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Biomedical subjects

A Baranov

Publications and source records attributed to A Baranov.

9 recordsLinked to original sources

Local and distant transfection of mdx muscle fibers with dystrophin and LacZ genes delivered in vivo by synthetic microspheres.

Patterns of dystrophin and beta-galactosidase expression were examined in mdx mice after i.m. injections of synthetic microspheres (MF-2) loaded with full-length (pHSADy) or mini-dystrophin gene (pSG5dys) cDNA plasmid constructs or with LacZ marker gene (pCMV-LacZ). A single injection of 25 microg pHSADy into quadriceps femoris muscle resulted in 6.8% of dystrophin positive myofibers (DPM) in a given muscle; 8.4% of DPM in glutaeus muscle and 4.3% of DPM in quadriceps femoris muscle of contralateral limb on day 21 after exposure compared with only 0.6% DPM in intact (non-injected) mdx mice. A high proportion of DPM (17.6% and 10.8%, respectively) was registered in both injected and contralateral muscles after mini- gene cDNA administration. MF-2/dystrophin cDNA particles were detected by FISH analysis in about 60-70% of myofiber nuclei in muscles of injected and contralateral limbs 7 days after application. The presence of human dystrophin cDNA and its products in all skeletal muscles and in different internal organs was proven by PCR and RT-PCR analysis. Patches of beta-galactosidase expression were abundant in injected muscle, and frequent in the contralateral and other skeletal muscles as well as in diaphragm, heart and lungs. High levels of dystrophin cDNA expression, and an efficient distant transfection effect with preferential intranuclei inclusion of MF-2 vehicle, are very encouraging for the development of a new constructive strategy in gene therapy trials of DMD.

Animals↗

Serum concentrations of neopterin, soluble interleukin 2 receptor, and soluble tumor necrosis factor receptor in Wegener's granulomatosis.

OBJECTIVE: To investigate the possible relationship between serum levels of neopterin, soluble tumor necrosis factor-55 receptor (sTNF-55R), and soluble interleukin 2 receptor (sIL-2R) with disease activity in patients with Wegener's granulomatosis (WG). METHODS: Serum neopterin was measured by radioimmunoassay, sTNF-55R and sIL-2R were measured by ELISA in 26 patients with WG. RESULTS: Serum neopterin, sTNF-55R, and sIL-2R were significantly elevated in patients with generalized WG compared with healthy controls. Concentrations of the analytes correlated with disease activity indices in patients without infectious complications. The highest elevations of all 3 variables were observed in patients with intercurrent infections. CONCLUSION: The increased serum levels of neopterin, sTNF-55R, and sIL-2R suggest activation of cellular immunity in WG.

Adult↗

Elastin degradation in systemic vasculitis.

The elastin peptide level (EP) and elastase-type activity (EA) were investigated in 89 patients with different types of systemic vasculitis (polyarteritis nodosa-14, non-specific aortoarteritis-33, temporal arteritis-23 and thromboangiitis obliterans-18) and compared to the controls: 31 patients with leg atherosclerosis and 12 aged subjects with no evident vascular pathology. EP and EA levels in patients with thromboangiitis obliterans were significantly lower as compared to leg atherosclerosis and the aged control group (p < 0.02 for EA, p < 0.05 for EP). The increase of EP predominated in giant-cell arteritis as compared to the other vasculitic groups (18/56 vs. 5/32, p < 0.05); EA in these patients was the lowest. The activation of elastin degradation after corticosteroid treatment was demonstrated by an increase of EP in temporal arteritis (p < 0.05) and of EA in thromboangiitis obliterans (p < 0.03). We suggest that the determination of the above parameters of elastin degradation may be helpful in the search for differences in mechanisms of vascular damage between atherosclerosis and inflammatory vascular diseases.

Adolescent↗

Cytogenetic and molecular findings in patients with Turner's syndrome stigmata.

Cytogenetic and DNA analysis in 12 people with stigmata of Turner's syndrome was carried out. Cytogenetic analysis of these patients showed two subjects with 46,X, i(Xq) karyotypes, one with 45,X/46,X, i(Xq), one with 46,X,t(X;Y), and eight with 45,X/46,X,mar. Molecular analysis of DNA samples was performed in nine out of 12 patients with marker chromosomes. PCR analysis with oligoprimers specific for SRY, DYZ1, or DYZ3 loci identified Y chromosome material in five patients in the latter group. The X chromosome origin of the marker chromosome was proved by FISH technique with biotin labelled pericentromeric X chromosome specific probe in four other patients. These results show that patients with a number of Turner's syndrome stigmata usually do not have a typical XO karyotype but have some structural chromosomal aberrations involving the X or Y chromosomes. Combined application of cytogenetic, molecular cytogenetic (FISH), and PCR techniques significantly improves the precision of marker chromosome identification and thus might be of practical importance for the proper management and treatment of affected patients. Peculiarities of pathological manifestations of different karyotypes bearing structural abnormalities of the X or Y chromosomes in patients with Turner's syndrome stigmata, as well as feasible genetic mechanisms of sex determination and differentiation abnormalities in these subjects, are briefly discussed.

Adolescent↗

X;Y translocation in a girl with short stature and some features of Turner's syndrome: cytogenetic and molecular studies.

A 13 year old girl referred for chromosome analysis because of disproportionate short stature (short neck, curved legs, pectus excavatum) with an initial clinical diagnosis of Turner's syndrome was found to have the karyotype 46,X, + der(X) in 100% of her blood lymphocytes. By means of conventional differential staining (QFH/AcD, FPG, and RBA banding) supplemented with distamycin A treatment, the karyotype of the proband was interpreted as 46,X,t(X;Y) (p22.3;q11). The rearranged marker X chromosome was found to be active in 91% of lymphocytes studied. PCR analysis with Y chromosome specific oligoprimers showed the presence of some Y chromosome long arm DNA in both lymphocyte and gonadal tissue biopsy cells. At laparoscopy the patient was found to have small gonads with a rudimentary uterus and fallopian tubes. Histological examination of gonadal tissue showed primary follicles with dystrophic changes of the germ cells and numerous follicular cysts (polycystic ovaries). The proband's phenotype and its correlation with the genetic imbalance of the rearranged X chromosomes, as well as with non-random t(X;Y) chromosome inactivation, are briefly discussed.

Child↗

Radiation accidents: primum non nocere.

BM toxicity is a major cause of morbidity and mortality after exposure to acute high dose total body radiation. Here, we consider therapeutic strategies useful in victims of radiation accidents including supportive care (antibiotics, protected environments and transfusions), hematopoietic growth factors and BMTs. Selecting the best strategy requires precise knowledge of the details of radiation exposure. This information is rarely available in accidents. An alternative is to assess risk:benefit ratios for different strategies at approximate radiation doses. Using this approach, we suggest supportive care be given to all persons at risk of developing BM failure. The favorable risk:benefit ratio of hematopoietic growth factors argues for their use when moderate to severe BM failure is predicted. Transplants, which have the least favorable risk:benefit ratio, should be used only when there is a substantial risk of irreversible BM damage.

Bone Marrow↗

Bone marrow transplantation after the Chernobyl nuclear accident.

On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.

Accidents↗