Biomedical subjects

I Grigorieva

Publications and source records attributed to I Grigorieva.

7 recordsLinked to original sources

PubMed2005

High efficiency, high quality x-ray optic based on ellipsoidally bent highly oriented pyrolytic graphite crystal for ultrafast x-ray diffraction experiments.

By the use of a thin highly oriented pyrolytic graphite crystal (HOPG) bent to a high-performance ellipsoidal shape it was possible to focus monochromatic x-rays of 4.5 keV photon energy with an efficiency of 0.0033, which is 30 times larger than for previously used bent crystals. Isotropic Ti K alpha radiation of a 150 microm source was focused onto a 450 microm spot. The size of the focal spot can be explained by broadening due to the mosaic crystal rocking curve. The rocking curve width (FWHM) of the thin graphite foil was determined to 0.11 degrees. The estimated temporal broadening of an ultrashort K alpha pulse by the crystal is not larger than 300 fs. These properties make the x-ray optic very attractive for ultrafast time-resolved x-ray measurements.

Journal Article↗

PubMed2001

Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer.

Dimebon, launched earlier in Russia as an antihistamine drug, was evaluated as a representative of a new generation of anti-Alzheimer's drugs that have two beneficial actions: (1) to alleviate symptoms, and (2) to prevent progression of the disease. The drug demonstrated cognition and memory-enhancing properties in the active avoidance test in rats treated with the neurotoxin AF64A, which selectively destroys cholinergic neurons. Dimebon protected neurons in the cerebellum cell culture against the neurotoxic action of beta-amyloid fragment (A beta 25-35, EC50 = 25 microM). In vitro, Dimebon displayed Ca(2+)-blocking properties (IC50 = 57 microM, on isolated rat ileum intestine) and pronounced anticholinesterase activity (IC50 = 7.9 microM and 42 microM for butyrylcholine esterase and acetylcholine esterase, respectively). It also exhibited strong anti-NMDA activity in the prevention of NMDA-induced seizures in mice (EC50 = 42 +/- 6 mg/kg i.p.). A beneficial effect of Dimebon in the therapy of Alzheimer's disease was demonstrated in a pilot clinical trial performed in the Moscow Center of Gerontology. Fourteen patients who participated in the trial were evaluated for their state of personality and for the severity of the disease. The evaluation included orientation (space, place, time, and patient personality), memory for the past and present, life in present, speech, irritability, and so forth. During and after the eight-week therapy with Dimebon, cognitive and self-service functions of patients improved significantly, and psychopathic symptoms, anxiety, depression, tearfulness, and headache were substantially diminished. The results of these studies suggest Dimebon as a new candidate for the therapy of Alzheimer's-like disorders.

Aged↗

PubMed2000

Regulation of c-myc transcription by interleukin-2 (IL-2). Identification of a novel IL-2 response element interacting with STAT-4.

Regulation of c-myc expression is known to occur at the level of transcription initiation. However, the participating promoter elements and their cognate binding proteins have not been fully characterized. c-myc transcription can be stimulated by a number of cytokines including interleukin-2 (IL-2). We have identified a novel IL-2-responsive element, located in the 5'-flanking region of the c-myc gene, between nucleotides -1406 and -1387 (relative to the P2 promoter). This element belongs to the family of interferon-gamma activation site-like responsive elements and has the core sequence TTCCAATAA. We confirmed that IL-2-mediated signaling involves activation by phosphorylation of Jak2 tyrosine kinase and subsequently STAT4. The transcription factor STAT4 binds the TTCCAATAA motif within this responsive element and, therefore, is probably involved in enhancing c-myc transcription upon IL-2 stimulation. Our results propose participation of Jak2 and STAT4 in IL-2-induced up-regulation of c-myc.

Binding Sites↗

PubMed1999

PTEN transcriptionally modulates c-myc gene expression in human breast carcinoma cells and is involved in cell growth regulation.

A novel tumor suppressor gene, PTEN, has recently been identified at chromosome 10q23, which is inactivated in a number of different tumor types including breast cancer. An investigation of the functional role suggested that PTEN transcriptionally represses both exogenous and endogenous c-myc expressions in human breast carcinoma cells. PTEN, when ectopically expressed in human breast carcinoma cells, exhibited an inhibition of phosphorylation of both activating residues of protein kinase B (PKB)/AKT at Ser-473 and Thr-308 without any significant alteration of AKT expression. Furthermore, introduction of PTEN into human breast carcinoma cells induced apoptotic cell death and inhibited cell growth and tumor formation in nude mice. Taken together, our data suggest that PTEN acts as a transcriptional repressor, inhibits the AKT-mediated cell survival signaling pathway, and negatively regulates human breast carcinoma cell growth. These results further emphasize the potential of PTEN as a gene therapeutic agent.

Animals↗

PubMed1998

The bone marrow stromal environment is a major factor in myeloma cell resistance to dexamethasone.

Dexamethasone (Dex), which is often used for the treatment of multiple myeloma, produces rapid reductions in tumor mass and improvement in disease symptoms; however, it is not curative, and drug-resistant cells eventually emerge. To elucidate this apparent paradox, we tested the effect of the bone marrow environment on myeloma cell response to this drug. To determine whether bone marrow stroma provides sufficient amounts of interleukin (IL)-6 to protect myeloma cells against the effects of Dex, we compared the production of IL-6 by marrow stromal cells from four myeloma patients before, during, and after exposure to 10(-7) M Dex, and found that even in the presence of this drug, stromal cells continued to produce IL-6, albeit in reduced concentrations. We tested the ability of stromal cells to protect myeloma cells, purified from the bone marrow of seven patients by cell sorting on the basis of CD38 and CD45 expression, and two light-scatter parameters, from Dex-induced apoptosis. In contrast to mature CD38+CD45- cells, which were not protected, coculture with stroma very effectively protected immature CD38+CD45+ myeloma cells from Dex. These data may explain the palliative efficacy of Dex treatment and provide a rationale for combining IL-6 antagonists with Dex to overcome the IL-6-mediated resistance of immature tumor cells.

Antigen-Antibody Reactions↗

PubMed1996

Senescent fibroblasts as feeder cells for lymphoid cell cloning.

Senescent primary human skin fibroblasts were used as feeder layers for cloning lymphoid cells by limiting dilution. B-cells including mouse hybridoma cells, human multiple myeloma cells C1R and DIG, as well as an immortalized T-cell line (Jurkat cells) were cloned using this approach. From heterogenous populations, homogeneous (clonal) populations were obtained and further analyzed. The major advantages of senescent fibroblasts as feeder cells are (i) the need to establish primary cultures from experimental animals for preparing feeder cells is obviated; (ii) the risk of contamination with infectious agents is diminished; (iii) primary skin fibroblasts are easily maintained in culture, can be kept at confluence for extended periods of time, and do not undergo spontaneous transformation; and (iv) lymphoid cells are readily separated from fibroblast monolayers. The use of senescent fibroblasts overcomes limitations inherent with primary mouse cell cultures and irradiated cells commonly used as feeder cells in cloning techniques.

Animals↗

PubMed1994

Interleukin-6 prevents dexamethasone-induced myeloma cell death.

The effects of dexamethasone on the growth of four human multiple myeloma cell lines were studied. In addition, the effects on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes were investigated by the use of reverse-transcriptase polymerase chain reaction. Dexamethasone (Dex) concentrations of 10(-7) to 10(-6) mol/L inhibited IL-6 gene expression in three of four cell lines studied, whereas the higher concentration of the hormone inhibited also IL-6R gene expression. Dex effects were modulated through the glucocorticoid receptor (GR). Dex treatment resulted in killing of sensitive cells associated with DNA fragmentation, which could be reversed by concomitant treatment with IL-6. The reversal of Dex-mediated effects by IL-6 did not result from an inhibition of GR function as measured by receptor nuclear translocation or Dex-regulated reporter gene function. These results indicate that blockage of the IL-6 signaling pathway is essential for effective myeloma cell kill by Dex.

Base Sequence↗