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Biomedical subjects

M Nguyen

Publications and source records attributed to M Nguyen.

At least 127 records · Page 7Linked to original sources

Pearls and perils in the management of prolonged, peculiar, penetrating esophageal foreign bodies in children.

BACKGROUND/PURPOSE: Most retained esophageal foreign bodies (FB) are identified soon after ingestion and are easily extracted. A minority of FB ingestions are not identified for weeks to years and present significant problems for retrieval. The purpose of this study was to describe the diagnostic and therapeutic strategies needed to care for children who have chronic esophageal FBs. METHODS: Five children were identified as having retained esophageal FBs 2 months to 2 years after ingestion. During the same 3-year period, 100 children who had acute FBs were identified and had their foreign bodies removed endoscopically. The average age of the children was 3 years (range, 2.4 to 3.5). RESULTS: The average age of the five children identified in this study was 3 years. The items ingested included coins, a heart pendant, a clothespin spring, and a toy soldier. Complications from chronically retained foreign bodies were bronchoesophageal fistula, mediastinitis, esophageal diverticulum, and lobar atelectasis. One patient died from an aortoesophageal fistula. In all children, endoscopic removal was attempted. Barium esophagram was then performed, and foreign bodies were eventually removed via right thoracotomy. CONCLUSIONS: Long-retained esophageal FBs are extremely morbid and life threatening. History most often identifies excess salivation, new onset asthma, and/or recurrent upper respiratory infections. Three diagnostic adjuncts are helpful in identifying the presence of a long retained FB: (1) Chest x-ray (PA and lateral), (2) barium swallow, and (3) esophagoscopy. Indications for thoracotomy for removal of foreign body include (1) Poor endoscopic visualization of FB because of inflammatory tissue and (2) Herald bleeding during endoscopy.

Aorta, Thoracic↗

Human microvascular endothelial cells differ from macrovascular endothelial cells in their expression of matrix metalloproteinases.

Matrix metalloproteinase (MMP) secretion by microvascular endothelial cells is an essential first step in the formation of new blood vessels (angiogenesis). Since angiogenesis does not occur in large blood vessels, we investigated whether the secretion of MMPs and tissue inhibitor of MMP (TIMP1) differs between micro- and macro-vascular endothelial cells. We compared the secretion of MMPs and TIMP1 by human endothelial cells derived from neonatal foreskin (FSE) and umbilical vein (HUVE) sources. The cells were incubated for 24 hr in the presence or absence of the angiogenic agents, phorbol myristate acetate (PMA, 100 ng/ml) or tumour necrosis factor-alpha (TNF, 100 ng/ml). The cell supernatants were removed and assayed for MMPs and TIMP1 using a spectrophotometric assay for MMP1, zymography, Western blotting and Northern analysis. When endothelial cells were incubated in basal medium for 24 hr they secreted MMP1, MMP2 and TIMP1 but not MMP9. HUVE secreted substantially higher levels of these proteins compared to FSE. In addition, HUVE secreted two low molecular mass bands representing activated forms of MMP2. These activated forms were not present in supernatants derived from FSE. In response to PMA, both FSE and HUVE increased secretion of MMP1 and TIMP1. However, there was a dramatic difference in level of response by the two cell types with FSE secreting substantially more TIMP1 and MMP9 compared to HUVE. These data clearly show that cultured endothelial cells derived from microvascular vs macrovascular tissues exhibit different MMP and TIMP secretory profiles.

Cells, Cultured↗

Angiogenic factors as tumor markers.

The process of angiogenesis plays a critical role in tumor growth and metastasis. Recently, there has been much interest in the possible use of angiogenic growth factors as tumor markers. This paper will review the results thus far of attempts at measuring various angiogenic factors in bodily fluids. In the future, angiogenic factors will most likely be useful as a monitor of therapy and/or a predictor of outcome after cancer has been diagnosed.

Biomarkers, Tumor↗

Prolonged effects of 3 week therapy in a spa resort on lumbar spine, knee and hip osteoarthritis: follow-up after 6 months. A randomized controlled trial.

Spa therapy is frequently used in daily rheumatological practice, but its benefit remains to be evaluated. A prospective randomized controlled study was conducted in 1993 in patients with osteoarthritis of the hip, knee or lumbar spine. Treatment was either spa therapy at Vichy (France) of 3 weeks duration (spa group) or usual therapy (control group). Assessment criteria were pain (visual analogue scale), functional impairment (Lequesne's index for hip or knee disease, Main and Waddell's for lumbar spinal diseases), quality of life index [revised Arthritis Impact Measurement Scale (AIMS2)], and analgesic and/or non-steroidal anti-inflammatory drug (NSAID) consumption. Patients were included by randomization into one of the two arms (spa or control) and assessment criteria were collected before spa therapy or the control period, and 3 and 24 weeks thereafter. A total of 188 patients (lumbar spine 95, knee 64, hip 29) were included in the study (spa group 91, control group 97). Changes in the assessment criteria after a 6 month follow-up period showed improvement in terms of pain, functional impairment and quality of life, with a reduced intake of symptomatic drugs (NSAID and analgesic drugs) in the spa group. This study suggests that spa therapy of 3 weeks duration has a prolonged, beneficial, symptomatic effect in osteoarthritis.

Aged↗

Characterization of the in vitro activity of the RNA-dependent RNA polymerase associated with the ribonucleoproteins of rice hoja blanca tenuivirus.

An RNA-dependent RNA polymerase (RdRp) activity associated with the ribonucleoproteins of rice hoja blanca tenuivirus (RHBV) was detected and analyzed. Conditions for in vitro RNA synthesis and for coupled RNA synthesis-translation of RHBV were established. In both cases, synthesis of the viral and viral complementary genomic and subgenomic RNA3 and RNA4 were observed, demonstrating that both transcription and replication occurred. Though coupling of RNA synthesis to translation allowed efficient translation of the newly synthesized subgenomic RNAs, studies of the effect of various inhibitors of protein synthesis revealed that RNA synthesis was independent of translation. Primer extension experiments demonstrated that in the presence of capped exogenous RNAs, a stretch of 10 to 16 nonviral nucleotides was added to the 5' end of a population of newly synthesized viral complementary RNA4. It appears that in addition to RdRp activity, RHBV-associated protein(s) also possessed cap-snatching capacity.

Blotting, Northern↗

Vascular expression of E-selectin is increased in estrogen-receptor-negative breast cancer: a role for tumor-cell-secreted interleukin-1 alpha.

Angiogenesis plays an important role in breast cancer growth and metastasis. Multiple adhesion molecules have been shown to perform critical functions in the process of angiogenesis. In this study, we analyzed 15 benign and 22 malignant estrogen-receptor-negative and estrogen-receptor-positive breast specimens for the presence of the endothelial cell adhesion molecules E-selectin and P-selectin. We found that E-selectin's expression was increased in the malignant breast tumors compared with their benign counterparts (23.86% of blood vessels versus 2.47%; P = 0.0005). Furthermore, E-selectin staining was found to be significantly increased in the estrogen-receptor-negative carcinomas compared with the estrogen-receptor-positive ones (P = 0.005). In vitro findings strongly correlated with the in vivo findings and showed a higher degree of E-selectin induction in endothelial cells exposed to conditioned media from estrogen-receptor-negative breast cancer cell lines than from estrogen-receptor-positive ones. The degree of E-selectin induction correlated with the amount of interleukin-1 alpha in the tumor-conditioned media. Neutralizing antibodies to interleukin-1 alpha significantly inhibited the E-selectin expression in endothelial cells exposed to tumor-conditioned media. The results indicate that the endothelial E-selectin expression during angiogenesis is related to breast carcinoma progression in vivo and that this component of angiogenesis may be due directly to tumor-cell-secreted interleukin-1 alpha.

Breast Neoplasms↗

Radiographic features predictive of radiographic progression of hip osteoarthritis.

OBJECTIVES: To evaluate potential radiographic predictors of hip osteoarthritis progression. PATIENTS AND METHODS: A prospective, longitudinal two-year study was conducted in patients meeting American College of Rheumatology criteria for hip osteoarthritis. Hip osteoarthritis progression was defined as a greater than 0.5-mm decrease in joint space width measured using a magnifying glass marked at intervals of 0.1 mm, at the site of maximum joint space narrowing, by a single investigator who was blinded to the chronological order of the radiographs. Radiographic parameters determined at study entry were as follows: presence of osteophytes, osteosclerosis, and subchondral cysts; femoral head migration (superolateral, superomedial, concentric); and severity (joint space width in mm, Kellgren and Lawrence grade, subjective evaluation of joint space narrowing). RESULTS: In the 463 study patients, joint space width decreased from 2.2 +/- 0.8 at baseline to 1.7 +/- 1.0 mm after two years (P < 0.0001). Radiographic progression was seen in 148 patients (32%). Radiologic parameters predictive of disease progression in the multivariate analyses were as follows: CONCLUSION: Our data suggest that a number of baseline radiological features including distribution of joint space loss, subchondral bone production, and severity of joint space loss are predictive of progression of hip osteoarthritis.

Aged↗

An update on core needle biopsy for radiologically detected breast lesions.

BACKGROUND: Traditionally, radiologically detected lesions of the breast have been evaluated by open surgical biopsy with wire localization. Recently, core needle biopsy has been introduced as an alternative to open surgical biopsy. The authors evaluated their own results with long term follow-up after core needle biopsy and reviewed the experience of other physicians with this new technique. METHODS: Four hundred thirty-one core needle biopsies performed at UCLA were analyzed. The outcome of these cases was determined by either surgery or long term follow-up. Statistical analysis was performed to determine the accuracy of the method. RESULTS: Definitive outcome was obtained in 96% of the core needle biopsy cases, with a median follow-up time of 18 months (range, 6-38 months). The authors achieved a sensitivity of 99% and a specificity of 100%. The false-negative rate was 1.7%. There were no complications in this series. CONCLUSIONS: Core needle biopsy is a highly accurate and safe method for the diagnosis of radiologically detected lesions of the breast.

Biopsy, Needle↗

Novel synthetic analogs of sialyl Lewis X can inhibit angiogenesis in vitro and in vivo.

Selectins have been shown to play an important role in angiogenesis. We have set out to synthesize multiple analogs of the selectin ligand sialyl Lewis X. We show here that analogs of sialyl Lewis X at concentrations of 50 micrograms/ml or greater significantly inhibited angiogenesis in in vitro assays of endothelial cell migration and proliferation (p < 0.05). These analogs also exerted significant inhibitory effects in in vivo angiogenesis assays using the chick chorioallantoic membrane at doses of 2 mg/chick or greater (p < 0.05). In contrast, the related carbohydrate Lewis X did not inhibit angiogenesis in both in vitro and in vivo assays. These data indicate that angiogenesis can be inhibited specifically by synthetic analogs of sialyl Lewis X. These analogs may potentially be useful in the treatment of angiogenesis-related diseases.

Animals↗

A genetic selection for Caenorhabditis elegans synaptic transmission mutants.

We have isolated 165 Caenorhabditis elegans mutants, representing 21 genes, that are resistant to inhibitors of cholinesterase (Ric mutants). Since mutations in 20 of the genes appear not to affect acetylcholine reception, we suggest that reduced acetylcholine release contributes to the Ric phenotype of most Ric mutants. Mutations in 15 of the genes lead to defects in a gamma-aminobutyric acid-dependent behavior; these genes are likely to encode proteins with general, rather than cholinergic-specific, roles in synaptic transmission. Ten of the genes have been cloned. Seven encode homologs of proteins that function in the synaptic vesicle cycle: two encode cholinergic-specific proteins, while five encode general presynaptic proteins. Two other Ric genes encode homologs of G-protein signaling molecules. Our assessment of synaptic function in Ric mutants, combined with the homologies of some Ric mutants to presynaptic proteins, suggests that the analysis of Ric genes will continue to yield insights into the regulation and functioning of synapses.

Acetylcholine↗

A human chromosome 22 fosmid resource: mapping and analysis of 96 clones.

We have created a resource for chromosome 22 consisting of 96 unique, well-characterized Fosmids. The Fosmid vector permits efficient cloning of DNA fragments averaging 40 kb in a single-copy vector based on the F factor of Escherichia coli. We have found that Fosmid clones from human chromosome 22 show remarkable stability and are useful for a wide variety of applications in genome analysis. These 96 clones have been localized by FISH, using high-resolution fluorescent banding and multicolor mapping techniques, and their position on the chromosome was correlated with their content of a number of common repeated sequence elements. We identified a subset of clones likely to contain genes by restriction analysis using the enzymes NotI, MluI, SacII, and BssHII. This collection of cytogenetically anchored clones, representing nearly 7% of the chromosome, is of immediate value for detecting chromosomal rearrangements, for use in gene isolation, and as a framework for physical mapping.

Binding Sites↗

Recombinant outer-surface protein A (des-Cys1-OspA) from the Lyme disease spirochete Borrelia burgdorferi: high production levels in Saccharomyces cerevisiae yeast cultures.

The recombinant outer-surface protein A with an N-terminally truncated form (des-Cys1-OspA) from the Lyme disease spirochete Borrelia burgdorferi was expressed in Saccharomyces cerevisiae at high production levels. Since the recombinant vaccine candidate expressed in Escherichia coli exhibits low production yields and the purification of lipoproteins appears to be difficult, we have investigated the secretion of a soluble recombinant OspA in the yeast S. cerevisiae. In this way, a Leu+ derivative of S. cerevisiae cI3ABYS86 was used as the host strain transformed with an expression plasmid containing the gene encoding des-Cys1-OspA and driven by the MF alpha 1 promoter. The fed-batch culture results revealed that an efficient secretion of des-Cys1-OspA is obtained with a high production level of about 2.1 g l-1 at a cell density of 101 g l-1 cell dry weight. The accumulation of recombinant protein in the supernatant exceeds 6% of the total yeast proteins when estimated by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. Moreover, des-Cys1-OspA showed lower solubilities at high cell densities and, as a consequence, a fraction of the recombinant protein precipitated. An internal cleavage of the MF alpha 1 pro::des-Cys1-OspA precursor was also detected. However, in this case the cleavage occurred at a frequency such that the large amounts of the secreted des-Cys1-OspA could be employed for the evaluation of an immunogenic effect on animal immunization. These studies will extend the knowledge of the usefulness of OspA as a vaccine for Lyme borreliosis.

Antigens, Surface↗

Effects of GABA uptake inhibitors on posthypoxic myoclonus in rats.

Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac arrest and resuscitation. Previous results showed that dysfunction of central GABAergic neurotransmission may contribute to the disease. In current studies, effects of GABA uptake inhibitors, guvacine hydrochloride (1,2,5,6-tetrahydro-3-pyridine carboxylic acid hydrochloride) and (+/-)-cis-4-hydroxynipecotic acid ([+/-]-cis-4-hydroxy-3-piperidine carboxylic acid), in the pathophysiology of posthypoxic myoclonus were investigated. Administration of guvacine (1 or 10 mg/kg, IP) or nipecotic acid (0.5 or 5 mg/kg, IP) significantly attenuated myoclonus scores of the animals. Tolerance to antimyoclonus effects of these two compounds did not develop after chronic administration (twice a day for 14 days) of guvacine (10 mg/kg, IP) or nipecotic acid (5 mg/kg, IP). On the other hand, tolerance was noticed with clonazepam (2.5 mg/kg, IP twice a day for 7 days). The results indicate that guvacine or nipecotic acid may be used in combination with (at reduced doses) or as alternatives to clonazepam to treat patients with the disease so as to reduce tolerance phenomenon usually associated with clonazepam.

Animals↗

Effects of glutamate receptor antagonists on posthypoxic myoclonus in rats.

Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac arrest and resuscitation. In current studies, roles of N-methyl-D-aspartate (NMDA), non-NMDA (a-amino-3-hydroxy-5-methylisoxazole-4-propionate, AMPA, and kainate), and metabotropic glutamate receptors in the pathophysiology of posthypoxic myoclonus were investigated. Treatments with the competitive or noncompetitive NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D[-]-AP-5) (ED50: 12.5 mg/kg, i.p.) or MK-801 maleate (ED50: 0.034 mg/kg, i.p.), and competitive or noncompetitive non-NMDA (AMPA/kainate) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (ED50: 9.25 nM/5 microliters, i.c.v.) or 1-(4-ami -nophenyl)-4-methyl-7,8-methylenedioxy -5H-2,3-benzodiazepine hydrochloride (GYKI 52466) (ED50: 0.67 mg/kg, IP), significantly decreased myoclonus episodes in rats. On the other hand, treatment with the metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L[+]-AP-3) (50 or 500 nM/5 microliters, i.c.v., exerted no significant effect on myoclonus scores in posthypoxic rats. These results indicate that activation of NMDA and non-NMDA receptors receptors may mediate posthypoxic myoclonus in rats, whereas, involvement of metabotropic glutamate receptors needs to be studied further.

2-Amino-5-phosphonovalerate↗

Radiological progression of hip osteoarthritis: definition, risk factors and correlations with clinical status.

OBJECTIVES: To determine a cut off value for changes in radiological joint space width that allowed definition of radiological progression of hip osteoarthritis not related to measurement method errors and, thereafter, to determine factors predictive of radiological progression of hip osteoarthritis and to evaluate the correlations between clinical and radiological parameters. METHODS: A prospective, longitudinal (one year duration), multicentre study was made of patients with osteoarthritis of the hip (American College of Rheumatology criteria). Data on clinical activity (pain, functional impairment), demographic data (age, gender, body mass index), and femoral head migration (superolateral, superomedial, concentric) were collected when the patient entered the study; radiological grade (joint space width in millimetres at the narrowest point using a 0.1 mm graduated magnifying glass, evaluated by a single observer unaware of the chronology of the films) was recorded at the patient's entry to the study and after one year. RESULTS: Analysis of the means of the differences between two analyses performed by a single observer of 30 pairs of radiographs (one performed after an interval of one year) (0.06 (SD 0.23)) suggested that a change of more than 0.56 mm (2 SD) after a one year follow up could define progression of osteoarthritis of the hip. Of the 508 patients recruited, 461 (91%) completed the one year follow up and radiological progression was observed in 102 (22%). The factors predictive of radiological progression that were identified in the multivariate analysis were: radiological joint space width at entry < or = 2 mm, superolateral migration of the femoral head, female gender, Lequesne's functional index > 10, age at entry > 65 years (odds ratios 2.11, 4.25, 2.51, 2.66, 1.90, respectively). The level of clinical parameters (pain, functional impairment) and the amount of symptomatic treatment required (non-steroidal anti-inflammatory drugs and analgesic intake) accounted for 20% (p < 0.0001) of the variability of the changes in radiological joint space width over the one year study period. CONCLUSION: These data suggest that radiological progression of hip osteoarthritis could be defined by a change in joint space width of at least 0.6 mm after a one year follow up period, is correlated with the changes in clinical status of the patients, and is related not only to demographic data (age, gender), but also to some specific characteristics of osteoarthritis (localisation, radiological severity, clinical activity).

Aged↗