[Stratification of the risk of malignization of intraductal papillary mucinous neoplasms of the pancreas].

The purpose of this review was to analyze the most perspective methods for risk stratification of malignant transformation of pancreatic intraductal papillary mucinous neoplasms (IPMN). Advisability of humoral predictors (tumor markers, inflammatory markers, circulating leptin and branched-chain amino acids, etc.) is in identifying prognostic signs suitable for risk stratification of IPMN malignant transformation and, therefore, determining treatment strategy for a particular patient.

[Results of laparoscopic pelvic exenterations].

Objective: To analyze clinical outcomes after pelvic exenteration for advanced primary or recurrent pelvic cancer.

Material And Methods: We analyzed the outcomes in 35 patients after pelvic exenteration for advanced primary or recurrent pelvic cancer (gynecological cancer, urologic cancers, colon cancer). There were 3 (8.

[Features and results of minimally invasive treatment of recurrent achalasia].

Objective: To evaluate the early and long-term postoperative outcomes in patients with recurrent achalasia, as well as the main features of surgical treatment.

Material And Methods: There were 7 patients (4 men and 3 women) with recurrent achalasia. Mean age of patients was 42.

[Esophageal achalasia: possible pathogenic concepts from the perspective of modern notions].

Esophageal achalasia is an esophageal motility disease characterized by impaired relaxation of lower esophageal sphincter (LES) and severe clinical symptoms. The main etiological factors and other essential aspects of pathogenesis and progression of this disorder are actively studied. To date, the question of significance of etiological factors is experimental and requires further study.

[Redo laparoscopic surgery for recurrent gastroesophageal reflux disease and hiatal hernia].

Aim: To assess mechanisms of recurrent gastroesophageal reflux disease and the ability to perform adequate surgical correction after previous surgery.

Material And Methods: The authors from various surgical centers have operated 2678 patients with gastroesophageal reflux disease and hiatal hernia for the period 1993-2018. 127 (4.

GPIHBP1 stabilizes lipoprotein lipase and prevents its inhibition by angiopoietin-like 3 and angiopoietin-like 4.

Glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) binds both LPL and chylomicrons, suggesting that GPIHBP1 is a platform for LPL-dependent processing of triglyceride (TG)-rich lipoproteins. Here, we investigated whether GPIHBP1 affects LPL activity in the absence and presence of LPL inhibitors angiopoietin-like (ANGPTL)3 and ANGPTL4. Like heparin, GPIHBP1 stabilized but did not activate LPL.

Identification of a new functional domain in angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) involved in binding and inhibition of lipoprotein lipase (LPL).

Angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are secreted proteins that regulate triglyceride (TG) metabolism in part by inhibiting lipoprotein lipase (LPL). Recently, we showed that treatment of wild-type mice with monoclonal antibody (mAb) 14D12, specific for ANGPTL4, recapitulated the Angptl4 knock-out (-/-) mouse phenotype of reduced serum TG levels. In the present study, we mapped the region of mouse ANGPTL4 recognized by mAb 14D12 to amino acids Gln(29)-His(53), which we designate as specific epitope 1 (SE1).

Routes to covalent catalysis by reactive selection for nascent protein nucleophiles.

Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection.

Phosphonate ester probes for proteolytic antibodies.

The reactivity of phosphonate ester probes with several available proteolytic antibody (Ab) fragments was characterized. Irreversible, active site-directed inhibition of the peptidase activity was evident. Stable phosphonate diester-Ab adducts were resolved by column chromatography and denaturing electrophoresis.

Monoclonal antibody light chain with prothrombinase activity.

Prothrombin is the precursor of thrombin, a central enzyme in coagulation. Autoantibodies to prothrombin are associated with thromboembolism, but the mechanisms by which the antibodies modulate the coagulation processes are not understood. We screened a panel of 34 monoclonal antibody light chains isolated from patients with multiple myeloma for prothrombinase activity by an electrophoresis method.

Inhibition and labeling of enzymes and abzymes by phosphonate diesters.

Reactive phosphonate diesters were designed and prepared as inhibitors of serine proteases and esterases. Inactivation of trypsin, chymotrypsin, and butyrylcholinesterase was determined by residual enzymatic activity as well as by the release of a chromogenic or fluorogenic product of the inhibition reaction. Second-order rate constants were determined from rates of nitrophenol formation.

Nucleophilic proteolytic antibodies.

Proteolytic antibodies appear to utilize catalytic mechanisms akin to nonantibody serine proteases, assessed from mutagenesis and protease-inhibitor studies. The catalytic efficiency derives substantially from the ability to recognize the ground state with high affinity. Because the proteolytic activity is germline-encoded, catalysts with specificity for virtually any target polypeptide could potentially be developed by applying appropriate immunogens and selection strategies.

DNA hydrolysis by monoclonal autoantibody BV 04-01.

Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the presence of Mg2+. Catalysis was associated with BV 04-01 IgG, Fab, and single-chain-antibody (SCA) proteins. Cleavage of both ss and dsDNA was observed with efficient hydrolysis of the C-rich region of A7C7ATATAGCGCGT2, as well as a preference for cleaving within CG-rich regions of dsDNA.

Natural catalytic immunity is not restricted to autoantigenic substrates: identification of a human immunodeficiency virus gp 120-cleaving antibody light chain.

The autoimmune repertoire is well known from previous studies to be capable of producing catalytic antibodies directed to self-antigens. In the present study, we explored the ability of 26 monoclonal light chains (L chains) from multiple myeloma patients to cleave radiolabeled gp120, a foreign protein. One L chain with this activity was identified.

Innate antibody catalysis.

Catalysis by antibodies is often assumed to require immunization with artificial haptens, which are proposed to stimulate adaptive immune processes and enable the development of catalytic sites with the ability to bind the transition state. Contrary to this assumption, we describe here a serine protease-like catalytic triad in an antibody light chain raised by immunization with vasoactive intestinal peptide (VIP), the structure and function of which is inherited via a germline V(L) gene. The serine protease mechanism was evident from loss of the catalytic activity by site directed mutagenesis at a framework region residue Asp1 (present study) and at two complementarity determining region residues Ser27a and His 93 (Gao, Q-S.

Stabilization of vasoactive intestinal peptide by lipids.

An anionic phospholipid, phosphatidylglycerol (PG), induced vasoactive intestinal peptide (VIP) to adopt a helical conformation, determined by circular dichroism studies. PG inhibited the trypsin-catalyzed, antibody-catalyzed and uncatalyzed cleavage of VIP, measured by radiometric and HPLC methods. Phosphatidylcholine, a neutral lipid, did not alter the circular dichroism spectra of VIP, and it was without detectable effect on the rates of VIP cleavage.

DNA hydrolysis by monoclonal anti-ssDNA autoantibody BV 04-01: origins of catalytic activity.

Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the presence of Mg2+ ions. DNA hydrolyzing activity was associated with BV 04-01 IgG, Fab, and SCA 04-01 proteins. Pronounced cleavage specificity for both ss and dsDNA was observed with efficient hydrolysis of the C-rich region of the oligonucleotide A7C7ATATAGCGCGT7 as well as preference for cleavage within CG-rich regions of double-stranded DNA.

Cleavage of supercoiled plasmid DNA by autoantibody Fab fragment: application of the flow linear dichroism technique.

A highly effective method consisting of two affinity chromatography steps and ion-exchange and gel-filtration chromatography steps was developed for purification of autoantibodies from human sera with DNA-hydrolyzing activity. Antibody Fab fragment, which had been purified 130-fold, was shown to catalyze plasmid DNA cleavage. The flow linear dichroism technique was used for quantitative and qualitative studying of supercoiled plasmid DNA cleavage by these autoantibodies in comparison with DNase I and EcoRI restriction endonuclease.

[Interaction of catalytically active antibodies with oligoribonucleotides].

The interaction of antibodies from blood sera of patients with autoimmune pathology, systemic lupus erythematosus with oligoribonucleotides was studied. The RNA-hydrolyzing activity was shown to be an intrinsic property of autoantibodies. Enzymic activity of antibodies in hydrolysis of poly(U) was estimated at 20-40% of that of RNase A.

DNA-protein complexes. Natural targets for DNA-hydrolyzing antibodies.

Sera of patients with different types of leukemia and acquired immune deficiency syndrome (AIDS) have been examined for the presence of the anti-DNA antibodies. DNA-hydrolyzing activity of antibodies was detected in the sera of patients with chronic lymphoid leukemia (CLL), pre-B-cell acute lymphoid leukemia (pre-B-All), acute myeloleukosis (AML), and AIDS in stages III and IV of the disease. In immunofluorescence tests, the DNA-hydrolyzing antibodies reacted preferentially with proliferating cell nuclei compared with resting cells.

DNA-hydrolyzing autoantibodies.

Catalysis by antibodies could be a frequent phenomenon if the immune system generates a sufficiently diverse number of antibody-active sites, some of which may possess catalytic activity. A catalytic antibody can be expected to do more damage than one that simply binds antigen. The best biochemical marker of systemic lupus erythematosus (SLE) is presence of autoantibodies to DNA.