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Biomedical subjects

H Nguyen

Publications and source records attributed to H Nguyen.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

The potential benefits of advanced therapeutic modalities in the treatment of diabetic foot wounds.

This article discusses the advantages and disadvantages of primary wound healing as compared with primary amputation in individuals with chronic diabetic foot wounds. The authors review the potential benefits of vascular surgical procedures and advanced dressings, including two of the most promising modalities in modern wound care: growth factors and bioengineered skin. In this era of cost-conscious health-care administration, it is incumbent on the practitioner to consider not only the basic science of wound care, but also the economic aspect of treatment rendered. These various interventions, dressings, growth factor delivery systems, and new modalities could significantly reduce healing time, thereby reducing the risk of infection, hospitalization, and amputation while improving quality of life. If so, they may be truly cost-effective.

Bandages↗
PubMed2000

Functional domains and expression of truncated atrial natriuretic peptide receptor-A: the carboxyl-terminal regions direct the receptor internalization and sequestration in COS-7 cells.

The objective of this study was to determine the role of cytoplasmic (protein kinase-like homology and guanylyl cyclase catalytic) domains of atrial natriuretic peptide (ANP) receptor-A (Npra) in postbinding events and metabolic turnover of ligand-receptor complexes. Using deletion mutagenesis, the specific regions in the intracellular domains of Npra relevant to the receptor function, namely ligand-binding, cGMP production, and internalization and sequestration of ligand-receptor complexes, have been determined in transiently expressing COS-7 cells. Deletion of 12 aa (aa) at the carboxyl-terminal end of receptor (Delta1045-Npra) affected neither ligand-binding efficiency nor cGMP production. However, deletion of 120 to 170 aa residues (Delta937-Npra, Delta916-Npra, Delta902-Npra, and Delta887-Npra) decreased ligand binding by 16 to 20% and cGMP production by 50 to 90%. Further deletion of 422 aa and 569 aa (Delta635-Npra and Delta488-Npra) reduced ligand binding efficiency by 40% and 90%, respectively. The deletion of 12 aa (Delta1045-Npra) did not affect the internalization of Npra; however, deletions up to 170 aa (Delta937-Npra, Delta916-Npra, Delta887-Npra) reduced the internalization of ligand-receptor complexes by 60%. Cells expressing either full-length (wild-type) Npra or 120 aa deleted receptor (Delta937-Npra) released 40 to 45% (125)I-ANP radioactivity into culture medium, but only 10 to 15% radioactivity was released from the cells that expressed Delta635-Npra. Furthermore, 35 to 40% (125)I-ANP radioactivity was detected into the intracellular compartments of cells that expressed the wild-type Npra, and only 5 to 10% (125)I-ANP radioactivity was observed in cells expressing the Delta635-Npra (-422 aa) or Delta488-Npra (-569 aa) mutant receptors. These results show that specific regions within the intracellular domains of Npra determine the extent of ligand-binding efficiency, cGMP production, endocytosis, and intracellular sequestration of ligand-receptor complexes in cDNA expressing COS-7 cells.

Animals↗
PubMed2000

HIV risk behaviors among Asian drug users in San Francisco.

This study identified patterns of drug use and HIV risk behaviors in relation to cultural factors among Asian drug users in San Francisco. A sample of 92 Asian drug users (35 Chinese, 31 Filipino, 26 Vietnamese) who were not currently enrolled in drug treatment programs were recruited through targeted sampling methods and interviewed using a questionnaire with open-ended questions. The study evaluated responses of the participants based on content analyses. Compared with Chinese and Vietnamese, Filipino drug users had engaged in riskier behaviors in terms of injection drug use, having sex while on drugs, and having sex with injection drug users (IDUs). Cultural factors such as stigma of injection drug use and fear of needles were cited as reasons for not injecting drugs. Among IDUs, half cited trust as a reason for having shared needles. AIDS prevention programs targeting Asian drug users should consider specific cultural factors among high-risk groups (i.e., Filipinos, immigrants, women, and IDUs).

Adult↗
PubMed1999

Increased TIMP-1 activity results in increased expression of gelatinases and altered cell motility.

Matrix metalloproteinases are proteolytic enzymes which play a major role in resorption of collagen and other components of the extracellular matrix. They are controlled by specific inhibitors, so-called tissue inhibitors of metalloproteinases (TIMPs). The balance between matrix metalloproteinases and TIMPs seems to play a major role in controlling extracellular matrix homeostasis and cell migration. The influence of TIMP-1 on migration behaviour was explored in human hepatoma cells transiently and stably transfected with mouse TIMP-1, and incubated with biologically active TIMP-1. Transfection and biosynthesis were verified by Northern blotting, Western blotting, metabolic labeling, and reverse zymography. Overexpression of and incubation with TIMP-1 resulted in suppressed migration and seemed to enhance cell-cell contact. Using gelatin zymography and Western blotting we measured a significant increase of matrix metalloproteinases-2 and matrix metalloproteinases-9 in cells transfected with TIMP-1. This new phenomenon may be of important physiological significance in modulating TIMP and MMP expression. Our results indicate a functional involvement of TIMP-1 in matrix homeostasis and some automatic control in matrix turnover.

Animals↗
PubMed1999

Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation.

Interferon Regulatory Factor (IRF)-1 is a multifunctional transcription factor, involved in cell growth regulation, pathogen response and immune activation. To identify novel gene targets that may contribute to IRF-1 mediated activities, RNA fingerprinting was performed using NIH3T3 cells that inducibly express a hybrid form of IRF-1 under tetracycline regulated control. Secretory leukocyte protease inhibitor (SLPI) - a regulator of inflammation and an inhibitor of the LPS response - was identified as a gene repressed after doxycycline induced IRF-1 expression. Preliminary analysis of the human SLPI promoter identified an ISRE-like site located within the -221 to -200 region to which IRF-1 binds and a second, putative IRF-1 binding site upstream of the TATA box. Furthermore, co-transfection studies demonstrated that SLPI expression was inhibited by IRF-1 co-expression. The identification of SLPI as a target of IRF-1 regulation reveals a unique involvement of IRF-1 in repression of gene transcription and assigns a novel role for IRF-1 in inflammation.

3T3 Cells↗
PubMed1999

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.

BACKGROUND: The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials. METHODS: In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months. RESULTS: The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant. CONCLUSIONS: Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.

Acute Disease↗
PubMed1999

Nitric oxide and thromboxane A2-mediated pulmonary microvascular dysfunction.

OBJECTIVES: To examine whether the lung releases nitric oxide (NO) in response to thromboxane A2 and to examine the local release of NO as a protective compensatory mechanism by which the lung responds to the proinflammatory and vasoactive effects of thromboxane A2. DESIGN: The lungs of anesthetized Sprague-Dawley rats were perfused in vitro with Krebs-Henseleit buffer that contained an inhibitor of NO synthase (nitroglycerinenitro-L-arginine methyl ester [L-NAME]) (10(-4) mol/L), an NO donor (sodium nitroprusside) (10(-8) mol/L), or perfusate alone. Following equilibration, the thromboxane A2 receptor agonist 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha(U-46619) (7.1 X 10(-8) mol/L) was added to the perfusate. Fifteen minutes later, the capillary filtration coefficient, pulmonary arterial pressure, and vascular resistance were measured. Pulmonary NO release was assessed by quantitating the release of cyclic guanosine monophosphate into the perfusate. RESULTS: The capillary filtration coefficient of lungs exposed to U-46619 was 3.5 times greater than that of lungs perfused with buffer alone (P<.05). The addition of sodium nitroprusside reduced the increase in capillary filtration coefficient associated with U-46619 by 50% (P<.05) whereas L-NAME had no effect. The addition of U-46619 to the perfused lung caused a 3.0+/-0.4 mm Hg increase in pulmonary artery pressure (P<.01) with a corresponding rise in total vascular resistance (P<.05). This effect was exacerbated by L-NAME (P<.05) and inhibited by sodium nitroprusside (P<.05). Exposure of the isolated lungs to U-46619 caused a 4-fold increase in cyclic guanosine monophosphate levels within the perfusate. CONCLUSION: These data are consistent with the hypothesis that NO release may be an important protective mechanism by which the lung responds to thromboxane A2.

Animals↗
PubMed1999

Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo-controlled trial and long-term follow-up.

PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to test the effect of intra-anal glyceryl trinitrate ointment in patients with chronic anal fissures that would normally have been treated by sphincterotomy. Long-term follow-up was then performed to assess fissure healing. METHODS: Patients with chronic anal fissures were randomly assigned to 0.2 percent topical glyceryl trinitrate ointment or placebo. Anal manometry was performed before treatment, one week later, and 48 hours after treatment ceased at four weeks. Fissure healing was assessed by an observer blinded to the treatment arm. Pain was recorded on a linear analog scale. At the completion of the trial, treatment was continued with glyceryl trinitrate until fissure healing was obtained or lateral sphincterotomy was performed if required for ongoing pain. A long-term follow-up assessment was made at a mean of 29 (range, 25-33) months. RESULTS: There was a significant reduction in anal resting pressure at Week 1 with glyceryl trinitrate (P = 0.001) but not placebo, and at Week 4 there was a significant reduction in pain score with glyceryl trinitrate (P = 0.001) and placebo (P = 0.01) and a significant reduction in fissure grade with glyceryl trinitrate (P = 0.0001) and placebo (P = 0.02). Forty-six percent of fissures healed with glyceryl trinitrate and 16 percent healed with placebo (P = 0.001). At long-term follow-up in 40 of 43 patients, 14 patients (35 percent) had undergone lateral sphincterotomy, and in the remainder who were treated with glyceryl trinitrate there was a significant reduction in pain score (P = 0.0002). Seventeen patients attended for repeat manometry and fissures were healed with glyceryl trinitrate in ten (59 percent) cases. High internal sphincter pressures persisted at long-term follow-up in patients successfully treated with glyceryl trinitrate, indicating that the sphincter is the cause rather than effect of anal fissure. CONCLUSION: Topical glyceryl trinitrate produces a successful internal sphincterotomy, which resulted in long-term healing of 59 percent of chronic anal fissures and significant improvement in pain. Internal sphincter spasm is the cause of chronic anal fissure.

Administration, Topical↗
PubMed1999

Microscopic evidence against HIV-1 infection of germ cells or attachment to sperm.

For a number of years we have intensively investigated the localization of HIV-1 in male genital tract tissues and secretions using a variety of microscopy techniques including immunocytochemistry, in situ hybridization, in situ PCR and electron microscopy. Our studies have failed to demonstrate an association between HIV-1 and either testicular germ cells or spermatozoa. In this article we present our results in the context of other related studies, and discuss the strengths and weaknesses of the techniques that have been used to address this important research question.

HIV Infections↗
PubMed1999

Effect of interleukin-6 secreted by engineered human stromal cells on osteoclasts in human bone.

The effect of elevated human IL-6 (hIL-6) production by human bone marrow (Hu-BM) stromal cells on osteoclasts in human bone was examined. Human bone was implanted into nonobese diabetic mice with severe combined immunodeficiency (Hu-Bone-NOD/SCID mice). Immunohistochemistry of bone implants and mouse spleens (at 20 weeks), showed human CD45+ cells, B cells, and macrophages in both tissues. Thus, Hu-BM cells survive human bone transplantation and infiltrate mouse tissue. Bone implants had 75 +/- 12% (mean +/- SD) human CD45+ cells, and 9 +/- 4% mouse hematopoietic cells. A retrovirus vector containing the human IL-6 gene was used to transduce Hu-BM stromal cells (IL-6/stromal) and the PA317 cell line (IL-6/PA317). IL-6/ stromal cells (secreting, on average, 17 microg of hIL-6/10(6) cells per 24 h) were injected directly into human bone implants in Hu-Bone-NOD/SCID mice. IL-6/PA317 cells (secreting 16 microg/mL of hIL-6/10(6) cells per 24 h) were injected intraperitoneally into Hu-Bone-NOD/SCID mice. Analyses of sera from both groups of animals showed elevated levels of IL-6. However, only bone implants engrafted with IL-6/stromal cells had a statistically significant increase in osteoclast-lined mineralized trabecular bone surface (BS). Thus, a high concentration of serum hIL-6 in Hu-Bone-NOD/SCID mice alone does not increase osteoclast-lined BS in bone implants. Most importantly, it is the type of human BM cell that secretes the high levels of hIL-6 that is most critical.

Animals↗
PubMed1999

Radiation hybrid map of the mouse genome.

Radiation hybrid (RH) maps are a useful tool for genome analysis, providing a direct method for localizing genes and anchoring physical maps and genomic sequence along chromosomes. The construction of a comprehensive RH map for the human genome has resulted in gene maps reflecting the location of more than 30,000 human genes. Here we report the first comprehensive RH map of the mouse genome. The map contains 2,486 loci screened against an RH panel of 93 cell lines. Most loci (93%) are simple sequence length polymorphisms (SSLPs) taken from the mouse genetic map, thereby providing direct integration between these two key maps. We performed RH mapping by a new and efficient approach in which we replaced traditional gel- or hybridization-based assays by a homogeneous 5'-nuclease assays involving a single common probe for all genetic markers. The map provides essentially complete connectivity and coverage across the genome, and good resolution for ordering loci, with 1 centiRay (cR) corresponding to an average of approximately 100 kb. The RH map, together with an accompanying World-Wide Web server, makes it possible for any investigator to rapidly localize sequences in the mouse genome. Together with the previously constructed genetic map and a YAC-based physical map reported in a companion paper, the fundamental maps required for mouse genomics are now available.

Animals↗
PubMed1999

Calcium influx through NMDA receptors, chronic receptor inhibition by ethanol and 2-amino-5-phosponopentanoic acid, and receptor protein expression.

Chronic treatment of neurons with either ethanol or competitive and noncompetitive antagonists of NMDA receptors leads to enhanced expression of NMDA receptor density and function in neurons. The signal transduction pathways for such receptor up-regulation are not known. The focus of the present study was on the role of Ca2+ entry into neurons, either through receptor or voltage-gated channels, in the expression of the NMDA receptor subunit NR1 and the 71-kDa glutamate-binding protein (GBP) of a glutamate/NMDA receptor-like complex. Chronic inhibition of NMDA receptors in cortical neurons in primary cultures by either 100 mM ethanol or 100 microM 2-amino-5-phosphonopentanoic acid (2-AP5) increased the expression of NR1 and GBP. The effect of 2-AP5 on the expression of the two proteins was not additive with that of ethanol when neuronal cultures were treated with both agents at the same time. However, the effects of ethanol on NR1 and GBP expression were blocked by the simultaneous treatment with NMDA (50 microM). Activation or inhibition of other glutamate ionotropic receptors had no effect on the expression of NR1 and GBP. The inhibition of L- or N-type voltage-sensitive Ca2+ channels and voltage-gated Na+ channels also had little effect on the expression of either protein; neither did exposure of neurons to elevated extracellular Ca2+ concentrations (3 or 5 mM). On the other hand, treatment of neurons for 48 h with the intracellular Ca2+ chelator BAPTA-AM as well as partial chelation of extracellular Ca2+ with EGTA caused an up-regulation in NR1 and GBP expression. The enhanced expression of NR1 in neurons treated for 48 h with either ethanol or EGTA was correlated with increases in the activity of NMDA receptors demonstrated as a doubling of the NMDA-stimulated rise in intracellular free Ca2+ concentration. The effects of chronic administration of EGTA on both NR1 expression as well as NMDA receptor function were probably related to an acute inhibition by EGTA of NMDA-induced Ca2+ influx into neurons. It appears that the expression of both the NR1 subunit of NMDA receptors and the GBP of a receptor-like complex is regulated by intracellular Ca2+, especially that entering through NMDA receptor ion channels.

2-Amino-5-phosphonovalerate↗
PubMed1999

Effects of nitric oxide on platelet activation during plateletpheresis and in vivo tracking of biotinylated platelets in humans.

BACKGROUND: The use of platelet transfusions has risen considerably over the last few years, which leads to the collection and transfusion of a greater number of donor plateletpheresis units. Plateletpheresis activates platelets in platelet concentrates, which determines the degree of the storage lesion subsequently observed. STUDY DESIGN AND METHODS: As nitric oxide (NO) is a potent inhibitor of platelet aggregation and activation, a placebo-controlled crossover trial was performed in healthy young male volunteers to determine whether the NO-donating compound, sodium nitroprusside (SNP), decreases platelet activation during apheresis and whether activated (p-selectin+) platelets circulate in vivo after transfusion. The study also investigated whether nonradioactive biotin labeling of apheresis platelets is feasible for the study of platelet recovery after transfusion in humans. RESULTS: Platelet activation increased after plateletpheresis in the platelet components, but SNP did not inhibit platelet activation during apheresis, as measured by the percentage of p-selectin expression and the secretion of soluble p-selectin and RANTES. Only a minor increase in p-selectin+ platelets was seen in peripheral blood at 60 minutes after transfusion of the platelets, a rise that was considerably less than that calculated in p-selectin+ platelets if they all were recovered as activated platelets after transfusion. Biotin-labeled platelets averaged 1.5 percent at 10 minutes after transfusion and increased slowly to 2.6 and 3.4 percent after 60 minutes and 24 hours, respectively (p<0.05). CONCLUSION: SNP does not decrease platelet activation during apheresis and subsequent storage, and only a minor proportion of activated (p-selectin+) platelets circulate after transfusion in men. Moreover, biotin labeling of PCs can safely be used in humans for the study of platelet recovery after transfusion, and measuring recovery at 1 hour may lead to an underestimation of the true recovery when activated platelets are transfused.

Biotinylation↗