PubMed Health⌕ Search

Biomedical subjects

G Chernenko

Publications and source records attributed to G Chernenko.

9 recordsLinked to original sources
PubMed2005

Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia.

The optimal amount of endurance exercise required to elevate proteins involved in neuroplasticity during stroke rehabilitation is not known. This study compared the effects of varying intensities and durations of endurance exercise using both motorized and voluntary running wheels after endothelin-I-induced focal ischemia in rats. Hippocampal levels of brain-derived neurotrophic factor, insulin-like growth factor I and synapsin-I were elevated in the ischemic hemisphere even in sedentary animals suggesting an intrinsic restorative response 2 weeks after ischemia. In the sensorimotor cortex and the hippocampus of the intact hemisphere, one episode of moderate walking exercise, but not more intense running, resulted in the greatest increases in levels of brain-derived neurotrophic factor and synapsin-I. Exercise did not increase brain-derived neurotrophic factor, insulin-like growth factor I or synapsin-I in the ischemic hemisphere. In voluntary running animals, both brain and serum insulin-like growth factor I appeared to be intensity dependent and were associated with decreasing serum levels of insulin-like growth factor I and increasing hippocampal levels of insulin-like growth factor I in the ischemic hemisphere. This supports the notion that exercise facilitates the movement of insulin-like growth factor I across the blood-brain barrier. Serum corticosterone levels were elevated by all exercise regimens and were highest in rats exposed to motorized running of greater speed or duration. The elevation of corticosterone did not seem to alter the expression of the proteins measured, however, graduated exercise protocols may be indicated early after stroke. These findings suggest that relatively modest exercise intervention can increase proteins involved in synaptic plasticity in areas of the brain that likely subserve motor relearning after stroke.

Analysis of Variance↗
PubMed2001

Prognostic significance of BAG-1 expression in nonsmall cell lung cancer.

The purpose of this study was to evaluate the expression of BAG-1 in a cohort of patients with nonsmall cell lung cancer (NSCLC). The intensity and subcellular distribution of BAG-1 expression were correlated with overall survival. Tumor samples were collected from 85 patients diagnosed with NSCLC between 1993-1995 in St. John's, Newfoundland. Expression of BAG-1 was determined by immunohistochemistry using polyclonal anti-BAG-1 antibody. There was significant variation in the immunohistochemical staining patterns of BAG-1, including nonstaining and staining of either the cytoplasm, nucleus or both. Univariate Cox regression analysis showed that those patients whose tumor overexpressed BAG-1 had a significant reduction in the risk of death (hazard ratio = 0.53, p = 0.03). The survival advantage of patients with BAG-1 overexpression tumor was also demonstrated by Kaplan-Meier analysis and log-rank tests (median survival 30.10 months versus 17.04 months, p = 0.05). In addition, multivariate Cox regression analysis showed that patients whose tumor exhibited intense cytoplasmic staining had a further reduction of the risk of death (hazard ratio = 0.42, p = 0.03) and this effect was independent of age, stage and histology. All stages were included in the analysis. Our preliminary data strongly indicate that further investigation is warranted to better define the role of BAG-1 as an independent prognostic factor in NSCLC.

Adult↗
PubMed2000

Human papillomavirus type 16-immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype.

Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is a highly effective chemotherapeutic agent against cervical cancer, but drug resistance is a major obstacle in its clinical application. The mechanism of drug resistance in human cervical cancer is not well understood. Here, we established an in vitro endocervical, cisplatin-resistant cell system that mimics the development of cisplatin resistance in the human cervix. Human papillomavirus (HPV) type 16-immortalized human endocervical cells (HEN-16-2) were treated with cisplatin, and the cisplatin-selected cells (HEN-16-2/CDDP) were resistant to cisplatin, paclitaxel, actinomycin D, doxorubicin, etoposide, and 5-fluorouracil, thus demonstrating a multidrug resistance (MDR) phenotype. Furthermore, compared with a similar passage of drug-sensitive HEN-16-2 cells, HEN-16-2/CDDP cells exhibited the general growth characteristics of cancer cell lines: faster growth in medium containing serum and high calcium levels, higher saturation density, anchorage-independent growth, and formation of tumors in nude mice. These results provided the first in vitro evidence that cisplatin selection can transform HPV-immortalized endocervical cells and cause a phenotype of MDR.

Animals↗
PubMed1999

Expression of BAG-1 in invasive breast carcinomas.

PURPOSE: The purpose of this study was to retrospectively evaluate the expression of BAG-1 in invasive breast carcinomas. The intensity and subcellular distribution of BAG-1 expression was correlated with conventional prognostic factors and with disease-free and overall survival. PATIENTS AND METHODS: One hundred forty patients diagnosed with invasive breast cancer in St. John's, Newfoundland, between 1986 and 1996 were included in the study. The median follow-up of the study was 8 years. Expression of BAG-1 was determined by immunohistochemical staining of paraffin-embedded breast tumor tissues. RESULTS: Of the 140 breast carcinomas examined, 77.1% were positive for BAG-1 expression. Except for differentiation, no correlation was observed between BAG-1 expression and conventional prognostic factors such as age, histology, stage, and estrogen and progesterone receptor status. In multivariate analysis, BAG-1 expression was significantly associated with shorter disease-free (P =.0052) and overall survival (P =.0033). Patients whose tumors expressed nuclear BAG-1 tended to have a shorter disease-free (63 v 84 months; P = 0.4493) and overall (69 v 99 months, P =.1009) survival. CONCLUSION: BAG-1 is overexpressed in the majority of invasive breast carcinomas. Although BAG-1 did not correlate with conventional prognostic factors, its overexpression, especially the nuclear expression, may be associated with a shorter disease-free and overall survival. Our preliminary data strongly indicate that further investigation is warranted to define the role of BAG-1 as an independent prognostic factor in patients with newly diagnosed breast cancer.

Adult↗
PubMed1998

Human BAG-1/RAP46 protein is generated as four isoforms by alternative translation initiation and overexpressed in cancer cells.

Previously, a Bcl-2-interacting protein, BAG-1, was cloned from mouse cells and was shown to interact with several other proteins and to be important for inhibition of apoptosis. Human BAG-1 (hBAG-1) cDNA, recently isolated by us and two other groups, has been shown to be identical to a hormone receptor-binding protein, RAP46. However, different molecular masses of hBAG-1 protein products were noted by these three groups. Here we demonstrated that hBAG-1 protein was expressed as four isoforms, designated p50, p46, p33 and p29, with apparent molecular masses of 50 kDa, 46 kDa, 33 kDa and 29 kDa, respectively. Deletion, site-directed mutagenesis and in vitro transcription/translation analysis showed that the four protein products of hBAG-1 were expressed by alternative initiation from four different start codons through a leaky scanning mechanism. Furthermore, we demonstrated that the distinct forms of hBAG-1 have different subcellular localizations, suggesting that they may have distinct functions in the cells. Characterization of hBAG-1 RNA and protein also showed that hBAG-1 was overexpressed in human cervical, breast and lung cancer cell lines. Taken together, these data clarify the conflicting observations reported in the literature and suggest that hBAG-1 is expressed as four forms of protein products, which may play a differential role in apoptosis and oncogenesis of human cells.

Alternative Splicing↗
PubMed1991

The acute pancreatotoxic effects of the plant nitrile 1-cyano-2-hydroxy-3-butene.

The effects of synthetic 1-cyano-2-hydroxy-3-butene (CHB), a racemic mixture of the (R)- and (S)-enantiomers, were studied in adult male rats. The compound given by gavage in olive oil at doses of 25-200 mg/kg causes toxic effects on the pancreas that resemble those seen when naturally occurring CHB is given to rats. At 6 h after dosing, pancreatic edema is seen with doses of 100 mg/kg and greater. The edema fluid had a high protein content, indicating a marked increase in macromolecular permeability of the pancreatic microcirculation. A loss of zymogen granules from the acinar cells and a lacy supranuclear vacuolation of the acinar cell cytoplasm was observed. At 4 h after dosing, pancreatic nonprotein thiols were depleted and rebounded at 24 h to three times control values. At 120 h nonprotein thiol levels decreased but were still elevated compared with control values. Glutathione-S-transferase activity in the pancreas had a similar pattern of change with initial reduction, followed by elevation at 24 h. In rats with pancreatic and biliary fistulas, intraduodenal CHB caused a transient early stimulation of pancreatic juice secretion followed by a return to control values in the case of the lower doses of CHB and depression of flows at larger doses. All doses of CHB caused a dose-related depression of protein concentration in pancreatic juice. Pancreatic juice flow was almost abolished at doses of 200 mg/kg. CHB caused a dose-dependent choleresis accompanied by a marked reduction in bile acid concentrations in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

The effect of ferrous sulfate and pH on L-dopa absorption.

Ferrous sulfate decreases L-dopa bioavailability in humans probably as a result of binding of L-dopa by iron in the gastrointestinal tract. This study was conducted to determine if iron by binding L-dopa decreases L-dopa absorption and to investigate the effect of different pH buffers on intestinal absorption of L-dopa in the presence and absence of ferrous sulfate. A rat model developed to examine drug absorption was used. Control animals had buffered [14C]L-dopa solutions injected into two in vivo closed segments of intestine; a 5-cm duodenal and a 5-cm proximal jejunal segment. These studies were conducted using solutions buffered at pH 5.5, 6.5, 7.5, and 8.5. An identical procedure was followed for experimental animals except ferrous sulfate was injected with the buffered L-dopa solutions. Ferrous sulfate resulted in a reduction in L-dopa absorption in the buffers at all pHs in both the duodenum and jejunum. The average reduction in L-dopa absorption in the presence of iron was 22.6% in the duodenum and 23.9% in the jejunum. There was a tendency for ferrous sulfate to cause a greater reduction in L-dopa absorption as the buffer pH increased. There was also a decrease in L-dopa absorption in the higher pH buffers in the absence of iron. Despite this latter result, in the jejunum there was an increase in the percent reduction in L-dopa absorption associated with ferrous sulfate as pH increased. Although this tendency was not as consistent in the duodenum as the jejunum, the combined results are compatible with the chemical model of increased L-dopa--iron binding as pH increases.

Animals↗
PubMed1976

Abolition of direction selectivity in the visual cortex of the cat.

Cats were reared in a stroboscopically illuminated environment, which deprived them of expereience with visual movement but allowed them form vision. In these cats, neurons of the visual cortex displayed normal orientation selectivity, but direction selectivity was virtually abolished. The effect remained unaltered by long periods of normal visual exposure.

Animals↗