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Mel Berger, Mingyao Liu, Marc E Uknis, Maria Koulmanda
Limited availability of donor organs and risk of ischemia-reperfusion injury (IRI) seriously restrict organ transplantation. Therapeutics that can prevent or reduce IRI could potentially increase the number of transplants by increasing use of borderline organs and decreasing discards. Alpha-1 antitrypsin (AAT) is an acute phase reactant and serine protease inhibitor that limits inflammatory tissue damage. Purified plasma-derived AAT has been well tolerated in more than 30 years of use to prevent emphysema in AAT-deficient individuals...
April 1, 2018: American Journal of Transplantation
R A Montgomery, B J Orandi, L Racusen, A M Jackson, J M Garonzik-Wang, T Shah, E S Woodle, C Sommerer, D Fitts, K Rockich, P Zhang, M E Uknis
Antibody-mediated rejection (AMR) is typically treated with plasmapheresis (PP) and intravenous immunoglobulin (standard of care; SOC); however, there is an unmet need for more effective therapy. We report a phase 2b, multicenter double-blind randomized placebo-controlled pilot study to evaluate the use of human plasma-derived C1 esterase inhibitor (C1 INH) as add-on therapy to SOC for AMR. Eighteen patients received 20 000 units of C1 INH or placebo (C1 INH n = 9, placebo n = 9) in divided doses every other day for 2 weeks...
December 2016: American Journal of Transplantation
F Poppelaars, J Damman, E L de Vrij, J G M Burgerhof, J Saye, M R Daha, H G Leuvenink, M E Uknis, M A J Seelen
Complement activation is of major importance in numerous pathological conditions. Therefore, targeted complement inhibition is a promising therapeutic strategy. C1-esterase inhibitor (C1-INH) controls activation of the classical pathway (CP) and the lectin pathway (LP). However, conflicting data exist on inhibition of the alternative pathway (AP) by C1-INH. The inhibitory capacity of C1-INH for the CP is potentiated by heparin and other glycosaminoglycans, but no data exist for the LP and AP. The current study investigates the effects of C1-INH in the presence or absence of different clinically used heparinoids on the CP, LP and AP...
June 2016: Clinical and Experimental Immunology
Amy E DeZern, Marc Uknis, Xuan Yuan, Galina L Mukhina, Juan Varela, JoAnne Saye, Jeffrey Pu, Robert A Brodsky
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, hematopoietic stem cell disorder that manifests with a complement-mediated hemolytic anemia, bone marrow failure, and a propensity for thrombosis. These patients experience both intra- and extravascular hemolysis in the context of underlying complement activation. Currently eculizumab effectively blocks the intravascular hemolysis PNH. There remains an unmet clinical need for a complement inhibitor with activity early in the complement cascade to block complement at the classical and alternative pathways...
October 2014: Experimental Hematology
Audrey B Uknis
No abstract text is available yet for this article.
April 2014: Arthritis & Rheumatology
Marc A Riedl, William R Lumry, H Henry Li, Timothy J Craig, David Fitts, Ira Kalfus, Marc E Uknis
BACKGROUND: Laryngeal edema is a life-threatening manifestation of hereditary angioedema (HAE), an autosomal-dominant disorder caused by quantitative or functional C1 esterase inhibitor (C1 INH) deficiency. The preparation of nanofiltered C1 INH (C1 INH-nf) used in this study is indicated for routine prophylaxis against angioedema attacks in the United States and for treatment, preprocedure prevention, and routine prevention of HAE in Europe. The objective of this analysis was to evaluate the effectiveness and tolerability of C1 INH-nf when used for the treatment of laryngeal attacks...
November 2013: American Journal of Rhinology & Allergy
J A Grant, M V White, H H Li, D Fitts, I N Kalfus, M E Uknis, W R Lumry
Patients with hereditary angioedema (HAE) may have attacks triggered by dental, medical, or surgical procedures. This analysis evaluated the efficacy and safety of preprocedural administration of nanofiltered C1 esterase inhibitor (C1 INH-nf;human) for the prevention of HAE attacks during and after dental, medical, or surgical procedures. Data were reviewed retrospectively from two acute treatment trials in which at least 1000 U of C1 INH-nf was administered i.v. within 24 hoursbefore an emergency or noncosmetic medical, surgical, or dental procedure...
June 5, 2012: Allergy and Asthma Proceedings:
James W Baker, Timothy J Craig, Marc A Riedl, Aleena Banerji, David Fitts, Ira N Kalfus, Marc E Uknis
Data are limited on hereditary angioedema (HAE) in pregnant women and the safety and efficacy of therapies for treatment and prevention of HAE attacks during pregnancy. Prospective studies are unlikely given the rarity of HAE and ethical considerations regarding enrollment of pregnant female subjects in clinical trials. A retrospective analysis of clinical trial and compassionate-use data was conducted to identify subjects who received nanofiltered C1 esterase inhibitor (C1 INH-nf; human) during pregnancy. This study evaluates the efficacy and safety of human C1 INH-nf for treatment and prevention of HAE attacks in pregnant women...
March 2013: Allergy and Asthma Proceedings:
William Lumry, Michael E Manning, David S Hurewitz, Mark Davis-Lorton, David Fitts, Ira N Kalfus, Marc E Uknis
OBJECTIVES: To evaluate the use of Cinryze (nanofiltered C1-esterase inhibitor [C1 INH-nf]) for the acute management and prevention of hereditary angioedema attacks in the subgroup of children and adolescents who participated in 2 placebo-controlled and 2 open-label extension studies. STUDY DESIGN: In the acute-attack treatment studies, the efficacy of 1000 U of C1 INH-nf (with an additional 1000 U given 1 hour later if needed) was assessed based on the time to the start of symptomatic relief and the proportion of patients experiencing relief within 4 hours of therapy...
May 2013: Journal of Pediatrics
D J Winston, F Saliba, E Blumberg, M Abouljoud, J B Garcia-Diaz, J A Goss, L Clough, R Avery, A P Limaye, B G Ericzon, M Navasa, R I Troisi, H Chen, S A Villano, M E Uknis
Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease...
November 2012: American Journal of Transplantation
J Andrew Grant, Martha V White, H Henry Li, David Fitts, Ira N Kalfus, Marc E Uknis, William R Lumry
Patients with hereditary angioedema (HAE) may have attacks triggered by dental, medical, or surgical procedures. This analysis evaluated the efficacy and safety of preprocedural administration of nanofiltered C1 esterase inhibitor (C1 INH-nf; human) for the prevention of HAE attacks during and after dental, medical, or surgical procedures. Data were reviewed retrospectively from two acute treatment trials in which at least 1000 U of C1 INH-nf was administered i.v. within 24 hours before an emergency or noncosmetic medical, surgical, or dental procedure...
July 2012: Allergy and Asthma Proceedings:
S M Shahidullah, M M Hanafi, M Ashrafuzzaman, M A Hakim, M R Karim
Plant stature of a rice crop is an important selection criterion. As plant height is a quantitative trait it is influenced by environmental conditions. A field experiment was conducted with 40 rice genotypes to assess the fluctuation and stability of plant height in a series of 16 environmental situations. The effects of genotype (G), environment (E) and all the components of GxE interaction were highly significant. Among the genotypes, Jamai sohagi was extremely sensitive (bi = 1.37) to environmental changes, and indicating lowest adaptability over the environments...
November 2011: Journal of Environmental Biology
Martha Pavlakis, Khalid Khwaja, Didier Mandelbrot, Hongying Tang, James W Whiting, Marc I Lorber, Amitabh Gautam, Scott R Johnson, Marc E Uknis
BACKGROUND: The reasons for kidney allograft failure subsequent to pancreas after kidney (PAK) are multifactorial; therefore, we examined these factors to identify a meaningful risk assessment that could assist in patient selection. METHODS: Five transplant centers in New England collaborated for this multiinstitutional retrospective study of 126 PAK transplantation recipients who had a functioning pancreas allograft 7 days after transplantation. Host factors (age at pancreas transplant, gender, body weight, glomerular filtration rate at 3 months pre-PAK and at 3-, 6-, 9-, and 12-month post-PAK, presence of proteinuria, pre- or post-PAK kidney rejection, pancreas rejection, cytomegalovirus disease, and HbA1C at 6-month post-PAK) and transplant factors (time to PAK, use of induction antibody therapy, and combinations of immunosuppressive medications) were assessed in both univariate and multivariate analyses for the primary outcome of kidney allograft failure...
June 15, 2010: Transplantation
Gabor Bodonyi-Kovacs, Prabhakar Putheti, Miguel Marino, Yingyos Avihingsanon, Marc E Uknis, Anthony P Monaco, Terry B Strom, Martha Pavlakis
We have previously demonstrated that biomarkers of inflammation and immune activity detected within intraoperative renal transplant allograft biopsies are linked to adverse short-term post-transplantation clinical outcomes. Now we provide a post hoc analysis of our earlier data in the light of longer clinical follow-up. A total of 75 consecutively performed renal allografts were analyzed for gene expression of proinflammatory molecules, inflammation-induced adhesion molecules, and antiapoptotic genes expressed 15 minutes after vascular reperfusion to determine whether this analysis can aid in predicting long-term quality of renal function, proteinuria, graft loss, and death-censored graft...
May 2010: Human Immunology
Mario C Rico, Joanne M Manns, Jeffrey B Driban, Audrey B Uknis, Satya P Kunapuli, Raul A Dela Cadena
Thrombospondin-1 (TSP1/THBS1) plays a major role in the pathophysiology of rheumatoid arthritis (RA); however, its interface with the cytokine network involved in RA has not been delineated. Correlations were performed between plasma levels of TSP1 and selected cytokines from blood samples collected from 20 patients affected by RA and 13 healthy donors (control). Plasma levels of TSP1 and tissue growth factor beta (TGFbeta) were determined by standard enzyme-linked immunosorbent assay, and cytokines were measured by protein profiling rolling-circle amplification (RCA)...
August 2008: Translational Research: the Journal of Laboratory and Clinical Medicine
Jay A Fishman, Vincent Emery, Richard Freeman, Manuel Pascual, Lionel Rostaing, Hans J Schlitt, Dino Sgarabotto, Julian Torre-Cisneros, Marc E Uknis
BACKGROUND: Cytomegalovirus (CMV) infection of solid organ transplant (SOT) recipients causes both ''direct'' and ''indirect'' effects including allograft rejection, decreased graft and patient survival, and predisposition to opportunistic infections and malignancies. Options for CMV prevention include pre-emptive therapy, whereby anti-CMV agents are administered based on sensitive viral assays, or universal prophylaxis of all at-risk patients. Each approach has advantages and disadvantages in terms of efficacy, costs, and side effects...
March 2007: Clinical Transplantation
Francis L Weng, Anup M Patel, Rimda Wanchoo, Yasmin Brahmbhatt, Kezia Ribeiro, Marc E Uknis, Shamkant Mulgaonkar, A Scott Mathis
BACKGROUND: The optimal regimen for prophylaxis of cytomegalovirus (CMV) disease after kidney and/or pancreas transplantation remains unclear. We compared the effectiveness of three months of oral ganciclovir (3 g/day) versus low-dose valganciclovir (450 mg/day) for CMV prophylaxis. METHODS: We performed a retrospective cohort study of patients at our center who received kidney and/or pancreas transplants between January 2000 and April 2003. We used a Cox proportional hazards model to examine the relationship between baseline covariates, including type of CMV prophylaxis, and time to development of CMV disease...
February 15, 2007: Transplantation
Mario C Rico, Julian L Castaneda, Joanne M Manns, Audrey B Uknis, Irma M Sainz, Fayez F Safadi, Steve N Popoff, Raul A Dela Cadena
OBJECTIVE: To evaluate the effect of a thrombospondin 1 (TSP1)-derived peptide on inflammation and angiogenesis in an animal model of erosive arthritis and to assess the relationship between TSP1 and connective tissue growth factor (CTGF) in the pathophysiology of rheumatoid arthritis. METHODS: Erosive arthritis in Lewis rats was induced by peptidoglycan-polysaccharide (PG-PS). Animals were divided into four groups: (1) negative control and groups receiving, (2) no treatment, (3) treatment with a TSP1-derived peptide, and (4) treatment with a scrambled peptide...
May 2007: Journal of Cellular Physiology
E Asham, M E Uknis, C Rastellini, G Elias, L Cicalese
Following small bowel transplantation (SBTx), approximating the midline abdominal fascia can be problematic in patients with severely retracted abdominal cavities. We first report the use of acellular dermal matrix (ADM) for abdominal closure following living related SBTx. A 44-year-old woman with ultra-short gut syndrome secondary to multiple bowel resections received a 160-cm segmental intestinal graft from her daughter. The graft ileocolic vessels were anastomosed end to side to the inferior vena cava and distal aorta...
July 2006: Transplantation Proceedings
S P Bradley, M Pahari, M E Uknis, C Rastellini, L Cicalese
BACKGROUND: The cellular and histological events that occur during the regeneration process in invertebrates have been studied in the field of visceral regeneration. We would like to explore the molecular aspects of the regeneration process in the small intestine. The aim of this study was to characterize the gene expression profiles of the intestinal graft to identify which genes may have a role in regeneration of graft tissue posttransplant. METHODS: In a patient undergoing living related small bowel transplantation (LRSBTx) in our institution, mucosal biopsies were obtained from the recipient intestine and donor graft at the time of transplant and at weeks 1, 2, 3, and 6 posttransplant...
July 2006: Transplantation Proceedings
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