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4. Zu Beginn von vierter Corona-Welle: Eltern bei geöffneten Kitas und Schulen zufriedener und mit weniger Sorgen

Author

Huebener, M., Pape, A., Siegel, N., Spieß, K., and Wagner, G.

Subjects
ddc:330
Abstract

Eltern waren zu Beginn der vierten Corona-Welle im Oktober deutlich zufriedener mit dem Familienleben, der Kinderbetreuung und dem Leben allgemein als in den Lockdowns im vergangenen Winter und Frühjahr. Gleichzeitig äußerten sie deutlich weniger Sorgen als im April, etwa mit Blick auf die Bildung und wirtschaftliche Zukunft ihrer Kinder. Trotz vergleichsweiser hoher Inzidenzen unter jungen Menschen bei zugleich weitgehendem Präsenzbetrieb in Kitas und Schulen sind auch die Sorgen um die Gesundheit der Kinder deutlich zurückgegangen. Dies könnte darauf hindeuten, dass Eltern sich zur Zeit des eingeschränkten Kita- und Schulbetriebs auch um andere gesundheitliche Auswirkungen als die einer Covid-19-Infektion bei ihren Kindern gesorgt haben. Geöffnete Kitas und Schulen sind für Eltern und Kinder gleichermaßen wichtig. Regelmäßige Tests, eine hohe Impfquote unter den Beschäftigten und entsprechende Hygienemaßnahmen scheinen die zentralen Bausteine zu sein, um erneute Schließungen abzuwenden und einen vielschichtigen und langfristigen Einfluss selbiger auf Familien und Kinder zu minimieren.

Published
2021

7. Integration von SPICE in eine CAD/CAE-Umgebung

Author

Spiess, K. R., Hoffmann, G., Holzmann, D., Jäger, F., Riedling, K., Schwuttke, G. H., Pandelisev, K. A., White, R. C., Holzmann, H., Kausel, W., Nanz, G., Selberherr, S., Pötzl, H., Leopold, H., Röhrer, R., Winkler, G., Thurner, M., Seiner, K., Tritremmel, W., Walther, G., Schoitsch, Erwin, Hertl, S., Schaffar, G., Schmidt, K., Steinbrecher, H., Voggenberger, F., Windischhofer, W., Turba, R., Grabner, J., Aberl, H., Seifert, F., Buschbeck, F., Wallisch, K., Eichtinger, Ch., Wach, P., Bittinger, W., Kainz, A., Jestl, M., Beinstingl, W., Berthold, K., Köck, A., Gornik, E., Kloiber, G., Kreid, F., Schröcker, K. P., Schrödl, M., Brazda, E., Niedrist, G., Dietz, K., Fey, P., Frenkenberger, S., Furtner, M., Dejneka, B., Goiser, A., Sust, M., Kowatsch, M., Jorde, Ch., Thallinger, G. G., Mothwurf, E., Schubert, E., Steger, J., Trzeba, E., Awramow, I., Pucher, R., Auer, L. M., Schuy, S., Schima, H., Huber, L., Prodinger, A., Schmallegger, H., Thoma, H., Stöhr, H., Mayr, W., Steiner, R., Wiedenbauer, O., List, G., Wießpeiner, G., Petsch, Th., Doblhoff, G., Kirchner, D., Koudelka, O., Gierlinger, A., Ullrich, A., Braune, B., Horvat, H., Mayer, U., Gauby, A., Richter, A., Spiess, K. R., Klösch, W., Böck, N., Rosenkranz, H., Mitter, H., Hengl, M., Nussbaum, G., Gutternigh, K., Hahn, H., Koutny, P., Pühringer, K., Schwabach, H., Hirschler, M., Haas, M., Renner, A., Bratengeyer, E., Scholz-Nauendorff, C. C., Lebutsch, K., Volkmann, W., Gerner, H., Girsch, W., Holle, J., Kluger, P., Meister, B., Moritz, E., Schwanda, G., Prager, L., Wieβpeiner, G., Grübler, R., Dorfer, E., Oitzl, E., Pribyl, W., Bähring, M., Harter, J., and Sommer, D.

Published
1987
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8. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

Author

Krishna, B.A., Spiess, K., Poole, E.L., Lau, B., Voigt, S., Kledal, T.N., Rosenkilde, M.M., Sinclair, J.H., Krishna, Benjamin Anthony Cates [0000-0003-0919-2961], Poole, Emma [0000-0003-3904-6121], Sinclair, John [0000-0002-2616-9571], and Apollo - University of Cambridge Repository

Subjects
Genes, Viral, Science, Recombinant Fusion Proteins, Lipopolysaccharide Receptors, Cytomegalovirus, Antigens, CD34, Article, Monocytes, Viral Proteins, SDG 3 - Good Health and Well-being, Humans, Herpes virus, Cells, Cultured, Disease Reservoirs, Cell Death, Stem Cells, fungi, Hematopoietic Stem Cell Transplantation, food and beverages, Viral Load, Antivirals, Endocytosis, Virus Latency, Receptors, Chemokine, Virus Activation, Chemokines
Abstract

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation., Reactivation of human cytomegalovirus in immunosuppressed transplant patients can cause severe complications. Here, Krishna et al. show that a fusion toxin protein that specifically binds the viral surface protein US28 can be used to kill latently infected monocytes and their progenitor cells in vitro.

Published
2017
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9. The UK-PBC Risk Scores: Derivation and Validation of a Scoring System for Long-Term Prediction of End-Stage Liver Disease in Primary Biliary Cholangitis

Author

CARBONE, MARCO, Sharp, S, Flack, S, Paximadas, D, Spiess, K, Adgey, C, Griffiths, L, Lim, R, Trembling, P, Williamson, K, Wareham, N, Aldersley, M, Bathgate, A, Burroughs, A, Heneghan, M, Neuberger, J, Thorburn, D, Hirschfield, G, Cordell, H, Alexander, G, Jones, D, Sandford, R, Mells, G, Kirby, J, Taylor Robinson, S, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Williams, S, Grellier, L, Banim, P, Chilton, A, Curtis, H, Gess, M, Drake, I, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Marshall, E, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Das, D, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Null, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, Denise O'Donnell, N, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, Lynn O'Donohoe, N, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, Kordul, J., Carbone, M, Sharp, S, Flack, S, Paximadas, D, Spiess, K, Adgey, C, Griffiths, L, Lim, R, Trembling, P, Williamson, K, Wareham, N, Aldersley, M, Bathgate, A, Burroughs, A, Heneghan, M, Neuberger, J, Thorburn, D, Hirschfield, G, Cordell, H, Alexander, G, Jones, D, Sandford, R, Mells, G, Kirby, J, Taylor Robinson, S, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Williams, S, Grellier, L, Banim, P, Chilton, A, Curtis, H, Gess, M, Drake, I, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Marshall, E, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Das, D, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Null, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, Denise O'Donnell, N, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, Lynn O'Donohoe, N, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, and Kordul, J

Subjects
Male, medicine.medical_specialty, Prognostic variable, Cholangitis, Risk Assessment, Article, Biliary disease, End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, Primary biliary cirrhosis, Retrospective Studie, Internal medicine, medicine, Humans, Retrospective Studies, Hepatology, business.industry, Proportional hazards model, Cholangiti, Ursodeoxycholic Acid, Retrospective cohort study, Middle Aged, medicine.disease, Surgery, Algorithm, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, business, Risk assessment, Algorithms, Human
Abstract

The biochemical response to ursodeoxycholic acid (UDCA)—so-called “treatment response”—strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90). Conclusions: The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care. (Hepatology 2016;63:930–950)

Published
2015

12. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

Author

Krishna, B. A., Spiess, K., Poole, E. L., Lau, B., Voigt, S., Kledal, Thomas N, Rosenkilde, M. M., Sinclair, J. H., Krishna, B. A., Spiess, K., Poole, E. L., Lau, B., Voigt, S., Kledal, Thomas N, Rosenkilde, M. M., and Sinclair, J. H.

Abstract

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

Published
2017

13. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease

Author

Ji, S, Juran, B, Mucha, S, Folseraas, T, Jostins, L, Melum, E, Kumasaka, N, Atkinson, E, Schlicht, E, Liu, J, Shah, T, Gutierrez Achury, J, Boberg, K, Bergquist, A, Vermeire, S, Eksteen, B, Durie, P, Farkkila, M, Müller, T, Schramm, C, Sterneck, M, Weismüller, T, Gotthardt, D, Ellinghaus, D, Braun, F, Teufel, A, Laudes, M, Lieb, W, Jacobs, G, Beuers, U, Weersma, R, Wijmenga, C, Marschall, H, Milkiewicz, P, Pares, A, Kontula, K, Chazouillères, O, Invernizzi, P, Goode, E, Spiess, K, Moore, C, Sambrook, J, Ouwehand, W, Roberts, D, Danesh, J, Floreani, A, Gulamhusein, A, Eaton, J, Schreiber, S, Coltescu, C, Bowlus, C, Luketic, V, Odin, J, Chopra, K, Kowdley, K, Chalasani, N, Manns, M, Srivastava, B, Mells, G, Sandford, R, Alexander, G, Gaffney, D, Chapman, R, Hirschfield, G, de Andrade, M, Rushbrook, S, Franke, A, Karlsen, T, Lazaridis, K, Anderson, C, INVERNIZZI, PIETRO, Anderson, C., Ji, S, Juran, B, Mucha, S, Folseraas, T, Jostins, L, Melum, E, Kumasaka, N, Atkinson, E, Schlicht, E, Liu, J, Shah, T, Gutierrez Achury, J, Boberg, K, Bergquist, A, Vermeire, S, Eksteen, B, Durie, P, Farkkila, M, Müller, T, Schramm, C, Sterneck, M, Weismüller, T, Gotthardt, D, Ellinghaus, D, Braun, F, Teufel, A, Laudes, M, Lieb, W, Jacobs, G, Beuers, U, Weersma, R, Wijmenga, C, Marschall, H, Milkiewicz, P, Pares, A, Kontula, K, Chazouillères, O, Invernizzi, P, Goode, E, Spiess, K, Moore, C, Sambrook, J, Ouwehand, W, Roberts, D, Danesh, J, Floreani, A, Gulamhusein, A, Eaton, J, Schreiber, S, Coltescu, C, Bowlus, C, Luketic, V, Odin, J, Chopra, K, Kowdley, K, Chalasani, N, Manns, M, Srivastava, B, Mells, G, Sandford, R, Alexander, G, Gaffney, D, Chapman, R, Hirschfield, G, de Andrade, M, Rushbrook, S, Franke, A, Karlsen, T, Lazaridis, K, Anderson, C, INVERNIZZI, PIETRO, and Anderson, C.

Abstract

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC

Published
2017

14. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

Author

Krishna, B A, Spiess, K, Poole, E L, Lau, B, Voigt, S, Kledal, Thomas N, Rosenkilde, M M, Sinclair, J H, Krishna, B A, Spiess, K, Poole, E L, Lau, B, Voigt, S, Kledal, Thomas N, Rosenkilde, M M, and Sinclair, J H

Abstract

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

Published
2017

16. The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis

Author

Carbone, M, Sharp, S, Flack, S, Paximadas, D, Spiess, K, Adgey, C, Griffiths, L, Lim, R, Trembling, P, Williamson, K, Wareham, N, Aldersley, M, Bathgate, A, Burroughs, A, Heneghan, M, Neuberger, J, Thorburn, D, Hirschfield, G, Cordell, H, Alexander, G, Jones, D, Sandford, R, Mells, G, Kirby, J, Taylor Robinson, S, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Williams, S, Grellier, L, Banim, P, Chilton, A, Curtis, H, Gess, M, Drake, I, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Marshall, E, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Das, D, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Null, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, Denise O'Donnell, N, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, Lynn O'Donohoe, N, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, Kordul, J, CARBONE, MARCO, Kordul, J., Carbone, M, Sharp, S, Flack, S, Paximadas, D, Spiess, K, Adgey, C, Griffiths, L, Lim, R, Trembling, P, Williamson, K, Wareham, N, Aldersley, M, Bathgate, A, Burroughs, A, Heneghan, M, Neuberger, J, Thorburn, D, Hirschfield, G, Cordell, H, Alexander, G, Jones, D, Sandford, R, Mells, G, Kirby, J, Taylor Robinson, S, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Williams, S, Grellier, L, Banim, P, Chilton, A, Curtis, H, Gess, M, Drake, I, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Marshall, E, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Das, D, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Null, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, Denise O'Donnell, N, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, Lynn O'Donohoe, N, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, Kordul, J, CARBONE, MARCO, and Kordul, J.

Abstract

The biochemical response to ursodeoxycholic acid (UDCA)-so-called "treatment response"-strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90). Conclusions: The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care.

Published
2016

17. The future of antiviral immunotoxins

Author

Spiess, K., Høy Jakobsen, Mette, Kledal, Thomas N, Rosenkilde, Mette M., Spiess, K., Høy Jakobsen, Mette, Kledal, Thomas N, and Rosenkilde, Mette M.

Abstract

There is a constant need for new therapeutic interventions in a wide range of infectious diseases. Over the past few years, the immunotoxins have entered the stage as promising antiviral treatments. Immunotoxins have been extensively explored in cancer treatment and have achieved FDA approval in several cases. Indeed, the design of new anticancer immunotoxins is a rapidly developing field. However, at present, several immunotoxins have been developed targeting a variety of different viruses with high specificity and efficacy. Rather than blocking a viral or cellular pathway needed for virus replication and dissemination, immunotoxins exert their effect by killing and eradicating the pool of infected cells. By targeting a virus-encoded target molecule, it is possible to obtain superior selectivity and drastically limit the side effects, which is an immunotoxin-related challenge that has hindered the success of immunotoxins in cancer treatment. Therefore, it seems beneficial to use immunotoxins for the treatment of virus infections. One recent example showed that targeting of virus-encoded 7 transmembrane (7TM) receptors by immunotoxins could be a future strategy for designing ultraspecific antiviral treatment, ensuring efficient internalization and hence efficient eradication of the pool of infected cells, both in vitro and in vivo. In this review, we provide an overview of the mechanisms of action of immunotoxins and highlight the advantages of immunotoxins as future anti-viral therapies.

Published
2016

20. O080 : Early clinical features associated with long-term risk of transplantation in primary sclerosing cholangitis: Results from the UK-PSC consortium

Author

Goode, E.C., primary, Srivastava, B., additional, Clark, A.B., additional, Spiess, K., additional, Hirschfield, G.M., additional, Gelson, W.T.H., additional, Trivedi, P.J., additional, Mells, G.F., additional, Sandford, R.N., additional, Alexander, G.J., additional, Chapman, R.W., additional, and Rushbrook, S.M., additional

Published
2015
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21. Mikroelektronik 87

Author

Hoffmann, G., primary, Holzmann, D., additional, Jäger, F., additional, Riedling, K., additional, Schwuttke, G. H., additional, Pandelisev, K. A., additional, White, R. C., additional, Holzmann, H., additional, Kausel, W., additional, Nanz, G., additional, Selberherr, S., additional, Pötzl, H., additional, Leopold, H., additional, Röhrer, R., additional, Winkler, G., additional, Thurner, M., additional, Seiner, K., additional, Tritremmel, W., additional, Walther, G., additional, Schoitsch, Erwin, additional, Hertl, S., additional, Schaffar, G., additional, Schmidt, K., additional, Steinbrecher, H., additional, Voggenberger, F., additional, Windischhofer, W., additional, Turba, R., additional, Grabner, J., additional, Aberl, H., additional, Seifert, F., additional, Buschbeck, F., additional, Wallisch, K., additional, Eichtinger, Ch., additional, Wach, P., additional, Bittinger, W., additional, Kainz, A., additional, Jestl, M., additional, Beinstingl, W., additional, Berthold, K., additional, Köck, A., additional, Gornik, E., additional, Kloiber, G., additional, Kreid, F., additional, Schröcker, K. P., additional, Schrödl, M., additional, Brazda, E., additional, Niedrist, G., additional, Dietz, K., additional, Fey, P., additional, Frenkenberger, S., additional, Furtner, M., additional, Dejneka, B., additional, Goiser, A., additional, Sust, M., additional, Kowatsch, M., additional, Jorde, Ch., additional, Thallinger, G. G., additional, Mothwurf, E., additional, Schubert, E., additional, Steger, J., additional, Trzeba, E., additional, Awramow, I., additional, Pucher, R., additional, Auer, L. M., additional, Schuy, S., additional, Schima, H., additional, Huber, L., additional, Prodinger, A., additional, Schmallegger, H., additional, Thoma, H., additional, Stöhr, H., additional, Mayr, W., additional, Steiner, R., additional, Wiedenbauer, O., additional, List, G., additional, Wießpeiner, G., additional, Petsch, Th., additional, Doblhoff, G., additional, Kirchner, D., additional, Koudelka, O., additional, Gierlinger, A., additional, Ullrich, A., additional, Braune, B., additional, Horvat, H., additional, Mayer, U., additional, Gauby, A., additional, Richter, A., additional, Spiess, K. R., additional, Klösch, W., additional, Böck, N., additional, Rosenkranz, H., additional, Mitter, H., additional, Hengl, M., additional, Nussbaum, G., additional, Gutternigh, K., additional, Hahn, H., additional, Koutny, P., additional, Pühringer, K., additional, Schwabach, H., additional, Hirschler, M., additional, Haas, M., additional, Renner, A., additional, Bratengeyer, E., additional, Scholz-Nauendorff, C. C., additional, Lebutsch, K., additional, Volkmann, W., additional, Gerner, H., additional, Girsch, W., additional, Holle, J., additional, Kluger, P., additional, Meister, B., additional, Moritz, E., additional, Schwanda, G., additional, Prager, L., additional, Wieβpeiner, G., additional, Grübler, R., additional, Dorfer, E., additional, Oitzl, E., additional, Pribyl, W., additional, Bähring, M., additional, Harter, J., additional, and Sommer, D., additional

Published
1987
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23. Familienroman und Heilsgeschichte

Author

Spiess, Karl-Heinz, Spiess, K ( Karl-Heinz ), Kiening, Christian, Spiess, Karl-Heinz, Spiess, K ( Karl-Heinz ), and Kiening, Christian

Published
2009

29. [Phase-specific function of denial in type 1 diabetic patients after disease onset]

Author

Spiess K, Gabriele Sachs, Frischenschlager O, Moser G, and Prager R

Subjects
Adult, Blood Glucose, Glycated Hemoglobin, Male, Adolescent, Depression, Sick Role, Social Support, Denial, Psychological, Anxiety, Diabetes Mellitus, Type 1, Adaptation, Psychological, Humans, Patient Compliance, Female, Longitudinal Studies, Follow-Up Studies
Abstract

In a longitudinal study we examined 43 patients with type 1 diabetes one week after onset as well as 8 and 24 month later in order to analyze the psychological role of denial processes in correlation to metabolic functions. Only depression decreased over the studied period while coping and denial remained stable. However, the adaptive function of denial after onset with low anxiety, good coping and few complaints became maladaptive over the first two years and the correlation of denial with a centripetal kinship behavior loosened. The destructive effect of denial was indicated only by delayed requests for assistance while no correlation could be shown for phase-specific internal restructuring of the psychological function of denial to compliance and metabolic control.

Published
1994

34. [Effect of structured ambulatory training of patients with chronic respiratory tract diseases on the efficiency of long-term care]

Author

Haber P, Gabriele Sachs, Röggla G, Spiess K, and Schnack C

Subjects
Adult, Male, Vital Capacity, Sick Role, Middle Aged, Asthma, Self Care, Patient Education as Topic, Forced Expiratory Volume, Adaptation, Psychological, Humans, Female, Lung Diseases, Obstructive, Aged, Follow-Up Studies
Abstract

In spite of the availability and widespread use of a number of effective medications, the frequency of severe attacks of asthma bronchiale including those with fatal outcome has not decreased. One possible reason for this is the delay in therapeutic intervention of up to 30 minutes resulting either from transport time to a hospital or from the response time of mobile ambulance services. Treatment delays are also frequent co-factors for decreased well-being in non-emergency cases. Prompt initiation of countermeasures, regardless of time or place, can only be guaranteed when the patient himself is capable of carrying them out with the same expertise as his attending physician. Toward this end, a model patient-training program was investigated. The didactic goal of the training was to make the patient an expert in his chronic disease. The medical goal of the training was to improve the quality of a complex long-term therapy and with it, the patient's well-being and quality of life. The content of the training corresponded largely to that contained in a lecture series for medical students or physicians on the same subject. Style and choice of words (avoidance or explanation of medical terminology) was of course adapted to the lay-status of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1991

42. [The significance of psychosocial complaints in the initial interview--a study of unselected patients of an internal medicine/polyclinic university ambulatory service]

Author

Moser G, Kiss A, Gabriele Sachs, Spiess K, and Schwarzmeier J

Subjects
Adult, Male, Depressive Disorder, Adolescent, Sick Role, Middle Aged, Psychophysiologic Disorders, Interview, Psychological, Ambulatory Care, Humans, Female, Interpersonal Relations, Social Adjustment, Aged
Abstract

In clinical practice one is repeatedly confronted with patients, who report psycho-social problems during the first interview. In this study 128 patients have been examined in the outpatient clinic at the Department of Medicine 1 of the University Hospital in Vienna. The most important issue investigated was to clarify whether or not the psycho-social complaints expressed at the initial interview could be correlated with either functional disorders or somatic disease. Further we tried to determine whether or not the complaints influenced the course of the disease and gave any indication for the presence of a depressive disorder or complicated a somatic disorder by additional psychosomatic complaints. Our results indicate that the expression of psycho-social problems indeed correlates with stronger psychosomatically conditioned body dysfunctions, but do not sufficiently explain whether or not functional disease can be expected. However, the reported psycho-social problems result in a stronger inclination towards depressive mood and lead the patient to his/her own explanation how the illness has developed. Both facts are of importance for the patient-physician relationship and constitute an integral part of the (non-)compliance.

Published
1989

48. [Effectiveness of relaxation groups in patients with chronic respiratory tract diseases]

Author

Gabriele Sachs, Haber P, Spiess K, and Moser G

Subjects
Adult, Male, Adaptation, Psychological, Sick Role, Humans, Female, Lung Diseases, Obstructive, Middle Aged, Relaxation Therapy, Lung Volume Measurements, Combined Modality Therapy, Aged
Abstract

In the long-term treatment of patients with chronic respiratory diseases, patient education contributes significantly towards improving the effectiveness of conventional drugs in the treatment of asthma-specific complaints and anxiety, as well as playing a role in improved disease coping. The aim of this study was to verify whether relaxation training programs undertaken subsequent to patient education may have an additional effect with regard to both medical and psychological variables. Relaxation training encompasses the basic exercises of autogenics, as well as exercises of functional relaxation. 49 patients participated in the relaxation group (22 male, 27 female). The mean age was 50.5 +/- 16.5 years. The control group used was made up of 37 patients with chronic respiratory diseases (17 male, 20 female) who had received asthma education, but no further therapeutic intervention. Prior to and immediately after the relaxation training, the following investigations were undertaken: lung function, patient diary, Spielberger anxiety scale, Giessen list of complaints (modified and augmented) and Ziegler coping questionnaire. The linear rating scale model was used for measuring changes. The following significant changes were observed in the relaxation group as compared with the control group: decrease of trait fear, alleviation of asthma-specific complaints and asthma attacks, decrease in sleep disturbances and in morning coughing urge, reduction in the required quantities of controlled-dosage aerosol, and a modified attitude toward the disease in the sense of an improved subjective coping competence.(ABSTRACT TRUNCATED AT 250 WORDS)

49. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

Author

Krishna, B. A., Spiess, K., Poole, E. L., Lau, B., Voigt, S., Kledal, T. N., Rosenkilde, M. M., and Sinclair, J. H.

Subjects
Herpes virus, Antivirals, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik, 3. Good health
Abstract

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

50. Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

Author

Krishna, BA, Spiess, K, Poole, EL, Lau, B, Voigt, S, Kledal, TN, Rosenkilde, MM, and Sinclair, JH

Subjects
Cell Death, Genes, Viral, Recombinant Fusion Proteins, Stem Cells, Hematopoietic Stem Cell Transplantation, Lipopolysaccharide Receptors, Cytomegalovirus, Antigens, CD34, Viral Load, Endocytosis, Monocytes, 3. Good health, Virus Latency, Viral Proteins, Humans, Receptors, Chemokine, Virus Activation, Chemokines, Cells, Cultured, Disease Reservoirs
Abstract

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.

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