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Biomedical subjects

H H Nguyen

Publications and source records attributed to H H Nguyen.

At least 37 records · Page 2Linked to original sources

Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma.

OBJECTIVE: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. STUDY DESIGN: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV1) > or =70% of the predicted value and a fall in FEV1 > or =20% after exercise on 2 occasions. Patients received montelukast (5-mg chewable tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV1 versus time curve (AAC0-60 min), maximum percent fall in FEV1 from pre-exercise baseline, and time to recovery of FEV1 to within 5% of pre-exercise baseline. RESULTS: Montelukast significantly reduced AAC0-60 min (265 vs 590% x min for montelukast and placebo, respectively, P < or = .05; approximately 59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P < or = .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). CONCLUSIONS: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma.

Acetates↗

Influenza virus-infected epithelial cells present viral antigens to antigen-specific CD8+ cytotoxic T lymphocytes.

We have investigated the mechanisms involved in the clearance of viral infection at the epithelium level by analyzing the activity of influenza virus-specific cytotoxic T lymphocytes (CTL) against virus-infected CMT-93 intestinal epithelial cells. Epithelial cells infected with live influenza virus effectively present viral antigens and were lysed by both homotypic and heterotypic influenza virus-specific CD8+ T cells. These results shed new light on the control of viral infection through the elimination of virus-infected epithelial cells by virus-specific CTL and demonstrate that CMT-93 cells furnish an appropriate model for in vitro evaluation of CTL activity against virus-infected epithelial cells.

Animals↗

Nasal lymphoid tissue (NALT) as a mucosal immune inductive site.

Intranasal (i.n.) immunization is a very effective route for inducing mucosal immunity, but the cellular mechanism responsible for regulating and disseminating these responses is not fully understood. The authors studied the role of nasal lymphoid tissue (NALT) as a mucosal inductive site by using highly purified NALT cells obtained by a new method of mechanical isolation. The NALT cells, like Peyer's patch (PP) cells, were smaller in size and less granular than lymphocytes from salivary glands (SG) and small intestinal lamina propria (LP). The NALT cells isolated from i.n. immunized mice contained antigen-specific antibody-secreting cells (ASC) predominantly of immunoglobulin (Ig)A isotype, similar to those also recovered from salivary glands in a time course study. However, the higher proportion of smaller sized sports formed by NALT cells in ELISPOT assays suggested that these cells were less differentiated precursors of those found in salivary glands. This was supported by the fact that after i.n. immunization, IgA ASC appeared in NALT, as well as in mucosal effector sites SG and LP, but none or very few in another mucosal inductive site, PP. In contrast, after intragastric (i.g.) immunization, IgA ASC were detected in PP, along with the SG and LP, but none or very few in NALT. Furthermore, after i.n. immunization, lymphocytes from NALT but not PP proliferated in response to the specific antigen in culture. These findings imply that NALT served as an inductive site for IgA antibody responses at mucosal effector sites.

Administration, Intranasal↗

Inhibitory effects of hypercholesterolemia and ox-LDL on angiogenesis-like endothelial growth in rabbit aortic explants. Essential role of basic fibroblast growth factor.

Hypercholesterolemic (HC) rabbits exhibit suppressed compensatory vascular growth after restriction of arterial supply. However, neovascularization is commonly found in atheromas containing inflammatory cells. We used an in vitro model to determine the effects of hypercholesterolemia on angiogenesis in the absence or presence of inflammatory cells. HC rabbit aortic explants (1 mm2) with or without (n = 90 each) lesion-forming inflammatory cells were cultured in a collagen matrix with serum-free medium. Explant-derived endothelial cell growth was organized into capillary-like microtubes (CLM) that could be videomicroscopically quantified. CLM growth from lesion-free HC explants was significantly reduced to 13 +/- 4% of the value in explants (n = 90) from normocholesterolemic (NC, n = 15) rabbits (P < .001). In contrast, in lesion-containing HC explants, the matrix was invaded by foam cells, and CLM growth was not inhibited. Immunoassayable basic fibroblast growth factor (bFGF, in pg/mL) in the culture medium was significantly lower in lesion-free HC (< 5) than NC explants (11 +/- 2, P < .01) or HC explants with lesions (14 +/- 3). In addition, CLM growth was reduced in NC explants incubated with oxidized LDL (ox-LDL, 50-100 micrograms/mL). Exogenous bFGF (10 ng/mL) reversed the inhibitory effects of hypercholesterolemia and ox-LDL, whereas bFGF-neutralizing antibody (10 micrograms/mL) abolished CLM growth in all groups. In cultured rabbit aortic endothelial cells, ox-LDL reduced DNA synthesis, but this inhibition was reversed by bFGF. We conclude that hypercholesterolemia and ox-LDL inhibit angiogenesis like endothelial growth because of a suppressed availability of endogenous bFGF. Retained responsiveness to exogenous bFGF suggests that inducing bFGF expression at targeted sites may improve collateral growth in hyperlipidemic arterial disease.

Animals↗

Time course of Bell palsy.

This study was designed to quantitatively characterize the time course of facial palsy and the relationship between electroneurography and the facial nerve grading percentage as a function of onset time. Bilateral electroneurographic recordings during different stages in the course of the disease were repeated and compared with categorized videotaped facial movements using the House-Brackmann facial nerve grading system in 32 patients with Bell palsy. Preliminary results of this study demonstrate a time gap between the percentage of electroneurographic response and the category of the facial nerve grading system during the same period of disease progress. A theoretical model of the time course and specific patterns regarding the recovery of facial function is established. The theoretical time course of facial palsy is divided into 3 stages; preclinical, clinical, and postclinical. Based on the time course of electroneurographic and facial grading functions, the period between 10 and 14 days after onset was found to be most valuable for prediction of recovery. According to this theoretical model, a given time course pattern based on the results of serial electroneurographic recordings provides reliable prognostic information on recovery from Bell palsy.

Action Potentials↗

Effects of brain stem lesions on cochlear function: mechanism of hearing improvement after removal of a brain stem tumor.

EOAEs are well correlated with changes of hearing sensitivity during the clinical course of brain stem lesions, as shown in this case study. They may serve as sensitive indicators to evaluate the possible effects of a brain stem lesion on cochlear function and monitor the attempted preservation of hearing during CPA or brain stem surgeries. It is thereby suggested that EOAEs should be included in an audiologic test battery in a differential diagnosis of retrocochlear lesions.

Audiometry, Pure-Tone↗

Natural killer cell activity in coeliac disease: effect of in vitro treatment on effector lymphocytes and/or target lymphoblastoid, myeloid and epithelial cell lines with gliadin.

To analyze the possible involvement of natural killer (NK) cell activity in the pathogenetic mechanism of coeliac disease (CD) we measured the spontaneous cytotoxic cell activity of peripheral blood mononuclear cells (PMNC) from patients with CD and from healthy donors. No significant differences were found between the NK cell activity of PMNC from healthy donors and from patients with CD using a standard 51 Cr release assay. However, a 30-min treatment of PMNC with gliadin inhibited NK cell activity in patients with CD. On the other hand, a 1-d incubation with gliadin induced cytotoxic cell activity of PMNC against the NK-resistant target cells such as the epithelial HT-29 and the lymphoblastoid RAJI cell lines, suggesting that activation of PMNC by cultivation with gliadin can occur.

Adult↗

Basic fibroblast growth factor reverses atherosclerotic impairment of human coronary angiogenesis-like responses in vitro.

The influence of atherosclerosis on vascular growth in humans was evaluated in an in vitro model of angiogenesis. Coronary artery intima-media explants from patients (n = 10) with coronary artery disease (CAD) (in all cases Stary type V lesions) and patients without CAD (n = 10) were cultured in a collagen matrix containing serum-free medium. Endothelial cell growth from explants was organized as capillary-like microtubes (CLM); the sum of their lengths was morphometrically quantitated as an index of angiogenesis. CLM growth was suppressed in CAD explants (n = 120), the index values at two weeks averaging only 20% +/- 3% of non-CAD explants (n = 120, P < 0.001). Addition of exogenous basic fibroblast growth factor (bFGF) (10 ng/ml) stimulated CLM growth substantially more in the CAD than in the non-CAD group, whereas bFGF-neutralizing antibodies nearly abolished growth in both. Endothelial cells isolated from non-CAD coronary arteries exhibited in culture typical endothelial characteristics, including cobblestone appearance, staining for von Willebrand factor, CLM formation on Matrigel substrate, and sensitivity to bFGF and to bFGF-neutralizing antibody. Inhibition of cell replication by oxidized low-density lipoprotein (OxLDL) was reversed by bFGF. We conclude that human atherosclerosis is associated with impairment of angiogenesis-like endothelial growth and that decreased bFGF availability contributes to the impairment.

Cell Count↗

False popliteal aneurysm after femoral embolectomy.

An unusual case with delayed presentation of a false popliteal aneurysm following transfemoral embolectomy is reported. It highlights that arterial embolectomy, despite its well-established merits, may have major complications.

Aged↗

The nature of the copper ions in the membranes containing the particulate methane monooxygenase from Methylococcus capsulatus (Bath).

It is shown that the particulate methane monooxygenase (pMMO) has an obligate requirement for copper. The MMO activity in the particulate fractions obtained from Methylococcus capsulatus (Bath) cells is found to increase with increasing copper content of the membranes. The enzyme activity from membranes obtained from cells grown at low copper levels can be stimulated further by the addition of Cu(II) ions to the assay medium. The membrane-bound copper ions can exist in both Cu(II) and Cu(I) forms. EPR and magnetic susceptibility characterizations of the membranes indicate the presence of an exchange-coupled trinuclear Cu(II) cluster when the bulk of the copper ions is oxidized. However, the functional form of the enzyme is the reduced or partially reduced form. The copper ions in the membrane fractions as isolated often exhibit a high level of reduction. An EPR spectrum with one unpaired electron spin delocalized over three copper nuclei has been observed for the two-electron reduced trinuclear copper cluster. The high correlation between the copper level in the membranes and enzymatic activity as well as the high reactivity of the reduced copper clusters toward dioxygen strongly indicate that the membrane-bound copper ions constitute the active sites of the pMMO.

Cell Membrane↗

The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness.

The effects of the 5 alpha-reductase inhibitor, finasteride, on scalp skin testosterone (T) and dihydrotestosterone (DHT) levels were studied in patients with male pattern baldness. In a double blind study, male patients undergoing hair transplantation were treated with oral finasteride (5 mg/day) or placebo for 28 days. Scalp skin biopsies were obtained before and after treatment for measurement of T and DHT by high pressure liquid chromatography-RIA. In 10 male subjects studied at baseline, mean (+/- SEM) DHT levels were significantly higher in bald (7.37 +/- 1.24 pmol/g) compared to hair-containing (4.20 +/- 0.65 pmol/g) scalp, whereas there was no difference in mean T levels at baseline. In bald scalp from 8 patients treated with finasteride, the mean DHT concentration decreased from 6.40 +/- 1.07 pmol/g at baseline to 3.62 +/- 0.38 pmol/g on day 28. Scalp T levels increased in 6 of 8 subjects treated with finasteride. Finasteride decreased the mean serum DHT concentration from 1.36 +/- 0.18 nmol/L (n = 8) at baseline to 0.46 +/- 0.10 nmol/L on day 28 and had no effect on serum T. There were no significant changes in scalp or serum T or DHT in placebo-treated patients. In this study, male subjects treated with 5 mg/day finasteride for 4 weeks had significantly decreased concentrations of DHT in bald scalp, resulting in a mean level similar to the baseline levels found in hair-containing scalp.

5-alpha Reductase Inhibitors↗

Tests for qualitative treatment-by-centre interaction using a 'pushback' procedure.

In multicentre clinical trials using a common protocol, the centres are usually regarded as being a fixed factor, thus allowing any treatment-by-centre interaction to be omitted from the error term for the effect of treatment. However, we feel it necessary to use the treatment-by-centre interaction as the error term if there is substantial evidence that the interaction with centres is qualitative instead of quantitative. To make allowance for the estimated uncertainties of the centre means, we propose choosing a reference value (for example, the median of the ordered array of centre means) and converting the individual centre results into standardized deviations from the reference value. The deviations are then reordered, and the results 'pushed back' by amounts appropriate for the corresponding order statistics in a sample from the relevant distribution. The pushed-back standardized deviations are then restored to the original scale. The appearance of opposite signs among the destandardized values for the various centres is then taken as 'substantial evidence' of qualitative interaction. Procedures are presented using, in any combination: (i) Gaussian, or Student's t-distribution; (ii) order-statistic medians or outward 90 per cent points of the corresponding order statistic distributions; (iii) pooling or grouping and pooling the internally estimated standard deviations of the centre means. The use of the least conservative combination--Student's t, outward 90 per cent points, grouping and pooling--is recommended.

Clinical Trials as Topic↗

Evaluation of multicentre clinical trial data using adaptations of the Mosteller-Tukey procedure.

Two procedures, based on proposals discussed by Mosteller and Tukey, are described for obtaining a combined estimate of the difference between two treatment means and its confidence interval from multicentre clinical trial data. Both procedures provide estimates in the possible presence of heteroscedasticity. The first procedure is designated the primary analysis for efficacy assessment. It omits treatment-by-centre interaction from the error term for treatment, unless there is substantial evidence of qualitative interaction (Ciminera et al.) or other special circumstances. The second procedure is the primary analysis whenever there is substantial evidence of qualitative interaction, and can be used whenever there are other reasons to make an analysis allowing for interaction.

Asthma↗

Spectroscopic characterization of heme A reconstituted myoglobin.

The focus of this study was to examine the functional role of the unusual peripheral substitution of heme A. The effects of heme A stereochemistry on the reconstitution of the porphyrin have been examined in the heme A-apo-myoglobin complex using optical absorption and resonance Raman and electron paramagnetic resonance spectroscopies. The addition of one equivalent of heme A to apo-Mb produces a complex which displays spectroscopic signals consistent with a distribution of high- and low-spin heme chromophores. These results indicate that the incorporation of heme A into apo-Mb significantly perturbs the protein refolding.

Animals↗

Contemporary evaluation of unilateral vocal cord paralysis.

Unilateral vocal cord paralysis is a common finding in the practice of otolaryngology. Multiple etiologies have been described and have not changed appreciably in the last century. We attempted to characterize the contemporary evaluation of unilateral vocal cord paralysis, with consideration given to cost-effectiveness. Thirty-one board-certified otolaryngologists were interviewed to determine their typical evaluation protocol. The average cost of an evaluation totaled $1706.18, with a range of $112.56 to $3439.52. Otolaryngologists with more years of experience tended to pursue briefer and less expensive evaluations. The charts of 187 patients with a diagnosis of vocal paralysis from 1983 to 1991 were reviewed, of which 113 were evaluable. Eighty-four of these 113 (74%) were unilateral. In 48 of 84 cases (57%), the cause was apparent at the time of diagnosis. In 36 of 84 cases (43%), an evaluation was necessary. A diagnosis was achieved in 27 of these 36 instances (75%), with the most useful test being a chest roentgenogram (n = 13, 48%). The most common cause of unilateral vocal cord paralysis in our series was neoplasm (n = 34, 40%), followed by surgical trauma (n = 29, 35%). In no instance was a malignancy discovered subsequent to the initial evaluation. The most cost-efficient, inclusive diagnostic evaluation of unilateral vocal cord paralysis involves a stepwise progression through the tests that are most likely to yield a diagnosis, with endoscopy reserved for those cases in which simpler, less invasive tests have not indicated a cause.

Adult↗

Degradation of glomerular basement membrane by purified mammalian metalloproteinases.

Neutral metalloproteinases degrade components of the extracellular matrix, including collagen types I-V, fibronectin, laminin and proteoglycan. However, their ability to degrade intact glomerular basement membrane (GBM) has not previously been investigated. Incubation of [3H]GBM (50,000 c.p.m.; pH 7.5; 24 h at 37 degrees C) with purified gelatinase or stromelysin (2 units) resulted in significant GBM degradation: gelatinase, 46 +/- 2.2; stromelysin, 59 +/- 5.8 (means +/- S.E.M.; percentage release of non-sedimentable radioactivity; n = 4). In contrast, 2 units of collagenase released only 5.6 +/- 0.52% (n = 3) of the [3H]GBM radioactivity compared with 2.0 +/- 0.15% (n = 7) released from [3H]GBM incubated alone. Sephadex G-200 gel chromatography of supernatants obtained from incubations of [3H]GBM with either gelatinase or stromelysin confirmed the ability of these enzymes to degrade GBM and revealed both high-(800,000) and relatively low-(less than 20,000) Mr degradation products for both enzymes. GBM degradation by gelatinase and stromelysin was dose-dependent (range 0.02-2.0 units), near maximal between pH 6.0 and 8.6, and was completely inhibited (greater than 95%) by 2 mM-o-phenanthroline. Collagenase (2 units) did not enhance the degradation of GBM by either gelatinase (0.02 or 0.2 unit) or stromelysin (0.02 or 0.2 unit). Our results indicate that metalloproteinase-mediated GBM degradation by neutrophils and glomeruli may be attributable to gelatinase (neutrophils) and/or stromelysin (glomeruli) and suggest an important role for these proteinases in glomerular pathophysiology.

Animals↗