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Biomedical subjects

C Nguyen

Publications and source records attributed to C Nguyen.

157 records · Page 9Linked to original sources

Localization of the human NCAM gene to band q23 of chromosome 11: the third gene coding for a cell interaction molecule mapped to the distal portion of the long arm of chromosome 11.

cDNA clones containing sequences coding for the murine neural cell adhesion molecule (N-CAM) were used in Southern hybridizations on human genomic DNA and demonstrated approximately 90% homology between human and murine NCAM genes. In situ hybridization with one of these clones was performed on human metaphase chromosomes and allowed the localization of the human NCAM gene to band q23 of chromosome 11. The genes for two other cell surface molecules believed to be involved in cell-cell interactions, Thy-1 and the delta chain of the T3-T cell receptor complex, have recently been localized to the same region of chromosome 11 in man. Moreover, this region of the human chromosome 11 appears to be syntenic to a region of murine chromosome 9 that also contains the staggerer locus: staggerer mice show abnormal neurological features which may be related to abnormalities in the conversion of the embryonic to the adult forms of the N-CAM molecule.

Animals↗

Cardiac valve surgery in patients with poor left ventricular function.

Of 316 patients who underwent operation for valvular heart disease at the Toronto Western Hospital, between January 1978 and December 1981, 41 (31 men, 10 women), ranging in age from 24 to 74 years, had severely impaired left ventricular function (ejection fraction less than 40% and left ventricular end-diastolic pressure more than 18 mm Hg). All 41 patients were in New York Heart Association (NYHA) class III or IV. Fourteen patients had disease of the aortic valve, 13 of the mitral valve and 14 of both aortic and mitral valves. Twenty-two patients also had serious coronary artery disease. The valve dysfunction was corrected in all patients by replacement or repair and all severe coronary artery stenoses were bypassed with saphenous vein grafts. There were three hospital deaths and five late deaths during a mean follow-up of 26 months (range from 6 to 48 months). All patients improved symptomatically by a least one functional NYHA class. The actuarial survival including operative deaths was 79%.

Adult↗

Radioimmunoassay and heat denaturation enzyme assay for the detection of Tay-sachs heterozygotes during pregnancy.

Tay-Sachs disease results from a loss of activity of hexosaminidase A (HEXA) in body tissues and fluids. Heterozygotes for the disease are usually identified by their relatively low ratio of heat-labile HEX A to total hexosaminidase. During pregnancy an intermediate isoenzyme (HEX I) increases in activity in serum and obscures the heterozygote status. HEX I dose not increase in leucocytes, tears and other body tissues but because of technical difficulties in these assays we examined the feasibility of using a radioimmunoassay for HEX A. By univariate analysis, the heat denaturation assay gave a lower cost of misclassification for non-pregnant normals while RIA did so for pregnant normals. A combination of both tests led to reduced cost of misclassification compared to either alone. Bayesian analysis of bivariate gaussian density functions for heat denaturation and for radioimmunoassay of HEX isoenzymes was employed to calculate misclassification frequencies. Among the parameters examined, HEX A measured by RIA and % HEX A by heat-denaturation assay were the two having the best discriminatory power.

Acetylglucosaminidase↗

Carcinoma in situ of the glottic larynx: excision or irradiation?

BACKGROUND: The management of glottic carcinoma in situ (CIS) is controversial, with vocal cord stripping (S) generally accepted as the standard treatment, and radiotherapy (RT) as an alternative. We present our experience with 34 patients treated by either stripping or RT. METHODS: ++Between 1974 and 1990, 34 patients with CIS of the glottic larynx larynx were treated at McGill University teaching hospitals. The median age at diagnosis was 67 years, with a male:female ratio of 6:1. All patients had CIS involving the glottis and the pathology was reviewed on all patients. Twenty-one patients were treated by S and 13 patients by RT as the primary treatment. RESULTS: With a median follow-up of 96 months (25-209 months), the 15-year actuarial survival rate is 95% for all patients, with 100% and 87% survival rates for S and RT groups, respectively (p = 0.25). One patient in the RT group developed a subglottic invasive squamous cell carcinoma. On the other hand, 11 patients in the S group developed recurrence and were treated by repeat S (6 patients) or RT (5 patients), with a salvage rate of 100%. CONCLUSION: Although most patients with CIS of the glottis are traditionally treated with vocal cord S, RT is effective in terms of freedom from recurrence; it is an attractive option and should be considered in patients with lesions recurring after stripping as well as in those whose follow-up presents a problem.

Adult↗

Cytogenetic and physical mapping in the region of the X chromosome surrounding the fragile site.

Seven DNA probes have been mapped within the Xq27-Xq28 region using in situ hybridization, in some cases on chromosomes expressing the fragile site to enhance the resolution. To complement these studies and investigate the relationship between genetic, cytogenetic and physical distance some of these probes were used for large scale mapping using pulsed field gels. Physical linkage was demonstrated between two loci, F9 and MCF2, which are separated by less than 270 kb, and a restriction map extending over 1,300 kb has been generated.

Chromosome Fragile Sites↗

Metastatic squamous cell carcinoma to cervical lymph nodes from unknown primary mucosal sites.

Between 1978 and 1991, 54 patients with metastatic squamous cell or undifferentiated carcinoma to the cervical lymph nodes, with unknown primary mucosal sites, were treated with curative intent at McGill University teaching hospitals. The median age at diagnosis was 58 years with a male:female ratio of 6:1. All patients presented with a painless neck mass. Five patients (9%) presented with N1 disease, 28 (52%) with N2a disease, four (7%) with N2b disease, three (6%) with N2c disease, and 14 (26%) with N3 disease. Twenty-four patients (44%) underwent neck dissection, and 30 (56%) had only excisional lymph node biopsy. Fifty-three patients (98%) were treated with radiotherapy to a median dose of 60 Gy (range 38 to 66 Gy) in 30 fractions. With a median follow-up time of 49 months, the overall actuarial survival was 63% and 59% at 5 and 10 years, respectively. Three patients were found to have a subsequent primary head and neck tumor. The single most important prognostic factor was the N stage, which influences both neck control and long-term survival. There was no statistically significance difference in survival or local neck control rates between patients who had neck dissection or excisional lymph node biopsy (p > 0.05).

Adult↗

Differential regulation of heterodimerization by 1alpha,25-dihydroxyvitamin D(3) and its 20-epi analog.

Twenty-epi analogs of 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) are 100-1000 times more potent transcriptionally than the natural hormone. To determine to what extent this enhanced activity is mediated through modulation of the dimerization process, we performed quantitative dimerization assays with in vitro translated vitamin D receptor (ivtVDR) and fusion proteins containing glutathione-S-transferase (GST) and either the ligand-binding domain of VDR (GST-VDR) or retinoid X receptor (RXR)alpha (GST-RXR). We found that VDR did not form homodimers in either the presence or absence of ligand, but heterodimerization of the ligand-binding domains of RXRalpha and VDR was primarily deltanoid-dependent. The ED(50) for induction of heterodimerization was 1-2 x 10(-)(9) M for 1alpha,25(OH)(2)D(3) and 0.5 x 10(-)(11) M for 20-epi 1alpha,25(OH)(2)D(3). Mutations in VDR's activation function 2 domain (AF-2) diminished the abilities of 1alpha,25(OH)(2)D(3) to induce a protease-resistant conformation and heterodimerization. These mutations changed neither the potency of 20-epi-1alpha,25(OH)(2)D(3) to induce protease-resistant conformation nor its potency to induce dimerization. Mutations in heptad 9/helix 10 abolished the ability of both 1alpha,25(OH)(2)D(3) and the 20-epi analog to induce dimerization, but not their potency to fold VDR into a protease-resistant conformation. We hypothesize that both the hormone and the analog stabilize receptor conformations that expose VDR's dimerization interface, and that interfaces exposed by these ligands are probably not significantly different. However, the mechanisms by which the two ligands expose the dimerization interface are different with respect to participation of the AF-2 domain.

Animals↗

[Sun exposure and sun protection behavior and attitudes among the French population].

INTRODUCTION: The number of new skin cancers has constantly increased in France over the past two decades. The role of sun exposure can partly explain this phenomenon and justifies the development of information and prevention campaigns to change peoples' attitude towards sun bathing. To be effective, we need to know how much information and what attitudes the population currently has with regard to the sun. Although several studies in France have targeted children, little data is available regarding adults. This trial was aimed at pinpointing the knowledge, attitude and behavior of adults regarding sun exposure. MATERIAL AND METHODS: Data were collected during a randomized multicenter study on the prevention and early diagnosis of cutaneous tumors, conducted in 26 Health Centers from 1998 to 2000. Standardized questionnaires were handed to those consulting to assess their knowledge, attitudes and behavior towards sun bathing. The population was composed of 41 143 adults aged over 30, consulting one of the 26 Health Check-up units. Analysis of the data was made using SAS v 6.12 and STATA 7.0 software. Logistic regression identified the explicative factors of knowledge and behavior. All the statistical analyses were considered significant above a threshold of alpha<5%. RESULTS: A total of 33 021 persons filled-in the self-questionnaire. Forty-nine percent were women and 51% were men, with a mean age of 50 years. Geographically, 25% lived in the North-East, 16% in the North-West, 25 p.cent in the South-East and 34% in the South-West. Thirty percent claimed that they tanned without burning and 2% of the population studied had often suffered from sun burn, generally when they were adult. The risks related to sun burn were known, because 92% knew that the sun increased the risk of skin aging and 89% knew that it increased the risk of skin cancer. Regarding sun screens, knowledge was not so good; 42% thought that all products were the same and 53% that they allowed one to sun bathe longer. This knowledge was better in those with fair skins, in those who had a history of sun burn, in women and in those who lived in the northern areas of France. Conversely, knowledge decreased with age and was limited in those aged over 60. Regarding behavior, those with fair skin and who reddened under the sun without tanning, protected themselves more. The women declared they protected themselves more than the men, but they used less sun protective measures (clothing, hats...), other than sun screens, than men. Subjects aged over 60 protected themselves more than younger subjects. Lastly, a personal cutaneous history increased protective behavior, and those from northern France protected themselves more than those from the South. DISCUSSION: This analysis of 33 021 adults aged over 30 shows the good global knowledge of the consequences of sun bathing, but also the lack of knowledge on the interest of using external sun protection and the role of physical means of protection. Attitudes varied depending on gender, age and phototype and also depending on the area where they lived. Despite good knowledge, the most frequent behavior of adults aged over 30 is still not appropriate with differences depending on age, gender and area, which must prompt more appropriate targeting of prevention campaigns according to the populations concerned.

Adult↗

Allelism in the HLA class I multigene family.

Recent data on the structure of functional HLA class I genes shows that, at least at the HLA-A locus, the allelic genes are more related to each other than to HLA genes from other loci. This "A-ness" is discernible at the protein sequence level but much more evident when nucleotide sequences are compared; the homology is particularly striking in the 3' non-coding region. Genes coding for the same HLA specificity in different genetic backgrounds show no obvious difference, although in one case the 3' flanking regions are clearly different; the restriction maps around the HLA-A3 and HLA-AW24 genes are also compared to see whether the chromosomal environments of these two genes are recognizably similar.

Alleles↗

The role of the p53 gene in the malignant transformation of pleomorphic adenomas of the parotid gland.

Pleomorphic adenoma (PA), the most common neoplasm of the parotid gland in adults, undergoes malignant transformation in only two to six percent of cases. In order to determine whether or not the p53 gene is involved in the malignant transformation of PA of the parotid gland, we have analyzed archival specimens from four patients with carcinoma ex-pleomorphic adenoma (CEPA) by immunohistochemistry and sequencing of the amplified DNA. Tissue specimens from each patient contained both the CEPA and the precursor PA. Immunostaining revealed that while all CEPA were p53 positive, only one of the four precursor PA was positive for p53. In this case, DNA was isolated from both the PA and CEPA and exons five through eight were amplified using the polymerase chain reaction. The same p53 mutation (single base substitution) was found in both the PA and the CEPA at codon 248. Adjacent normal tissue contained the wild-type p53 sequence. To our knowledge, this is the first report of the same p53 point mutation in both a PA and the associated CEPA of the parotid. These results strongly suggest a role for p53 gene mutation in the malignant transformation of some PA of the parotid gland.

Adenocarcinoma↗

Production of radiolabeled neuropeptide precursors by in vitro transcription and translation.

Bioactive peptide hormones and neurotransmitters are required for neuroendocrine regulation of cellular functions. Importantly, proteolytic processing of inactive neuropeptide precursors is required to generate physiologically active peptide hormones and neurotransmitters. Studies of the processing enzymes require authentic neuropeptide precursors as substrates, rather than peptide substrates. This study demonstrates an efficient method to general 35S-precursors from cloned cDNAs by in vitro transcription and translation. In vitro transcription of neuropeptide cDNAs with SP6 RNA polymerase generates large amounts (micrograms) of corresponding RNAs. Subsequent in vitro translation of RNAs with wheat germ extract and 35S-methionine generates large quantities of 35S-precursors (10-25 million cpm 35S-precursor protein per reaction) with high specific radioactivity. The radiolabeled precursor substrates offer a reliable, sensitive and accurate method for detecting the proteolytic activity. Importantly, specific detection of the primary proenkephalin processing activity in chromaffin granules by 35S-enkephalin precursor as substrate, but not by peptide methylcoumarinamide (MCA) substrates, illustrates the significance of using full-length precursor to detect appropriate processing enzymes. This study demonstrates that efficient production of radiolabeled neuropeptide precursors by in vitro transcription and translation will be useful for in vitro assays of relevant processing proteases.

Animals↗