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Biomedical subjects

L Nguyen

Publications and source records attributed to L Nguyen.

At least 91 records · Page 5Linked to original sources
PubMed1998

Outbreak of nosocomial urinary tract infections due to Pseudomonas aeruginosa in a paediatric surgical unit associated with tap-water contamination.

An outbreak of 14 cases of urinary tract infections by Pseudomonas aeruginosa, including six symptomatic infections, occurred from September to November 1994 in a paediatric surgical unit. During the outbreak, urine samples from patients and multiple samples from the environment of patients were tested for the presence of P. aeruginosa. Bacterial isolates were studied by pulsed-field gel electrophoresis. Genotypic analysis showed that most of the isolates from children were different. Multiple P. aeruginosa isolates were also found in the tap water, as the only putative source of contamination. Two of these isolates were identified in two infected patients, indicating possible direct contamination of patients via tap water and this was related to the distal colonization of faucets. Bacteria were eradicated from tap water by replacement of taps. The cluster of cases of P. aeruginosa urinary infection was, therefore, related to multiple contaminations through tap water. These results illustrate an unexpected risk of nosocomial infection and emphasizes the importance of checking tap water to prevent bacterial contamination through handwashing in contaminated water.

Child↗
PubMed1998

L-type Ca2+ currents in ventricular myocytes from neonatal and adult rats.

Postnatal changes in the slow Ca2+ current (I(Ca)(L)) were investigated in freshly isolated ventricular myocytes from neonatal (1-7 days old) and adult (2-4 months old) rats, using whole-cell voltage clamp and single-channel recordings. The membrane capacitance (mean+/-SEM) averaged 23.2+/-0.5 pF in neonates (n = 163) and 140+/-4.1 pF in adults (n = 143). I(Ca)(L) was measured as the peak inward current at a test potential of +10 mV (or +20 mV) by applying a 300-ms pulse from a holding potential of -40 mV; 1.8 mM Ca2+ was used as charge carrier. The basal ICa(L) density was 6.7+/-0.2 pA/pF in neonatal and 7.8+/-0.2 pA/pF in adult cells (p < 0.05). The time course of inactivation of the fast component (at +10 ms) was significantly longer in the neonatal (10.7+/-1.4 ms) than in the adult (6.6+/-0.4 ms) cells (p < 0.05). Ryanodine (10+/-M) significantly increased this value to 18.0+/-1.9 in neonate (n = 8) and to 17.7+/-2.0 in adult (n = 9). For steady-state inactivation, the half-inactivation potential (Vh) was not changed in either group. For steady-state activation, Vh was 5.1 mV in the neonatal (n = 6) and -7.9 mV in the adult cells (n = 7). Single-channel recordings revealed that long openings (mode-2 behavior) were occasionally observed in the neonatal cells (11 events from 1080 traces/11 cells), but not in the adult cells (400 traces/4 cells). Slope conductance was 24 pS in both the neonatal and adult cells. Results in rat ventricular myocytes suggest the following: (i) the peak Ca2+ current density is already well developed in the neonatal period (being about 85% of the adult value); (ii) the fast component of inactivation is slower in neonates than in adults; and (iii) naturally occurring long openings are occasionally observed in the neonatal stage but not in the adult. Thus, the L-type Ca2+ channels of the neonate were slightly lower in density, were inactivated more slowly, and occasionally exhibited mode-2 behavior as compared with those of the adult.

Age Factors↗
PubMed1997

Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356.

Hepatocyte growth factor/scatter factor is a multifunctional factor that induces mitogenesis, motility, invasion, and branching tubulogenesis of several epithelial and endothelial cell lines in culture. The receptor for hepatocyte growth factor has been identified as the Met-tyrosine kinase. Upon stimulation with hepatocyte growth factor, the Met beta subunit becomes highly phosphorylated on tyrosine residues, one of which, tyrosine 1356 within the carboxyl terminus, is crucial for dissociation, motility, and branching tubule formation in Madin-Darby canine kidney epithelial cells. Tyrosine 1356 forms a multisubstrate binding site for the Grb2 and Shc adaptor proteins, the p85 subunit of phosphatidylinositol 3'-kinase, phospholipase Cgamma, and a phosphatase, SHP2. To investigate additional signaling molecules that are activated by the Met receptor, we have identified hepatocyte growth factor-induced phosphoproteins in tubular epithelial cells. We have established that proteins of 100-130 kDa are highly phosphorylated following stimulation of epithelial cells and that one of these is the Grb2-associated binding protein Gab1, a possible insulin receptor substrate-1-like signal transducer. We show that Gab1 is the major substrate for the Met kinase in vitro and in vivo. Association of Gab1 with Met requires a functional Grb2 binding site involving tyrosine 1356 and to a lesser extent tyrosine 1349. Met receptor mutants that fail to induce branching tubulogenesis are impaired in their ability to interact with Gab1, suggesting that Gab1 may play a role in these processes.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1.

The Tpr-Met oncoprotein consists of the catalytic kinase domain of the hepatocyte growth factor/scatter factor receptor tyrosine kinase (Met) fused downstream from sequences encoded by the tpr gene. Tpr-Met is a member of a family of tyrosine kinase oncoproteins generated following genomic rearrangement and has constitutive kinase activity. We have previously demonstrated that a single carboxyl-terminal tyrosine residue, Tyr489, is essential for efficient transformation of Fr3T3 fibroblasts by Tpr-Met and forms a multisubstrate binding site for Grb2, phosphatidylinositol 3' kinase, phospholipase Cgamma, SHP2, and an unknown protein of 110 kDa. A mutant Tpr-Met protein that selectively fails to bind Grb2 has reduced transforming activity, implicating pathways downstream of Grb2 in Tpr-Met mediated cell transformation. We show here that the 110-kDa Tpr-Met substrate corresponds to the recently identified Grb2-associated protein, Gab1. Moreover, we show that tyrosine phosphorylation of the Cbl protooncogene product as well as Gab1 required Tyr489 and correlated with the ability of Tpr-Met to associate with Grb2 and to transform cells, providing evidence that pathways downstream of Gab1 and/or Cbl may play a role in Tpr-Met-mediated cell transformation.

3T3 Cells↗
PubMed1997

Sitosterolemia.

Explore the source record for details and available documents.

Bile Acids and Salts↗
PubMed1997

Physiologic motion after laryngeal nerve reinnervation: a new method.

In this study a new method of reinnervation for unilateral recurrent laryngeal nerve paralysis was performed in canines, producing physiologic vocal fold motion in each of a small series of animals. During the procedure the left anterior division of the recurrent laryngeal nerve was reinnervated with axons from the thyroarytenoid branch of the contralateral recurrent laryngeal nerve. The posterior branch of the left recurrent laryngeal nerve was divided and sutured to the ansa cervicalis to maintain tone in the posterior cricoarytenoid muscle. In all four animals, the right distal vocalis stump was reinnervated with an ansa cervicalis nerve branch. After 3 months physiologic vocal fold motion and electromyographic activity could be demonstrated during mechanical stimulation of the supraglottis (adduction) and during tracheostomy obstruction (abduction). Acoustic data revealed improvement of jitter, shimmer, signal-to-noise ratio, and vocal efficiency in reinnervated animals compared with paralyzed canines before treatment, although the results lacked statistical significance. This approach to the rehabilitation of unilateral vocal fold paralysis is discussed.

Acoustics↗
PubMed1997

Collagen implants do not preserve periodontal ligament homeostasis in periodontal wounds.

An improved understanding of the differentiation of periodontal ligament cells could facilitate the development of new treatment approaches for overcoming the loss of specialized cell types caused by periodontitis. To study healing of wounded periodontal tissues and the differentiation of mineralizing connective tissue cells in periodontal ligament, we have examined the influence of wound size and collagen implantation on the regeneration of periodontium and on immunohistochemical staining for osteopontin and bone sialoprotein. Four groups of Wistar rats were wounded by drilling through the alveolar bone and by extirpation of the periodontal ligament. Wounds were 0.6 or 1.8 mm in diameter and defects were either implanted with collagen gels or were treated without implants. Rats were killed at 1 wk or 2 months after wounding and tissue sections were stained with monoclonal antibodies against rat osteopontin and bone sialoprotein. Collagen implants strongly increased staining for osteopontin and bone sialoprotein in defects at 1 wk. By 2 months alveolar bone healed completely regardless of the wound size but in large defects, periodontal ligament width was significantly reduced with or without implants. In large wounds at 2 months, collagen implants inhibited bone regeneration and there was stronger staining for osteopontin and bone sialoprotein in the bone replacing the implant, indicating that collagen prolonged bone remodelling. We conclude that implantation of exogenous collagen affects alveolar bone healing but does not preserve the width of the regenerated periodontal ligament. Therefore collagen does not appear to contribute to homeostasis in the periodontium following wounding.

Alveolar Process↗
PubMed1997

Molecular epidemiology of Streptococcus pyogenes in an area where acute pharyngotonsillitis is endemic.

During an open clinical trial in an area where streptococcal infections are hyperendemic, we studied the genetic polymorphism of Streptococcus pyogenes isolates collected from patients and from healthy carriers living in close contact with them. The clonal diversity of isolates was analyzed by pulsed-field gel electrophoresis with three restriction enzymes (SmaI, ApaI, and SacII). The pharynx of each patient and healthy carrier was colonized by a single clone, suggesting the clonal nature of streptococcal colonization in individuals. Among 52 isolates obtained from patients with acute pharyngotonsillitis, we found 14 genetically unrelated clones, showing the genetic diversity of S. pyogenes. However, two clones belonging to the M1 and M12 serotypes represented about 70% of isolates in carriers and patients. Pharyngeal colonization in cured patients was monitored for 3 to 4 months. After the initial elimination of S. pyogenes following antibiotic therapy, the rate of recolonization was high by day 30 (about 20%) and was also at that level between days 90 and 120; this was similar to the carriage rate in family contacts. Thus, cured patients can be recontaminated by unrelated clones, suggesting that colonization of healthy carriers might be a potential source of spread and redistribution of S. pyogenes isolates.

Acute Disease↗
PubMed1997

[Inefficacy of exchange-transfusion in case of a methotrexate poisoning].

We report on a case of methotrexate (MTX) intoxication occurring in a 19-year-old man treated for a leukemia. Exchange-transfusion (ET) was performed in attempt to remove the MTX from the body. This exchange-transfusion was unable to decrease the MTX plasma concentration. This inefficacy of ET in MTX intoxication is in contradiction with previously reported recommendations. However, this result is easily explained by MTX pharmacokinetics parameters.

Acute Kidney Injury↗
PubMed1996

Differences in isoproterenol stimulation of Ca2+ current of rat ventricular myocytes in neonatal compared to adult.

The developmental changes in the isoproterenol stimulation of the L-type calcium current (ICa(L)) were studied in freshly isolated neonatal (3-5-day-old) and adult (2-3-month-old) rat ventricular myocytes using whole-cell voltage clamp (at room temperature). ICa(L) was measured as the peak inward current at a test potential of +10 mV (or +20 mV) by applying a 300 ms pulse from a holding potential of -40 mV. The pipette solution was Cs(+)-rich and Ca(2+)-free. The external solution was Na(+)-free and K(+)-free. Isoproterenol stimulated ICa(L) in a dose-dependent manner. The concentrations of isoproterenol for half-maximal effect were 6.8 nM in neonatal and 13.3 nM in adult. The maximal stimulation of ICa(L) was 147 +/- 14% in neonatal and 97 +/- 7% in adult. The steady-state inactivation curves were not affected by isoproterenol, whereas the steady-state activation curve was shifted to the left in both neonatal and adult. Forskolin (10 microM) increased ICa(L) by 105 +/- 10% in neonatal and 90 +/- 12% in adult. After stimulating ICa(L) by forskolin, the addition of isoproterenol produced a further increase of ICa(L) by 99 +/- 27% in neonatal, but only by 19 +/- 3% in adult. The presence of an inhibitor of cAMP-dependent protein kinase in the pipette did not affect this marked difference between neonatal (87 +/- 23%) and adult (11 +/- 8%). We conclude that, in rat ventricular myocytes, (1) stimulation of ICa(L) by the beta-adrenoceptor agonist, isoproterenol, is already fully developed in the neonatal stage and actually decreases during development; (2) there is evidence for a cAMP-independent stimulation of Ca2+ channels by isoproterenol, and this is greater in neonatal than in adult. We believe that the cAMP-independent pathway is the direct pathway mediated by Gs alpha protein.

Adrenergic beta-Agonists↗
PubMed1996

Genetic analysis of macromolecular transport across the nuclear envelope.

Numerous factors that promote movement of macromolecules in and out of the nucleus have now been identified. These include both soluble cytoplasmic and nucleoplasmic proteins and proteins of the nuclear pore complex (NPC). Genetic analyses of the nuclear transport process in the model organism, the budding yeast Saccharomyces cerevisiae, have revealed remarkable conservation of all of these factors. In addition, important clues as to how these factors promote the unique bidirectional movement across the NPC have emerged from studies of yeast. We summarize the characterization and genetic interactions of the soluble transport factors and present data to illustrate how genetic experiments can be used to further define the import and export pathways.

Biological Transport, Active↗
PubMed1996

Viral RNA trafficking is inhibited in replicase-mediated resistant transgenic tobacco plants.

Transgenic tobacco (Nicotiana tabacum cv. Turkish Samsun NN) plants expressing a truncated replicase gene sequence from RNA-2 of strain Fny of cucumber mosaic virus (CMV) are resistant to systemic CMV disease. This is due to suppression of virus replication and cell-to-cell movement in the inoculated leaves of these plants. In this study, microinjection protocols were used to directly examine cell-to-cell trafficking of CMV viral RNA in these resistant plants. CMV RNA fluorescently labeled with the nucleotide-specific TOTO-1 iodide dye, when coinjected with unlabeled CMV 3a movement protein (MP), moved rapidly into the surrounding mesophyll cells in mature tobacco leaves of vector control and untransformed plants. Such trafficking required the presence of functional CMV 3a MP. In contrast, coinjection of CMV 3a MP and CMV TOTO-RNA failed to move in transgenic resistant plants expressing the CMV truncated replicase gene. Furthermore, coinjection of 9.4-kDa fluorescein-conjugated dextran (F-dextran) along with unlabeled CMV 3a MP resulted in cell-to-cell movement of the F-dextran in control plants, but not in the transgenic plants. Similar results were obtained with viral RNA when the 30-kDa MP of tobacco mosaic virus (TMV) was coinjected with TMV TOTO-RNA into replicase-resistant transgenic tobacco expressing the 54-kDa gene sequence of TMV. However, in these transgenic plants, the TMV-MP was still capable of mediating cell-to-cell movement of itself and the 9.4-kDa F-dextran. These results indicate that an inhibition of cell-to-cell viral RNA trafficking is correlated with replicase-mediated resistance. This raises the possibility that the RNA-2 product is potentially involved in the regulation of cell-to-cell movement of viral infectious material during CMV replication.

Cell Communication↗
PubMed1996

Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function.

Alpha-hydroxy acids are effective agents for the treatment of skin xerosis and it is known that, following treatment with lotions containing D,L-lactic acid, the stratum corneum prevents xerosis more effectively. To date, the relative efficacy of the different isomers of lactic acid has not been evaluated and the mode of action of lactic acid in improving stratum corneum resilience is not known. The objective of the present studies was to determine the effects of lactic acid isomers on keratinocyte ceramide biosynthesis, stratum corneum barrier function and the resistance of the stratum corneum to the appearance of skin xerosis. In vitro, lactic acid enhanced the production of ceramides by keratinocytes. L-Lactic acid was more effective than the D isomer (300% increase vs 100% increase). Carbon label from lactic acid was incorporated into all keratinocyte lipid species and a greater incorporation of label into ceramides was achieved with L-lactate than with D-lactate. In vivo, lactic acid increased the levels of stratum corneum ceramides. Whereas, lotions containing L-lactic acid resulted in the greatest increase (48% increase) followed by D,L-lactic acid (25% increase), D-lactic acid had no effect on stratum corneum ceramide levels. The increases in stratum corneum ceramide levels following lactic acid treatment also led to improvements in stratum corneum barrier function, measured by transepidermal water loss following a challenge to the skin with SLS and in the regression phase of a moisturization efficacy study. Significant improvements in barrier function and resistance to the appearance of skin xerosis were observed following L-lactic acid and D,L-lactic acid, but not following D-lactic acid treatment. From these results we believe that lactic acid, particularly the L isomer, stimulates ceramide biosynthesis leading to increased stratum corneum ceramide levels which results in superior lipid barrier and a more effective resistance against xerosis.

Adult↗
PubMed1996

Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease.

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-E (APOE) including, but not limited to, avid binding with beta-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer's disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, after the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD.

Black or African American↗