Marshall R. Posner
Beth Israel Deaconess Medical Center
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Featured researches published by Marshall R. Posner.
Journal of Immunology | 2004
Gerald B. Pier; Debra Boyer; Michael J. Preston; Fadie T. Coleman; Nicolas Llosa; Simone Mueschenborn-Koglin; Christian Theilacker; Hannah Goldenberg; Jeffrey Uchin; Gregory P. Priebe; Martha Grout; Marshall R. Posner; Lisa A. Cavacini
Two fully human mAbs specific for epitopes dependent on intact carboxylate groups on the C6 carbon of the mannuronic acid components of Pseudomonas aeruginosa alginate were found to promote phagocytic killing of both mucoid and nonmucoid strains as well as protection against both types of strains in a mouse model of acute pneumonia. The specificity of the mAbs for alginate was determined by ELISA and killing assays. Some strains of P. aeruginosa did not make detectable alginate in vitro, but in vivo protection against lethal pneumonia was obtained and shown to be due to rapid induction of expression of alginate in the murine lung. No protection against strains genetically unable to make alginate was achieved. These mAbs have potential to be passive therapeutic reagents for all strains of P. aeruginosa and the results document that alginate is a target for the proper type of protective Ab even when expressed at low levels on phenotypically nonmucoid strains.
Archive | 1997
Pedro M. Sanz-Altamira; Liam D. Spence; Mark S. Huberman; Marshall R. Posner; Glenn SteeleJr.; Laura J. Perry; Keith Stuart
PURPOSE: Metastatic involvement of the liver frequently determines the evolution of the clinical picture in colorectal cancer patients. We examined the efficacy and toxicity of chemoembolization in this setting, identifying prognostic factors to define patients most likely to benefit from the procedure. METHODS: Forty patients underwent chemoembolization of metastatic liver lesions from colorectal carcinoma. Selective angiography of the hepatic artery was performed to identify the feeding vessels of the metastatic lesions. The injected chemoemulsion consisted of 1,000 mg of 5-fluorouracil, 10 mg of mitomycin C, and 10 ml of ethiodized oil in a total volume of 30 ml. Gelfoam embolization then followed, until stagnation of blood flow was achieved. Patients were evaluated for response, overall survival, and toxicities. RESULTS: Overall median survival from date of first chemoembolization was ten months. Factors that predicted a longer median survival included favorable performance status (24 months), serum alkaline phosphatase and lactate dehydrogenase levels less than three times normal (24 and 12 months, respectively), and metastatic disease confined to the liver (14 months). Most patients tolerated the procedure well. The most common side effects were transient fevers, abdominal pain, and fatigue. Three patients died within one month from the procedure. CONCLUSION: This study suggests that chemoembolization of hepatic metastases in colorectal cancer should be further evaluated; it may be beneficial in patients who have failed systemic chemotherapy, have a good performance status, and have metastatic disease confined to the liver.
Journal of Clinical Investigation | 1993
David C. Montefiori; Barney S. Graham; Jing Zhou; R A Bucco; David H. Schwartz; Lisa A. Cavacini; Marshall R. Posner
Sera from 11 volunteers immunized with a recombinant HIV-1 gp160-expressing vaccinia virus (HIVAC-1e; Oncogen/Bristol-Myers Squibb, Seattle, WA) and boosted with baculovirus-derived rgp160 (VaxSyn; MicroGeneSys, Inc., Meriden, CT) were evaluated for functional serum antibodies and their epitopes. Sera obtained prior to boosting had undetectable HIV-1-specific IgG and neutralizing activity, and did not block HIV-1 from binding or fusing to CD4+ MT-2 cells. 14 d after boosting, sera from each volunteer contained HIV-1-specific IgG titers of 1:40 to 1:1,280. Five of these sera also contained neutralizing antibodies, where most or all neutralizing activity was blocked by a synthetic peptide corresponding to amino acids 307-330 of the V3 loop of gp120, indicating that neutralizing antibodies were mostly V3 loop-specific. All sera obtained after boosting contained HIV-1 binding/fusion-inhibition antibodies, and a significant portion of their activity was blocked by the V3 loop peptide, a result consistent with the presence of antibodies against the region of the V3 loop that participates in fusion. Three sera with V3 loop-specific neutralizing and fusion-inhibition antibodies were studied further. In competitive antibody binding experiments, antibodies reactive with the conformation-dependent, CD4 binding site of gp120 were undetectable in each serum. When evaluated in combination with a monoclonal antibody to the CD4 binding site of gp120, two sera demonstrated synergism in neutralizing assays, and all three sera demonstrated synergism in binding/fusion-inhibition assays, further indicating that the functional antibodies were primarily V3 loop-specific. The synergism also suggests that a vaccine that elicits strong serum antibody responses to both regions of gp120 may improve the potential for inducing protective immunity.
Pharmacotherapy | 1995
Karen Marchbanks; Michael N. Dudley; Marshall R. Posner; James Darnowski
Study Objective. To investigate the pharmacokinetics and pharmacodynamics of high‐dose intravenous zidovudine (ZDV).
PLOS ONE | 2016
Agnes Lo; Xuming Mao; Eric M. Mukherjee; Christoph T. Ellebrecht; Xiaocong Yu; Marshall R. Posner; Aimee S. Payne; Lisa A. Cavacini
Pemphigus vulgaris (PV) is characterized by IgG1 and IgG4 autoantibodies to desmoglein (Dsg) 3, causing suprabasal blistering of skin and mucous membranes. IgG4 is the dominant autoantibody subclass in PV and correlates with disease activity, whereas IgG1 can be associated with remittent disease. It is unknown if switching the same variable region between IgG4 and IgG1 directly impacts pathogenicity. Here, we tested whether three pathogenic PV monoclonal antibodies (mAbs) from three different patients demonstrate differences in antigen affinity, epitope specificity, or pathogenicity when expressed as IgG1 or IgG4. F706 anti-Dsg3 IgG4 and F779 anti-Dsg3 IgG1, previously isolated as heterohybridomas, and Px43, a monovalent anti-Dsg3/Dsg1 IgG antibody isolated by phage display, were subcloned to obtain paired sets of IgG1 and IgG4 mAbs. Using ELISA and cell surface staining assays, F706 and F779 demonstrated similar antigen binding affinities of IgG1 and IgG4, whereas Px43 showed 3- to 8-fold higher affinity of IgG4 versus IgG1 by ELISA, but identical binding affinities to human skin, perhaps due to targeting of a quaternary epitope best displayed in tissues. All 3 mAb pairs targeted the same extracellular cadherin (EC) domain on Dsg3, caused Dsg3 internalization in primary human keratinocytes, and caused suprabasal blisters in human skin at comparable doses. We conclude that switching IgG1 and IgG4 subclasses of pathogenic PV mAbs does not directly affect their antigen binding or pathogenic properties.
Journal of Immunology | 2007
Gerald B. Pier; Debra Boyer; Michael J. Preston; Fadie T. Coleman; Nicolas Llosa; S. Mueschenborn-Koglin; Christian Theilacker; H. Goldenberg; J. Uchin; Gregory P. Priebe; Martha Grout; Marshall R. Posner; Lisa A. Cavacini
Analysis of the nucleotide and amino acid sequences indicated that clones F428 and F429 contained the same H chain V region but different L chain V region, whereas clone F431 had a distinct H chain V region but shared the L chain V region of clone F428 (GenBank accession numbers: AY626661, IGLV-J of mAbs F428 and F431; AY626662, IGLV-J of mAb F429; AY626664, IGHV-D-J of mAbs F428 and F429; and AY626663, IGHV-D-J of mAb F431).
Journal of Acquired Immune Deficiency Syndromes | 1993
Marshall R. Posner; Lisa A. Cavacini; Emes Cl; Power J; Byrn R
Diseases of The Colon & Rectum | 1997
Pedro M. Sanz-Altamira; Liam D. Spence; Mark S. Huberman; Marshall R. Posner; Glenn Steele; Laura J. Perry; Keith Stuart
Journal of Immunology | 1995
Lisa A. Cavacini; Emes Cl; Power J; F D Desharnais; Mark Duval; David C. Montefiori; Marshall R. Posner
Journal of Acquired Immune Deficiency Syndromes | 1993
Lisa A. Cavacini; Emes Cl; Power J; Buchbinder A; Susan Zolla-Pazner; Marshall R. Posner