Publications by authors named "Nudelman E"

Following the outbreak of the COVID-19 pandemic, the U.S. government declared a state of emergency and many applied behavior analysis clinics temporarily closed.

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In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-galactosidases (CAZy GH110) with highly restricted substrate specificity and neutral pH optimum (Liu, Q. P., Sulzenbacher, G.

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Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical practice has been the lack of efficient glycosidase enzymes. Here we report two bacterial glycosidase gene families that provide enzymes capable of efficient removal of A and B antigens at neutral pH with low consumption of recombinant enzymes.

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De novo production of phosphatidic acid (PA) in tumor cells is required for phospholipid biosynthesis and growth of tumor cells. In addition, PA production by phospholipase D has been cited among the effects of certain oncogenes and growth factors. In this report, it has been demonstrated that enhanced phospholipid metabolism through PA in tumor cells can be exploited pharmacologically for development of anticancer agents, such as CT-2584, a cancer chemotherapeutic drug candidate currently in Phase II clinical trials.

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An improvement of current methods is needed for simple, rapid, and precise quantification of cellular lipids, including rare species of biologically active cellular lipids, such as phosphatidic acid (PA) and diradylglycerol (DG). In addition, further analysis of hydrolyzed acyl chains from these species by methods such as gas chromatography requires complete separations. Methods have been developed for the quantification of neutral lipids and several phospholipids extracted from mammalian cells and sera.

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Lisofylline (LSF), a novel anti-inflammatory compound that modulates stress-associated changes in lipid metabolism, is under development to modify toxicity for patients undergoing dose-intensive cytotoxic therapy for neoplasia and to prevent multiorgan failure and acute respiratory distress syndrome after oxidative injury. The present investigation, a component of a pharmacokinetics study, was performed to assess the effect of LSF on serum-free fatty acids (FFA). LSF was administered at doses of either 1, 2 or 3 mg/kg every 24 hr for 3 days by 10 min intravenous infusion to 12 healthy volunteers, followed 24 hr later by a single oral dose of 6 mg/kg, which was determined not to be bioavailable.

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Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acetyltransferase (EC 2.3.

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Phosphatidic acid (PA) is a phospholipid involved in signal transduction and in glycerolipid biosynthesis. CDP-diacylglycerol synthase (CDS) or CTP:phosphatidate cytidylyltransferase (EC 2.7.

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An IgM human monoclonal antibody (human MAb) was generated by fusing lymph node cells isolated from a surgical specimen of malignant melanoma with the heteromyeloma cell line SHMD-33. The antibody, designated 7c11.e8, reacted with surface antigens on human melanoma cells as shown by live cell immunofluorescence and absorption assays.

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We established a mouse monoclonal antibody (Mab) KM93 which recognized sialyl Le(x)-carbohydrate epitope determined by solid phase radioimmunoassay using a panel of authentic glycolipids. The specificity of KM93 was similar to another anti-sialyl Le(x) Mab CSLEX-1 established previously, and different from that of Mab FH6 which recognized sialyl Le(x)-i (sialyl dimeric Le(x)). In a further study, however, we found that KM93 reacted with some glycolipids much more strongly than CSLEX-1 did on thin-layer chromatography (TLC) plates.

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Women with a history of recurrent Escherichia coli urinary tract infections (UTIs) are two to three times more likely to be nonsecretors of histo-blood group antigens than are women without such a history. Further, uroepithelial cells from women who are nonsecretors show enhanced adherence of uropathogenic E. coli compared with cells from secretors.

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A glycosphingolipid component of human brain, having long-chain cyclic acetals, has been isolated and characterized. This compound incorporates a novel type of natural glycan modification, in which a long-chain aliphatic aldehyde is conjugated through a cyclic acetal (plasmal) linkage to the galactosyl moiety of cerebroside. In addition to components normally observed by gas chromatography-mass spectrometry (GC-MS) following methanolysis of cerebroside (fatty acid methyl esters, methyl alpha- and beta-galactosides, sphingosine), this compound produced 16:0, 18:0, and 18:1 fatty aldehydes, unequivocally identified as their enol methyl ether derivatives.

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Through a systematic examination of basic (cationic) lipids separated on Folch's lower phase from extracts of human brain by cation exchange chromatography on carboxymethyl Sephadex in a chloroform/methanol mixture, followed by successive chromatographies on Florisil and Iatrobeads columns, five compounds of basic lipids were separated. Two major unknown compounds A and B and a minor unknown compound C were separated, in addition to minor compounds sphingosine and N,N-dimethylsphingosine. This paper describes the isolation and chemical characterization of major unknown compounds A and B, which were found only in the white matter but not in the gray matter of the human brain.

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Phenotypic expression of sialylated Lewis(x) antigen by means of the monoclonal antiserum SNH3 was studied in 87 livers, which included normal and steatotic livers and livers with chronic persistent and chronic active hepatitis, alcoholic hepatitis, allograft rejection, focal nodular hyperplasia, hepatocellular carcinoma, cholangiocarcinoma, metastatic carcinoma, cirrhosis of various causes (autoimmune, alcoholic, viral, drug induced, Wilson's disease, and primary biliary cirrhosis). The biotin-streptavidin-peroxidase method was used on formaldehyde-fixed, paraffin-embedded sections. Sialylated Lewis(x) antigen was not demonstrated in normal livers.

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GMP-140 (CD62; PADGEM) is a member of the selectin family expressed highly at the surface of platelets and endothelial cells by agonists such as thrombin or phorbol esters. Previous studies indicate that the lectin domain of GMP-140 recognizes sialosyl-Le(x) (SLex) and to a lesser extent Le(x) (Polley MJ, et al., Proc Natl Acad Sci USA 88:6224, 1991).

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Classic galactosemia, an inborn error of human galactose metabolism, is characterized by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). The current model for the pathophysiology of this disease ascribes most of its symptoms to the toxicity of intracellular galactose-1-phosphate (Gal-1-P), one of the substrates of GALT which accumulates in the untreated disease state. Recently, a reduction in the intracellular concentration of UDP-Gal (uridine diphosphogalactose), one of the products of GALT, has been described in treated galactosemic patients.

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The leukocyte receptor CD62, which is expressed on activated platelets and endothelial cells, is shown to mediate cell adhesion by binding a sialylated carbohydrate structure, sialyl-Lewis x, found on neutrophils, monocytes, and tumor cells. This structure has previously been identified as the ligand for another member of the LEC-CAM family of cell adhesion molecules, endothelial cell-leukocyte adhesion molecule 1, which also binds neutrophils and monocytes. The results demonstrate that although the two LEC-CAMs differ in their biological activities by their distribution and mode of expression, they are capable of mediating cell adhesion by recognition of the same carbohydrate ligand.

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Glycolipid extracts from various human cancer tissues and cell lines showed the presence of a slow-migrating glycolipid component which was strongly reactive with monoclonal antibody (mAb) NCC-ST-421 (raised against human gastric adenocarcinoma) and weakly cross-reactive with anti-Lea mAbs. The slow-migrating glycolipid was isolated from human colonic adenocarcinoma cell line Colo205 grown in nude mice, and was purified by high-performance liquid chromatography followed by preparative thin-layer chromatography. Its structure was elucidated by sequential enzymatic degradation and thin-layer chromatography immunostaining of the degradation products with various mAbs, 1H NMR spectroscopy, positive-ion fast atom bombardment mass spectrometry, and methylation analysis.

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Immunochemical studies of human colorectal carcinoma with various monoclonal antibodies against Le(X)-related carbohydrate antigens previously revealed that the amount of sialyl-dimeric Le(X) antigen (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-R: SLX) associated with metastatic lesions was greater than in the primary tumors. To assess whether an experimental model can be used to study the direct relationship between this carbohydrate antigen and the tumor cell's metastatic behavior, we selected variant cells with increased surface SLX from established human colon carcinoma cell line HT-29. The cells in the upper 5% or lower 5% population in fluorescence intensity after reacting with a monoclonal antibody, FH6, were retrieved separately by a fluorescence-activated cell sorter and propagated.

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A murine monoclonal antibody (MAb), NCC-ST-421 (IgG3), was raised by using a human gastric cancer xenograft St-4 as immunogen. Immunization was achieved by transferring immunocompetent normal BALB/c mouse spleen cells into BALB/c-nu/nu mice bearing St-4 tumors. Hybridomas were produced from spleen cells of the mice after rejection of the tumors and were screened for preferential reactivity with cancers on formalin-fixed paraffin sections, as described previously for establishment of MAb NCC-ST-439 (M.

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