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Biomedical subjects

M A Ivanov

Publications and source records attributed to M A Ivanov.

At least 19 recordsLinked to original sources

TNR/11q#1 trinucleotide (GCC)n repeat alleles and predisposition to acute and chronic leukemia.

TNR/11q#1 is a polymorphic trinucleotide (GCC)n repeat located within the minimal region of the 11q deletion in chronic lymphocytic leukemia (CLL). It was recently shown that certain alleles of this repeat are associated with a worse prognosis in CLL patients. To investigate the role of TNR/11q#1 variants as risk-modifying factors in leukemogenesis, we conducted a case-control study on 113 acute lymphotic leukemia (ALL) patients, 82 CLL patients and 146 healthy controls of Russian origin. Comparison of allele and genotype distributions in the control, ALL and CLL groups, performed by Fisher's exact test with two-sized P-value, showed significant decrease in the presence of the GCC(6) allele in the ALL and CLL groups compared to controls. Moreover, 'rare' alleles GCC(7-8) and GCC(13-14) were significantly overrepresented in the ALL group versus controls. We found that CLL risk genotypes were those with both alleles containing more than 6 GCC repeats (P = 0,0212, odds ratio = 1,68 (95% CI, 1,121...2,531)). ALL risk genotypes include three allele combination variants: 1) both alleles containing more than 6 GCC repeats (P = 0,0019, odds ratio = 1,756 (95% CI 1,223...2,502)); 2) one of the alleles containing 7 or 8 repeats (P = 0,0155, odds ratio = 18,22 (95% CI 1,93...136.37)); 3) one of the alleles containing more than 12 repeats (P = 0,0209, Odds ratio = 2,599 (95% CI 1,161...5,815)). Association of certain alleles and genotypes of the TNR/11q#1 repeat with both acute and chronic lymphocytic leukemia suggests the presence of a cancer related gene, involved in a wide spectrum of neoplasia, in the vicinity of this repeat.

Adult↗

Efficient DNA electrotransfer into tumors.

DNA transfer to tumor cells of antiproliferative genes or of genes coding for immunomodulatory or antiangiogenic products is a promising approach for cancer therapy. However, intratumoral injection of plasmid DNA either naked or associated to chemical vectors results in a low level of gene expression. Recently, electrically mediated gene transfer has been described to strongly increase foreign gene expression in various tissues. We confirm and extend these observations using long duration electric pulses for several murine and human tumor models, using a reporter gene encoding for luciferase. After plasmid intratumoral injection, eight electric pulses of 20-ms duration were delivered at a frequency of 1 Hz through two flat parallel stainless steel electrodes placed at each side of the tumor. Optimal gene transfer was obtained using a voltage-to-distance ratio comprising between 400 and 600 V/cm. Two days after electrotransfer, we obtained a 10- to 1200-fold increase in gene expression over the naked DNA injection alone, leading to the expression of 0.6 to 300 ng luciferase per tumor. Moreover, histological results using beta-Gal reporter gene injected in H1299 tumor indicate that electrotransfer leads to a substantial increase in the percentage of beta-Gal positive cells. These results confirm the wide potential of electrotransfer for gene therapy in cancer.

Animals↗

Possible ancient oceans on Mars: evidence from Mars Orbiter Laser Altimeter data.

High-resolution altimetric data define the detailed topography of the northern lowlands of Mars, and a range of data is consistent with the hypothesis that a lowland-encircling geologic contact represents the ancient shoreline of a large standing body of water present in middle Mars history. The contact altitude is close to an equipotential line, the topography is smoother at all scales below the contact than above it, the volume enclosed by this contact is within the range of estimates of available water on Mars, and a series of extensive terraces parallel the contact in many places.

Evolution, Planetary↗

Synthetic DNA-compacting peptides derived from human sequence enhance cationic lipid-mediated gene transfer in vitro and in vivo.

Cationic lipids can deliver genes efficiently in vitro, but are generally inhibited by the presence of serum, and their efficiency in vivo is much lower than in vitro. An attractive strategy is to induce strong DNA compaction by its association with proteins, before addition of lipids. However the use of whole proteins might present both production and immunological limitations. We have devised a system in which DNA is associated with short peptides derived from human histone or protamine, before the addition of a cationic lipid or polymer. Peptides strongly associating with DNA confer to such peptide-DNA-lipid particles an enhanced in vitro transfection efficiency over that observed with classical DNA/lipid lipoplexes, and particularly confer the capacity to transfect in the presence of serum. This acquisition of serum resistance is cell type-independent, and observed with all four lipopolyamines tested and polyethylenimine. Precompacting DNA with a histone H1-derived peptide enhances cationic lipid RPR 115335-mediated gene transfer in an in vivo model of Lewis lung carcinoma. Apart from their use in peptide-DNA-lipid association, such peptides could be useful as part of chimeric gene delivery vectors presenting a DNA-binding moiety that can be easily associated with other functional domains.

3T3 Cells↗

[End-to-end anastomosis as a method of choice in right hemicolectomy].

The newest and long-term results of treatment of 239 patients were analyzed in whom right hemicolectomy with ileotransverse anastomoses "end-to side", "side-to side" and "end-to-end" were fulfilled. When estimating the results, the data of original methods developed and tested in the clinic were used for studying the motility and bioelectrical activity of the intestine in addition to clinical parameters. The main regularities of the development of postoperative complications were found in randomized groups. It was established that choice of the optimum variant of the anastomosis in right hemicolectomy was dependent on the understanding of pathophysiological consequences of either intestinal anastomosis. The anastomosis "end-to-end" is the quickest to fulfil, less traumatic and safe of the 3 types of ileotransverse anastomosis.

Anastomosis, Surgical↗

[Our experience and the outlook for the development of surgery in esophageal cancer].

Results of resections and simultaneous plasty of the esophagus in 178 patients with the III and III-IV stages of the malignant process are analyzed. The overwhelming majority of the patients were elderly and senile people. The total intrahospital lethality was 14.1%, lethality due to incompetent anastomoses was 5.6%. A comparative evaluation of results of the Lewis operations and operations performed by the Savinykh-Kariakin method has shown that lethality in the first group of patients was 3.5 times higher than in the second group. Pulmonary and cardio-vascular complications as well as infectious complications were significantly more frequent after the intrapleural access and plasty of the esophagus. Less amount of such complications after the posteromedial plasty of the esophagus by the Savinykh-Kariakin method resulted in less total lethality (7.9%). The authors consider the better results of operative treatment to be related both with less traumatic method of resection and plasty of the esophagus and with the adequate control of possible complications and prophylactic measures.

Adult↗

[Control over the function of the anastomosed segments of the digestive tract].

One of the most effective methods of prophylactics of incompetence of anastomoses sutures is the intraoperative registration of bioelectrical activity of the connected segments of the digestive tract when performing operations on the stomach and esophagus. The implanted electrodes allow analysis of the action potential fluctuation during the postoperative period followed by the corresponding conclusions about the state of blood circulation in hollow organs. The effectiveness and adequacy of management of the patients after the interventions is estimated by means of rheography of the intestine wall. The proposed program of controlling the state of proximal segments of the digestive tract gave good results in 42 patients after total and partial gastrectomies.

Anastomosis, Surgical↗

[The importance of monitoring the motor activity of the small intestine in the postoperative period].

Monitor control of the digestive tract activity used in the postoperative period is of considerable significance in prophylactics of most dangerous complications. Monitoring at different levels of the digestive tract allows to at most decrease the danger of early enteral feeding, and to estimate the efficiency of numerous measures for the stimulation of intestinal activity.

Anastomosis, Surgical↗

Rat adult hepatocytes in primary pure and mixed monolayer culture. Comparison of the maintenance of mixed function oxidase and conjugation pathways of drug metabolism.

The stabilities of several drug oxidation and conjugation pathways in adult rat hepatocytes were investigated in two systems: a primary pure culture lasting 3 days and a primary mixed culture (hepatocytes co-cultured with epithelial cells) lasting 10 days. The cytochrome P450 content in hepatocytes drastically declined within 48 hr in both culture systems. Cytochrome P450-dependent mixed function oxidase was measured by the O-dealkylation of ethoxyresorufin (EROD) and of pentoxyresorufin (PROD). UPD-glucuronosyl transferase (UDP-GT) activity was measured using 1-naphthol and morphine as substrates. In both culture systems, the activities of enzymes belonging to the 3-methylcholanthrene-inducible family, namely EROD and 1-naphthol UDP-GT, were much better maintained than those of PROD and morphine UDP-GT, which belong to the phenobarbitone-inducible family: in pure cultures, EROD and 1-naphthol UDP-GT activities declined to 60% of initial values within 3 days; in mixed cultures, EROD activity was stable throughout the 10 day culture period, whereas that of 1-naphthol UDP-GT was stable until day 4 but had declined to 70% of the initial value by day 8. In contrast, PROD and morphine UDP-GT activities declined to approx. 30% of the initial values within 2 days in both culture systems, and had dropped to approx. 10% of the initial value within 8 days in mixed culture. Reduced glutathione (GSH) levels fluctuated, but remained high throughout culture. GSH conjugation declined to 40% of initial values within 3 days in pure culture, whereas it remained relatively constant in mixed culture. Comparison of these two culture systems therefore showed that although the inclusion of epithelial cells did prolong hepatocyte viability, there was a change in relative enzyme activities in both systems, suggesting a shift towards a more de-differentiated drug metabolism pattern.

Animals↗

Regulation of fatty-acid metabolism by pancreatic hormones in cultured human hepatocytes.

The effects of pancreatic hormones and cyclic AMP on long-chain fatty-acid metabolism were investigated in human hepatocytes isolated from 12 liver biopsy specimens and cultured for 4 days in an insulin-free medium. Glucagon (10(-6) mol/L) increased endogenous ketone body production by 150%. This resulted from alterations in the partition of long-chain fatty acids from esterification toward oxidation. Glucagon or cyclic AMP enhanced (14C) oleate oxidation (basal = 45.8% +/- 5.0%; glucagon = 66.8% +/- 5.3%; cyclic AMP = 67.6% +/- 5.0% of metabolized oleate) at the expense of oleate esterification. Insulin (10(-7) mol/L) antagonized the glucagon-induced oleate oxidation. After 24 hr in basal culture conditions, the rate of lipogenesis decreased to the same low rate as in glucagon-treated cells. The presence of insulin did not restore a high rate of lipogenesis. These results are the first direct evidence of a control of ketone body production by glucagon in the human liver.

Adult↗