Biomedical subjects

A G Baranovskii

Publications and source records attributed to A G Baranovskii.

6 recordsLinked to original sources

PubMed2006

Proteolytic activity of IgG antibodies from blood of acquired immunodeficiency syndrome patients.

Proteolytic activity of polyclonal IgG antibodies (Abs) from the blood of AIDS patients was analyzed for the first time. These Abs were shown to display higher activity in hydrolysis of beta-casein than in hydrolysis of human immunodeficiency virus (HIV)-1 reverse transcriptase (RT) or human serum albumin (HSA). Several abzymatic criteria were applied and it was shown that RT, HSA, and beta-casein hydrolyzing activities are an intrinsic property of polyclonal Abs from AIDS patients. Casein-hydrolyzing Abs were detected in the blood serum for 95% of AIDS patients, and it was shown that they possess serine protease-like catalytic activity. The substrate specificities of polyclonal Ab proteases and typical human proteases are different. Depending on the patient, the IgGs exhibit various pH optima of proteolytic activity. The products of casein hydrolysis by Ab proteases were different from those in the case of trypsin, chymotrypsin, and proteinase K.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Human deoxyribonucleases.

Although mammalian deoxyribonucleases were discovered more than 60 years ago, interest in these enzymes is not weakening. During the last decade, intensive studies of human DNases culminated in discovery of several novel enzymes exhibiting DNase activity. These include an unusual DNase, lactoferrin. For some enzymes, their three-dimensional structure and molecular mechanisms underlying their functioning have been elucidated. In patients with some autoimmune and viral diseases, catalytic antibodies also contribute to alternative pathways of DNA hydrolysis. Some enzymes exhibiting DNase activity play an important role in pathogenesis of various diseases and also in programmed cell death (apoptosis). This review highlights recent achievement in human deoxyribonuclease research. It also considers mechanisms of DNA hydrolysis. The review also summarizes modern data on the biological role of these enzymes in functioning of the human organism, realization of its protective mechanisms, and possible applications of DNases in medicine.

Deoxyribonuclease I↗

PubMed2004

Comparison of enzymatic properties of DNA-abzymes and human DNAses.

DNA-hydrolyzing antibodies (DNA-abzymes, Abz) were shown to be good biochemical markers of some autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). To better understand mechanisms of abzyme generation, one needs to know optimal conditions for DNA hydrolysis by DNA-abzymes, as well as their enzymatic properties in comparison with those of enzymes possessing the same activity. In contrast to human urine deoxyribonucleases, DNA-hydrolyzing antibodies efficiently digested both single- and double-strand DNA. It was shown that polyclonal antibodies (Abs) in MS may contain up to several types of DNase activities, either activated by metal ions or not.

Antibodies, Catalytic↗

PubMed2001

Catalytic heterogeneity of polyclonal DNA-hydrolyzing antibodies from the sera of patients with multiple sclerosis.

Various catalytic antibodies or abzymes have been detected recently in the sera of patients with several autoimmune pathologies, where their presence is most probably associated with autoimmunization. Recently we have shown that DNase activity is associated with IgGs from the sera of patients with multiple sclerosis (MS) but not with those from the sera of normal humans. Here we present evidence showing that MS IgG, its F(ab) fragments, and separated L-chains catalyze DNA hydrolysis. The properties of the DNase activity of these polyclonal IgGs distinguish them from other known human DNases. In addition, their specific activities with different oligonucleotide substrates and the range of optimal pHs, apparent K(M) values and substrate specificities varied widely for different patients. The findings speak in favor of the generation by the immune systems of individual patients of a variety of polyclonal catalytic IgG pools, from relatively small to extremely large ones.

Antibodies, Catalytic↗

PubMed1998

Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA.

It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.

Antibodies, Catalytic↗

PubMedDate not supplied

Effect of different drugs on the level of DNA-hydrolyzing polyclonal IgG antibodies in sera of patients with Hashimoto's thyroiditis and nontoxic nodal goiter.

BACKGROUND: DNA-hydrolyzing IgG antibodies have been detected recently in the sera of patients with several autoimmune diseases. MATERIAL AND METHODS: The relative activity of DNA-hydrolyzing IgG from the sera of patients with Hashimoto's thyroiditis and with non-toxic nodal goiter as a function of the patient's condition were measured. The effect of different drugs on the level of DNA-hydrolyzing IgG, functional activity of thyroid gland, and improvement of clinical condition of two groups of patients were analyzed. RESULTS: We demonstrate here for the first time that IgG from peripheral blood of patients with Hashimoto's thyroiditis (65%) and non-toxic nodal goiter (38%) possesses DNAse activity. The relative level-specific activity of IgGs in hydrolysis of DNA increases with the enhancement of the relative amount of antibodies against thyroglobulin and all patients with hypothyroidism (namely a reduced concentration of thyroxine and triiodothyronine and enhanced level of thyrotropic hormone) are characterized by a high level of catalytic antibodies. CONCLUSIONS: The very widely used therapy of patients with thyroxine led only to a temporary change of the hormone concentration in the blood but did not affect the level of DNA-hydrolyzing antibodies. However, treatment with an immunosuppressive drug plaquenil (7-chloro-4(beta-diethylamine-alpha-methylbutylamie)quinoline), significantly decreased the DNA-hydrolyzing activity of Abs, which correlated with enhancement of thyroid hormone concentrations, elevation of functional activity of the thyroid gland, and improvement of the clinical state of the patients.

Antibodies, Antinuclear↗