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N Gavrilova

Publications and source records attributed to N Gavrilova.

17 recordsLinked to original sources
PubMed2001

PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1) through the ubiquitin E3 ligase SCF(SKP2).

The PTEN tumor suppressor acts as a phosphatase for phosphatidylinositol-3,4,5-trisphosphate (PIP3) [1, 2]. We have shown previously that PTEN negatively controls the G1/S cell cycle transition and regulates the levels of p27(KIP1), a CDK inhibitor [3, 4]. Recently, we and others have identified an ubiquitin E3 ligase, the SCF(SKP2) complex, that mediates p27 ubiquitin-dependent proteolysis [5-7]. Here we report that PTEN and the PI 3-kinase pathway regulate p27 protein stability. PTEN-deficiency in mouse embryonic stem (ES) cells causes a decrease of p27 levels with concomitant increase of SKP2, a key component of the SCF(SKP2) complex. Conversely, in human glioblastoma cells, ectopic PTEN expression leads to p27 accumulation, which is accompanied by a reduction of SKP2. We found that ectopic expression of SKP2 alone is sufficient to reverse PTEN-induced p27 accumulation, restore the kinase activity of cyclin E/CDK2, and partially overcome the PTEN-induced G1 cell cycle arrest. Consistently, recombinant SCF(SKP2) complex or SKP2 protein alone can rescue the defect in p27 ubiquitination in extracts prepared from cells treated with a PI 3-kinase inhibitor. Our findings suggest that SKP2 functions as a critical component in the PTEN/PI 3-kinase pathway for the regulation of p27(KIP1) and cell proliferation.

Animals↗
PubMed2001

Risk analysis: divergent models and convergent interpretations.

Material presented at a NASA-sponsored workshop on risk models for exposure conditions relevant to prolonged space flight are described in this paper. Analyses used mortality data from experiments conducted at Argonne National Laboratory on the long-term effects of external whole-body irradiation on B6CF1 mice by 60Co gamma rays and fission neutrons delivered as a single exposure or protracted over either 24 or 60 once-weekly exposures. The maximum dose considered was restricted to 1 Gy for neutrons and 10 Gy for gamma rays. Proportional hazard models were used to investigate the shape of the dose response at these lower doses for deaths caused by solid-tissue tumors and tumors of either connective or epithelial tissue origin. For protracted exposures, a significant mortality effect was detected at a neutron dose of 14 cGy and a gamma-ray dose of 3 Gy. For single exposures, radiation-induced mortality for neutrons also occurred within the range of 10-20 cGy, but dropped to 86 cGy for gamma rays. Plots of risk relative to control estimated for each observed dose gave a visual impression of nonlinearity for both neutrons and gamma rays. At least for solid-tissue tumors, male and female mortality was nearly identical for gamma-ray exposures, but mortality risks for females were higher than for males for neutron exposures. As expected, protracting the gamma-ray dose reduced mortality risks. Although curvature consistent with that observed visually could be detected by a model parameterized to detect curvature, a relative risk term containing only a simple term for total dose was usually sufficient to describe the dose response. Although detectable mortality for the three pathology end points considered typically occurred at the same level of dose, the highest risks were almost always associated with deaths caused by tumors of epithelial tissue origin.

Aerospace Medicine↗
PubMed1999

PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway.

To investigate the molecular basis of PTEN-mediated tumor suppression, we introduced a null mutation into the mouse Pten gene by homologous recombination in embryonic stem (ES) cells. Pten-/- ES cells exhibited an increased growth rate and proliferated even in the absence of serum. ES cells lacking PTEN function also displayed advanced entry into S phase. This accelerated G1/S transition was accompanied by down-regulation of p27(KIP1), a major inhibitor for G1 cyclin-dependent kinases. Inactivation of PTEN in ES cells and in embryonic fibroblasts resulted in elevated levels of phosphatidylinositol 3,4,5,-trisphosphate, a product of phosphatidylinositol 3 kinase. Consequently, PTEN deficiency led to dosage-dependent increases in phosphorylation and activation of Akt/protein kinase B, a well-characterized target of the phosphatidylinositol 3 kinase signaling pathway. Akt activation increased Bad phosphorylation and promoted Pten-/- cell survival. Our studies suggest that PTEN regulates the phosphatidylinositol 3,4, 5,-trisphosphate and Akt signaling pathway and consequently modulates two critical cellular processes: cell cycle progression and cell survival.

Animals↗
PubMed1996

[Analgesia in traumatism in childhood].

The current trends of pain treatment from anesthesiological viewpoint mark considerable progress. The ever increasing incidence of injuries in childhood (traffic accidents and home injuries alike), the different mechanism involved, and the multiple damage to organs and systems make mandatory prompt assessment of the condition, diagnosing and adequate therapeutic approach. Analgesia as an essential element of anesthesia is routinely applied to pediatric trauma cases.

Adolescent↗
PubMed1996

[The intensive treatment of children with laparoscopies after ileus peritonitis].

Experience gained with the treatment of children undergoing laparostomies, necessitating numerous anesthesias and operative revisions in the early post-operative period, is shared. The open abdominal cavity is the cause of additional loss of liquids, requiring in turn adequate compensation with electrolyte solutions. Early administration of parenteral feeding contributes to prompt postoperative recovery. The active complex management, including antibacterial and immunostimulating therapy, as well as application of hyperbaric oxygenation in the event of severe infection, lead to a favourable outcome.

Acute Disease↗
PubMed1990

[The effect of the induction of anesthesia on human cardiac activity].

The authors studied the effect of intravenous induction with thiopental, myorelaxant and subsequent laryngoscopy and intubation on cardiac rhythm, Q-T interval and cardiac stroke volume in children without accompanying diseases. Cardiac dysrhythmias in adults have been reported in the literature; low fentanil doses have been recommended for their suppression. Thirty five children (20 of them younger than 10 years and 15-10 to 14 years of age) were tested in five stages. Records were taken of ECG, impedance cardiography by the method of Kubicek; the stroke volume, the duration of the Q-T interval and the cardiac rate were estimated. Children younger than 10 had no dysrhythmia during the induction in anesthesia, which made unnecessary prophylactic administration of low fentanil doses. More pronounced were the changes in the Q-T interval and the stroke volume in the age group beyond 10; one child in this group had dysrhythmia as well.

Adolescent↗