Search PubMed⌕ Search

Biomedical subjects

H Nguyen

Publications and source records attributed to H Nguyen.

At least 55 records · Page 3Linked to original sources

Adaptive electric field control of epileptic seizures.

We describe a novel method of adaptively controlling epileptic seizure-like events in hippocampal brain slices using electric fields. Extracellular neuronal activity is continuously recorded during field application through differential extracellular recording techniques, and the applied electric field strength is continuously updated using a computer-controlled proportional feedback algorithm. This approach appears capable of sustained amelioration of seizure events in this preparation when used with negative feedback. Seizures can be induced or enhanced by using fields of opposite polarity through positive feedback. In negative feedback mode, such findings may offer a novel technology for seizure control. In positive feedback mode, adaptively applied electric fields may offer a more physiological means of neural modulation for prosthetic purposes than previously possible.

Algorithms↗

Exposure to ethanol and nicotine during the brain growth spurt: spatial DMP performance in male rats.

Male Long-Evans rats were reared artificially and, using a 2x2 design, were exposed from postnatal days (PD) 6-9 to ethanol (ET: 6.5 g kg(-1) day(-1) "binge" exposure) and/or nicotine bitartrate (NIC: 6 mg kg(-1) day(-1) continuous exposure) via gastrostomy tubes. Controls were administered maltose-dextrin in amounts isocaloric to ET and/or sodium bitartrate. A fifth suckled-control group was reared normally. NIC accelerated eye opening on PD 14; whereas ET delayed eye opening and hindlimb support on PD 16. Beginning in postnatal week 7, rats were tested on a spatial delayed matching-to-place (DMP) version of the Morris water maze, which entailed a series of problems, each consisting of search and recall trials, that required the rats to use extra-maze cues to locate a hidden escape platform. In Phase 1 of testing, the ET-exposed groups were impaired in the recall trials, but there was no effect of NIC. A longer encoding time (45 vs. 10 s) improved performance across all groups. In contrast, acute administration of NIC (0.1 mg/kg ip) immediately prior to testing in Phase 2 failed to improve performance in any group. In conclusion, these results confirm previous findings of impaired spatial DMP-task performance in ET-exposed rats and further suggest that these memory deficits are amenable to amelioration.

Animals↗

A radiation hybrid map of mouse genes.

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.

Animals↗

Curricular trends in instruction of pathology: a nationwide longitudinal study from 1993 to present.

Medical schools throughout the United States continue to respond to various external and internal challenges and make modifications in their curricula. Responses obtained from 66% (n = 83) of schools on a longitudinal survey conducted during the year 2000 to study trends in instruction of pathology over a 7-year period (ie, for classes entering 1993 to 1999) indicate the following. There have been steady shifts in instruction of systemic and clinical pathology from discipline-based courses to integrated formats from 1993 to 1999. The degree of integration with other disciplines varies among schools, and may take one or more of the following formats: joint course (pathology and another discipline); multidisciplinary systems course; a combination of pathology course and another integrated course; and completely integrated in the form of problem-based or case-based small group discussion. Presently, at least some degree of integration occurs in 51% of schools for instruction of systemic pathology and 65% for clinical pathology, up from 31% and 48%, respectively, in 1993. Although there has been an increased trend toward integration in instruction of general pathology as well, it is still taught predominantly in a discipline-based manner in the vast majority of schools. Although often difficult to identify with certainty, the best estimates indicate that the overall scheduled length of pathology instruction time has stabilized over the years; the mean total for the entering classes of 1999 was 196 hours versus 201 hours for the classes entering in 1993. However, internal rearrangements of time for various components of delivery of instruction continue. The lecture remains unchanged as an important mode comprising the largest component of pathology curriculum time (53% in 1999, 52.2% in 1993) during the 7-year period examined. The mean traditional laboratory instruction time has decreased slightly from 27% in 1993 to 24% in 1999. This decrease may be accounted for by a shift toward use of laboratory materials in various other formats and venues not included in the traditional laboratory instruction (eg, small group sessions, clinicopathologic correlation conferences, study of kodachrome slides, and computer programs). The use of electronic educational resources has increased remarkably, but for the most part it is not measurable because of the lack of any designated hours. Because pathology instruction occurs exclusively or primarily during year 2 in most schools, the classes entering in 1999 would have studied it during 2000 and 2001, which means the present study provides the most updated curricular trends at this time.

Computer-Assisted Instruction↗

Reversible acute renal failure in association with bilateral ureteral obstruction and hydronephrosis in pregnancy.

This is a case report of a 16-year-old girl with renal failure in pregnancy in association with bilateral ureteral obstruction and hydronephrosis. The presenting symptom was a common nonspecific type of abdominal pain. The diagnosis was made on incidental laboratory work to rule out preeclampsia. Renal function reverted back to normal after induced vaginal delivery.

Abdominal Pain↗

Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population.

OBJECTIVE: The prevalence of psychiatric problems and substance abuse is high in the veteran population with hepatitis C. The purpose of this study was to retrospectively analyze the effect of preexisting psychiatric conditions in veteran patients undergoing treatment with interferon a-2b (IFN-alpha) with respect to adverse events, compliance, and treatment response. METHODS: Thirty-three veterans with chronic hepatitis C were treated with IFN-alpha (5 million units three times weekly) for 6 months, followed by a tapering dose for an additional 6 months. All patients fulfilled standard criteria for treatment eligibility. Psychiatric diagnoses, adverse events, and virological and biochemical responses to therapy were determined. RESULTS: Nineteen of 33 (58%) patients with hepatitis C had documented psychiatric conditions before starting IFN-alpha therapy. Of the patients with preexisting psychiatric diagnoses, 13/19 (68%) developed major adverse events requiring intervention or discontinuation of therapy. In contrast, 4/14 (29%) patients without psychiatric diagnoses developed major adverse events (p = 0.024) In the psychiatric group, 6/19 (32%) developed major neuropsychiatric side effects compared with 2/14 patients (14%) in the nonpsychiatric group (p = 0.25). Patients with and without psychiatric diagnoses had equivalent biochemical and virological responses to therapy. Overall, only 2/33 (6%) patients had a sustained virological response. CONCLUSIONS: Veterans with chronic hepatitis C and psychiatric diagnoses experienced a significantly greater number of major adverse events during treatment with IFN-alpha. Veteran patients with hepatitis C should be carefully screened for psychiatric conditions and may require more intensive monitoring during IFN-alpha therapy.

Adult↗

Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors.

The olfactory bulb, neocortex and archicortex arise from a common pool of progenitors in the dorsal telencephalon. We studied the consequences of supplying excess Notch1 signal in vivo on the cellular and regional destinies of telencephalic precursors using bicistronic replication defective retroviruses. After ventricular injections mid-neurogenesis (E14.5), activated Notch1 retrovirus markedly inhibited the generation of neurons from telencephalic precursors, delayed the emergence of cells from the subventricular zone (SVZ), and produced an augmentation of glial progeny in the neo- and archicortex. However, activated Notch1 had a distinct effect on the progenitors of the olfactory bulb, markedly reducing the numbers of cells of any type that migrated there. To elucidate the mechanism of the cell fate changes elicited by Notch1 signals in the cortical regions, short- and long-term cultures of E14.5 telencephalic progenitors were examined. These studies reveal that activated Notch1 elicits a cessation of proliferation that coincides with an inhibition of the generation of neurons. Later, during gliogenesis, activated Notch1 triggers a rapid cellular proliferation with a significant increase in the generation of cells expressing GFAP. To examine the generation of cells destined for the olfactory bulb, we used stereotaxic injections into the early postnatal anterior subventricular zone (SVZa). We observed that precursors of the olfactory bulb responded to Notch signals by remaining quiescent and failing to give rise to differentiated progeny of any type, unlike cortical precursor cells, which generated glia instead of neurons. These data show that forebrain precursors vary in their response to Notch signals according to spatial and temporal cues, and that Notch signals influence the composition of forebrain regions by modulating the rate of proliferation of neural precursor cells.

Animals↗

Genomic exploration of the hemiascomycetous yeasts: 7. Saccharomyces servazzii.

The genome of Saccharomyces servazzii was analyzed with 2570 random sequence tags totalling 2.3 Mb. BLASTX comparisons revealed a minimum of 1420 putative open reading frames with significant homology to Saccharomyces cerevisiae (58% aa identity on average), two with Schizosaccharomyces pombe and one with a human protein, confirming that S. servazzii is closely related to S. cerevisiae. About 25% of the S. servazzii genes were identified, assuming that the gene complement is identical in both yeasts. S. servazzii carries very few transposable elements related to Ty elements in S. cerevisiae. Most of the mitochondrial genes were identified in eight contigs altogether spanning 25 kb for a predicted size of 29 kb. A significant match with the Kluyveromyces lactis linear DNA plasmid pGKL-1 encoded RF4 killer protein suggests that a related plasmid exists in S. servazzii. The sequences have been deposited with EMBL under the accession numbers AL402279-AL404848.

Ascomycota↗

Genomic exploration of the hemiascomycetous yeasts: 14. Debaryomyces hansenii var. hansenii.

By analyzing 2830 random sequence tags (RSTs), totalling 2.7 Mb, we explored the genome of the marine, osmo- and halotolerant yeast, Debaryomyces hansenii. A contig 29 kb in length harbors the entire mitochondrial genome. The genes encoding Cox1, Cox2, Cox3, Cob, Atp6, Atp8, Atp9, several subunits of the NADH dehydrogenase complex 1 and 11 tRNAs were unambiguously identified. An equivalent number of putative transposable elements compared to Saccharomyces cerevisiae were detected, the majority of which are more related to higher eukaryote copia elements. BLASTX comparisons of RSTs with databases revealed at least 1119 putative open reading frames with homology to S. cerevisiae and 49 to other genomes. Specific functions, including transport of metabolites, are clearly over-represented in D. hansenii compared to S. cerevisiae, consistent with the observed difference in physiology of the two species. The sequences have been deposited with EMBL under the accession numbers AL436045-AL438874.

Ascomycota↗

Saccharomyces uvarum, a proper species within Saccharomyces sensu stricto.

Saccharomyces uvarum is proposed as a proper species within the complex Saccharomyces sensu stricto. Molecular characteristics including the similarity of the restriction profile of the non-transcribed spacer 2 (NTS2) and of the D1/D2 sequences of the rDNA, as well as other genotypic and phenotypic characteristics confirm that this group of strains is highly homogeneous and distinguishable from other species of the Saccharomyces sensu stricto group.

DNA, Bacterial↗

Mechanisms of tolerance induction by a gene-transferred peptide-IgG fusion protein expressed in B lineage cells.

A gene therapy model has been designed to induce tolerance to multiple epitopes expressed in-frame on a soluble IgG fusion protein scaffold. Tolerance to the lambda repressor cI sequence p1-102 or its immunodominant epitopes (p12-26, p73-88) can be elicited when bone marrow (BM) or LPS blasts are transduced and injected into naive or even primed recipients. To explore the mechanism of tolerance, class II(-/-) (knockout, KO) BM cells were transduced with p1-102-IgG and transferred to irradiated recipients. These cells failed to induce tolerance to challenge with p1-102 epitopes, whereas transduced +/+ BM cells did. This supports the importance of class II MHC on the tolerogenic APC rather than secretion and representation in tolerogenesis. When BM cells from muMT KO mice were transfected with p12-26-IgG and injected into irradiated mice, these transduced BM cells also failed to induce tolerance to an immunodominant epitope. These results suggest the direct involvement of B cells in tolerance to p1-102 epitopes. IL-10 KO BM cells infected with a p12-26-IgG construct were still tolerogenic. Importantly, anti-CTLA-4 injections reversed tolerance in primed, but not in naive, recipients of transduced LPS blasts. These data emphasize the importance of MHC class II presentation, B cell involvement, and CTLA-4 engagement in induction and/or maintenance of tolerance.

Abatacept↗

Montelukast, a leukotriene receptor antagonist, in combination with loratadine, a histamine receptor antagonist, in the treatment of chronic asthma.

BACKGROUND: Montelukast sodium, a potent, oral, specific leukotriene-receptor antagonist, has demonstrated clinical efficacy in the treatment of chronic asthma. Loratadine, a selective histamine type 1 (H(1))-receptor antagonist, has demonstrated antiallergic properties. Leukotriene-receptor antagonists given concomitantly with H(1)-receptor antagonists have been shown to have additive effects in the prevention of bronchospasm in antigen-challenge models. OBJECTIVE: To determine whether montelukast plus loratadine provides improved efficacy to montelukast alone in the treatment of chronic asthma. METHODS: The efficacy of montelukast alone vs montelukast-loratadine was studied in a 10-week, multicenter, randomized, double-blind, 2 x 2 crossover study. After a 2-week placebo run-in period, patients received montelukast sodium (10 mg) plus loratadine (20 mg), or montelukast sodium (10 mg) plus placebo once daily for 2 weeks. After a 2-week placebo washout period, patients were crossed over to receive 2 weeks of the other active treatment regimen, followed by another 2-week placebo washout period. RESULTS: Montelukast given concomitantly with loratadine caused significant improvement in percentage of change from baseline in forced expiratory volume in 1 second (FEV(1)) compared with montelukast alone (13.86% vs 9.72%; P =.001). The average additional effect of loratadine (least square mean difference in percentage of change from baseline in FEV(1)) was 4.15% (95% confidence interval, 1.65%-6.65%). Key secondary end points (mean daily beta-agonist use, daytime and nighttime symptom scores, morning and evening peak expiratory flow rate, and the Patient Global Evaluation) all showed significant improvement with montelukast-loratadine (P<.05). CONCLUSION: Montelukast-loratadine significantly improved end points of asthma control during a 2-week treatment period.

Acetates↗

Syntheses of four D- and L-hexoses via diastereoselective and enantioselective dihydroxylation reactions.

An expeditious approach to various protected hexoses has been developed by the use of the Sharpless catalytic asymmetric dihydroxylation reaction. Applying the Sharpless catalytic asymmetric dihydroxylation reaction on vinylfuran, diols with high enantioexcess are produced. The resulting diols can be stereoselectively transformed into either protected D- or L-mannose in five steps and approximately 39% yield from furfural. Similarly, both D- and L-talose and gulose have been synthesized in 19% overall yields, respectively. Using a modified strategy, both protected D- and L-gulo- and allo-sugar-delta-lactones were synthesized in eight steps and approximately 20%, overall yield from furfural.

Furaldehyde↗

An optimized set of human telomere clones for studying telomere integrity and architecture.

Telomere-specific clones are a valuable resource for the characterization of chromosomal rearrangements. We previously reported a first-generation set of human telomere probes consisting of 34 genomic clones, which were a known distance from the end of the chromosome ( approximately 300 kb), and 7 clones corresponding to the most distal markers on the integrated genetic/physical map (1p, 5p, 6p, 9p, 12p, 15q, and 20q). Subsequently, this resource has been optimized and completed: the size of the genomic clones has been expanded to a target size of 100-200 kb, which is optimal for use in genome-scanning methodologies, and additional probes for the remaining seven telomeres have been identified. For each clone we give an associated mapped sequence-tagged site and provide distances from the telomere estimated using a combination of fiberFISH, interphase FISH, sequence analysis, and radiation-hybrid mapping. This updated set of telomeric clones is an invaluable resource for clinical diagnosis and represents an important contribution to genetic and physical mapping efforts aimed at telomeric regions.

Chromosomes, Artificial, Yeast↗

Complex roles of Stat1 in regulating gene expression.

Stat1 is a fascinating and complex protein with multiple, yet contrasting transcriptional functions. Upon activation, it drives the expression of many genes but also suppresses the transcription of others. These opposing characteristics also apply to its role in facilitating crosstalk between signal transduction pathways, as it participates in both synergistic activation and inhibition of gene expression. Stat1 is a functional transcription factor even in the absence of inducer-mediated activation, participating in the constitutive expression of some genes. This review summarizes the well studied involvement of Stat1 in IFN-dependent and growth factor-dependent signaling and then describes the roles of Stat1 in positive, negative and constitutive regulation of gene expression as well as its participation in crosstalk between signal transduction pathways. Oncogene (2000).

Animals↗

Regulation of c-myc expression by IFN-gamma through Stat1-dependent and -independent pathways.

Interferons (IFNs) inhibit cell growth in a Stat1-dependent fashion that involves regulation of c-myc expression. IFN-gamma suppresses c-myc in wild-type mouse embryo fibroblasts, but not in Stat1-null cells, where IFNs induce c-myc mRNA rapidly and transiently, thus revealing a novel signaling pathway. Both tyrosine and serine phosphorylation of Stat1 are required for suppression. Induced expression of c-myc is likely to contribute to the proliferation of Stat1-null cells in response to IFNs. IFNs also suppress platelet-derived growth factor (PDGF)-induced c-myc expression in wild-type but not in Stat1-null cells. A gamma-activated sequence element in the promoter is necessary but not sufficient to suppress c-myc expression in wild-type cells. In PKR-null cells, the phosphorylation of Stat1 on Ser727 and transactivation are both defective, and c-myc mRNA is induced, not suppressed, in response to IFN-gamma. A role for Raf-1 in the Stat1-independent pathway is revealed by studies with geldanamycin, an HSP90-specific inhibitor, and by expression of a mutant of p50(cdc37) that is unable to recruit HSP90 to the Raf-1 complex. Both agents abrogated the IFN-gamma-dependent induction of c-myc expression in Stat1-null cells.

Animals↗