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5. Lifelong effect of therapy in young patients with the cOL4A5 alport missense variant p.(Gly624Asp): a prospective cohort study

Author

Boeckhaus, J., Hoefele, J., Riedhammer, K.M., Nagel, M., Beck, B., Choi, M., Gollasch, M., Bergmann, C., Sonntag, J.E., Troesch, V., Stock, J., and Gross, O.

Subjects
Cardiovascular and Metabolic Diseases
Abstract

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEis) have evolved as a first-line therapy for delaying end-stage renal failure (ESRF) in Alport syndrome. The present study tested the hypothesis of a superior nephroprotective potential of an early ACEi intervention, examining a cohort with the COL4A5 missense variant p.(Gly624Asp). METHODS: In this observational cohort study (NCT02378805), 114 individuals with the identical gene-variant were explored for "age at ESRF" and "life-expectancy" in correlation with treatment as endpoints. RESULTS: All 13 untreated hemizygous patients developed ESRF (mean age 48.9+/-13.7 years) as did three very late treated hemizygotes (51.7+/-4.2 years), with a mean life-expectancy of 59.2+/-9.6 years. All 28 earlier (eGFR 60 ml/min or higher) treated hemizygous patients were still alive and still had not reached ESRF. Therapy minimized the annual loss of their glomerular filtration rate, similar to the annual loss in healthy individuals. Out of 65 heterozygotes, 4 untreated individuals developed ESRF at an age of 53.3+/-20.7 years. None of the treated heterozygous females developed ESRF. CONCLUSIONS: For the first time, this study shows that in Alport syndrome, early therapy in individuals with missense variants might have the potential to delay renal failure for their lifetime and thus to improve life-expectancy and quality of life without the need for renal replacement therapy. Some treated patients have reached retirement age with still-functioning kidneys whereas untreated relatives have already reached ESRF at the same or younger age. Thus, in children with glomerular hematuria, early testing for Alport-related gene variants could lead to timely nephroprotective intervention.

Published
2022

6. Study on Technical Parameters and Suitability of Platinum-Based Metallic Glasses for Jewellery Applications.

Author

Schmitt, L.-Y., Neuber, N., Eisenbart, M., Ciftci, L., Gross, O., Klotz, U. E., and Busch, R.

Subjects
JEWELRY making, METALLIC glasses, CORROSION resistance, PLATINUM alloys, ABRASION resistance, MICROCRACKS
Abstract

Jewellery-specific standardised tests as well as bulk metallic glass (BMG)-specific testing methods were performed on a series of platinumbased BMGs with and without phosphorus, to evaluate their suitability as jewellery items. Their mechanical properties (elasticity, Young's modulus and yield stress) were determined by three-point beam bending measurements. Hardness, wear and corrosion resistance were tested in comparison to state-of-the-art crystalline platinum-based jewellery alloys. The platinum-BMG alloys exhibit elastic elongation of about 2%. Compared to conventional crystalline platinum-alloys, their fracture strength of ca. 2 GPa and their hardness of ca. 450 HV1 is four and two times higher, respectively. However, the BMGs show less abrasion resistance in the pinon- disc test than the conventional benchmark alloys due to adhesive wear and microcracking. Regarding the corrosion resistance in simulated body fluids, the BMG alloys reveal a slightly higher release of metals, while the tarnishing behaviour is comparable to the benchmark alloys. The phosphorus-free platinum-BMG alloy showed pronounced tarnishing during exposure to air at elevated temperature. The outstanding thermoplastic formability, a special feature of amorphous metals that can be crucial for enabling novel and filigree designs, was determined and quantified for all BMG alloys. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Management of Lupus Nephritis

Author

Merkel F, Gross O, and Weber M

Subjects
Systemic lupus erythematosus, Autoimmunity, Immunosuppressive therapy, Lupus nephritis, Glomerulonephritis., Medicine
Abstract

Summary : Renal disease is common in systemic lupus erythematosus (SLE) and significantly influences patient prognosis. Immunosuppressive therapy has markedly improved outcome, however, it increases the risk of infection and cancer induction. Although several therapeutic regimens have proved to be effective in controlling lupus nephritis (LN), optimal therapy is still a matter of discussion. The following review summarizes our current knowledge in treating LN and discusses new aspects in pathogenesis. Hopefully, continuing progress in uncovering details about the pathogenesis of SLE might lead to more disease-specific approaches to treat the underlying immunological disorder.

Published
2000

16. Contributions to the Theory of Games (AM-28), Volume II

Author

ARROW, K. J., BARANKIN, E. W., BLACKWELL, D., BOTT, R., DALKEY, N., DRESHER, M., GALE, D., GILLIES, D. B., GLICKSBERG, I., GROSS, O., KARLIN, S., KUHN, H. W., MAYBERRY, J. P., MILNOR, J. W., MOTZKIN, T. S., VON NEUMANN, J., RAIFFA, H., SHAPLEY, L. S., SHIFFMAN, M., STEWART, F. M., THOMPSON, G. L., THRALL, R. M., Kuhn, H. W., Tucker, A. W., ARROW, K. J., BARANKIN, E. W., BLACKWELL, D., BOTT, R., DALKEY, N., DRESHER, M., GALE, D., GILLIES, D. B., GLICKSBERG, I., GROSS, O., KARLIN, S., KUHN, H. W., MAYBERRY, J. P., MILNOR, J. W., MOTZKIN, T. S., VON NEUMANN, J., RAIFFA, H., SHAPLEY, L. S., SHIFFMAN, M., STEWART, F. M., THOMPSON, G. L., THRALL, R. M., Kuhn, H. W., and Tucker, A. W.

Published
2016
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17. Contributions to the Theory of Games (AM-39), Volume III

Author

BERGE, C., BERKOVITZ, L. D., DUBINS, L. E., EVERETT, H., FLEMING, W. H., GALE, D., GILLETTE, D., GROSS, O., HANNAN, J. F., HOLLADAY, J. C., ISBELL, J. R., KARLIN, S., KEMENY, J. G., MILNOR, J., OXTOBY, J. C., RABIN, M. O., RESTREPO, R., SCARF, H. E., SHAPLEY, L. S., SION, M., THOMPSON, G. L., WALDEN, W., WOLFE, P., Dresher, M., Tucker, A. W., Wolfe, P., BERGE, C., BERKOVITZ, L. D., DUBINS, L. E., EVERETT, H., FLEMING, W. H., GALE, D., GILLETTE, D., GROSS, O., HANNAN, J. F., HOLLADAY, J. C., ISBELL, J. R., KARLIN, S., KEMENY, J. G., MILNOR, J., OXTOBY, J. C., RABIN, M. O., RESTREPO, R., SCARF, H. E., SHAPLEY, L. S., SION, M., THOMPSON, G. L., WALDEN, W., WOLFE, P., Dresher, M., Tucker, A. W., and Wolfe, P.

Published
2016
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18. Advances in Game Theory. (AM-52)

Author

AUMANN, R. J., MYCIELSKI, J., BERKOVITZ, L. D., NERING, E. D., DAVIS, M., NIKAIDO, H., FLEMING, W. H., OWEN, G., GALMARINO, A. R., PELEG, B., GROSS, O., RADSTROM, H., HARSANYI, J. C., RESTREPO, R. A., HEBERT, M., ROSENFELD, J. L., ISBELL, J. R., RYLL-NARDZEWSKI, C., JENTZSCH, G., SELTEN, R., JOHNSON, S. M., SHAPLEY, L. S., MASCHLER, M., STEARNS, R. E., MIYASAWA, K., ZACHRISSON, L. E., Dresher, M., Shapley, L. S., Tucker, A. W., AUMANN, R. J., MYCIELSKI, J., BERKOVITZ, L. D., NERING, E. D., DAVIS, M., NIKAIDO, H., FLEMING, W. H., OWEN, G., GALMARINO, A. R., PELEG, B., GROSS, O., RADSTROM, H., HARSANYI, J. C., RESTREPO, R. A., HEBERT, M., ROSENFELD, J. L., ISBELL, J. R., RYLL-NARDZEWSKI, C., JENTZSCH, G., SELTEN, R., JOHNSON, S. M., SHAPLEY, L. S., MASCHLER, M., STEARNS, R. E., MIYASAWA, K., ZACHRISSON, L. E., Dresher, M., Shapley, L. S., and Tucker, A. W.

Published
2016
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23. Abstracts of papers presented at the United States/Israel bard workshop on new targets for insect management in crop protection

Author

Masler, E. P., Kelly, T. J., Menn, J. J., Nachman, R. J., Holman, G. M., Zitnan, D., Takeda, M., Sauman, I., Sehnal, F., Segal, D., Altaratz, Michal, Richard, D. S., Gilbert, L. I., Applebaum, S. W., Shaaya, E., Lehmberg, E., Schooley, D. S., Ferenz, H. -J., Raina, A. K., Altstein, Miriam, Gazit, Y., Dunkelblum, E., Rafaeli, Ada, Hirsch, J., Soroker, Victoria, Kamensky, B., Shani, A., Ujvary, I., Dickens, J. C., Kamm, J. A., McDonough, L. M., Mazor, Michal, Kehat, M., Hefetz, A., Bar-Zakay, I., Peleg, B. A., Tumlinson, J. H., Casida, J. E., Cole, L. C., Deng, Y. L., Palmer, C. J., Hollingworth, R. M., Orr, Nailah, Orr, G. L., Eldefrawi, M. E., Eldefrawi, Amira T., Prestwich, G. D., Zlotkin, E., Eitan, M., Fowler, E., Moyer, M., Adams, M. E., Gordon, Dalia, Moskowitz, H., Handler, A. M., Gomez, S. P., O’Brochta, D. A., Raccah, B., Gal-On, A., Antignus, Y., Federici, B. A., Miller, L. K., Tomalski, M. D., O’Reilly, D. R., Eldridge, J. R., Gross, O., Tussen, P., Tal, J., Ward, V., Umetsu, T., Possee, R., McCutchen, B. F., Maeda, S., Ichinose, R., Harshman, L., Choudary, P., Beethan, J., Bonning, B., Hammock, B. D., Cohen, E., Ishaaya, I., Yamamoto, I., Yawetz, A., Zook-Rimon, Z., Dotan, A., Aharonson, N., Katan, J., Mingelgrin, U., Gerstl, Z., Muszkat, Lea, Bir, Lina, and Ascher, K. R. S.

Published
1991
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29. Advances and unmet needs in genetic, basic and clinical science in Alport syndrome::report from the 2015 International Workshop on Alport Syndrome

Author

Gross, O, Kashtan, CE, Rheault, MN, Flinter, F, Savige, J, Miner, JH, Torra, R, Ars, E, Deltas, C, Savva, I, Perin, L, Renieri, A, Ariani, F, Mari, F, Baigent, C, Judge, P, Knebelman, B, Heidet, L, Lagas, S, Blatt, D, Ding, J, Zhang, Y, Gale, DP, Prunotto, M, Xue, Y, Schachter, AD, Morton, LC, Blem, J, Huang, M, Liu, S, Vallee, S, Renault, D, Schifter, J, Skelding, J, Gear, S, Friede, T, Turner, AN, and Lennon, R

Subjects
Collagen Type IV, nephroprotection, Podocytes, Reviews, Nephritis, Hereditary, Genetic Therapy, Quality Improvement, hereditary kidney disease, Mutation, Animals, Humans, Alport syndrome, chronic kidney disease, guidelines, Needs Assessment
Abstract

Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the alpha 3 alpha 4 alpha 5(IV) collagen heterotrimer. AS is rare, but it accounts for > 1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis.

Published
2016
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32. Corrections

Author

Masler, E. P., Kelly, T. J., Menn, J. J., Nachman, R. J., Holman, G. M., Zitnan, D., Takeda, M., Sauman, I., Sehnal, F., Segal, D., Altaratz, Michal, Richard, D. S., Gilbert, L. I., Applebaum, S. W., Shaaya, E., Lehmberg, E., Schooley, D. S., Ferenz, H. -J., Raina, A. K., Altstein, Miriam, Gazit, Y., Dunkelblum, E., Rafaeli, Ada, Hirsch, J., Soroker, Victoria, Kamensky, B., Shani, A., Ujvary, I., Dickens, J. C., Kamm, J. A., McDonough, L. M., Mazor, Michal, Kehat, M., Hefetz, A., Bar-Zakay, I., Peleg, B. A., Tumlinson, J. H., Casida, J. E., Cole, L. C., Deng, Y. L., Palmer, C. J., Hollingworth, R. M., Orr, Nailah, Orr, G. L., Eldefrawi, M. E., Eldefrawi, Amira T., Prestwich, G. D., Zlotkin, E., Eitan, M., Fowler, E., Moyer, M., Adams, M. E., Gordon, Dalia, Moskowitz, H., Handler, A. M., Gomez, S. P., O’Brochta, D. A., Raccah, B., Gal-On, A., Antignus, Y., Federici, B. A., Miller, L. K., Tomalski, M. D., O’Reilly, D. R., Eldridge, J. R., Gross, O., Tussen, P., Tal, J., Ward, V., Umetsu, T., Possee, R., McCutchen, B. F., Maeda, S., Ichinose, R., Harshman, L., Choudary, P., Beethan, J., Bonning, B., Hammock, B. D., Cohen, E., Ishaaya, I., Yamamoto, I., Yawetz, A., Zook-Rimon, Z., Dotan, A., Aharonson, N., Katan, J., Mingelgrin, U., Gerstl, Z., Muszkat, Lea, Bir, Lina, and Ascher, K. R. S.

Published
1991
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34. Inhibitor of apoptosis (IAP) proteins limit RIP3 dependent IL-1 activation

Author

Vince, J E, Wong, W Wei-Lynn, Gentle, I E, Lawlor, K E, Allam, R, O'Reilly, L, Mason, K, Gross, O, Ma, S, Guarda, G, Anderton, H, Castillo, R, Häcker, G, Silke, J, Tschopp, J, and University of Zurich

Subjects
2403 Immunology, 2723 Immunology and Allergy, 570 Life sciences, biology, 610 Medicine & health, 2725 Infectious Diseases, 10263 Institute of Experimental Immunology
Published
2012

36. Interstitial inflammation in Alport syndrome

Author

Jedlicka, J, Soleiman, A, Draganovici, D, Mandelbaum, J, Ziegler, U, Regele, H, Wüthrich, R P, Gross, O, Anders, H J, Segerer, S, University of Zurich, and Segerer, S

Subjects
2734 Pathology and Forensic Medicine, 570 Life sciences, biology, 610 Medicine & health, 10035 Clinic for Nephrology, 10024 Center for Microscopy and Image Analysis
Published
2010
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37. Generation and analysis of card9-deficient mice

Author

Groß, O.

Abstract

Fungal infections are increasing worldwide with the dramatic rise in immunodeficiencies including AIDS. However, the immune responses to such infections remain poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for fungal cell wall components. In this work, Card9 was identified as a key transducer of Dectin-1 signaling. Card9 controls Dectin-1 mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates via Bcl10/Malt1 fungus-induced NF-κB activation. Card9-deficient mice have been generated, which show severe defects in the immune response to the pathogenic yeast Candida albicans. Furthermore, Card9 controls the activation of adaptive immune responses against fungal infections. These results represent a potential basis for the development of therapeutic strategies for the specific manipulation of anti-fungal immune responses.

Published
2008

43. X-Linked Alport Syndrome: Natural History and Genotype-Phenotype Correlations in Girls and Women Belonging to 195 Families: A 'European Community Alport Syndrome Concerted Action' Study

Author

Jais, Jp, Knebelmann, B, Giatras, I, DE MARCHI, Mario, Rizzoni, Gf, Renieri, A, Weber, M, Gross, O, Netzer, Ko, Flinter, F, Pirson, Y, Dahan, K, Wieslander, J, Persson, U, Tryggvason, K, Martin, P, Hertz, Pm, Schrder, C, Sanak, M, Carvalho, Mf, Saus, J, Antignac, C, and AND GUBLER MC, SMEETS H.

Subjects
Alport Syndrome, glomerular basement membrane, genotype-phenotype correlations, mutation diagnosis, type IV collagen, end stage renal disease
Published
2003

48. Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase C inducer bryostatin

Author

Sredni, B, Kalechman, Y, Albeck, M, Gross, O, Aurbach, D, Sharon, P, Sehgal, S N, Gurwith, M J, and Michlin, H

Subjects
Male, Mice, Inbred BALB C, Tumor Necrosis Factor-alpha, Drug Synergism, Ethylenes, Bryostatins, Biological Factors, Interferon-gamma, Lactones, Mice, Adjuvants, Immunologic, Leukocytes, Mononuclear, Animals, Cytokines, Humans, Interleukin-2, Macrolides, Cell Division, Cells, Cultured, Research Article
Abstract

AS101, a synthetic organotellurium compound, was found to have immunomodulating properties by initiation of cytokine production in vitro and in vivo. Phase I/II clinical trials currently in progress on AIDS and cancer patients treated with AS101 show significant increases in various immunological parameters, with minimal toxicity. Recently, AS101 and the protein kinase C (PKC) inducer, phorbol myristate acetate (PMA), were shown to synergize in the secretion of interleukin-2 (IL-2) and colony-stimulating factor (CSF) in vitro, by human and mouse lymphoid cells. The bryostatins, a group of natural macrocyclic lactones isolated from marine invertebrates (Bugula neritina) have been reported to be potent PKC activators with no tumour promoting activity. In this study, we investigated the synergistic effect of AS101 and a partially purified preparation of bryostatin on the production of several cytokines. Our data confirm the presence of synergism, which greatly enhances cell proliferation, IL-2, tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) secretion by human mononuclear cells (MNC) and the production of IL-2 and TNF by mouse cells. The absence of tumour-promoting activity of the bryostatins makes them particularly good candidates, in combination with AS101, for immunomodulation in vivo in clinically immunosuppressed conditions.

Published
1990

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