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Biomedical subjects

C Nguyen

Publications and source records attributed to C Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gene expression profiling of primary breast carcinomas using arrays of candidate genes.

Breast cancer is characterized by an important histoclinical heterogeneity that currently hampers the selection of the most appropriate treatment for each case. This problem could be solved by the identification of new parameters that better predict the natural history of the disease and its sensitivity to treatment. A large-scale molecular characterization of breast cancer could help in this context. Using cDNA arrays, we studied the quantitative mRNA expression levels of 176 candidate genes in 34 primary breast carcinomas along three directions: comparison of tumor samples, correlations of molecular data with conventional histoclinical prognostic features and gene correlations. The study evidenced extensive heterogeneity of breast tumors at the transcriptional level. A hierarchical clustering algorithm identified two molecularly distinct subgroups of tumors characterized by a different clinical outcome after chemotherapy. This outcome could not have been predicted by the commonly used histoclinical parameters. No correlation was found with the age of patients, tumor size, histological type and grade. However, expression of genes was differential in tumors with lymph node metastasis and according to the estrogen receptor status; ERBB2 expression was strongly correlated with the lymph node status (P < 0.0001) and that of GATA3 with the presence of estrogen receptors (P < 0.001). Thus, our results identified new ways to group tumors according to outcome and new potential targets of carcinogenesis. They show that the systematic use of cDNA array testing holds great promise to improve the classification of breast cancer in terms of prognosis and chemosensitivity and to provide new potential therapeutic targets.

Adult↗
PubMed2000

Correlation of preoperative plasma IGF-I levels with pathologic parameters and progression in patients undergoing radical prostatectomy.

OBJECTIVES: To test whether preoperative insulin-like growth factor (IGF)-I levels could predict pathologic stage and prognosis of prostate cancer in patients undergoing radical prostatectomy. METHODS: The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer. Preoperative plasma IGF-I levels were measured using the DSL-IGF-I Elisa assay. Surgically removed prostate specimens were analyzed pathologically, using a whole-mount step-section technique. Preoperative plasma IGF-I levels were compared with final pathologic parameters and with prostate-specific antigen (PSA) progression-free survival. Preoperative IGF-I levels in this cohort were also compared with IGF-I levels measured in 20 healthy men without any cancer and in 10 men with untreated, metastatic prostate cancer. RESULTS: Plasma IGF-I levels predicted neither organ-confined disease (P = 0.5611) nor the risk of PSA progression (P = 0.8125) at a median follow-up of 48.6 months after prostatectomy. Furthermore, IGF-I levels did not correlate with preoperative PSA level (P = 0. 2811) or final Gleason score (P = 0.4906). IGF-I levels in radical prostatectomy patients were not significantly higher than those in healthy subjects or in patients with metastatic disease (mean 156.7 +/- 66 ng/mL, 148.6 +/- 49 ng/mL, and 148.6 +/- 93 ng/mL, respectively; P = 0.8442). CONCLUSIONS: Circulating IGF-I levels may predict the future risk of developing prostate cancer, but our study found no association with other established markers of biologically aggressive disease or with disease progression in patients with clinically localized prostate cancer.

Adenocarcinoma↗
PubMed2000

The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9.

Chemokines are key regulators of migration in lymphoid tissues. In the thymus, maturing thymocytes move from the outer capsule to the inner medulla and thereby interact with different types of stromal cells that control their maturation and selection. In the process of searching for molecules specifically expressed at different stages of mouse thymic differentiation, we have characterized the cDNA coding for the thymus-expressed chemokine (TECK) and its receptor CCR9. The TECK receptor gene was isolated and shown to be localized on the mouse chromosome 9F1-F4. Thymic dendritic cells have been initially thought to be a prevalent source of TECK. In contrast, our results indicate that thymic epithelial cells constitute the predominant source of TECK. Consistent with the latter distribution, the TECK receptor is highly expressed by double-positive thymocytes, and TECK can chemoattract both double-positive and single-positive thymocytes. The TECK transcript is also abundantly expressed in the epithelial cells lining the small intestine. In conclusion, the interplay of TECK and its receptor CCR9 is likely to have a significant role in the recruitment of developing thymocytes to discrete compartments of the thymus.

Animals↗
PubMed2000

Global analysis of gene expression in cells of the immune system II. Cell-free translation products and high-density filter hybridization data.

We have developed an experimental system for linking information on cell-free transcription and translation products from cDNA clones with data obtained from hybridization signals from complex probes. The work described in this paper consists of two distinct processes, one being the construction of a system of clonal addresses and the other the identification of expressed genes involved in the studied processes. We describe the use of this system to identify genes involved in thymus development. Complex probes from fetal thymuses (GD15, 17 and newborn) of Balb/c mice were used to identify genes, which are up- or downregulated during the process of differentiation. The full set of information is available in the Clone-base of the Basel Institute for Immunology and will be retrievable from the website of the collaborating laboratories.

Animals↗
PubMed2000

Paternity in horseshoe crabs when spawning in multiple-male groups.

Unpaired or satellite male horseshoe crabs, Limulus polyphemus, are attracted to and often form a group around a pair (a female with an attached male) that is nesting in the high intertidal zone. These males are engaged in sperm competition. We observed nesting pairs and their associated satellites in the wild, collected and reared their eggs and used genetic markers to examine paternity. We found that the unpaired, satellite males are highly successful at fertilizing eggs; two satellites can leave the attached male with few fertilizations. Two satellites together are each as successful as one spawning with a pair. A satellite's location around the female greatly affects his success, and males compete for access to a position over the dorsal canal between the prosoma and opisthosoma of the female and under the front margin of the paired male where they are most likely to fertilize eggs. Although eggs and sperm retain their viability for some time after spawning, nearly all eggs are fertilized by the satellites that are around the nesting pair at the time of egg laying and by the attached male. A number of factors including beach current, female size and male behaviour affect the outcome of sperm competition in this externally fertilizing species. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2000

Biological cages.

Restoring a stable anterior column is essential to achieve normal spinal biomechanics. A variety of mechanical spacers have been developed and advocated for both anterior and posterior approaches. The ability to radiographically assess the "biology" of bone incorporation in these mechanical (metal) spacers is an inherent limitation. The femoral ring allograft (FRA) and posterior lumbar interbody fusion (PLIF) spacers have been developed as biological cages that permit restoration of the anterior column with a machined allograft bone (biological cage). Test results demonstrate that the FRA and PLIF Spacers have a compressive strength over 25,000 N. The pyramid shaped teeth on the surfaces and the geometry of the implant increase the resistance to expulsion at clinically relevant loads (1053 and 1236 N). The technique of anterior column reconstruction with both the FRA and the PLIF biological cages are discussed. Clinical experience with the PLIF biological cage (10 patients) and the FRA biological cage (90 patients) has not revealed any graft migration, infection, or subsidence. Additional posterior instrumentation may increase the stability of the motion segment, but the degree of stability necessary to achieve a biological union remains unclear. The incorporation of these biological cages can be monitored by conventional radiographic techniques. The method of insertion preserves the vertebral end-plates and can be performed by a minimally invasive or standard open procedure.

Adult↗
PubMed2000

Antithrombin activity of medicinal plants of the Azores.

A chromogenic bioassay was utilized to determine the antithrombin activity of methylene chloride and methanol extracts prepared from 50 plants of Azores. Extracts of the six plants Hedychium gardneranum, Tropaeolum majus, Gunnera tinctoria, Hedera helix, Festuca jubata and Laurus azorica demonstrated activity of 78% or higher in this bioassay system.

Azores↗
PubMed2000

A new HLA-DPA1 allele, DPA1*02016, identified in African-American population.

A new HLA-DPA1 allele has been found in the African-American population. This newly discovered type is homologous with the DPA1*02011 allele, except in codon 38 of the DPA1 sequence. The variant of DPA1 was detected by sequence-specific oligonucleotide (SSO) typing, and specified by cloning and sequencing methods. GenBank accession number is AF165160. The WHO Nomenclature Committee has officially assigned the name DPA1*02016.

Alleles↗
PubMed2000

Peritubular capillary loss is associated with chronic tubulointerstitial injury in human kidney: altered expression of vascular endothelial growth factor.

Chronic tubulointerstitial injury (CTI) including tubular atrophy and interstitial fibrosis represents one major determinant for the progression of chronic renal disease regardless of cause. Although peritubular capillaries (PTCs) are essential to maintain the normal structure and function of renal tubules, little is known about the role of PTCs in the development of CTI. The integrity of PTCs seems to be regulated by growth factors. Vascular endothelial cell growth factor (VEGF) has recently been recognized as a potent regulator of angiogenesis, vascular survival, and vascular permeability. Knowledge of the role of VEGF in renal disease is still rudimentary, and its role in CTI has not been explored. We analyzed the morphologic changes of PTCs and correlated them with other morphologic parameters of CTI in 32 human kidneys with various types of chronic tubulointerstitial disease. The VEGF expression was immunohistochemically evaluated. Compared with normal kidney, PTC loss (41% to 55% of control) and reduced size of PTCs (55% to 88% of control) were noted in kidneys with CTI. The PTC density was positively correlated with the proximal tubular density (r = 0.66, P <.0001), proximal tubular size (r = 0.54, P <.001), and negatively correlated with interstitial volume (r = -0.84, P <.0001). Compared with normal kidney, where podocytes were the only cell type that constantly expressed VEGF, an interesting pattern of increased VEGF expression by renal tubules, especially morphologically intact or hypertrophic ones, was shared by all cases with CTI. Loss of VEGF in sclerotic glomeruli was noted. PTC injury is pathogenetically linked to tubular atrophy, tubular loss, and interstitial fibrosis in human kidneys with CTI and might be a key factor for the progression of chronic tubulointerstitial disease. The characteristic and uniform pattern of altered VEGF expression in kidneys with CTI may result from ischemia induced by PTC loss and represent a protective mechanism against further PTC injuries. HUM PATHOL 31:1491-1497.

Capillaries↗
PubMed2000

Management of stage I cervical cancer in pregnancy.

UNLABELLED: Although cervical carcinoma is the most common gynecologic malignancy associated with pregnancy, its occurrence is rare with an incidence of approximately 1 per 1,200 to 10,000 pregnancies. There are inadequate data addressing both the obstetric implications of the diagnostic evaluation and the impact of intervention on maternal and infant outcomes. Certain conclusions and recommendations, however, can be drawn from the available data. Diagnostic evaluation includes cytological screening, colposcopy and if necessary, biopsy, and selective conization. Staging of the pregnant patient is modified to minimize radiation exposure to the developing fetus. The treatment schema for patients with stage I cervical cancer in pregnancy varies with the stage of disease and gestational age at diagnosis. With close surveillance, deliberate delay of therapy to achieve fetal maturity is a reasonable option for patients with microinvasive and early stage IB cervical cancer. Tumor characteristics and maternal survival are not adversely affected by pregnancy. Conversely, cervical cancer does not seem adversely to affect pregnancy. However, timing and type of therapy may have a significant influence on the fate of the fetus. In counseling patients with cervical cancer during pregnancy, many factors must be considered, including the patient's desire for the pregnancy, stage of disease, and gestational age at diagnosis. Pregnant patients with stage I cervical cancer should be fully informed of all possible treatment options and consequences. The care of these patients should be closely coordinated by experts in perinatology and gynecologic oncology. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the signs and symptoms of cervical cancer during pregnancy and the indications for conization during pregnancy, as well as being able to outline management strategies for the various stages of cervical cancer during pregnancy.

Adult↗
PubMed2000

Expression-based genetic/physical maps of single-nucleotide polymorphisms identified by the cancer genome anatomy project.

SNPs (Single-Nucleotide Polymorphisms), the most common DNA variant in humans, represent a valuable resource for the genetic analysis of cancer and other illnesses. These markers may be used in a variety of ways to investigate the genetic underpinnings of disease. In gene-based studies, the correlations between allelic variants of genes of interest and particular disease states are assessed. An extensive collection of SNP markers may enable entire molecular pathways regulating cell metabolism, growth, or differentiation to be analyzed by this approach. In addition, high-resolution genetic maps based on SNPs will greatly facilitate linkage analysis and positional cloning. The National Cancer Institute's CGAP-GAI (Cancer Genome Anatomy Project Genetic Annotation Initiative) group has identified 10,243 SNPs by examining publicly available EST (Expressed Sequence Tag) chromatograms. More than 6800 of these polymorphisms have been placed on expression-based integrated genetic/physical maps. In addition to a set of comprehensive SNP maps, we have produced maps containing single nucleotide polymorphisms in genes expressed in breast, colon, kidney, liver, lung, or prostate tissue. The integrated maps, a SNP search engine, and a Java-based tool for viewing candidate SNPs in the context of EST assemblies can be accessed via the CGAP-GAI web site (http://cgap.nci.nih.gov/GAI/). Our SNP detection tools are available to the public for noncommercial use.

Chromosome Mapping↗
PubMed2000

Regulation of ligand-induced heterodimerization and coactivator interaction by the activation function-2 domain of the vitamin D receptor.

Twenty-epi analogs of 1alpha,25-dihydroxyvitamin D3 (1,25D3) are 100-1000 times more potent transcriptionally than the natural hormone. To determine whether this enhanced activity is mediated through modulation of the dimerization process or through interaction with coactivators, we performed quantitative protein-protein interaction assays with in vitro translated vitamin D receptor (ivtVDR) and fusion proteins containing glutathione-S-transferase (GST) and either the ligand-binding domain of retinoid X receptor (RXRalpha), or the nuclear receptor-interacting domain of the steroid receptor coactivator 1 (SRC-1), or the glucocorticoid receptor-interacting protein 1 (GRIP-1). We found that heterodimerization of the ligand-binding domains of RXRalpha and VDR was primarily deltanoid dependent as was the interaction of VDR with the SRC-1 or with GRIP-1. The ED50 for induction of heterodimerization was 2 nM for 1,25D3 and 0.05 nM for 20-epi-1,25D3. However, the ED50 for induction of VDR interaction with SRC-1 was similar for both 1,25D3 and the 20-epi analog (ED50 = 0.7-1.0 nM) as was the ED50 for ligand-mediated interaction of VDR with GRIP-1 (ED50 = 0.1-0.3 nM). Mutations in heptad 9 diminished both 1,25D3 and the 20-epi analog-mediated dimerization, without changing binding of these ligands to VDR. Mutations in VDR's activation function 2 (AF-2) domain/helix 12 residues diminished the ability of 1,25D3 to induce heterodimerization and interaction with SRC-1. These mutations did not change the ability of 20-epi-1,25D3 to induce dimerization but did diminish its ability to induce interaction with SRC-1. We hypothesize that both the hormone and the analog stabilize receptor conformations that expose VDR's functional interfaces. The mechanisms by which the two ligands expose these functional interfaces differ with respect to participation of the AF-2 domain.

Animals↗
PubMed2000

PNA-dependent gene chemistry: stable coupling of peptides and oligonucleotides to plasmid DNA.

Two approaches are described for stably conjugating peptides, proteins and oligonucleotides onto plasmid DNA. Both methods use a peptide nucleic acid (PNA) clamp, which binds irreversibly and specifically to a binding site cloned into the plasmid. The first approach uses a biotin-conjugated PNA clamp that can be used to introduce functional biotin groups onto the plasmid to which streptavidin can bind. Atomic force microscopy images of linearized plasmid show streptavidin localized at the predicted PNA binding site on the DNA strand. Peptides and oligonucleotides containing free thiol groups were conjugated to maleimide streptavidin, and these streptavidin conjugates were bound to the biotin-PNA-labeled plasmid. In this way, peptides and oligonucleotides could be brought into stable association with the plasmid. A second approach used a maleimide-conjugated PNA clamp. Methods are described for conjugating thiolated peptides and oligonucleotides directly to the maleimide-PNA-DNA hybrid. This straightforward technology offers an easy approach to introduce functional groups onto plasmid DNA without disturbing its transcriptional activity.

Animals↗
PubMed2000

Osteoporosis of the spine: correlation between vertebral deformity and bone mineral density in postmenopausal women.

The purpose of this study is to evaluate the relation of bone mineral density (BMD) or the age-matched z score and osteoporotic vertebral fractures. The radiographs and spinal bone mineral density of 131 consecutive postmenopausal patients were retrospectively reviewed. The vertebral fractures between T4 and L4 were graded. Sixty-two patients had no fractures, and 69 had 1 or more fractures. In the nonfracture group, the mean age was 62.6 years, BMD was 0.88 g/cm2, and the z score was -1.00. In the fracture group, the mean age was 69.6 years, BMD was 0.788 g/cm2, and the z score was -1.26. Patients with 2 and 3 or more fractures had a lower mean BMD than that of the nonfracture group (P < .01). The z score (adjusted for age) was significantly lower only in patients with 3+ fractures (P < .05). Patients with grade 2 and grade 3 of any fracture type had significantly lower BMD (P < .01). The z score was lower only in those with grade 3 fracture (P < .05). Our study indicates that the clinical use of BMD z score adjusted for age is a better predictor of severity of vertebral fractures than is BMD alone.

Adult↗
PubMed1999

Enhanced biological activity of 1alpha,25-dihydroxy-20-epi-vitamin D3, the C-20 epimer of 1alpha,25-dihydroxyvitamin D3, is in part due to its metabolism into stable intermediary metabolites with significant biological activity.

1alpha,25-dihydroxy-20-epi-vitamin D3 (1alpha,25(OH)2-20-epi-D3), the C-20 epimer of the natural hormone 1alpha,25(OH)2D3, is several fold more potent than the natural hormone in inhibiting cell growth and inducing cell differentiation. At present, the various mechanisms responsible for the enhanced biological activities of this unique vitamin D3 analog are not fully understood. In our present study we compared the target tissue metabolism of 1alpha,25(OH)2D3 with that of 1alpha,25(OH)2-20-epi-D3 using the technique of isolated perfused rat kidney. The results indicated that the C-24 oxidation pathway plays a major role in the metabolism of both compounds in the rat kidney. However, it was noted that the concentrations of two of the intermediary metabolites of 1alpha,25(OH)2-20-epi-D3, namely, 1alpha,24(R),25(OH)3-20-epi-D3 and 1alpha,25(OH)2-24-oxo-20-epi-D3 in the kidney perfusate, exceeded the concentrations of the corresponding intermediary metabolites of 1alpha,25(OH)2D3. Furthermore, 1alpha,25(OH)2-24-oxo-20-epi-D3 induces the conformation of the vitamin D receptor similar to that induced by its parent analog and is nearly as potent as its parent in inducing transactivation of a gene construct containing the human osteocalcin vitamin D-responsive element. We conclude that 1alpha,25(OH)2-20-epi-D3 by itself is not metabolically stable when compared to 1alpha,25(OH)2D3, but it acquires its metabolic stability because of the reduced rate of catabolism of its intermediary metabolites. Furthermore, 1alpha,25(OH)2-24-oxo-20-epi-D3, the stable bioactive intermediary metabolite plays a significant role in generating the enhanced biological activities ascribed to 1alpha,25(OH)2-20-epi-D3.

Animals↗
PubMed1999

Expression scanning of an array of growth control genes in human tumor cell lines.

Analysis of gene expression on a medium- or large-scale is an increasingly recognized method for functional and clinical investigations based on the now extensive catalog of known or partially sequenced genes. The accessibility of this approach can be enhanced by using readily available technology (macroarrays on Nylon, radioactive detection) and the IMAGE resource to assemble sets of targets. We have set up such a medium-scale, flexible system and validated it by the study of quantitative expression levels for 120 genes in six cell lines, including three mammary carcinoma cell lines. A number of important parameters are identified as necessary for the assembly of a valid set and the obtention of good-quality quantitative data. The extensive data assembled in this survey identified potential targets of carcinogenesis, for example the CRABP2 and GATA3 transcription factor genes. We also demonstrate the feasibility of this procedure for relatively small tumor samples, without recourse to probe amplification methods.

Breast Neoplasms↗
PubMed1999

Increased peripheral nerve microvessels in early experimental diabetic neuropathy: quantitative studies of nerve and dorsal root ganglia.

Microangiopathy is an important complication of diabetes mellitus and neovascularity is a feature of human diabetic retinopathy. The objective of this work was to evaluate numbers, areas and size distributions of whole nerve, endoneurial and dorsal root ganglia perfused microvessels in a detailed fashion using unfixed tissues from rats with experimental diabetes. Experimental neuropathy was studied in male Sprague-Dawley rats 12 weeks after streptozotocin or citrate buffer injection. Electrophysiological recordings of sciatic-tibial motor and caudal sensory fibers identified conduction slowing in diabetes indicating neuropathy. Diabetics had a rise in the numbers of whole nerve microvessels and endoneurial microvessels with associated rises in vessel densities and total vessel luminal areas. Increased vessel numbers in 15-30 microm diameter size ranges were particularly prominent. There was a rise in summed vascular areas in diabetics but the mean luminal area of vessels was not increased. Similar, but not significant trends were observed in a selective analysis of endoneurial vessels alone. In contrast, dorsal root ganglia microvessels were not increased in number. Early experimental diabetic neuropathy is associated with increased numbers of microvessels supplying the peripheral nerve trunk, likely representing neovascularity.

Animals↗