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Biomedical subjects

C Nguyen

Publications and source records attributed to C Nguyen.

At least 109 records · Page 6Linked to original sources
PubMed1996

Combinatorial modification of natural products: preparation of unencoded and encoded libraries of Rauwolfia alkaloids.

We report the preparation of combinatorial libraries which consist of derivatives of the stereoisomeric alkaloids yohimbine and rauwolscine-members of the Rauwolfia genus. The chemistry was performed on solid support using the divide-and-pool method, and involved the derivatization of the E-ring carboxylates and hydroxyls of these alkaloids with 36 amino acids and 22 carboxylic acids, respectively, to afford 792 bifunctionalized derivatives. The rauwolscine library was prepared using an encoding strategy in which the identity of each incorporated amino acid was recorded by cosynthesizing chemically inert tags prior to the pooling step. The general strategy for library synthesis exploits existing functionality present on the natural products, and should be applicable to other families of secondary metabolites.

Chromatography, High Pressure Liquid↗
PubMed1996

From hybridization image to numerical values: a practical, high throughput quantification system for high density filter hybridizations.

Hybridization to sets of bacterial colonies or PCR products arrayed on high density filters is used in a number of experimental schemes. In many cases it is desirable to collect quantitative information ('hybridization signatures') rather than indications on 'positive' and 'negative' colonies. We present a practical system, based on an imaging plate analyser and a customized version of commercial software, that makes such quantification feasible, and define its performance in terms of reproducibility and linearity. The system is far superior to methods based on autoradiography and should be useful in many projects that involve the increasingly popular high density filter format.

Animals↗
PubMed1996

Glottic microinvasive carcinoma: is it different from carcinoma in situ?

OBJECTIVE: To determine the impact of different treatment modalities on the outcome of microinvasive carcinoma. DESIGN: Retrospective review of patients presenting between 1976 and 1990. SETTING: Fifteen patients with microinvasive carcinoma (MIC) of the glottic larynx treated at McGill University teaching hospitals. METHODS: All patients had MIC involving the glottis confirmed pathologically. Nine patients (60%) had right vocal cord involvement, four (27%) had left vocal cord involvement, and two (13%) had involvement of both cords. Five patients (33%) were treated by stripping(S), three patients (20%) by stripping and radiotherapy (S + RT), and six patients (40%) by radiotherapy (RT) alone as the primary treatment. Only one patient underwent hemilaryngectomy. RESULTS: With a median follow-up time of 63 months (range 20-208 months), the 15-year actuarial survival rate is 100% for all patients. CONCLUSIONS: Surgery alone, RT alone, or S + RT is equally effective in treating MIC of the glottic larynx; however, single-modality therapy is preferred. The choice of treatment modality should be individualized for each patient.

Adult↗
PubMed1995

TNF alpha receptor expression in rat cardiac myocytes: TNF alpha inhibition of L-type Ca2+ current and Ca2+ transients.

Tumor necrosis factor-alpha (TNF alpha) is a potentially powerful anti-neoplastic agent; however, its therapeutic usefulness is limited by its cardiotoxic and negative inotropic effects. Accordingly, studies were undertaken to gain a better understanding of the mechanisms of TNF alpha-mediated cardiodepression. Single cell RT-PCR, [125I]TNF alpha ligand binding and Western immunoblotting experiments demonstrated that rat cardiac cells predominantly express type I TNF alpha receptors (TNFRI or p60). TNF alpha inhibited cardiac L-type Ca2+ channel current (ICa) and contractile Ca2+ transients. Thus, it is possible that the negative inotropic effects of TNF alpha are the result of TNFRI-mediated blockade of cardiac excitation-contraction coupling.

Animals↗
PubMed1995

Differential gene expression in the murine thymus assayed by quantitative hybridization of arrayed cDNA clones.

High-throughput measurement of hybridization signatures obtained using complex probes prepared from poly(A)+ RNA and high-density cDNA colony filters is described. The performance of the system, elimination of artifacts, and verification of the validity of the data are discussed. cDNAs corresponding to sequences present at levels of approximately 0.01% in the complex probe can be detected. Good correlation is observed between expression profiles determined by this method and by Northern blotting. The method is applied to a preliminary investigation of differential expression in three cell types present in the murine thymus.

Animals↗
PubMed1995

Can we distinguish between benign versus malignant compression fractures of the spine by magnetic resonance imaging?

STUDY DESIGN: The authors investigate the usefulness of magnetic resonance imaging in differentiating benign versus malignant compression fractures by reviewing patients and a fracture model in a canine model. OBJECTIVES: To determine the sensitivity and specificity of magnetic resonance imaging in differentiating benign versus malignant compression fractures of the spine and to obtain distinguishing features in magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: The differentiation between benign and abnormal compression fractures of the thoracolumbar spine has important implications regarding patient treatment and prognosis. Plain radiographs, bone scans, and computed tomography are not accurate imaging modalities for this purpose. METHODS: Magnetic resonance imaging scans of 22 patients with confirmed lesions of the thoracolumbar spine were studied. There were 11 malignant and 11 benign lesions. Two experienced neuroradiologists blindly reviewed the magnetic resonance imaging scans and determined benign or malignant lesions. A canine study was performed to simulate a compression fracture model with a vertebral osteotomy in two dogs, and serial contrast-enhanced magnetic resonance imaging scans were performed 15, 30, 60 and 90 days after surgery. RESULTS: The correct interpretation between two neuroradiologists was 77% and 95%. The combined sensitivity rate was 88.5%, and the specificity rate was 89.5%. Magnetic resonance imaging reliably distinguished benign versus malignant lesions based on the anatomic distribution and intensity of signal changes of bone and adjacent tissues, contrast enhancement characteristics, and changes over time. Only one malignant lesion was misinterpreted by both neuroradiologists as benign, whereas there was one additional missed malignant lesion and three misinterpreted benign lesions by one radiologist. In the canine study, signal changes and enhancement were found 60 days after surgery, but no signal changes or enhancement were noted on the scan 90 days after surgery. CONCLUSIONS: Magnetic resonance imaging scans can detect malignant vertebral lesions early, but acute healing compression fractures may mimic the findings of metastatic lesions. The use of contrast-enhanced magnetic resonance imaging scans and serial magnetic resonance imagings are helpful for additional differentiation between benign and malignant compression fractures. In addition to magnetic resonance imaging scans, other diagnostic tests and clinical findings should be correlated before biopsy or surgery of the suspected lesion.

Adult↗
PubMed1995

Specificity and VH sequence of two monoclonal antibodies against the N-terminus of dystrophin.

We have used a random library of 15-mer peptides expressed on phage to show that two monoclonal antibodies (mAbs) require only the first three amino acids of dystrophin (Leu-Trp-Trp) for binding. Since the mAbs recognize dystrophin in frozen muscle sections, the results suggest that this hydrophobic N-terminus of dystrophin is accessible to antibody in situ. Quantitative binding studies suggested minor differences in specificity between the two mAbs, so the Ig heavy-chain variable region (VH) sequences of the two hybridomas were determined by RT-PCR and cDNA sequencing. After elimination of PCR errors, the two cDNA sequences were found to be identical except for five somatic mutations which resulted in three amino acid changes in the second hypervariable region (CDR2). The results suggest that the two hybridomas originated from the same lymphocyte clone in a germinal centre of the spleen, but underwent different point mutations and subtype switches during clonal expansion to form blast cells.

Amino Acid Sequence↗
PubMed1995

Expression of bovine heart fructose 6-phosphate,2-kinase:fructose 2,6-bisphosphatase and determination of the role of the carboxyl terminus by mutagenesis.

Bovine heart fructose 6-P,2-kinase:fructose 2,6-bisphosphatase was expressed in Escherichia coli. In order to determine the role of the carboxyl-terminal peptide, 49 and 78 amino acids from the C-terminus were deleted using oligonucleotide-directed mutagenesis. The expressed wild-type and mutant enzymes were purified to homogeneity, and the steady-state kinetics of the mutant enzymes were compared to those of the wild-type enzyme. Deletion of 49 residues (Del 49) resulted in a 35% decrease in KmFru6P, a 36% increase in Vmax, and a 2-fold increase in Kcat/Km of the kinase. There was no change in the kinetic properties of the phosphatase activity. Deletion of 78 residues (Del 78) resulted in a 4.5-fold decrease in KmFru6P, a 2.5-fold increase in Vmax, a 12-fold increase in kcat/Km of the kinase, and a 3-fold increase in kcat/Km of the phosphatase. Phosphorylation of the wild-type and Del 49 enzymes resulted in decreased KmFru6P and activation of the kinase without affecting the phosphatase activity. Thermal inactivation rates of the wild-type and Del 49 enzymes were similar, but the rate of Del 78 was more rapid. The phosphorylated wild-type and Del 49 enzymes were more sensitive to thermal inactivation than the dephospho forms. Urea inactivation of the kinase and phosphatase of wild-type and Del 49 were similar, but Del 78 was more sensitive to urea. All phosphorylated enzymes were more susceptible to urea inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

The respiratory system of Kluyveromyces lactis escapes from HAP2 control.

A functional homolog of the Saccharomyces cerevisiae HAP2 gene, coding for one element of a transcriptional activator complex, was cloned from the yeast Kluyveromyces lactis and its nucleotide sequence was determined. Inactivation of the gene had no significant effect on respiration-dependent growth, suggesting that the HAP2/3/4 complex has no major control over the formation of the mitochondrial respiratory system in K. lactis.

Amino Acid Sequence↗
PubMed1995

High-dose-rate brachytherapy as the primary treatment of medically inoperable stage I-II endometrial carcinoma.

Between 1984 and 1992, 27 patients with clinical stage I-II histologically proven adenocarcinoma of the endometrium who had significant medical risks precluding surgery underwent radiotherapy (RT) as the primary treatment. The median age at diagnosis was 74 years. There were 20 patients (74%) with stage I and 7 patients (26%) with stage II disease. Patients were treated with high-dose-rate brachytherapy (HDRB) alone (19/27) or with a combination of external-beam RT and HDRB (2 stage I; 6 stage II). HDRB was delivered using a cobalt-60 HDR remote afterloading unit, with a median dose of 2000 cGy to point A, in two to three fractions given once a week. All HDRB treatments were performed under spinal anesthesia on an outpatient basis. External-beam irradiation to the pelvis was given using 4- to 6-MV photons and a median dose of 4200 cGy was delivered. In all patients, vaginal bleeding was controlled within a few days after completion of RT. With a median follow-up of 47 months, the 8-year disease-specific survival rate was 76%. Patients with stage I had an 8-year survival rate superior to that of patients with stage II (95% vs 21%, P < 0.001). No complications were experienced during HDRB. Late serious complications were seen in 3 patients (11%). Based on this retrospective review, primary RT with HDRB appears to be an effective and safe treatment for those patients with medically inoperable clinical stage I endometrial carcinoma. Because HDRB is given on an outpatient basis, it is an attractive option for these patients. However, in stage II disease the results of treatment are poor and RT alone should be considered only when the surgical risks are too high.

Aged↗
PubMed1995

Functional evidence for the presence of nitric oxide synthase in the dorsal motor nucleus of the vagus.

BACKGROUND & AIMS: Histochemical studies indicate that reduced nicotinamide adenine dinucleotide phosphate diaphorase, the nitric oxide synthase-related enzyme, is present in the dorsal motor nucleus of the vagus of the cat. We have previously shown in vitro that NO synthase is present in this nucleus in the rat and that the excitatory effect of N-methyl-D-aspartate on these neurons is in part caused by NO formation. The aim of this study was to obtain functional evidence for the presence of NO synthase in the cat dorsal motor nucleus of the vagus. METHODS: L-Glutamate, L-arginine, D-arginine, the NO donor S-nitroso-N-acetyl-penicillamine, and the NO synthase inhibitor NG-nitro-L-arginine-methyl ester were unilaterally microinjected into the rostral dorsal motor nucleus of anesthetized cats, and antral and pyloric motility were monitored using extraluminal force transducers. RESULTS: Microinjection of L-arginine increased gastric motility, whereas D-arginine had no effect. Vagotomy eliminated the L-arginine-induced increases. Microinjection of S-nitroso-N-acetyl-penicillamine increased antral motility. NG-Nitro-L-arginine-methyl ester prevented L-arginine from exerting an effect on gastric motility. CONCLUSIONS: Motility increases obtained after microinjection of L-arginine into the dorsal motor nucleus and prevention of these motility increases with microinjection of a NO synthase inhibitor provide functional evidence for the presence of NO synthase in the dorsal motor nucleus of the vagus in the cat.

Animals↗
PubMed1995

Contrast enhancement in spinal nerve roots: an experimental study.

PURPOSE: To examine histopathologically the endothelium of contrast-enhancing spinal nerve roots. METHODS: In five adult baboons, chronic compression of the left S-1 spinal nerve root sufficient to produce a change in the evoked potential was produced by means of a suture tied around the nerve. The animals were studied with MR at 8 and 16 days after nerve compression and then killed for histopathologic and electron microscopic studies. Histopathologic changes in the nerve roots demonstrating contrast enhancement were described. RESULTS: In all compressed spinal nerves, contrast enhancement was observed. Histopathologically, wallerian degeneration of the root and inflammation and disruption of the endothelium of capillaries in the spinal nerve were evident. CONCLUSIONS: Degenerative changes in the nerve root and the capillary endothelium of a lumbar spinal nerve are associated with contrast enhancement.

Animals↗
PubMed1994

Accumulation and degranulation of mast cells in experimental neuromas.

Mast cell accumulation and degranulation occur within the endoneurium of injured peripheral nerves. We investigated the time course of mast cell accumulation and degranulation in experimental neuromas of the sciatic nerve in rats. Mast cell accumulation and degranulation were significant only after the first week following neuroma creation and were prominent at 14 days within the neuroma stump. Mast cell degranulation could account for microvascular changes within neuromas after the first week following injury.

Animals↗
PubMed1994

Gadolinium-enhancement characteristics of magnetic resonance imaging in distinguishing herniated intervertebral disc versus scar in dogs.

STUDY DESIGN: This study is an experimental investigation on the gadolinium contrast magnetic resonance imaging (MRI) in distinguishing sequestered disc fragment versus scar in dogs. The conspicousness of the disc fragment and signal intensities of the disc fragment and laminectomy scar were evaluated using gadolinium-enhanced MRI and histology. OBJECTIVES: This study investigated the effects of timing of gadolinium injections, gadolinium doses, and aging of scar or disc on the enhancement characteristics and conspicuousness of disc fragment in MRI. SUMMARY OF BACKGROUND DATA: Contrast-enhanced MRI has been frequently used as a procedure to evaluate patients with suspected recurrent herniated discs. In contrast-enhanced MRI, the postoperative scar tissue enhances to a greater extent than disc fragments. Previous reports suggest different contrast enhancement characteristics of scar depending on doses, timing of gadolinium, or maturity of scar. There are different compounds of gadolinium agents and different doses are becoming available. There is no previous report on the evaluation of gadolinium enhancement characteristics in dogs with concurrent herniated disc and scar. METHODS: Six conditioned Beagle dogs underwent hemilaminectomies and discectomies at the L3-L4 level. An autogenous disc fragment was obtained from the intervertebral disc of the tail. This disc fragment was placed anterolateral to the thecal sac, simulating a sequestered disc herniation. Three control animals underwent hemilaminectomies and discectomies alone. Each dog underwent MRI on a 1.5 Tesla scanner (3.0 mm slice in sagittal and axial projections with TR 500, TE 30 msec and high dose 0.3 mmol/kg of gadoteridol). Images were obtained at 15 days, 30 days, 60 days, and 90 days after surgery. At each imaging session, contrast enhancement was measured at 2 minutes, 25 minutes, and 45 minutes after gadolinium injection for kinematic analysis. Two animals at a time were killed on 30 days, 60 days, and 90 days postoperatively. Magnetic resonance imaging was done with conventional low dose 0.1 mmol/kg of gadopentetate at 15 days and before death. RESULTS: Results revealed that the difference of enhancement between disc and the scar and therefore conspicuousness of disc fragment was greater on 2-23-minute images as compared with 45- minute images, and the distinction decreased with aging of the scar. The high dose contrast-enhanced MRI increased signal intensities for both disc and scar. Conspicuousness of disc fragment seemed to be better with the high-dose gadolinium compound. CONCLUSIONS: In conclusion, contrast enhancement characteristics in MRI may depend on the timing of MRI after gadolinium injection, doses of gadolinium, and aging of scar or disc.

Animals↗
PubMed1994

Utility of high-dose contrast enhancement for detecting recurrent herniated intervertebral disks.

PURPOSE: To study the utility of high-dose contrast enhancement in the detection of recurrent herniated disk fragments. METHODS: Recurrent herniated disks were modeled in nine dogs by placing a fragment of normal autologous disk tissue in the epidural space at laminectomy. MR was performed at 30, 60, and 90 days with 0.3 mmol/kg of gadoteridol and repeated 24 hours later with 0.1 mmol/kg of gadopentetate dimeglumine. Contrast enhancement in the disk and scar tissue was measured and conspicuousness of the disk fragments assessed. RESULTS: In 70% of the animals, disk fragments were more conspicuous with the larger dose of contrast medium than with the smaller dose. In 30% of animals the conspicuousness was approximately equal. Contrast between disk fragment and scar decreased with time elapsed since surgery, with time elapsed since contrast-medium injection, and with decreasing dose of contrast medium. CONCLUSION: In the experimental model, increased conspicuousness of disk fragments was achieved with the larger dose of contrast medium. A clinical study is needed to confirm that a contrast-medium dose of 0.3 mmol/kg improves detection of recurrent herniated disks over a dose of 0.1 mmol/kg.

Animals↗