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Biomedical subjects

H Nguyen

Publications and source records attributed to H Nguyen.

At least 163 records · Page 9Linked to original sources
PubMed1995

Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions.

Oxidant-mediated damage is suspected to be involved in the pathogenesis of several neurodegenerative disorders. Iron promotes conversion of hydrogen peroxide to hydroxyl radical and, thus, may contribute to oxidant stress. We measured iron and its transport protein transferrin in caudate, putamen, globus pallidus, substantia nigra, and frontal cortex of subjects with Alzheimer's disease (n = 14) and Parkinson's disease (n = 14), and in younger adult (n = 8) and elderly (n = 8) normal controls. Although there were no differences between control groups with regard to concentrations of iron and transferrin, iron was significantly increased (p < 0.05) in Alzheimer's disease globus pallidus and frontal cortex and Parkinson's disease globus pallidus, and transferrin was significantly increased in Alzheimer's disease frontal cortex, compared with elderly controls. The transferrin/iron ratio, a measure of iron mobilization capacity, was decreased in globus pallidus and caudate in both disorders. Regional transferrin and iron concentrations were generally more highly correlated (Pearson's correlation coefficient) in elderly controls than in Alzheimer's and Parkinson's disease. The altered relationship between iron and transferrin provides further evidence that a disturbance in iron metabolism may be involved in both disorders.

Adult↗
PubMed1995

Loss of cell surface syndecan-1 causes epithelia to transform into anchorage-independent mesenchyme-like cells.

Simple epithelial cells are polygonal in shape, polarized in an apical-basal orientation, and organized into closely adherent sheets, characteristics that result from a variety of cellular specializations and adhesive proteins. These characteristics are lost when the epithelia transform during embryogenesis into mesenchymal cells or after neoplasia into invasive carcinoma cells. Of the syndecan family of transmembrane heparan sulfate proteoglycans, simple epithelia produce predominantly syndecan-1, which is found at basolateral surfaces and within adhesive junctions. To elucidate the function of this syndecan-1, normal murine mammary gland epithelia were made deficient in syndecan-1 by transfection with an expression vector containing the syndecan-1 cDNA in the antisense configuration. Several independently derived clones of stable transfectants contained the antisense cDNA in their genome and expressed the antisense transcript. These grew either as epithelial islands of closely adherent polygonal cells, identical to both the parental cells and the vector-only control transfectants, or as individual elongated fusiform cells that invaded and migrated within collagen gels, like mesenchymal cells, but were anchorage-independent for growth. The clones that retained epithelial characteristics were moderately deficient in cell surface syndecan-1 (greater than 48% of control levels) but did not differ from control cells in expression of beta 1-integrins and E-cadherin, or in F-actin organization. However, the clones of fusiform cells were severely deficient in cell surface syndecan-1 (less than 12% of control levels) and showed rearranged beta 1-integrins, markedly reduced E-cadherin expression, and disorganized F-actin filaments, but retained mammary epithelial markers. Therefore, depleting epithelia of cell surface syndecan-1 alters cell morphology and organization, the arrangement and expression of adhesion molecules, and anchorage-dependent growth controls. Thus, cell surface syndecan-1 is required to maintain the normal phenotype of simple epithelia.

Actins↗
PubMed1995

Cardiorespiratory transfer during sleep: a study in healthy young men.

This study tested the concept that changes in breathing parameters account for modifications in respiratory-related blood pressure (BP) and R-R interval (RRI) variability during nocturnal sleep. BP (Finapres), electrocardiogram, respiration (Respitrace), and polygraphic sleep recordings were recorded continuously in 13 healthy men aged 18-37 yr. The transfer characteristics identified by coherence and gain measures between the calibrated thoraco-abdominal motion and the respiratory-related BP and RRI variability evidenced a consistent increase during transitions from wake to light sleep and from light to deep sleep but returned to waking levels during rapid-eye-movement sleep (P < 0.0001). These changes were related to the specific modifications occurring in the respiratory rate, tidal volume, and ribcage-to-abdominal motion ratio during the different sleep stages (0.28 < r < 0.39; P < 0.0001). This study demonstrates 1) that modifications in the breathing pattern account for 8-15% of the variance in the cardiorespiratory transfer, and 2) that respiratory modulation of vagal activity is not the main mechanism controlling the magnitude of the respiratory-related BP and RRI variability during sleep.

Adolescent↗
PubMed1995

Magnetic resonance versus computed tomographic imaging in acute stroke.

BACKGROUND AND PURPOSE: This study was an attempt to determine whether CT and MRI are comparable or if one is superior to the other in the early detection of ischemic stroke or hematoma. METHODS: Patients with acute stroke were sought within 3 hours of onset for clinical examination and prospective evaluation by concurrently performed CT and MRI. Repeated clinical and imaging studies were undertaken when possible immediately after imaging and at 24 hours, 3 to 5 days, and 3 months. The study neurologists were blinded to the results of imaging, as were the study radiologists to the clinical findings. The study radiologists read the scans in sequence, mapping each imaging on standard templates before viewing a later scan. No retrospective revisions of imaging mapping of earlier images were undertaken. RESULTS: Sixty-eight patients were recruited within 4 hours and an additional 12 patients within 24 hours. Seventy-five strokes were due to infarction and five to hemorrhage. The median time to first scan was 132 minutes. Although some of the infarctions in 75 patients were detected within 1 hour, the fraction of positive first scans approached an asymptote at 2 to 3 hours. Overall, with the use of conventional non-contrast-enhanced CT and T1- and T2-weighted MRI, neither was superior in the very early detection of either hematoma or infarction. There was a marginally significant correlation between early positive brain imaging and the severity of the stroke. Some patients had initially positive CT and/or MRI scans, but their neurological examination had returned to normal by 24 hours. Overall, CT was better than baseline MRI at predicting 24-hour outcome. After 24 hours, both CT and MR more conspicuously defined the lesion limits than they did at baseline. CONCLUSIONS: With the technology available through 1991, neither CT nor MRI proved superior in the detection of the earliest signs of stroke.

Adolescent↗
PubMed1995

The role of free radicals in paraquat-induced corneal lesions.

Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following accidental splashing of paraquat solutions onto the eyes. These studies were designed to document the generation of paraquat free radicals in corneal tissue, and to describe the histological nature of the corneal injuries in experimental animals (rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. after intrastromal injection of paraquat, showed the signal of the free radical of paraquat. Ultrastructural studies of corneas 8 days after intrastromal injections (100 microliters) of paraquat solutions showed that the initial lesions occur at the epithelium/basement membrane interface. In rabbit cornea, dose dependent lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to the epithelial basement membrane, 75 mM caused complete dissolution to the basement membrane with some damage to stromal collagen, and loss of epithelium with stromal ulceration and severe inflammatory response were observed with 150 mM paraquat. Monkey corneas were less susceptible than those of rabbits to the effects of paraquat. No lesions were observed following intrastromal injections of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and 150 mM) the primary injuries were to the proximal and lateral plasma membranes of basal epithelial cells; basement membrane alterations were detected only adjacent to areas of significant plasma membrane damage. The underlying Bowman's membrane and stroma were not affected. Anatomical differences between the corneas of rabbit and monkeys as well as possible biochemical differences may account for the species differences observed.

Animals↗
PubMed1995

Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic breast epithelial cells.

The MDM2 gene is a nuclear phosphoprotein that is regulated by p53 and functions, in one capacity, to inhibit the transcriptional activity of the wild-type p53 protein. Multiple MDM2 transcripts were detected in human breast epithelial cells. In estrogen receptor-negative normal, immortal, and tumorigenic breast epithelial cells, we found a good correlation between MDM2 mRNA levels and expression of wild-type p53. When wild-type p53 was overexpressed in estrogen receptor-negative tumor cells containing a mutant or no endogenous p53, MDM2 mRNA levels increased significantly, indicating that wild-type p53 positively influences MDM2 mRNA levels in these tumor cells. Because all estrogen receptor-positive breast tumor cells had high MDM2 mRNA levels regardless of the status of their endogenous p53 protein, other factors likely influence MDM2 expression in these cells. Distinct MDM2 proteins (range, Mr 54,000-68,000 and 90,000-100,000, respectively) were differentially expressed in human breast epithelial cells. The lower molecular weight MDM2 proteins were most abundant in the normal mammary cells but present at varying levels in many of the tumor cells examined. MDM2 was a nuclear protein; however, nuclear staining intensity did not always correlate with the amount of MDM2-immunoreactive protein as determined by Western blot analysis. This discrepancy suggests that MDM2 interacts with novel cellular proteins in different kinds of breast epithelial cells.

Breast↗
PubMed1995

Cytotoxic effects of adenovirus-mediated wild-type p53 protein expression in normal and tumor mammary epithelial cells.

To evaluate the effects of the wild-type p53 expression in normal and tumor cells, we have constructed a recombinant adenovirus vector (E1 minus) expressing human wild-type p53 cDNA (AdWTp53). Infection of normal and tumor cells of lung and mammary epithelial origin with AdWTp53 resulted in high levels of wild-type p53 expression. Production of p53 protein following infection was dependent on the dose of AdWTp53 with maximum amounts of p53 produced following infection with 50 plaque-forming units/cell. AdWTp53 infection inhibited the growth of all human cell lines studied. However, tumor cells that were null for p53 prior to infection (H-358 and MDA-MB-157) and tumor cells that expressed mutant endogenous p53 protein (MDA-MB-231 and MDA-MB-453) were more sensitive to AdWTp53 cytotoxicity than cells that contained the wild-type p53 (MCF-7, MCF-10, 184B5, and normal mammary epithelial cells). All cells exhibited WAF1/Cip1 mRNA and protein induction following AdWTp53 infection. AdWTp53-induced cytotoxicity of human tumor cell lines expressing mutant p53 was mediated by apoptosis as revealed by nucleosomal DNA fragmentation analysis. No detectable nucleosomal DNA fragmentation was observed following AdWTp53 infection of human cells expressing wild-type p53. These data suggest that endogenous p53 status is a determinant of AdWTp53-mediated cell killing of human tumor cells.

Adenoviruses, Human↗
PubMed1994

Mutational analysis of interferon (IFN) regulatory factors 1 and 2. Effects on the induction of IFN-beta gene expression.

Interferon (IFN) regulatory factor 1 (IRF-1) and IRF-2 are structurally similar but functionally distinct transcription factors that bind to the positive regulatory domains I and III (PRDI/III) within the human IFN-beta promoter. To begin structure-function analysis of IRF-1 and IRF-2, the regulatory potential of carboxyl-terminal deletion mutants was analyzed by co-transfection studies in human cells and was correlated with DNA binding capacity. Transcriptional repression by IRF-2 was contained within the first 125 amino-terminal amino acids and correlated directly with IRF-2 DNA binding; deletion to a protein of 100 amino acids resulted in loss of repression and IRF-2 DNA binding. Thus, the carboxyl terminus appears dispensible for trans-repression. Hybrid constructs which fuse the DNA binding domain of IRF-1 and IRF-2 to the trans-activation domain of NF-kappa B p65 were also generated; both IRF-1/p65 and IRF-2/p65 chimeras were strong transcriptional activators. IRF-2-mediated repression was also dominant over trans-activation by these fusion proteins. The trans-activation region of IRF-1 resides in the carboxyl terminus, primarily carboxyl-terminal to amino acid 250. Mutation of three potential casein kinase II phosphorylation sites within the IRF carboxyl terminus failed to identify an essential site that contributes to IRF-1 trans-activation potential.

Base Sequence↗
PubMed1994

Na-K-2Cl cotransport in intestinal epithelial cells. Influence of chloride efflux and F-actin on regulation of cotransporter activity and bumetanide binding.

Although cAMP-dependent epithelial chloride secretion is largely regulated via apical membrane chloride channels, cAMP also remodels basolateral F-actin and activates basolateral Na-K-2Cl cotransport. Whether activation of cotransport is a primary event or secondary to activation of chloride efflux is not established, and the basis for the cytoskeletal dependence is unknown. We studied cotransport in the intestinal line HT29 (which lacks cAMP-regulated chloride efflux) and in its subclone Cl.19A (in which this pathway is present). Cotransporter activity was enhanced by forskolin in both lines but to a considerably greater extent in subclone Cl.19A, in which the number of bumetanide binding sites was also observed to increase. The F-actin stabilizer phalloidin markedly attenuated cAMP-stimulated cotransport in Cl.19A monolayers, but the increase in bumetanide binding was preserved. These studies identify two mechanisms for activation of Na-K-2Cl cotransport by cAMP: components independent and dependent of cAMP-elicited chloride efflux. Additional Na-K-2Cl cotransporters become accessible to the cell surface coincident with the salt efflux-dependent activation of cotransport. While F-actin rearrangements influence salt efflux-dependent up-regulation of the cotransporter, this influence occurs independently of increases in bumetanide-accessible cotransporters.

Actins↗
PubMed1994

A faster-acting and more potent form of tissue plasminogen activator.

Current treatment with tissue plasminogen activator (tPA) requires an intravenous infusion (1.5-3 h) because the clearance of tPA from the circulation is rapid (t 1/2 approximately 6 min). We have developed a tPA variant, T103N,N117Q, KHRR(296-299)AAAA (TNK-tPA) that has substantially slower in vivo clearance (1.9 vs. 16.1 ml per min per kg for tPA in rabbits) and near-normal fibrin binding and plasma clot lysis activity (87% and 82% compared with wild-type tPA). TNK-tPA exhibits 80-fold higher resistance to plasminogen activator inhibitor 1 than tPA and 14-fold enhanced relative fibrin specificity. In vitro, TNK-tPA is 10-fold more effective at conserving fibrinogen in plasma compared to tPA. Arterial venous shunt models of fibrinolysis in rabbits indicate that TNK-tPA (by bolus) induces 50% lysis in one-third the time required by tPA (by infusion). TNK-tPA is 8- and 13-fold more potent in rabbits than tPA toward whole blood clots and platelet-enriched clots, respectively. TNK-tPA conserves fibrinogen and, because of its slower clearance and normal clot lysis activity, is effective as a thrombolytic agent when given as a bolus at a relatively low dose.

Animals↗
PubMed1994

An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures.

Basic fibroblast growth factor (bFGF) is a hematopoietic cytokine that stimulates stromal and stem cell growth. It binds to a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan on human bone marrow (BM) stromal cells. The bFGF-proteoglycan complex is biologically active and is released by addition of exogenous phosphatidylinositol-specific phospholipase C. In this study, we show the presence of an endogenous GPI-specific phospholipase D (GPI-PLD) that releases the bFGF-binding heparan sulfate proteoglycan and the variant surface glycoprotein (a model GPI-anchored protein) from BM cultures. An involvement of proteases in this process is unlikely, because released proteoglycan contained the GPI anchor component, ethanol-amine, and protease inhibitors did not diminish the release. The mechanism of release is likely to involve a GPI-PLD and not a GPI-specific phospholipase C, because the release of variant surface glycoprotein did not reveal an epitope called the cross-reacting determinant that is exposed by phospholipase C-catalyzed GPI anchor cleavage. In addition, phosphatidic acid (which is specifically a product of GPI-PLD-catalyzed anchor cleavage) was generated during the spontaneous release of the GPI-anchored variant surface glycoprotein. We also detected GPI-PLD-specific enzyme activity and mRNA in BM cells. Therefore, we conclude that an endogenous GPI-PLD releases bFGF-heparan sulfate proteoglycan complexes from human BM cultures. This mechanism of GPI anchor cleavage could be relevant for mobilizing biologically active bFGF in BM. An endogenous GPI-PLD could also release other GPI-anchored proteins important for hematopoiesis and other physiologic processes.

Adult↗
PubMed1994

Release of GPI-anchored membrane proteins by a cell-associated GPI-specific phospholipase D.

Although many glycosylphosphatidylinositol (GPI)-anchored proteins have been observed as soluble forms, the mechanisms by which they are released from the cell surface have not been demonstrated. We show here that a cell-associated GPI-specific phospholipase D (GPI-PLD) releases the GPI-anchored, complement regulatory protein decay-accelerating factor (DAF) from HeLa cells, as well as the basic fibroblast growth factor-binding heparan sulfate proteoglycan from bone marrow stromal cells. DAF found in the HeLa cell culture supernatants contained both [3H]ethanolamine and [3H]inositol, but not [3H]palmitic acid, whereas the soluble heparan sulfate proteoglycan present in bone marrow stromal cell culture supernatants contained [3H]ethanolamine. 125I-labeled GPI-DAF incorporated into the plasma membranes of these two cell types was released in a soluble form lacking the fatty acid GPI-anchor component. GPI-PLD activity was detected in lysates of both HeLa and bone marrow stromal cells. Treatment of HeLa cells with 1,10-phenanthroline, an inhibitor of GPI-PLD, reduced the release of [3H]ethanolamine-DAF by 70%. The hydrolysis of these GPI-anchored molecules is likely to be mediated by an endogenous GPI-PLD because [3H]ethanolamine DAF is constitutively released from HeLa cells maintained in serum-free medium. Furthermore, using PCR, a GPI-PLD mRNA has been identified in cDNA libraries prepared from both cell types. These studies are the first demonstration of the physiologically relevant release of GPI-anchored proteins from cells by a GPI-PLD.

Antigens, CD↗
PubMed1994

Cloning and sequencing of the gene encoding spinach ferredoxin-dependent glutamate synthase.

The nucleotide sequences of two cDNA clones, totalling 4948 bp in length, encoding 98% of the 1483 amino acids of the mature form of the ferredoxin-dependent glutamate synthase of spinach chloroplasts have been determined. The amino-terminal sequence of the enzyme has been determined by direct sequencing of the protein. The deduced amino-acid sequence of the spinach enzyme is 83% identical to that of the ferredoxin-dependent maize enzyme and shows significant sequence homology to two prokaryotic NAD(P)H-dependent glutamate synthases. Analysis of spinach genomic DNA indicates the presence of a single-copy gene for the spinach enzyme. Northern analysis reveals the presence of a single 5.5 kb transcript, which is present in higher levels in young spinach leaves than in older leaves.

Amino Acid Sequence↗
PubMed1994

Mechanisms and sites of mannitol permeability of small and large intestine in the rat.

Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms of its penetration of the intestinal barrier are not entirely clear. Therefore, we studied mannitol's permeability of different segments of the intestine and studied the kinetics and influence of intraluminal factors on mannitol permeability in vivo in perfused intestinal segments of rats. There was linear relationship between permeability rate of mannitol and its luminal concentration (y = 7.2x + 1.7; r = 0.98), indicating that passive diffusion is involved in mannitol's permeability. Increased luminal fluid osmolarity from 0.3 to 0.6 osmol/liter resulted in decreased net water flux with a corresponding decrease in mannitol permeability in both jejunum and colon (P < 0.01), indicating the prominent influence of solvent drag on net mannitol permeability. The relationship between mannitol permeability and water absorption at different osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3 osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and 65.4% was mediated by solvent drag in the jejunum. Mannitol permeability was much more dependent on solvent drag in the colon (88.9%) than in the small intestine (65.4%). The net permeability rate of mannitol was similar in the jejunum and ileum but was much higher in the colon (P < 0.01). Addition of chenodeoxycholate (5 mM) to the perfusate resulted in a significant decrease in absorption of water (P < 0.01) with a corresponding decrease in mannitol permeability (P < 0.01). These studies indicate that mannitol permeability of the intestinal barrier is mediated by passive diffusion and solvent drag, with the latter accounting for a greater fraction of the total permeability.

Animals↗
PubMed1994

Management of full thickness burns to lactating breasts.

A 19-year-old female sustained 8 per cent full thickness petrol flame burns to the neck, chest, breasts, upper abdomen and portions of the right upper limb. The patient had been breast-feeding until the time of the injury. Following assessment of the risks of potential complications such as engorgement, hyperprolactinaemia, mastitis, milk fistulae, glandular loss, scarring and nipple distortion, surgical tangential excision was delayed until bromocriptine produced cessation of lactation and breast involution occurred. This case report demonstrates that consideration of the potential problems in burns to the lactating breasts and prophylactic management can lead to successful healing and probable restoration of function.

Adult↗
PubMed1994

A randomized double-blind trial of vancomycin versus teicoplanin for the treatment of gram-positive bacteremia in patients with cancer.

In a prospective, randomized, double-blind study comparing teicoplanin and vancomycin for the treatment of gram-positive bacteremias in neutropenic patients, teicoplanin was given at 6 mg/kg of body weight every 24 h intravenously (i.v.) after initial loading every 12 h for three doses, while vancomycin was administered at 15 mg/kg every 12 h i.v. At enrollment, both groups were comparable in age, sex, underlying hematologic or neoplastic disorder, baseline renal functions, and incidence of neutropenia. Treatment was successful in 19 (90%) of 21 patients who received teicoplanin and 24 (96%) of 25 who received vancomycin (P = .58). Adverse reactions occurred more often in the vancomycin group (31%) than in the teicoplanin group (9%; P = .06) and were primarily cutaneous or gastrointestinal. In conclusion, teicoplanin was better tolerated than vancomycin, and no statistically significant difference in efficacy was detected with the sample size in this study.

Adult↗
PubMed1994

Bilateral simultaneous groin flaps in the salvage of a pediatric blast-injured hand.

The groin flap was first described by McGregor and Jackson in 1972. Since then it has been applied to a wide variety of reconstructive problems. The flap is amenable to both staged and free tissue transfer and can provide cutaneous or composite tissues. However, use of this flap in the pediatric population has been limited. We herein describe the first known case of simultaneous bilateral staged groin flaps for salvage of a blast-injured hand in a child.

Blast Injuries↗