Search PubMed⌕ Search

Biomedical subjects

K Nguyen

Publications and source records attributed to K Nguyen.

At least 73 records · Page 4Linked to original sources
PubMed1995

CYP-2E1 inhibitors partially ameliorate the changes in hepatic fatty acid composition induced in rats by chronic administration of ethanol and a high fat diet.

The objective of this study was to determine if ethanol-induced cytochrome P450 2E1 (CYP2E1) was responsible for the changes in hepatic fatty acids observed in rats fed ethanol intragastrically. We hypothesized that if CYP2E1 was responsible for these changes then CYP2E1 inhibitors fed with ethanol should prevent the ethanol-induced changes in fatty acids. We compared the fatty acid composition of the liver in rats fed ethanol alone with that in rats fed ethanol with the CYP2E1 inhibitors, diallyl sulfide and phenethyl isothiocyanate. In each experiment, rats pair-fed isocaloric glucose were included to determine the effect of the inhibitors alone on the hepatic fatty acid composition. The lobular distribution of succinic dehydrogenase was determined histochemically because the lobular distribution of CYP2E1 shifts to the periportal area in livers of rats fed CYP2E1 inhibitors. The CYP2E1 inhibitors ameliorated both the ethanol-induced changes in fatty acids and the shift in succinic dehydrogenase. Rats fed ethanol but no inhibitors had significantly greater hepatic total fatty acids and triglyceride fractions than when inhibitors were fed ethanol. Ethanol altered the fatty acid composition compared with rats fed ethanol with CYP2E1 inhibitors. The ratio of 20:4/18:2 was significantly lower and that of 18:1/18:0 was greater in alcohol-fed rats compared with their pair-fed controls. The CYP2E1 inhibitors inhibited many of the above effects of alcohol. The data suggest that the changes in the fatty acid composition due to ethanol ingestion are the result of CYP2E1-dependent lipid peroxidation and fatty acid metabolism.

Allyl Compounds↗
PubMed1995

Regional and segmental localization of AE2 anion exchanger mRNA and protein in rat kidney.

Chloride/base exchange activity has been detected in every mammalian nephron segment in which it has been sought. However, in contrast to the Cl-/HCO3- exchanger AE1 in type A intercalated cells, localization of AE2 within the kidney has not been reported. We therefore studied AE2 expression in rat kidney. AE2 mRNA was present in cortex, outer medulla, and inner medulla. Semiquantitative polymerase chain reaction of cDNA from microdissected tubules revealed AE2 cDNA levels as follows [copies of cDNA derived per mm tubule (+/- SE)]: proximal convoluted tubule, 688 +/- 161; proximal straight tubule, 652 +/- 189; medullary thick ascending limb, 1,378 +/- 226; cortical thick ascending limb, 741 +/- 24; cortical collecting duct, 909 +/- 71; and outer medullary collecting duct, 579 +/- 132. AE2 cDNA was also amplified in thin limbs and in inner medullary collecting duct. AE2 polypeptide was detected in all kidney regions. AE2 mRNA and protein were also detected in several renal cell lines. The data are compatible with the postulated roles of AE2 in maintenance of intracellular pH and chloride concentration and with its possible participation in transepithelial transport.

Animals↗
PubMed1994

Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13.

A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.

Breast Neoplasms↗
PubMed1994

Comparison of cord blood and peripheral blood mononuclear cells as targets for viral isolation and drug sensitivity studies involving human immunodeficiency virus type 1.

We have shown that umbilical cord blood mononuclear cells (CBMC) are at least as sensitive as peripheral blood mononuclear cells (PBMC) for isolation of human immunodeficiency virus type 1 from the PBMC of infected individuals. Viral replication was more efficiently monitored by a p24 antigen capture assay than by a viral reverse transcriptase test, regardless of whether CBMC or PBMC were employed. We also found that CBMC and PBMC yielded similar results with regard to the susceptibility profiles of both wild-type and drug-resistant variants of human immunodeficiency virus type 1 for 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine. Finally, viruses isolated on CBMC could be routinely grown on PBMC and vice versa.

Antiviral Agents↗
PubMed1994

Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus.

Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.

Animals↗
PubMed1993

Peripheral nerve regeneration across 14-mm gaps: a comparison of autograft and entubulation repair methods in the rat.

A study was conducted to compare the regeneration across 1.4-cm peroneal nerve gaps in rats, repaired with sutured autografts or with artificial nerve grafts. The artificial models were composed of a biodegradable passive conduit made of glycolide trimethylene carbonate, filled with either phosphate-buffered saline or a collagen extracellular matrix. Functional recovery was evaluated by walking track analysis throughout the experiment. After 9 months, the nerves were analyzed by electrophysiology and by qualitative and quantitative histology. Walking track analysis demonstrated the three repair methods to provide statistically equivalent recovery, except at day 195 post-engraftment, when the collagen-filled conduit was superior to the saline-filled conduit. Electrophysiologically, the autograft was superior to the collagen-filled conduit, while the collagen- and saline-filled conduits were equivalent. Quantitative histology demonstrated that normal intact nerve had larger mean myelinated axonal diameters but an equal number of axons to the three repair methods, and that the repair methods were statistically equivalent. While the repair methods had similar histologic and functional outcomes, combined standardized scoring demonstrated that the autograft was superior to the statistically-equivalent entubulation repairs. A collagen gel may serve as an ideal matrix in which to suspend neurotrop(h)ic factors or cells.

Action Potentials↗
PubMed1993

The effects of photofrin on human Tenon's capsule fibroblasts in vitro.

Pharmacological agents that modulate the wound healing process by inhibiting fibroblast proliferation may improve the success of proliferative vitreoretinopathy and glaucoma filtration surgery and may have applications in other surgical fields. It is possible that light-absorbing chemicals can be used to cause photo reactions in proliferating fibroblasts as a means of controlling this wound healing process. We present the effects of photofrin porfimer sodium (serial tenfold dilutions 1000-0.00001 micrograms/ml) on human fibroblasts from Tenon's capsule in vitro, with and without photoactivation with Argon green laser (700 mW for 1 and 5 minutes) and with bright sunlight (for 1 and 5 min). The cell density was measured on day 2 by 3H-thymidine uptake and on day 9 by means of a coulter counter, and optical density was measured in terms of the activity of the enzyme hexosaminidase. Each experiment was performed three times in quadruplicate. The counts were averaged for each drug concentration and mean cell count with a standard error as well as the 50% inhibitory doses (ID50s) were calculated. Photofrin demonstrated an inhibitory dose response curve (dark toxicity) to human fibroblasts. Concentrations greater than 100 micrograms/ml of photofrin alone completely inhibited cell growth. Concentrations less than 0.01 micrograms/ml did not have any effect on fibroblast proliferation. There was no significant log dose shift of the inhibitory effect of photofrin with the exposure to either sunlight or Argon laser. Photofrin may be used as a cytotoxic agent alone but does not appear to be activated by light to modulate subconjunctival fibroblast proliferation within the laser parameters used.

Cell Count↗
PubMed1993

Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye.

PURPOSE: To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues. METHODS: Two drops of 20 microliters FK506 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-FK506) drug. FK506 concentrations were measured at intervals of 30, 60, and 120 minutes by immunoassay. RESULTS: After application of OD-FK506, the highest concentrations of FK506 were found in the cornea and the conjunctiva (200-1200 ng/g) with substantial drug also present in anterior and posterior sclera. Relatively low concentrations were measured in the aqueous and vitreous humors (0.2-1.0 ng/g) of these animals. Using the same treatment regimen, LIP-FK506 was effective in delivering significantly higher drug concentrations (P < 0.05) to all ocular tissues and particularly aqueous humor (5-28 ng/g) and vitreous humor (12-22 ng/g) at all time points. During the observation period drug concentrations produced by LIP-FK506 remained well above the therapeutic range. FK506 levels were not detectable in serum (< 0.2 ng/ml) with either drug formulation. CONCLUSION: These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.

Absorption↗
PubMed1992

CI-973, a new platinum derivative with potential antileukemic activity.

We examined the effects of CI-973 (supplied by Parke-Davis) on several human leukemia cell lines and a Chinese hamster ovary (CHO) line and their drug-resistant counterparts. The cell lines used were HL-60, HL-60/mAMSA, HL-60/DOX, KBM3, KBM3/mAMSA 6, KBM3/mAMSA 6(85), CHO, and CHO/AC-7. DOX, mAMSA, and AC-7 indicate resistance to doxorubicin, amsacrine, or 1-beta-D-arabinofuranosylcytosine, respectively. Cells were incubated with CI-973, and the effect was evaluated by two methods: growth inhibition assay and inhibition of colony formation. All cell lines examined were inhibited by CI-973; two of three amsacrine-resistant lines and the one cytarabine-resistant line demonstrated collateral sensitivity. At equivalent dosages, a 4-day exposure provided much greater cell kill than a 1-h exposure. Clonogenic assay showed exponential killing over 3 log units. Maximum CI-973 levels required to kill 50% of cells were 10-fold lower than the peak plasma levels achieved in a phase I solid tumor study. A continuous infusion phase I study in acute leukemia has been initiated.

Animals↗
PubMed1991

Prejunctional effects of opioids in the perfused mesentery of the rat and rabbit: interactions with alpha 2-adrenoceptors.

Prejunctional effects of opioids were examined in the perfused mesentery of two species: the rat and rabbit. Use of agonists selective for subtypes of mu, delta, and kappa opioid receptors produced no effect on contractile responses to adrenergic nerve stimulation in the rat perfused mesentery, except for small effects of the kappa agonist EKC, which may be non specific. In contrast, mu, delta and kappa receptors appear to be present in the rabbit. The mu selective agonist, DAMGO, kappa agonist, ethylketocyclazocine, and delta agonists, DPDPE and [Leu5]-enkephalin, all produced significant inhibition of contractile responses to transmural nerve stimulation. The inhibitory effect was greatest for ethylketocyclazocine. To test the possibility that prejunctional activation of alpha 2 adrenoceptors with endogenous norepinephrine might decrease the activity of prejunctional opioid receptors in the rabbit, inhibitory effects of delta and kappa selective agonists were tested in the presence of 10(-7) M yohimbine. Inhibitory responses of the kappa selective agonist ethylketocyclazocine were enhanced, while that of delta selective agonists [Leu5]-enkephalin and DPDPE remained unchanged when yohimbine was present. Thus, the effects of opioids vary and depend on the tissue and receptor subtypes they act upon. Furthermore, the enhanced inhibitory effect of opioid receptor activation in the presence of yohimbine is not found for all opioid receptors.

Adrenergic Fibers↗
PubMed1991

Localization of the highly polymorphic microsatellite DXS456 on the genetic linkage map of the human X chromosome.

The CA repeat microsatellite DXS456, with a heterozygosity of 77%, has been localized by multipoint linkage analysis in relation to 20 other genetic markers. DXS456 mapped to a 4.2-cM interval defined by the flanking markers DXS178 and DXS287. The maximum likelihood order of markers, cen-(DXYS1X/DXYS13X/DXYS2X/DXYS12X)-DXS366 -DXS178-DXS456-DXS287-DXS358-DXS267- qter, is favored by odds greater than 1000:1 over the subset of most likely alternative orders. Linkage of DXS456 can be inferred for at least six disease genes that are known to be linked to markers in the region Xq21.31-Xq25 and the marker will serve as an important index point for orienting these and other disease and marker loci in the region.

Chromosome Mapping↗
PubMed1991

Plain film of intracardiac foreign bodies: the blurring effect.

We report two cases of gunshot wounds of the chest, in each of which a bullet was retained in the pericardial sac. Because the bullets appear to be out of focus, one may think they are in the cardiac chambers, but the images of bullets retained in the pericardial sac may also be blurred due to the spinning effect of the heartbeat on the bullet.

Adult↗