also calculated and reported. The results indicated that both swab systems exhibited low and highly variable recoveries from the seeded allograft tissues. Further analysis indicated there was no statistical difference ( proportional, variant=0.05) between the two swab systems. It is the recommendation of the authors that swab culturing not be used to assess relatively low levels of microbial contamination on allografts. Instead, alternative validated microbial detection methods with improved sensitivity and reproducibility should be employed and validated for this critical task. PMID:15973533

  17. Automated classification of immunostaining patterns in breast tissue from the human protein atlas

    PubMed Central

    Swamidoss, Issac Niwas; Kårsnäs, Andreas; Uhlmann, Virginie; Ponnusamy, Palanisamy; Kampf, Caroline; Simonsson, Martin; Wählby, Carolina; Strand, Robin

    2013-01-01

    Background: The Human Protein Atlas (HPA) is an effort to map the location of all human proteins (http://www.proteinatlas.org/). It contains a large number of histological images of sections from human tissue. Tissue micro arrays (TMA) are imaged by a slide scanning microscope, and each image represents a thin slice of a tissue core with a dark brown antibody specific stain and a blue counter stain. When generating antibodies for protein profiling of the human proteome, an important step in the quality control is to compare staining patterns of different antibodies directed towards the same protein. This comparison is an ultimate control that the antibody recognizes the right protein. In this paper, we propose and evaluate different approaches for classifying sub-cellular antibody staining patterns in breast tissue samples. Materials and Methods: The proposed methods include the computation of various features including gray level co-occurrence matrix (GLCM) features, complex wavelet co-occurrence matrix (CWCM) features, and weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND-CHARM)-inspired features. The extracted features are used into two different multivariate classifiers (support vector machine (SVM) and linear discriminant analysis (LDA) classifier). Before extracting features, we use color deconvolution to separate different tissue components, such as the brownly stained positive regions and the blue cellular regions, in the immuno-stained TMA images of breast tissue. Results: We present classification results based on combinations of feature measurements. The proposed complex wavelet features and the WND-CHARM features have accuracy similar to that of a human expert. Conclusions: Both human experts and the proposed automated methods have difficulties discriminating between nuclear and cytoplasmic staining patterns. This is to a large extent due to mixed staining of nucleus and cytoplasm. Methods for quantification

  18. Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

    PubMed

    Ronsoni, Marcelo Fernando; Remor, Aline Pertile; Lopes, Mark William; Hohl, Alexandre; Troncoso, Iris H Z; Leal, Rodrigo Bainy; Boos, Gustavo Luchi; Kondageski, Charles; Nunes, Jean Costa; Linhares, Marcelo Neves; Lin, Kátia; Latini, Alexandra Susana; Walz, Roger

    2016-04-01

    Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery. PMID:26586405

  19. Improved memory for reward cues following acute buprenorphine administration in humans.

    PubMed

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A; Montoya, Estrella R; Stein, Dan J; van Honk, Jack

    2015-03-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 0.2mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects (n38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues. PMID:25569708

  20. The Joy of Social Work Administration: An Exploratory Qualitative Study of Human Service Administrators' Positive Perceptions of Their Work

    ERIC Educational Resources Information Center

    Watson, Larry D.; Hoefer, Richard A.

    2016-01-01

    Positive organizational psychology suggests that researchers should focus on the rewarding elements of work life, yet those in the fields of social work and nonprofit administration have not conducted research in line with this admonition. Indeed, the current focus on administrative challenges and problems may be part of the reason there is…

  1. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics.

    PubMed

    Fagerberg, Linn; Hallström, Björn M; Oksvold, Per; Kampf, Caroline; Djureinovic, Dijana; Odeberg, Jacob; Habuka, Masato; Tahmasebpoor, Simin; Danielsson, Angelika; Edlund, Karolina; Asplund, Anna; Sjöstedt, Evelina; Lundberg, Emma; Szigyarto, Cristina Al-Khalili; Skogs, Marie; Takanen, Jenny Ottosson; Berling, Holger; Tegel, Hanna; Mulder, Jan; Nilsson, Peter; Schwenk, Jochen M; Lindskog, Cecilia; Danielsson, Frida; Mardinoglu, Adil; Sivertsson, Asa; von Feilitzen, Kalle; Forsberg, Mattias; Zwahlen, Martin; Olsson, IngMarie; Navani, Sanjay; Huss, Mikael; Nielsen, Jens; Ponten, Fredrik; Uhlén, Mathias

    2014-02-01

    Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody-based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to ∼80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body. PMID:24309898

  2. Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics*

    PubMed Central

    Fagerberg, Linn; Hallström, Björn M.; Oksvold, Per; Kampf, Caroline; Djureinovic, Dijana; Odeberg, Jacob; Habuka, Masato; Tahmasebpoor, Simin; Danielsson, Angelika; Edlund, Karolina; Asplund, Anna; Sjöstedt, Evelina; Lundberg, Emma; Szigyarto, Cristina Al-Khalili; Skogs, Marie; Takanen, Jenny Ottosson; Berling, Holger; Tegel, Hanna; Mulder, Jan; Nilsson, Peter; Schwenk, Jochen M.; Lindskog, Cecilia; Danielsson, Frida; Mardinoglu, Adil; Sivertsson, Åsa; von Feilitzen, Kalle; Forsberg, Mattias; Zwahlen, Martin; Olsson, IngMarie; Navani, Sanjay; Huss, Mikael; Nielsen, Jens; Ponten, Fredrik; Uhlén, Mathias

    2014-01-01

    Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody-based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to ∼80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body. PMID:24309898

  3. Tissue-specific expression of human CD4 in transgenic mice.

    PubMed

    Gillespie, F P; Doros, L; Vitale, J; Blackwell, C; Gosselin, J; Snyder, B W; Wadsworth, S C

    1993-05-01

    The gene for the human CD4 glycoprotein, which serves as the receptor for human immunodeficiency virus type 1, along with approximately 23 kb of sequence upstream of the translational start site, was cloned. The ability of 5' flanking sequences to direct tissue-specific expression was tested in cell culture and in transgenic mice. A 5' flanking region of 6 kb was able to direct transcription of the CD4 gene in NIH 3T3 cells but did not result in detectable expression in the murine T-cell line EL4 or in four lines of transgenic mice. A larger 5' flanking region of approximately 23 kb directed high-level CD4 transcription in the murine T-cell line EL4 and in three independent lines of transgenic mice. Human CD4 expression in all tissues analyzed was tightly correlated with murine CD4 expression; the highest levels of human CD4 RNA expression were found in the thymus and spleen, with relatively low levels detected in other tissues. Expression of human CD4 protein in peripheral blood mononuclear cells was examined by flow cytometry in these transgenic animals and found to be restricted to the murine CD4+ subset of lymphocytes. Human CD4 protein, detected with an anti-human CD4 monoclonal antibody, was present on the surface of 45 to 50% of the peripheral blood mononuclear cells from all transgenic lines. PMID:8474453

  4. Comparison of DNA adducts from exposure to complex mixtures in various human tissues and experimental systems

    PubMed Central

    Lewtas, Joellen; Mumford, Judy; Everson, Richard B.; Hulka, Barbara; Wilcosky, Tim; Kozumbo, Walter; Thompson, Claudia; George, Michael; Dobiáš, Lubomir; Šrám, Radim; Li, Xueming; Gallagher, Jane

    1993-01-01

    DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts compared to tobacco smoke in the in vitro calf thymus DNA model system, in cultured lymphocytes, and in the mouse skin assay. Using tobacco smoke as a model in human studies, we have compared relative DNA adduct levels detected in blood lymphocytes, placental tissue, bronchoalveolar lung lavage cells, sperm, and autopsy tissues of smokers and nonsmokers. Adduct levels in DNA isolated from smokers were highest in human heart and lung tissue with smaller but detectable differences in placental tissue and lung lavage cells. Comparison of the DNA adduct levels resulting from human exposure to different complex mixtures shows that emissions from coke ovens, aluminum smelters, and smoky coal result in higher DNA adduct levels than tobacco smoke exposure. These studies suggest that humans exposed to complex combustion mixtures will have higher DNA adduct levels in target cells (e.g., lung) as compared to nontarget cells (e.g., lymphocytes) and that the adduct levels will be dependent on the genotoxic and DNA adduct-forming potency of the mixture. ImagesFIGURE 1.FIGURE 1.FIGURE 2.FIGURE 3.FIGURE 3.FIGURE 3.FIGURE 3.FIGURE 3.FIGURE 3.FIGURE 4. PMID:8319665

  5. Human tissue monitoring and specimen banking: opportunities for exposure assessment, risk assessment, and epidemiologic research.

    PubMed

    Lee, L W; Griffith, J; Zenick, H; Hulka, B S

    1995-04-01

    A symposium on Human Tissue Monitoring and Specimen Banking: Opportunities for Exposure Assessment, Risk Assessment, and Epidemiologic Research was held from 30 March to 1 April 1993 in Research Triangle Park, North Carolina. There were 117 registered participants from 18 states and 5 foreign countries. The first 2 days featured 21 invited speakers from the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention, the National Institute of Environmental Health Sciences, various other government agencies, and universities in the United States, Canada, Germany, and Norway. The speakers provided a state-of-the-art overview of human exposure assessment techniques (especially applications of biological markers) and their relevance to human tissue specimen banking. Issues relevant to large-scale specimen banking were discussed, including program design, sample design, data collection, tissue collection, and ethical ramifications. The final group of presentations concerned practical experiences of major specimen banking and human tissue monitoring programs in the United States and Europe. The symposium addressed the utility and research opportunities afforded by specimen banking programs for future research needs in the areas of human exposure assessment, risk assessment, and environmental epidemiology. The third day of the symposium consisted of a small workshop convened to discuss and develop recommendations to the U.S. Environmental Protection Agency regarding applications and utility of large-scale specimen banking, biological monitoring, and biological markers for risk assessment activities. PMID:7635108

  6. Tissue Engineering for Human Urethral Reconstruction: Systematic Review of Recent Literature

    PubMed Central

    de Kemp, Vincent; de Graaf, Petra; Fledderus, Joost O.; Ruud Bosch, J. L. H.; de Kort, Laetitia M. O.

    2015-01-01

    Background Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. Purpose To review recent literature on tissue engineering for human urethral reconstruction. Methods A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language. Results A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial. Conclusions Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results. PMID:25689740

  7. Using gene expression to predict differences in the secretome of human omental vs. subcutaneous adipose tissue.

    PubMed

    Hoggard, Nigel; Cruickshank, Morven; Moar, Kim-Marie; Bashir, Shabina; Mayer, Claus-Dieter

    2012-06-01

    The objective of this study was to characterize differences in the secretome of human omental compared with subcutaneous adipose tissue using global gene expression profiling. Gene expression was measured using Affymetrix microarrays (Affymetrix, Santa Clara, CA) in subcutaneous and omental adipose tissue in two independent experiments (n = 5 and n = 3 independent subjects; n = 16 arrays in total, 2 for each subject). Predictive bioinformatic algorithms were employed to identify secreted proteins. Microarray analysis identified 22 gene probe sets whose expression was significantly different with a fold change (FC) greater than 5 in expression in both experiments between omental and subcutaneous adipose tissue. Using bioinformatic predictive programs 11 of these 22 probe sets potentially coded for secreted proteins. Pathway network analysis of the secreted proteins showed that three of the proteins are part of a common pathway network. These proteins gremlin 1 (GREM1), pleiotrophin (PTN), and secretory leukocyte peptidase inhibitor (SLPI) are expressed respectively 43×, 23×, and 5× in omental adipose tissue relative to subcutaneous adipose tissue as determined by real-time PCR. The presence of GREM1, PTN, and SLPI protein in human adipose tissue was confirmed by western blotting. All three proteins are expressed in the human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell line. The expression of GREM1, PTN, and SLPI changed with the differentiation of the preadipocytes into mature adipocytes. Gene expression coupled with predictive bioinformatic algorithms have identified several genes coding for secreted proteins which are expressed differently in omental adipose tissue compared to subcutaneous adipose tissue proving a valid alternative approach to help further define the adipocyte secretome. PMID:22286531

  8. Electrical resistance of human soft tissue sarcomas: an ex vivo study on surgical specimens.

    PubMed

    Campana, L G; Cesari, M; Dughiero, F; Forzan, M; Rastrelli, M; Rossi, C R; Sieni, E; Tosi, A L

    2016-05-01

    This paper presents a study about electrical resistance, which using fixed electrode geometry could be correlated to the tissue resistivity, of different histological types of human soft tissue sarcomas measured during electroporation. The same voltage pulse sequence was applied to the tumor mass shortly after surgical resection by means of a voltage pulse generator currently used in clinical practice for electrochemotherapy that uses reversible electroporation. The voltage pulses were applied by means of a standard hexagonal electrode composed by seven, 20-mm-long equispaced needles. Irrespective of tumor size, the electrode applies electric pulses to the same volume of tissue. The resistance value was computed from the voltage and current recorded by the pulse generator, and it was correlated with the histological characteristics of the tumor tissue which was assessed by a dedicated pathologist. Some differences in resistance values, which could be correlated to a difference in tissue resistivity, were noticed according to sarcoma histotype. Lipomatous tumors (i.e., those rich in adipose tissue) displayed the highest resistance values (up to 1700 Ω), whereas in the other soft tissue sarcomas, such as those originating from muscle, nerve sheath, or fibrous tissue, the electrical resistance measured was between 40 and 110 Ω. A variability in resistance was found also within the same histotype. Among lipomatous tumors, the presence of myxoid tissue between adipocytes reduced the electrical resistance (e.g., 50-100 Ω). This work represents the first step in order to explore the difference in tissue electrical properties of STS. These results may be used to verify whether tuning electric field intensity according to the specific STS histotype could improve tissue electroporation and ultimately treatment efficacy. PMID:26324245

  9. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    SciTech Connect

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M. )

    1990-08-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures.

  10. Human and Mouse Brown Adipose Tissue Mitochondria Have Comparable UCP1 Function.

    PubMed

    Porter, Craig; Herndon, David N; Chondronikola, Maria; Chao, Tony; Annamalai, Palam; Bhattarai, Nisha; Saraf, Manish K; Capek, Karel D; Reidy, Paul T; Daquinag, Alexes C; Kolonin, Mikhail G; Rasmussen, Blake B; Borsheim, Elisabet; Toliver-Kinsky, Tracy; Sidossis, Labros S

    2016-08-01

    Brown adipose tissue (BAT) plays an important role in mammalian thermoregulation. The component of BAT mitochondria that permits this function is the inner membrane carrier protein uncoupling protein 1 (UCP1). To the best of our knowledge, no studies have directly quantified UCP1 function in human BAT. Further, whether human and rodent BAT have comparable thermogenic function remains unknown. We employed high-resolution respirometry to determine the respiratory capacity, coupling control, and, most importantly, UCP1 function of human supraclavicular BAT and rodent interscapular BAT. Human BAT was sensitive to the purine nucleotide GDP, providing the first direct evidence that human BAT mitochondria have thermogenically functional UCP1. Further, our data demonstrate that human and rodent BAT have similar UCP1 function per mitochondrion. These data indicate that human and rodent BAT are qualitatively similar in terms of UCP1 function. PMID:27508873

  11. COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)

    EPA Science Inventory

    COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; ...

  12. Tissue-Specific Methylation of Human Insulin Gene and PCR Assay for Monitoring Beta Cell Death

    PubMed Central

    Husseiny, Mohamed I.; Kaye, Alexander; Zebadua, Emily; Kandeel, Fouad; Ferreri, Kevin

    2014-01-01

    The onset of metabolic dysregulation in type 1 diabetes (T1D) occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP) assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD) mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy. PMID:24722187

  13. Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium.

    PubMed

    Urieli-Shoval, S; Cohen, P; Eisenberg, S; Matzner, Y

    1998-12-01

    Serum amyloid A (SAA) is an acute-phase reactant whose level in the blood is elevated to 1000-fold as part of the body's responses to various injuries, including trauma, infection, inflammation, and neoplasia. As an acute-phase reactant, the liver has been considered to be the primary site of expression. However, limited extrahepatic SAA expression was described in mouse tissues and in cells of human atherosclerotic lesions. Here we describe nonradioactive in situ hybridization experiments revealing that the SAA mRNA is widely expressed in many histologically normal human tissues. Expression was localized predominantly to the epithelial components of a variety of tissues, including breast, stomach, small and large intestine, prostate, lung, pancreas, kidney, tonsil, thyroid, pituitary, placenta, skin epidermis, and brain neurons. Expression was also observed in lymphocytes, plasma cells, and endothelial cells. RT-PCR analysis of selected tissues revealed expression of the SAA1, SAA2, and SAA4 genes but not of SAA3, consistent with expression of these genes in the liver. Immunohistochemical staining revealed SAA protein expression that co-localized with SAA mRNA expression. These data indicate local production of the SAA proteins in histologically normal human extrahepatic tissues. PMID:9815279

  14. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.

    2015-01-01

    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

  15. Effect of Human Ovarian Tissue Vitrification/Warming on the Expression of Genes Related to Folliculogenesis

    PubMed Central

    Shams Mofarahe, Zahra; Ghaffari Novin, Marefat; Jafarabadi, Mina; Salehnia, Mojdeh; Noroozian, Mohsen; Ghorbanmehr, Nassim

    2015-01-01

    Background: Ovarian tissue cryopreservation is an alternative strategy to preserve the fertility of women predicted to undergo premature ovarian failure. This study was designed to evaluate the expression of folliculogenesis-related genes, including factor in the germline alpha (FIGLA), growth differentiation factor-9 (GDF-9), follicle-stimulating hormone receptor (FSHR), and KIT LIGAND after vitrification/warming of human ovarian tissue. Methods: Human ovarian tissue samples were collected from five transsexual women. In the laboratory, the ovarian medullary part was removed by a surgical blade, and the cortical tissue was cut into small pieces. Some pieces were vitrified and warmed and the others were considered as non-vitrified group (control). Follicular normality was assessed with morphological observation by a light microscope, and the expression of FIGLA, KIT LIGAND, GDF-9,, and FSHR genes was examined using real-time RT-PCR in both the vitrified and non-vitrified groups. Results: Overall, 85% of the follicles preserved their normal morphologic feature after warming. The percentage of normal follicles and the expression of FIGLA, KIT LIGAND, GDF-9, and FSHR genes were similar in both vitrified and non-vitrified groups (P > 0.05). Conclusion: Vitrification/warming of human ovarian tissue had no remarkable effect on the expression of folliculogenesis-related genes. PMID:26175108

  16. Importance of good manufacturing practices in microbiological monitoring in processing human tissues for transplant.

    PubMed

    Pianigiani, Elisa; Ierardi, Francesca; Fimiani, Michele

    2013-12-01

    Skin allografts represent an important therapeutic resource in the treatment of severe skin loss. The risk associated with application of processed tissues in humans is very low, however, human material always carries the risk of disease transmission. To minimise the risk of contamination of grafts, processing is carried out in clean rooms where air quality is monitored. Procedures and quality control tests are performed to standardise the production process and to guarantee the final product for human use. Since we only validate and distribute aseptic tissues, we conducted a study to determine what type of quality controls for skin processing are the most suitable for detecting processing errors and intercurrent contamination, and for faithfully mapping the process without unduly increasing production costs. Two different methods for quality control were statistically compared using the Fisher exact test. On the basis of the current study we selected our quality control procedure based on pre- and post-processing tissue controls, operator and environmental controls. Evaluation of the predictability of our control methods showed that tissue control was the most reliable method of revealing microbial contamination of grafts. We obtained 100 % sensitivity by doubling tissue controls, while maintaining high specificity (77 %). PMID:23271587

  17. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    NASA Technical Reports Server (NTRS)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  18. Activation of death-associated protein kinase in human peritumoral tissue: A potential therapeutic target.

    PubMed

    Gao, Xiang; Wang, Haiyan; Pollok, Karen E; Chen, Jinhui; Cohen-Gadol, Aaron A

    2015-10-01

    To further understand the molecular mechanisms of N-methyl-D-aspartate receptor 2B (NR2B) phosphorylation and its contribution to glioma-related seizures, we investigated the expression of death-associated protein kinase-1 (DAPK1), which is a kinase known to phosphorylate NR2B at S1303 in glioma and peritumoral tissue. The molecular mechanisms leading to glioma-associated seizures are poorly understood. We recently discovered that NR2B is phosphorylated at S1303 in glioma peritumoral tissue. NR2B is an excitatory glutamate receptor, suggesting that glutamate released from glioma tumor cells may excite the neurons in the peritumoral tissue and contribute to glioma-associated epileptogenesis. DAPK1 levels were assessed in an intracranial mouse model of human glioma and in primary patient peritumoral and glioma tissues using immunohistochemistry. DAPK1 is highly expressed in the peritumoral region, but is poorly expressed in glioma tissues in both a mouse model of human glioma and in the primary patient glioma. In our previous report, we found that NR2B is also highly phosphorylated in the same region. Upregulation of DAPK1 in the peritumoral tissues suggests that DAPK1 can phosphorylate NR2B, increase its excitability, lead to glioma-induced seizures, and could potentially be an important therapeutic target. Furthermore, the xenograft model offers an opportunity to develop and test therapeutic approaches that can block DAPK1 activity in vivo. PMID:26165472

  19. HIV-1 cellular and tissue replication patterns in infected humanized mice

    PubMed Central

    Araínga, Mariluz; Su, Hang; Poluektova, Larisa Y.; Gorantla, Santhi; Gendelman, Howard E.

    2016-01-01

    Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human. PMID:26996968

  20. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    PubMed Central

    Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

  1. The post-analytical phase of histopathology practice: Storage, retention and use of human tissue specimens

    PubMed Central

    Kapila, Supriya Nikita; Boaz, Karen; Natarajan, Srikant

    2016-01-01

    There are several aspects to a histopathology practice besides the acquisition of biopsy specimens and histopathological diagnosis. Pathology Departments are home to an abundant source of knowledge in the form of stored specimens and slides. We attempt to highlight the importance of regulation of storage, retention, and appropriate use of human tissue material in research and ownership rights to the same. We also discuss requirement and waiver of informed consent for scientific work involving the use of such tissues, which in the absence of defined laws come under the purview of Institution Review Boards. Pathology Departments, under the binding of the parent institution, are conceded the responsibility of maintenance and retention of pathology specimens. This communication highlights some of the important aspects in human tissue material handling and research, underscoring the necessity for established regulations regarding the same. PMID:26958513

  2. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

    SciTech Connect

    Timper, Katharina; Seboek, Dalma; Eberhardt, Michael; Linscheid, Philippe; Christ-Crain, Mirjam; Keller, Ulrich; Mueller, Beat; Zulewski, Henryk . E-mail: henryk.zulewski@unibas.ch

    2006-03-24

    Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.

  3. TOPICAL REVIEW: Human soft tissue analysis using x-ray or gamma-ray techniques

    NASA Astrophysics Data System (ADS)

    Theodorakou, C.; Farquharson, M. J.

    2008-06-01

    This topical review is intended to describe the x-ray techniques used for human soft tissue analysis. X-ray techniques have been applied to human soft tissue characterization and interesting results have been presented over the last few decades. The motivation behind such studies is to provide improved patient outcome by using the data obtained to better understand a disease process and improve diagnosis. An overview of theoretical background as well as a complete set of references is presented. For each study, a brief summary of the methodology and results is given. The x-ray techniques include x-ray diffraction, x-ray fluorescence, Compton scattering, Compton to coherent scattering ratio and attenuation measurements. The soft tissues that have been classified using x-rays or gamma rays include brain, breast, colon, fat, kidney, liver, lung, muscle, prostate, skin, thyroid and uterus.

  4. Measurement of optical penetration depth and refractive index of human tissue

    NASA Astrophysics Data System (ADS)

    Xie, Shusen; Li, Hui; Li, Buhong

    2003-01-01

    Experimental techniques for measurement of optical penetration depth and refractive index of human tissue are presented, respectively. Optical penetration depth can be obtained from the measurement of the relative fluence-depth distribution inside the target tissue. The depth of normal and carcinomatous human lung tissues irradiated with the wavelengths of 406.7, 632.8 and 674.4 nm in vitro are respectively determined. In addition, a novel simple method based on total internal reflection for measuring the refractive index of biotissue in vivo is developed, and the refractive indices of skin from people of different age, sex and skin color are measured. Their refractive indices are almost same and the average is 1.533.

  5. Immunohistochemical localization of the epidermal growth factor receptor in normal human tissues.

    PubMed

    Damjanov, I; Mildner, B; Knowles, B B

    1986-11-01

    A monoclonal antibody recognizing an epitope of the external domain of the human epidermal growth factor (EGF) receptor was used to localize this protein in selected normal human tissues. Two patterns of reactivity were recognized: strong linear or granular cell surface staining, and granular cytoplasmic staining. In one tissue, the endometrium, a change in the reaction pattern associated with changes in hormonal stimulation was observed. In some tissues such as epididymis and skin, the antibody showed surface reactivity with cells considered to represent part of the proliferating cell compartment, whereas in liver, pancreas, and prostate, all cells were reactive with the antibody, though the predominant reactivity was localized in the cytoplasm. The differential distribution of the epidermal growth factor receptor to specific cell types and cellular compartments may signify adaptations that permit growth factor responsiveness in a milieu of available ligand. PMID:3534450

  6. The post-analytical phase of histopathology practice: Storage, retention and use of human tissue specimens.

    PubMed

    Kapila, Supriya Nikita; Boaz, Karen; Natarajan, Srikant

    2016-01-01

    There are several aspects to a histopathology practice besides the acquisition of biopsy specimens and histopathological diagnosis. Pathology Departments are home to an abundant source of knowledge in the form of stored specimens and slides. We attempt to highlight the importance of regulation of storage, retention, and appropriate use of human tissue material in research and ownership rights to the same. We also discuss requirement and waiver of informed consent for scientific work involving the use of such tissues, which in the absence of defined laws come under the purview of Institution Review Boards. Pathology Departments, under the binding of the parent institution, are conceded the responsibility of maintenance and retention of pathology specimens. This communication highlights some of the important aspects in human tissue material handling and research, underscoring the necessity for established regulations regarding the same. PMID:26958513

  7. Expression of IL-10 in human normal and cancerous ovarian tissues and cells.

    PubMed

    Rabinovich, Alex; Medina, Liat; Piura, Benjamin; Huleihel, Mahmoud

    2010-06-01

    IL-10 is an 18-kd polypeptide that has been shown to be secreted by multiple cell types, including T and B cells, monocytes and some human tumors. However, which cell population is responsible for the elevated IL-10 levels in the serum and ascites of ovarian cancer patients, whether ovarian carcinoma cells produce IL-10, and how IL-10 influences the development and progression of ovarian carcinoma are issues that remain unclear. The aim of our study was to examine IL-10 production and secretion by ovarian carcinoma tissues and cells, and to determine its possible role in the cell and tumor micro-environment. The mean IL-10 protein levels expressed in normal ovarian tissue homogenates were significantly higher compared to cancerous ovarian tissue (p = 0.002). Yet, the IL-10 mRNA expression was significantly higher in cancerous ovarian tissues as compared to normal tissues (p = 0.021). The IL-10 receptor mRNA expression levels of the cancerous ovarian tissue homogenates were slightly, but not significantly, higher than the normal tissues. IL-10 immunostaining revealed that in both normal and cancerous ovarian tissues, IL-10 expression could be detected mainly in epithelial cells. In normal ovarian tissues, similar levels of IL-10R were demonstrated in epithelial and stromal cells. However, in cancerous ovarian tissues, epithelial cells expressed higher levels of IL-10R than the stroma. Primary normal and cancerous ovarian cell cultures and SKOV-3 cells secreted similar amounts of IL-10 after 24 hours of incubation. Our results suggest that epithelial cells are the main source of IL-10 in the ovary. Nevertheless, the target cells for IL-10 are different in normal and cancerous ovarian cells. Thus, IL-10 and its receptor could be involved in the pathogenesis of ovarian carcinoma. PMID:20430716

  8. MACRO AND MICRO APPROACHES TO THE DETERMINATION OF PESTICIDE RESIDUES IN HUMAN AND ANIMAL TISSUES

    EPA Science Inventory

    Analytical approaches to the determination of pesticides and metabolites in human and animal tissues will take many forms. Several factors must be considered in choosing an analytical scheme if the results are to be meaningful. Whenever possible the residue chemist will use stand...

  9. Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock ...

  10. TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT

    EPA Science Inventory

    TISSUE REMODELING IN THE HUMAN LUNG IN RELATION TO PARTICLE CONCENTRATION AND METAL CONTENT. J Gallagher1, J Inmon1, S Schlaegle2, A Levine2, T Rogers3, J Scott1, F Green4, M Schenker5, K Pinkerton5 1NHEERL, US-EPA, RTP, NC, USA; 2RJ Lee Group Inc, Monroeville, Pa, USA; ...

  11. Site-specific circadian expression of leptin and its receptor in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian variability of circulating leptin levels has been well established over the last decade. However, the circadian behavior of leptin in human adipose tissue remains unknown. This also applies to the soluble leptin receptor. We investigated the ex vivo circadian behavior of leptin and its rec...

  12. The evaluation of new multi-material human soft tissue simulants for sports impact surrogates.

    PubMed

    Payne, Thomas; Mitchell, Séan; Bibb, Richard; Waters, Mark

    2015-01-01

    Previous sports impact reconstructions have highlighted the inadequacies in current measures to evaluate the effectiveness of personal protective equipment (PPE) and emphasised the need for improved impact surrogates that provide a more biofidelic representation of human impact response. The skin, muscle and subcutaneous adipose tissues were considered to constitute the structures primarily governing the mechanical behaviour of the human body segment. A preceding study by Payne et al. (in press) investigated the formulation and characterisation of muscle tissue simulants. The present study investigates the development of bespoke blends of additive cure polydimethysiloxane (PDMS) silicones to represent both skin and adipose tissues using the same processes previously reported. These simulants were characterised mechanically through a range of strain rates and a range of hyperelastic and viscoelastic constitutive models were evaluated to describe their behaviour. To explore the worth of the silicone simulants, finite element (FE) models were developed using anthropometric parameters representative of the human thigh segment, derived from the Visible Human Project. The multi-material silicone construction was validated experimentally and compared with both organic tissue data from literature and commonly used single material simulants: Dow Corning Silastic 3480 series silicones and ballistics gelatin when subject to a representative sports specific knee impact. Superior biofidelic performance is reported for the PDMS silicone formulations and surrogate predictions. PMID:25448686

  13. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

    PubMed

    Grant, Christa N; Mojica, Salvador Garcia; Sala, Frederic G; Hill, J Ryan; Levin, Daniel E; Speer, Allison L; Barthel, Erik R; Shimada, Hiroyuki; Zachos, Nicholas C; Grikscheit, Tracy C

    2015-04-15

    Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells. PMID:25573173

  14. 75 FR 9226 - Agency Information Collection Activities; Proposed Collection; Comment Request; Human Tissue...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... immunodeficiency virus (HIV), hepatitis B, and hepatitis C through the use of human tissue for transplantation. The... (b) also requires recording and justification of any deviation from the written procedures. Section... excluded from the burden estimates as usual and customary business activities (5 CFR 1320.3(b)(2))....

  15. Circadian expression of adiponectin and its receptors in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is one of the most clinically relevant cytokines associated with obesity. However, circadian rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the mRNA levels of adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian ...

  16. Optical properties of human colon tissues in the 350 - 2500 nm spectral range

    NASA Astrophysics Data System (ADS)

    Bashkatov, A. N.; Genina, E. A.; Kochubey, V. I.; Rubtsov, V. S.; Kolesnikova, E. A.; Tuchin, V. V.

    2014-08-01

    We present the optical characteristics of the mucosa and submucosa of human colon tissue. The experiments are performed in vitro using a LAMBDA 950 spectrophotometer in the 350 - 2500 nm spectral range. The absorption and scattering coefficients and the scattering anisotropy factor are calculated based on the measured diffuse reflectance and total and collimated transmittance spectra using the inverse Monte Carlo method.

  17. Regulation of LPS-induced tissue factor expression in human monocytic THP-1 cells by curcumin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tissue factor (TF) is a transmembrane receptor, which initiates thrombotic episodes associated with various diseases. In addition to membrane-bound TF, we have discovered an alternatively spliced form of human TF mRNA. It was later confirmed that this form of TF mRNA expresses a soluble protein circ...

  18. Tissue-specific transcriptome sequencing analysis expands the non-human primate reference transcriptome resource (NHPRTR)

    PubMed Central

    Peng, Xinxia; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Nishida, Andrew; Pipes, Lenore; Bozinoski, Marjan; Thomas, Matthew J.; Kelly, Sara; Weiss, Jeffrey M.; Raveendran, Muthuswamy; Muzny, Donna; Gibbs, Richard A.; Rogers, Jeffrey; Schroth, Gary P.; Katze, Michael G.; Mason, Christopher E.

    2015-01-01

    The non-human primate reference transcriptome resource (NHPRTR, available online at http://nhprtr.org/) aims to generate comprehensive RNA-seq data from a wide variety of non-human primates (NHPs), from lemurs to hominids. In the 2012 Phase I of the NHPRTR project, 19 billion fragments or 3.8 terabases of transcriptome sequences were collected from pools of ∼20 tissues in 15 species and subspecies. Here we describe a major expansion of NHPRTR by adding 10.1 billion fragments of tissue-specific RNA-seq data. For this effort, we selected 11 of the original 15 NHP species and subspecies and constructed total RNA libraries for the same ∼15 tissues in each. The sequence quality is such that 88% of the reads align to human reference sequences, allowing us to compute the full list of expression abundance across all tissues for each species, using the reads mapped to human genes. This update also includes improved transcript annotations derived from RNA-seq data for rhesus and cynomolgus macaques, two of the most commonly used NHP models and additional RNA-seq data compiled from related projects. Together, these comprehensive reference transcriptomes from multiple primates serve as a valuable community resource for genome annotation, gene dynamics and comparative functional analysis. PMID:25392405

  19. Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance.

    PubMed Central

    Reubi, J. C.; Schaer, J. C.; Markwalder, R.; Waser, B.; Horisberger, U.; Laissue, J.

    1997-01-01

    This short review describes the localization of somatostatin receptors with in vitro receptor autoradiography techniques in several non-classical, normal human somatostatin target tissues as well as in selected human tumors. In addition to brain, gut and neuroendocrine localizations, somatostatin receptors are expressed in most lymphatic tissues, including gut-associated lymphatic tissue, spleen and thymus; in the cortical and medullary area of the kidney; in the stroma of the prostate and in the epithelial cells of the thyroid. Among human tumors, the extremely high density of somatostatin receptors in medulloblastomas should be stressed as well as the favorable prognostic role of the presence of somatostatin receptors in neuroblastomas. Moreover, several types of mesenchymal tumors have somatostatin receptors as well. The receptor subtypes expressed by distinct tumors may vary: Whereas medulloblastomas and neuroblastomas predominantly express sst2, prostate cancers express sst1 rather than sst2. A further emerging somatostatin target is represented by the peritumoral veins, also known to express sst2 receptors. The multiple somatostatin targets in normal and pathological human tissues represents the basis for potential diagnostic and clinical applications of somatostatin analogs. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9825475

  20. Neocollagenesis in human tissue injected with a polycaprolactone-based dermal filler.

    PubMed

    Kim, Jongseo Antonio; Van Abel, Daan

    2015-04-01

    A novel dermal filler containing polycaprolactone (PCL) has been introduced into the aesthetic market. A recently published study has shown that the PCL-based dermal filler induces neocollagenesis, a process associated with improvement in appearance of the skin, in rabbit tissue. In this pilot study, we investigated whether the PCL-based dermal filler induces neocollagenesis in human tissue by histological analysis. Two patients who were enrolled in the study, and were willing to undergo temple lifting surgery, were injected intra-dermally with the PCL-based dermal filler. Thirteen months post-injection, biopsies were obtained for subsequent histological analysis. Histological analysis of tissue obtained from the biopsies (13 months post-injection) revealed that the PCL-based dermal filler shows collagen formation around the PCL particles and, therefore, supports similar findings previously shown in rabbit tissue. In conclusion, PCL particles are maintained in their original state 13 months post-injection. PMID:25260139

  1. Guided Tissue Regeneration in Heart Valve Replacement: From Preclinical Research to First-in-Human Trials

    PubMed Central

    Iop, L.; Gerosa, G.

    2015-01-01

    Heart valve tissue-guided regeneration aims to offer a functional and viable alternative to current prosthetic replacements. Not requiring previous cell seeding and conditioning in bioreactors, such exceptional tissue engineering approach is a very fascinating translational regenerative strategy. After in vivo implantation, decellularized heart valve scaffolds drive their same repopulation by recipient's cells for a prospective autologous-like tissue reconstruction, remodeling, and adaptation to the somatic growth of the patient. With such a viability, tissue-guided regenerated conduits can be delivered as off-the-shelf biodevices and possess all the potentialities for a long-lasting resolution of the dramatic inconvenience of heart valve diseases, both in children and in the elderly. A review on preclinical and clinical investigations of this therapeutic concept is provided with evaluation of the issues still to be well deliberated for an effective and safe in-human application. PMID:26495295

  2. Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers.

    PubMed

    Brozek-Pluska, B; Kopec, M

    2016-12-01

    Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed. PMID:27376758

  3. Pharmacokinetics of difloxacin and its concentration in body fluids and endometrial tissues of mares after repeated intragastric administration.

    PubMed

    Adams, Aric R; Haines, Gregory R; Brown, Murray P; Gronwall, Ronald; Merritt, Kelly

    2005-07-01

    Pharmacokinetics of difloxacin and its distribution within the body fluids and endometrium of 6 mares were studied after intragastric (IG) administration of 5 individual doses. Difloxacin concentrations were serially measured in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal fluid, and endometrium over 120 h. Bacterial susceptibility to difloxacin was determined for 174 equine pathogens over a 7-month period. Maximum serum concentration (Cmax) was 2.25 +/- 0.70 microg/mL at 3.12 +/- 2.63 h and Cmax after the 5th dose was 2.41 +/- 0.86 microg/mL at 97.86 +/- 1.45 h. The mean elimination half-life (t(1/2)) was 8.75 +/- 2.77 h and area under the serum concentration versus time curve (AUC) was 25.13 +/- 8.79 microg h/mL. Highest mean synovial fluid concentration was 1.26 +/- 0.49 microg/mL at 100 h. Highest mean peritoneal fluid concentration was 1.50 +/- 0.56 microg/mL at 98 h. Highest mean endometrial concentration was 0.78 +/- 0.48 microg/g at 97.5 h. Mean cerebrospinal fluid concentration was 0.87 +/- 0.52 microg/mL at 99 h. Highest mean urine concentration was 92.05 +/- 30.35 microg/mL at 104 h. All isolates of Salmonella spp. and Pasteurella spp. were susceptible. In general, gram-negative organisms were more susceptible than gram-positives. Difloxacin appears to be safe, adequately absorbed, and well distributed to body fluids and endometrial tissues of mares and may be useful in the treatment of susceptible bacterial infections in adult horses. PMID:16187554

  4. Pharmacokinetics of difloxacin and its concentration in body fluids and endometrial tissues of mares after repeated intragastric administration

    PubMed Central

    2005-01-01

    Abstract Pharmacokinetics of difloxacin and its distribution within the body fluids and endometrium of 6 mares were studied after intragastric (IG) administration of 5 individual doses. Difloxacin concentrations were serially measured in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal fluid, and endometrium over 120 h. Bacterial susceptibility to difloxacin was determined for 174 equine pathogens over a 7-month period. Maximum serum concentration (Cmax) was 2.25 ± 0.70 μg/mL at 3.12 ± 2.63 h and Cmax after the 5th dose was 2.41 ± 0.86 μg/mL at 97.86 ± 1.45 h. The mean elimination half-life (t1/2) was 8.75 ± 2.77 h and area under the serum concentration versus time curve (AUC) was 25.13 ± 8.79 μg h/mL. Highest mean synovial fluid concentration was 1.26 ± 0.49 μg/mL at 100 h. Highest mean peritoneal fluid concentration was 1.50 ± 0.56 μg/mL at 98 h. Highest mean endometrial concentration was 0.78 ± 0.48 μg/g at 97.5 h. Mean cerebrospinal fluid concentration was 0.87 ± 0.52 μg/mL at 99 h. Highest mean urine concentration was 92.05 ± 30.35 μg/mL at 104 h. All isolates of Salmonella spp. and Pasteurella spp. were susceptible. In general, gram-negative organisms were more susceptible than gram-positives. Difloxacin appears to be safe, adequately absorbed, and well distributed to body fluids and endometrial tissues of mares and may be useful in the treatment of susceptible bacterial infections in adult horses. PMID:16187554

  5. Perception Versus Actual Performance in Timely Tissue Plasminogen Activation Administration in the Management of Acute Ischemic Stroke

    PubMed Central

    Lin, Cheryl B; Cox, Margueritte; Olson, DaiWai M; Britz, Gavin W; Constable, Mark; Fonarow, Gregg C; Schwamm, Lee; Peterson, Eric D; Shah, Bimal R

    2015-01-01

    Background Timely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA “door-to-needle” (DTN) time within 60 minutes and how DTN rates compare across different hospitals. Methods and Results DTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and lowDTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN ≤60 minutes among treated patients (10.6% versus 16.6%, P=0.002). Conclusions Hospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care. PMID:26201547

  6. Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

    PubMed Central

    Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

    2015-01-01

    Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 – 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery. PMID:25961911

  7. Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

    2015-05-01

    Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

  8. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C.

    PubMed

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-05-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the (14)C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of (14)C, produced by nuclear bomb tests in 1955-1963, which is reflected in all living organisms. Levels of (14)C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945-1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of (14)C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of (14)C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, (14)C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue. PMID:23401563

  9. Human colon tissue in organ culture: preservation of normal and neoplastic characteristics

    PubMed Central

    Bhagavathula, Narasimharao; Mankey, Cohra; DaSilva, Marissa; Paruchuri, Tejaswi; Aslam, Muhammad Nadeem; Varani, James

    2009-01-01

    Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the presence of elongated crypts with small, densely packed cells at the crypt base and mucin-containing goblet cells in the upper portion. Ki67 staining, for proliferating cells, was confined to the lower third of the crypt, while expression of extracellular calcium-sensing receptor was seen in the upper third and surface epithelium. E-cadherin and β-catenin were expressed throughout the epithelium and confined to the cell surface. In tumor tissue, the same disorganized, abnormal glandular structures seen at time zero were present after 2 d. The majority of cells in these structures were mucin-poor, but occasional goblet cells were seen and mucin staining was present. Ki67 staining was seen throughout the abnormal epithelium and calcium-sensing receptor expression was weak and variable. E-cadherin was seen at the cell surface (similar to normal tissue), but in some places, there was diffuse cytoplasmic staining. Finally, intense cytoplasmic and nuclear β-catenin staining was observed in cultured neoplastic tissue. PMID:19915935

  10. Hypoxia Created Human Mesenchymal Stem Cell Sheet for Prevascularized 3D Tissue Construction.

    PubMed

    Zhang, Lijun; Xing, Qi; Qian, Zichen; Tahtinen, Mitchell; Zhang, Zhaoqiang; Shearier, Emily; Qi, Shaohai; Zhao, Feng

    2016-02-01

    3D tissue based on human mesenchymal stem cell (hMSC) sheets offers many interesting opportunities for regenerating multiple types of connective tissues. Prevascularizing hMSC sheets with endothelial cells (ECs) will improve 3D tissue performance by supporting cell survival and accelerating integration with host tissue. It is hypothesized that hypoxia cultured hMSC sheets can promote microvessel network formation and preserve stemness of hMSCs. This study investigates the vascularization of hMSC sheets under different oxygen tensions. It is found that the HN condition, in which hMSC sheets formed under physiological hypoxia (2% O2 ) and then cocultured with ECs under normoxia (20% O2 ), enables longer and more branched microvessel network formation. The observation is corroborated by higher levels of angiogenic factors in coculture medium. Additionally, the hypoxic hMSC sheet is more uniform and less defective, which facilitates fabrication of 3D prevascularized tissue construct by layering the prevascularized hMSC sheets and maturing in rotating wall vessel bioreactor. The hMSCs in the 3D construct still maintain multilineage differentiation ability, which indicates the possible application of the 3D construct for various connective tissues regeneration. These results demonstrate that hypoxia created hMSC sheets benefit the microvessel growth and it is feasible to construct 3D prevascularized tissue construct using the prevascularized hMSC sheets. PMID:26663707

  11. Magnetic Resonance Microscopy at 14 Tesla and Correlative Histopathology of Human Brain Tumor Tissue

    PubMed Central

    Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel

    2011-01-01

    Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples. PMID:22110653

  12. Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors.

    PubMed

    Jarry, Ulrich; Chauvin, Cynthia; Joalland, Noémie; Léger, Alexandra; Minault, Sandrine; Robard, Myriam; Bonneville, Marc; Oliver, Lisa; Vallette, François M; Vié, Henri; Pecqueur, Claire; Scotet, Emmanuel

    2016-06-01

    Glioblastoma multiforme (GBM) represents the most frequent and deadliest primary brain tumor. Aggressive treatment still fails to eliminate deep brain infiltrative and highly resistant tumor cells. Human Vγ9Vδ2 T cells, the major peripheral blood γδ T cell subset, react against a wide array of tumor cells and represent attractive immune effector T cells for the design of antitumor therapies. This study aims at providing a preclinical rationale for immunotherapies in GBM based on stereotaxic administration of allogeneic human Vγ9Vδ2 T cells. The feasibility and the antitumor efficacy of stereotaxic Vγ9Vδ2 T cell injections have been investigated in orthotopic GBM mice model using selected heterogeneous and invasive primary human GBM cells. Allogeneic human Vγ9Vδ2 T cells survive and patrol for several days within the brain parenchyma following adoptive transfer and can successfully eliminate infiltrative GBM primary cells. These striking observations pave the way for optimized stereotaxic antitumor immunotherapies targeting human allogeneic Vγ9Vδ2 T cells in GBM patients. PMID:27471644

  13. Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue.

    PubMed

    Yang, Yi-Sheng; Song, Huai-Dong; Shi, Wen-Jing; Hu, Ren-Ming; Han, Ze-Guang; Chen, Jia-Lun

    2002-06-01

    To understand fully the physiologic functions of visceral adipose tissue and to provide a basis for the identification of novel genes related to obesity and insulin resistance, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. The characterization and chromosome localization of 400 expressed sequence tags (ESTs) strongly expressed in visceral adipose tissue were analyzed by searching PubMed, UniGene, the Human Genome Draft Database, and Location Data Base. Two hundred eighty-nine clones were classified into known genes among the 400 ESTs strongly expressed in the tissue. Among them, <20% have been previously reported to be expressed in adipose tissue. The chromosome localization of 389 ESTs strongly expressed in visceral adipose tissue showed that their relative abundance was significantly increased on chromosomes 1, 16, 19, 20, and 22 compared with the expected distribution of the same number of random genes. The intrachromosome distribution of the genes strongly expressed in visceral adipose tissue was concentrated in certain regions, such as 1p36.2-1p36.3, 6p21.3-6p22.1, 19p13.3 and 19q13.1. Among them, the region of 1p36.2-1p36.3 appeared to be specific for visceral adipose tissue. Interestingly, some genes playing an important role in the pathogenesis of insulin signal transduction and adipocyte differentiation, such as tumor necrosis factor-alpha and its receptors; CCAAT/enhancer-binding proteina; and phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85beta), were also localized in the concentrated regions, which may provide clues to identifying novel genes closely related to adipocyte function with potential pathophysiologic implications. PMID:12166625

  14. Regional Variation of Bone Tissue Properties at the Human Mandibular Condyle

    PubMed Central

    Kim, Do-Gyoon; Jeong, Yong-Hoon; Kosel, Erin; Agnew, Amanda M.; McComb, David W.; Bodnyk, Kyle; Hart, Richard T.; Kim, Min Kyung; Han, Sang Yeun; Johnston, William M.

    2015-01-01

    The temporomandibular joint (TMJ) bears different types of static and dynamic loading during occlusion and mastication. As such, characteristics of mandibular condylar bone tissue play an important role in determining the mechanical stability of the TMJ under the macro-level loading. Thus, the objective of this study was to examine regional variation of the elastic, plastic, and viscoelastic mechanical properties of human mandibular condylar bone tissue using nanoindentation. Cortical and trabecular bone were dissected from mandibular condyles of human cadavers (9 males, 54 to 96 years). These specimens were scanned using microcomputed tomography to obtain bone tissue mineral distribution. Then, nanoindentation was conducted on the surface of the same specimens in hydration. Plastic hardness (H) at a peak load, viscoelastic creep (Creep/Pmax), viscosity (η), and tangent delta (tan δ) during a 30 second hold period, and elastic modulus (E) during unloading were obtained by a cycle of indentation at the same site of bone tissue. The tissue mineral and nanoindentation parameters were analyzed for the periosteal and endosteal cortex, and trabecular bone regions of the mandibular condyle. The more mineralized periosteal cortex had higher mean values of elastic modulus, plastic hardness, and viscosity but lower viscoelastic creep and tan δ than the less mineralized trabecular bone of the mandibular condyle. These characteristics of bone tissue suggest that the periosteal cortex tissue may have more effective properties to resist elastic, plastic, and viscoelastic deformation under static loading, and the trabecular bone tissue to absorb and dissipate time-dependent viscoelastic loading energy at the TMJ during static occlusion and dynamic mastication. PMID:25913634

  15. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

    PubMed

    Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

    2016-08-16

    Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body. PMID:27521270

  16. Tissue-specific expression of the human type II collagen gene in mice.

    PubMed Central

    Lovell-Badge, R H; Bygrave, A; Bradley, A; Robertson, E; Tilly, R; Cheah, K S

    1987-01-01

    Type II collagen is crucial to the development of form in vertebrates as it is the major protein of cartilage. To study the factors regulating its expression we introduced a cosmid containing the human type II collagen gene, including 4.5 kilobases of 5' and 2.2 kilobases of 3' flanking DNA, into embryonic stem cells in vitro. The transformed cells contribute to all tissues in chimeric mice allowing the expression of the exogenous gene to be studied in vivo. Human type II collagen mRNA is restricted to tissues showing transcription from the endogenous gene and human type II collagen is found in extracellular matrix surrounding chondrocytes in cartilage. The results indicate that the cis-acting requirements for correct temporal and spatial regulation of the gene are contained within the introduced DNA. Images PMID:3033664

  17. Multipotent mesenchymal stem cells from human subacromial bursa: potential for cell based tendon tissue engineering.

    PubMed

    Song, Na; Armstrong, April D; Li, Feng; Ouyang, Hongsheng; Niyibizi, Christopher

    2014-01-01

    Rotator cuff injuries are a common clinical problem either as a result of overuse or aging. Biological approaches to tendon repair that involve use of scaffolding materials or cell-based approaches are currently being investigated. The cell-based approaches are focused on applying multipotent mesenchymal stem cells (MSCs) mostly harvested from bone marrow. In the present study, we focused on characterizing cells harvested from tissues associated with rotator cuff tendons based on an assumption that these cells would be more appropriate for tendon repair. We isolated MSCs from bursa tissue associated with rotator cuff tendons and characterized them for multilineage differentiation in vitro and in vivo. Human bursa was obtained from patients undergoing rotator cuff surgery and cells within were isolated using collagenase and dispase digestion. The cells isolated from the tissues were characterized for osteoblastic, adipogenic, chondrogenic, and tenogenic differentiation in vitro and in vivo. The results showed that the cells isolated from bursa tissue exhibited MSCs characteristics as evidenced by the expression of putative cell surface markers attributed to MSCs. The cells exhibited high proliferative capacity and differentiated toward cells of mesenchymal lineages with high efficiency. Bursa-derived cells expressed markers of tenocytes when treated with bone morphogenetic protein-12 (BMP-12) and assumed aligned morphology in culture. Bursa cells pretreated with BMP-12 and seeded in ceramic scaffolds formed extensive bone, as well as tendon-like tissue in vivo. Bone formation was demonstrated by histological analysis and immunofluorescence for DMP-1 in tissue sections made from the scaffolds seeded with the cells. Tendon-like tissue formed in vivo consisted of parallel collagen fibres typical of tendon tissues. Bursa-derived cells also formed a fibrocartilagenous tissue in the ceramic scaffolds. Taken together, the results demonstrate a new source of MSCs with a

  18. Multipotent Mesenchymal Stem Cells from Human Subacromial Bursa: Potential for Cell Based Tendon Tissue Engineering

    PubMed Central

    Song, Na; Armstrong, April D.; Li, Feng; Ouyang, Hongsheng

    2014-01-01

    Rotator cuff injuries are a common clinical problem either as a result of overuse or aging. Biological approaches to tendon repair that involve use of scaffolding materials or cell-based approaches are currently being investigated. The cell-based approaches are focused on applying multipotent mesenchymal stem cells (MSCs) mostly harvested from bone marrow. In the present study, we focused on characterizing cells harvested from tissues associated with rotator cuff tendons based on an assumption that these cells would be more appropriate for tendon repair. We isolated MSCs from bursa tissue associated with rotator cuff tendons and characterized them for multilineage differentiation in vitro and in vivo. Human bursa was obtained from patients undergoing rotator cuff surgery and cells within were isolated using collagenase and dispase digestion. The cells isolated from the tissues were characterized for osteoblastic, adipogenic, chondrogenic, and tenogenic differentiation in vitro and in vivo. The results showed that the cells isolated from bursa tissue exhibited MSCs characteristics as evidenced by the expression of putative cell surface markers attributed to MSCs. The cells exhibited high proliferative capacity and differentiated toward cells of mesenchymal lineages with high efficiency. Bursa-derived cells expressed markers of tenocytes when treated with bone morphogenetic protein-12 (BMP-12) and assumed aligned morphology in culture. Bursa cells pretreated with BMP-12 and seeded in ceramic scaffolds formed extensive bone, as well as tendon-like tissue in vivo. Bone formation was demonstrated by histological analysis and immunofluorescence for DMP-1 in tissue sections made from the scaffolds seeded with the cells. Tendon-like tissue formed in vivo consisted of parallel collagen fibres typical of tendon tissues. Bursa-derived cells also formed a fibrocartilagenous tissue in the ceramic scaffolds. Taken together, the results demonstrate a new source of MSCs with a

  19. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

    PubMed Central

    2012-01-01

    Background Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for

  20. Stromal Cells in Dense Collagen Promote Cardiomyocyte and Microvascular Patterning in Engineered Human Heart Tissue.

    PubMed

    Roberts, Meredith A; Tran, Dominic; Coulombe, Kareen L K; Razumova, Maria; Regnier, Michael; Murry, Charles E; Zheng, Ying

    2016-04-01

    Cardiac tissue engineering is a strategy to replace damaged contractile tissue and model cardiac diseases to discover therapies. Current cardiac and vascular engineering approaches independently create aligned contractile tissue or perfusable vasculature, but a combined vascularized cardiac tissue remains to be achieved. Here, we sought to incorporate a patterned microvasculature into engineered heart tissue, which balances the competing demands from cardiomyocytes to contract the matrix versus the vascular lumens that need structural support. Low-density collagen hydrogels (1.25 mg/mL) permit human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to form a dense contractile tissue but cannot support a patterned microvasculature. Conversely, high collagen concentrations (density ≥6 mg/mL) support a patterned microvasculature, but the hESC-CMs lack cell-cell contact, limiting their electrical communication, structural maturation, and tissue-level contractile function. When cocultured with matrix remodeling stromal cells, however, hESC-CMs structurally mature and form anisotropic constructs in high-density collagen. Remodeling requires the stromal cells to be in proximity with hESC-CMs. In addition, cocultured cardiac constructs in dense collagen generate measurable active contractions (on the order of 0.1 mN/mm(2)) and can be paced up to 2 Hz. Patterned microvascular networks in these high-density cocultured cardiac constructs remain patent through 2 weeks of culture, and hESC-CMs show electrical synchronization. The ability to maintain microstructural control within engineered heart tissue enables generation of more complex features, such as cellular alignment and a vasculature. Successful incorporation of these features paves the way for the use of large scale engineered tissues for myocardial regeneration and cardiac disease modeling. PMID:26955856

  1. Generation of Neural Stem Cells from Discarded Human Fetal Cortical Tissue

    PubMed Central

    Lu, Jie; Delli-Bovi, Laurent C.; Hecht, Jonathan; Folkerth, Rebecca; Sheen, Volney L.

    2011-01-01

    Neural stem cells (NSCs) reside along the ventricular zone neuroepithelium during the development of the cortical plate. These early progenitors ultimately give rise to intermediate progenitors and later, the various neuronal and glial cell subtypes that form the cerebral cortex. The capacity to generate and expand human NSCs (so called neurospheres) from discarded normal fetal tissue provides a means with which to directly study the functional aspects of normal human NSC development 1-5. This approach can also be directed toward the generation of NSCs from known neurological disorders, thereby affording the opportunity to identify disease processes that alter progenitor proliferation, migration and differentiation 6-9. We have focused on identifying pathological mechanisms in human Down syndrome NSCs that might contribute to the accelerated Alzheimer's disease phenotype 10,11. Neither in vivo nor in vitro mouse models can replicate the identical repertoire of genes located on human chromosome 21. Here we use a simple and reliable method to isolate Down syndrome NSCs from aborted human fetal cortices and grow them in culture. The methodology provides specific aspects of harvesting the tissue, dissection with limited anatomical landmarks, cell sorting, plating and passaging of human NSCs. We also provide some basic protocols for inducing differentiation of human NSCs into more selective cell subtypes. PMID:21654623

  2. The LKB1 Tumor Suppressor as a Biomarker in Mouse and Human Tissues

    PubMed Central

    Peña, Christopher G.; Zhang, Song; Zhao, Ni; Bardeesy, Nabeel; Sharpless, Norman E.; Wong, Kwok-Kin; Hayes, D. Neil; Castrillon, Diego H.

    2013-01-01

    Germline mutations in the LKB1 gene (also known as STK11) cause the Peutz-Jeghers Syndrome, and somatic loss of LKB1 has emerged as causal event in a wide range of human malignancies, including melanoma, lung cancer, and cervical cancer. The LKB1 protein is a serine-threonine kinase that phosphorylates AMP-activated protein kinase (AMPK) and other downstream targets. Conditional knockout studies in mouse models have consistently shown that LKB1 loss promotes a highly-metastatic phenotype in diverse tissues, and human studies have demonstrated a strong association between LKB1 inactivation and tumor recurrence. Furthermore, LKB1 deficiency confers sensitivity to distinct classes of anticancer drugs. The ability to reliably identify LKB1-deficient tumors is thus likely to have important prognostic and predictive implications. Previous research studies have employed polyclonal antibodies with limited success, and there is no widely-employed immunohistochemical assay for LKB1. Here we report an assay based on a rabbit monoclonal antibody that can reliably detect endogenous LKB1 protein (and its absence) in mouse and human formalin-fixed, paraffin-embedded tissues. LKB1 protein levels determined through this assay correlated strongly with AMPK phosphorylation both in mouse and human tumors, and with mRNA levels in human tumors. Our studies fully validate this immunohistochemical assay for LKB1 in paraffin-embedded formalin tissue sections. This assay should be broadly useful for research studies employing mouse models and also for the development of human tissue-based assays for LKB1 in diverse clinical settings. PMID:24086281

  3. [sup 90]Y-labeled antibody uptake by human tumor xenografts and the effect of systemic administration of EDTA

    SciTech Connect

    Rowlinson-Busza, G.; Snook, D.; Epenetos, A.A. )

    1994-03-30

    A human tumor xenograft model was used to compare the tumor and normal tissue uptake of a tumor-associated monoclonal antibody radiolabeled with [sup 125]I or [sup 90]Y. Nude mice bearing SC xenografts of the human colon adenocarcinoma, HT29, were injected with a mixture of [sup 125]I- and [sup 90]Y-DTPA-labeled AUA1 monoclonal antibody, which recognizes an antigen expressed on the surface of the tumor cells. In addition, the effect of systemic ethylenediaminetetraacetic acid (EDTA) administration on [sup 90]Y-labeled antibody clearance, tumor uptake of antibody and bone accumulation of [sup 90]Y was studied in a nude mouse model of intraperitoneal cancer. Both the absolute amount (%id[center dot]g[sup -1]) and the tumor:normal tissue ratios were superior for the [sup 90]Y-labeled antibody, compared with the iodinated antibody, with the notable exception of bone. These results suggest that [sup 90]Y is a preferable isotope to iodine for radioimmunotherapy of solid masses, but that myelotoxicity due to bone uptake of released [sup 90]Y will limit the radiation dose which can be given when DTPA is used to chelate the [sup 90]Y. The [sup 90]Y-labeled antibody showed similar serum stability in vitro in the presence or absence of EDTA after incubation for up to 48 h. In vivo, urine excretion of [sup 90]Y was significantly enhanced in mice receiving daily injections of 20 mg EDTA for 3 days, commencing 2 h after intraperitoneal antibody administration, compared with control mice. There was no significant difference in the tumor uptake of [sup 90]Y-labeled antibody in EDTA-treated and control mice at any time-point up to 9 days postinjection. However, the bone levels of [sup 90]Y were significantly reduced in EDTA-treated mice at all times from 1 to 9 days. Based on these results, it should be possible to increase the amount of [sup 90]Y-labeled antibody administered, by chelating the released [sup 90]Y with systemic EDTA to facilitate its excretion. 50 refs., 5 figs.

  4. O/sup 6/-methylguanine DNA methyltransferase in human fetal tissues: fetal and maternal factors

    SciTech Connect

    D'Ambrosio, S.M.; Samuel, M.J.; Dutta-Choudhury, T.A.; Wani, A.A.

    1986-03-01

    O/sup 6/-Methylguanine methyltransferase (O/sup 6/-MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race, and maternal smoking and drug usage. Activity was determined from the proteinase-K solubilized radioactivity transferred from the DNA to the O/sup 6/-MT. S9 homogenates were incubated with a heat depurinated (/sup 3/H)-methylnitrosourea alkylated DNA. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin and brain. Each of the tissues exhibited a 3- to 5-fold level of interindividual variation of O/sup 6/-MT. There did not appear to be any significant difference of O/sup 6/-MT in the tissues obtained from mothers who smoked cigarettes during pregnancy. Also, fetal race and age did not appear to account for the level of variation of O/sup 6/-MT. The fetal tissues obtained from an individual using phenobarbital and smoking exhibited 4-fold increases in O/sup 6/-MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest that the variation in human O/sup 6/-MT can not be explained by racial or smoking factors, but may be modulated by certain drugs.

  5. Characterization of Human Dental Pulp Tissue Under Oscillatory Shear and Compression.

    PubMed

    Ozcan, Burak; Bayrak, Ece; Erisken, Cevat

    2016-06-01

    Availability of material as well as biological properties of native tissues is critical for biomaterial design and synthesis for regenerative engineering. Until recently, selection of biomaterials and biomolecule carriers for dental pulp regeneration has been done randomly or based on experience mainly due to the absence of benchmark data for dental pulp tissue. This study, for the first time, characterizes the linear viscoelastic material functions and compressive properties of human dental pulp tissue harvested from wisdom teeth, under oscillatory shear and compression. The results revealed a gel-like behavior of the pulp tissue over the frequency range of 0.1-100 rps. Uniaxial compression tests generated peak normal stress and compressive modulus values of 39.1±20.4 kPa and 5.5±2.8 kPa, respectively. Taken collectively, the linear viscoelastic and uniaxial compressive properties of the human dental pulp tissue reported here should enable the better tailoring of biomaterials or biomolecule carriers to be employed in dental pulp regeneration. PMID:27093446

  6. Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo

    PubMed Central

    Sassi, Atfa; Brichacek, Beda; Hieny, Sara; Yarovinsky, Felix; Golding, Hana; Grivel, Jean-Charles; Sher, Alan; Margolis, Leonid

    2016-01-01

    Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii -encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants. PMID:19671446

  7. Magnetic iron compounds in the human brain: a comparison of tumour and hippocampal tissue

    PubMed Central

    Brem, Franziska; Hirt, Ann M; Winklhofer, Michael; Frei, Karl; Yonekawa, Yasuhiro; Wieser, Heinz-Gregor; Dobson, Jon

    2006-01-01

    Iron is a central element in the metabolism of normal and malignant cells. Abnormalities in iron and ferritin expression have been observed in many types of cancer. Interest in characterizing iron compounds in the human brain has increased due to advances in determining a relationship between excess iron accumulation and neurological and neurodegenerative diseases. In this work, four different magnetic methods have been employed to characterize the iron phases and magnetic properties of brain tumour (meningiomas) tissues and non-tumour hippocampal tissues. Four main magnetic components can be distinguished: the diamagnetic matrix, nearly paramagnetic blood, antiferromagnetic ferrihydrite cores of ferritin and ferrimagnetic magnetite and/or maghemite. For the first time, open hysteresis loops have been observed on human brain tissue at room temperature. The hysteresis properties indicate the presence of magnetite and/or maghemite particles that exhibit stable single-domain (SD) behaviour at room temperature. A significantly higher concentration of magnetically ordered magnetite and/or maghemite and a higher estimated concentration of heme iron was found in the meningioma samples. First-order reversal curve diagrams on meningioma tissue further show that the stable SD particles are magnetostatically interacting, implying high-local concentrations (clustering) of these particles in brain tumours. These findings suggest that brain tumour tissue contains an elevated amount of remanent iron oxide phases. PMID:17015303

  8. A model of the effects of heavy ion radiation on human tissue

    SciTech Connect

    Ponomarev, A.L.; Guida, P.; Ponomarev, A.L.; Sundaresan, A.; Vazquez, M.E.; Guida, P.; Kim, A.; Cucinotta, F.A.

    2010-08-09

    In heavy ion radiotherapy and space travel humans are exposed to energetic heavy ions (C, Si, Fe and others). This type of irradiation often produces more severe biological effects per unit dose than more common X-rays. A new Monte Carlo model generates a physical space with the complex geometry of human tissue or a cell culture based model of tissue, which is affected by the passage of ionizing radiation. For irradiation, the model relies on a physical code for the ion track structure; for tissues, cellular maps are derived from two- or three-dimensional confocal microscopy images using image segmentation algorithm, which defines cells as pixilated volumes. The model is used to study tissue-specific statistics of direct ion hits and the remote ion action on cells. As an application of the technique, we considered the spatial pattern of apoptotic cells after heavy ion irradiation. The pattern of apoptosis is modeled as a stochastic process, which is defined by the action cross section taken from available experimental data. To characterize the degree of apoptosis, an autocorrelation function that describes the spatial correlation of apoptotic cells is introduced. The values of the autocorrelation function demonstrate the effect of the directionality of the radiation track on the spatial arrangements of inactivated cells in tissue. This effect is intrinsic only to high linear-energy-transfer radiation.

  9. Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

    NASA Astrophysics Data System (ADS)

    Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

    2008-02-01

    Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

  10. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents.

    PubMed

    Bayes-Genis, Antoni; Soler-Botija, Carolina; Farré, Jordi; Sepúlveda, Pilar; Raya, Angel; Roura, Santiago; Prat-Vidal, Cristina; Gálvez-Montón, Carolina; Montero, José Anastasio; Büscher, Dirk; Izpisúa Belmonte, Juan Carlos

    2010-11-01

    Myocardial infarction caused by vascular occlusion results in the formation of nonfunctional fibrous tissue. Cumulative evidence indicates that cell therapy modestly improves cardiac function; thus, novel cell sources with the potential to repair injured tissue are actively sought. Here, we identify and characterize a cell population of cardiac adipose tissue-derived progenitor cells (ATDPCs) from biopsies of human adult cardiac adipose tissue. Cardiac ATDPCs express a mesenchymal stem cell-like marker profile (strongly positive for CD105, CD44, CD166, CD29 and CD90) and have immunosuppressive capacity. Moreover, cardiac ATDPCs have an inherent cardiac-like phenotype and were able to express de novo myocardial and endothelial markers in vitro but not to differentiate into adipocytes. In addition, when cardiac ATDPCs were transplanted into injured myocardium in mouse and rat models of myocardial infarction, the engrafted cells expressed cardiac (troponin I, sarcomeric α-actinin) and endothelial (CD31) markers, vascularization increased, and infarct size was reduced in mice and rats. Moreover, significant differences between control and cell-treated groups were found in fractional shortening and ejection fraction, and the anterior wall remained significantly thicker 30days after cardiac delivery of ATDPCs. Finally, cardiac ATDPCs secreted proangiogenic factors under in vitro hypoxic conditions, suggesting a paracrine effect to promote local vascularization. Our results indicate that the population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) may be valid candidates for future use in cell therapy to regenerate injured myocardium. PMID:20713059

  11. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

    PubMed

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

  12. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    PubMed Central

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

  13. Oxygen consumption rate of early pre-antral follicles from vitrified human ovarian cortical tissue.

    PubMed

    Ishikawa, Takayuki; Kyoya, Toshihiko; Nakamura, Yusuke; Sato, Eimei; Tomiyama, Tatsuhiro; Kyono, Koichi

    2014-01-01

    The study of human ovarian tissue transplantation and cryopreservation has advanced significantly. Autotransplantation of human pre-antral follicles isolated from cryopreserved cortical tissue is a promising option for the preservation of fertility in young cancer patients. The purpose of the present study was to reveal the effect of vitrification after low-temperature transportation of human pre-antral follicles by using the oxygen consumption rate (OCR). Cortical tissues from 9 ovaries of female-to-male transsexuals were vitrified after transportation (6 or 18 h). The follicles were enzymatically isolated from nonvitrified tissue (group I, 18 h of transportation), vitrified-warmed tissue (group II, 6 and 18 h of transportation) and vitrified-warmed tissue that had been incubated for 24 h (group III, 6 and 18 h of transportation). OCR measurement and the LIVE/DEAD viability assay were performed. Despite the ischemic condition, the isolated pre-antral follicles in group I consumed oxygen, and the mean OCRs increased with developmental stage. Neither the transportation time nor patient age seemed to affect the OCR in this group. Meanwhile, the mean OCR was significantly lower (P < 0.05) in group II but was comparable to that of group I after 24 h of incubation. The integrity of vitrified-warmed primordial and primary follicles was clearly corroborated by the LIVE/DEAD viability assay. These results demonstrate that the OCR can be used to directly estimate the effect of vitrification on the viability of primordial and primary follicles and to select the viable primordial and primary follicles from vitrified-warmed follicles. PMID:25262776

  14. Possible range of dioxin concentration in human tissues: simulation with a physiologically based model.

    PubMed

    Maruyama, Wakae; Yoshida, Kikuo; Tanaka, Takayuki; Nakanishi, Junko

    2002-12-27

    In risk evaluation of dioxins, monitoring chemical concentrations in human tissues is an important step, and these concentration data can be utilized along with animal toxicity data for extrapolation of human manifestation. However large differences in dioxin concentrations usually exist even among individuals who have never been accidentally exposed to high quantities of dioxin, and this may cause problems in risk analysis. Body size, age, and history of food consumption are factors respons