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Biomedical subjects

M Nguyen

Publications and source records attributed to M Nguyen.

At least 163 records · Page 9Linked to original sources

Comparative study of the acute effects of resistant starch and dietary fibers on metabolic indexes in men.

The effect of ingestion of the same amount (30 g) of a resistant starch (lintner) and cellulose on energy expenditure (EE), colonic fermentation (breath-hydrogen test), and blood glucose, insulin, and free fatty acid (FFA) concentrations were compared in seven healthy volunteers in a first experiment. In a second experiment the same indexes were measured in six healthy volunteers after the ingestion of diets composed of 50 g glucose alone or mixed with 30 g lintner, or cellulose, or pectin. In the first experiment no differences between lintner and cellulose were observed on the measured indexes. The notable difference was the increased apparent colonic fermentation with lintner after 6 h. In experiment 2, although insulin response was significantly lower in the pectin-added diet, the results obtained with the four different diets were not significantly different. The metabolic characteristics of lintner were closer to cellulose than to pectin. In conclusion, the acute effect of the ingestion of a resistant starch (lintner) on the measured metabolic indexes is similar to that of a known insoluble fiber--cellulose.

Adult↗

Ximoprofen in ankylosing spondylitis. A double blind placebo controlled dose ranging study.

Ximoprofen is a new propionic NSAID which has previously demonstrated its efficacy at a daily dose of 30 mg. The aim of the study was to evaluate the efficacy of different daily dosages of Ximoprofen in patients with active ankylosing spondylitis. For 2 weeks 5 parallel groups were studied: placebo and Ximoprofen at 5, 10, 20 and 30 mg daily. Response to treatment was defined as an improvement in pain (VAS 100 mm) of at least 50% during the study. 285 out of the 332 screened patients were included. At the end of the study, the percentage of responders was higher in the Ximoprofen groups (54%, 41%, 53%, 56% in the 5, 10, 20 and 30 mg groups, respectively) than in the placebo group (21%). The clearest dose related effect of Ximoprofen observed occurred after one week of treatment. This study 1/confirms the efficacy of Ximoprofen at a 30 mg daily dosage, 2/shows the persistence of this efficacy at lower dosages, 3/suggests that ankylosing spondylitis is a sensitive and relevant human model to assess NSAIDs at an early stage of clinical evaluation.

Adult↗

Outcome of liver transplantation in patients with hemochromatosis.

Recent preliminary reports suggest a poor outcome of orthotopic liver transplantation for patients with hemochromatosis. We analyzed an institutional experience with orthotopic liver transplantation for hemochromatosis, focusing on factors contributing to increased morbidity and mortality. Between March 1988 and October 1992, nine of 249 adults (3.6%) undergoing orthotopic liver transplantation had hemochromatosis. Mean age was 53 yr (range, 42 to 62 yr), and eight of nine patients were men. The diagnosis of hemochromatosis was based on transferrin saturation > 62% and hepatic iron index > 2.0. Only two patients were known to have hemochromatosis before liver transplantation. All nine patients underwent standard cardiac evaluation before transplantation, and no patient had detectable pre-existing cardiac disease. One patient had a major operative cardiac complication as a result of pulmonary embolism and made a full recovery. Postoperatively, congestive heart failure developed in three patients and four patients had arrhythmias. One patient is undergoing phlebotomy for post-transplant cardiac complications from hemochromatosis. Two patients had primary hepatic tumors in the explant liver. There were four deaths caused by multiorgan failure with congestive heart failure (1), infection (2), and/or malignancy (2). Five patients are alive 3 to 25 mo post-transplant. The actuarial survival of the nine patients was 53% at 25 mo vs. 89% for 18 age- and sex-matched control transplant recipients (p = 0.1) and 81% for all other adult liver transplant recipients (p < 0.01). In five of seven patients, post-transplant liver biopsies revealed hepatic iron accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence.

The protooncogene product Bcl-2 is an integral membrane protein that functions as a suppressor of programmed cell death. It contains a single predicted transmembrane segment located at its COOH terminus. Here, we show that the transmembrane domain of human Bcl-2 functions as a mitochondrial signal anchor sequence that targets and inserts the protein into the outer membrane in an Ncyto-C(in) orientation, leaving the bulk of the polypeptide facing the cytosol. Deletion of the COOH-terminal 22 amino acids of Bcl-2 abrogated protein targeting, whereas fusion of this domain to the COOH terminus of dihydrofolate reductase resulted in targeting and insertion of the hybrid protein into the outer membrane in a manner similar to that of Bcl-2. The sequence of the hydrophobic core of the Bcl-2 signal anchor is similar to the corresponding region of the NH2-terminal signal anchor of the mitochondrial outer membrane protein in yeast, Mas70p. A synthetic peptide comprising the Mas70p signal anchor sequence effectively competed for insertion of Bcl-2 into the outer membrane but had no effect on the comparatively low association that Bcl-2 makes with endoplasmic reticulum microsomes. Insertion of Bcl-2 into the mitochondrial outer membrane is mechanistically different than its association with microsomes.

Amino Acid Sequence↗

Basic fibroblast growth factor secreted by an animal tumor is detectable in urine.

Basic fibroblast growth factor (bFGF or FGF-2) is abnormally elevated in the serum and urine of patients with many types of cancer. However, the source of the bFGF is unclear. We developed a model that could distinguish between tumor-derived and host-derived bFGF. We gave athymic mice s.c. injections of cells of the murine K1000 tumor, which secretes a bFGF mutein (bFGF CS23) as its dominant angiogenic factor. Controls were given injections of Lewis lung carcinoma or saline. Urine was collected for 9 weeks, and bFGF was quantitated using two immunoassays which can discriminate between tumor bFGF CS23 and native bFGF. None of the mice had detectable urinary native bFGF, and no control mice had detectable urinary bFGF CS23. In contrast, urine from mice bearing the K1000 tumor revealed detectable bFGF CS23 by 2 weeks, and bFGF CS23 increased with increasing tumor volume throughout the study. Because bFGF CS23 is not produced by other cells, the bFGF CS23 in the urine most likely came from the K1000 tumor and not from the host. These results suggest that the source of elevated bFGF in the urine of human cancer patients is, at least in part, the tumor itself.

3T3 Cells↗

A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis.

To identify cell adhesion molecules required for angiogenesis, we used an in vitro model in which bovine capillary endothelial cells can be induced to form capillary-like tubes. Monoclonal antibodies directed against the carbohydrate epitopes sialyl Lewis-X and sialyl Lewis-A inhibited capillary formation. We postulated that a member of the selectin family of adhesion molecules may be involved in capillary formation because these proteins bind to sialyl Lewis-X/A-containing ligands. We isolated a 2.8-kilobase complementary DNA from a bovine capillary endothelial cell cDNA library which encodes a polypeptide with 71% identity to human E-selectin. We report here that antibody directed against the bovine E-selectin inhibited capillary formation, suggesting that in addition to its role in leukocyte adhesion to endothelium, a form of E-selectin is involved in capillary morphogenesis.

Amino Acid Sequence↗

Isolation and characterization of a bovine cDNA encoding a functional homolog of human P-selectin.

A cDNA encoding a homologue of human P-selectin has been isolated from a bovine capillary endothelial cDNA library. The 2.7 kb cDNA encodes a 646 amino acid polypeptide with 77% identity to the human P-selectin except that it lacks three of the consensus repeat domains found in human P-selectin. Human P-selectin, expressed in platelets and endothelium, is a Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. To determine if bovine P-selectin exhibits a similar binding activity, its cDNA was expressed in COS cells and the ability of the transfectants to bind HL-60 human myelogenous leukemia cells was examined. The bovine P-selectin bound the myeloid cells in a manner similar to human P-selectin, indicating that the altered domain structure of bovine P-selectin does not affect P-selectin function in this in vitro cell adhesion assay.

Amino Acid Sequence↗

Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation.

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.

Calcium↗

Coordinate expression of beta 1 and beta 2 integrin "activation" epitopes during T cell responses in secondary lymphoid tissue.

The monoclonal antibodies (mAb) 15/7 and 24 recognize unique activation-dependent, conformational epitopes on beta 1 and beta 2-integrins, respectively. The expression of both of these epitopes closely correlates with the ligand binding ability of their respective integrins, and thus serves as indicators of functional integrin "activation". Here, we have used six-parameter flow cytometry to examine the expression of these epitopes and conventional beta 1- and beta 2-integrin epitopes during human T cell activation in secondary lymphoid tissues in vivo, focusing particularly on the virgin to memory/effector cell transition. Fresh tonsil lymphocytes were stained with mAb against conventional or activation-dependent integrin epitopes, followed by staining with mAb against CD3, CD45RA, and CD45RO, thus allowing the determination of integrin epitope expression on virgin (CD3+) T cells (CD45RA+/RO-to+/-), memory/effector (CD45RA-/RO++) T cells, and T cells undergoing the virgin to memory/effector transition: transition region-1 (T1; CD45RA+to++/RO+); -2 (T2; CD45RA++/RO++); and -3 (T3; CD45RA+/RO++). Conventional beta 1- and beta 2-integrin epitopes progressively increase during the virgin to T3 stages of the transition in tonsil, in keeping with the generally higher levels of these adhesion molecules on memory/effector vs. virgin T cells. Expression of both the beta 1 (15/7)- and beta 2 (24)-integrin activation epitopes first appears on transitional T cells, and is maintained on a relatively constant number of cells (averaging 25-30%) throughout the T1-T3 stages. These epitopes are also noted on a subset of activated memory/effector T cells. Importantly, on both transitional and activated memory/effector T cell subsets, the expression patterns of the 15/7 and 24 epitopes vs. a variety of T cell activation antigens are identical, and the expression of these epitopes relative to each other is linearly correlated, findings strongly supporting the coordinate activation of beta 1 and beta 2 integrins during T cell activation in vivo. These results provide the first evidence of integrin activation during an in vivo immunologic response, and demonstrate the usefulness of mAb recognizing conformational epitopes and multiparameter flow cytometry in delineating the dynamic interplay of adhesion molecules during complex physiologic processes.

Adolescent↗

Complete nucleotide sequence of HTLV-II isolate NRA: comparison of envelope sequence variation of HTLV-II isolates from U.S. blood donors and U.S. and Italian i.v. drug users.

The entire nucleotide sequence of human T-cell lymphotropic virus type II (HTLV-II) from a previously described isolate of patient NRA (HTLV-IINRA) was determined. Clones encoding the 5' LTR and gag, pol, env and tax/rex open reading frames were subcloned and sequenced on both strands. The provirus consisted of 8957 nucleotides and showed 95.2% homology with the HTLV-IIMo prototype at the nucleotide level. Less than 5% amino acid variation between HTLV-IINRA and HTLV-IIMo was observed for coding regions. Although isolate HTLV-IINRA had an additional 25 amino acids at the 3' end of tax/rex, this region was 96% homologous with the 5' end of HTLV-IIMo 3' LTR. To further investigate HTLV-II variability, a portion of the env gp46 gene derived from 9 HTLV-II infected persons was amplified by polymerase chain reaction and sequenced. Sequence was obtained for 320 nucleotides corresponding to HTLV-IIMo positions 5291 to 5610. Isolates similar to the HTLV-IIMo and HTLV-IINRA prototypes were identified, and sequences were highly conserved.

Amino Acid Sequence↗

High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial.

Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee.

Aged↗

Defective and normal haematopoietic stem cells in paroxysmal nocturnal haemoglobinuria.

The expression of decay-accelerating factor (DAF or CD55) and CD59 during haematopoietic cell development in bone marrow aspirates of two patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared with that in normal bone marrow by five-dimensional flow cytometry. In contrast to early uncommitted haematopoietic progenitor cells (CD34+, CD38-) in normal bone marrow which uniformly express DAF and CD59, the majority of CD34+, CD38- cells in both patients' marrow exhibited the absence of the two proteins. In both specimens, however, subpopulations of CD34+, CD38- cells expressing DAF and CD59 were detectable, indicative of the presence of two lines of haematopoiesis, one abnormal and the other normal. Concurrent abnormal and normal haematopoietic development was further evident by the presence of subpopulations of DAF-, CD59- and DAF+, CD59+ cells along the differentiation and maturation pathways of the myeloid (CD33+, CD15(-)-->CD33+-->++, CD15+), the erythroid (CD45dim, CD71dim-->CD45-, CD71++), and the B-lymphoid cell lineages (CD10++, CD20(-)-->CD10-, CD20++). While the majority of cells differentiating into and maturing along each cell lineage lacked DAF and CD59, the majority of mature B (CD20++, CD10-) and T-lymphocytes lymphocytes (CD3+) expressed both proteins suggestive of the presence of lymphocytes with a long life span which were generated from normal haematopoietic progenitors before the onset of the disease. The detection of distinct sets of CD34+, CD38(-)--> + progenitor cells which are DAF+, CD59+ or DAF-, CD59- in marrow of PNH patients has relevance for the treatment of PNH. Cells with the phenotype CD34+, CD38-, DAF+, CD59+ are capable of self renewal and represent potential candidates for autologous bone marrow transplantation following depletion of CD34+, CD38-, DAF-, CD59- cells.

Adult↗

Molecular characterization of Lactobacillus curvatus and Lact. sake isolated from sauerkraut and their application in sausage fermentations.

Lactobacillus curvatus and Lact. sake are best adapted to meat fermentations and dominate the flora during the whole process. In fermenting sauerkraut, Leuconostoc mesenteroides subsp. mesenteroides is the major organism only during the early phase. In this environment Lact. curvatus and Lact. sake provide up to 50% of the microbial flora especially of the later phase, depending on the process conditions. Strains of Lact. curvatus and Lact. sake isolated from fermenting sauerkraut were identified by hybridization with species specific 23S rRNA-targeted oligonucleotide probes and further characterized. In 59 of 72 strains, plasmid DNA was detected. Small cryptic plasmids of 20 strains were found to be homologous with pLc2, a 2.6 kb plasmid from Lact. curvatus LTH683, which was originally isolated from meat. The ability to compete was investigated in fermenting sausages of two strains each of Lact. curvatus and Lact. sake isolated from sauerkraut. One strain each of Lact. curvatus and Lact. sake was found to outnumber the meat-borne flora and govern the process.

Brassica↗

A single administration of LFA-1 antibody confers prolonged allograft survival.

C57BL/6 (B6) thyroid gland transplanted to the left kidney capsule of an allogeneic (BALB/c) host was typically rejected in 14 days. A single administration of 500 micrograms of an antibody to the adhesion molecule, leucocyte function-associated antigen (LFA-1, CD11a), prevented all thyroid allograft rejection for at least 70 days. Fifty percent of the treated recipients retained intact allografts for 470 days. However, the same treatment with anti-CD11a could not protect a sensitized BALB/c mouse from rejecting a second B6 thyroid allograft. Production of donor-specific alloantibodies elicited by allograft rejection was also inhibited in this system. In this transplant model, the Ab therapy is more efficacious than that of FK506, administered daily for 14 days at 15 mg/kg. These results demonstrate the remarkable effect of an anti-LFA-1 antibody in promotion of allograft survival.

Animals↗

[The French diabetic population. Results of a study using a representative sample].

The aim of this study was to assess the prevalence of diabetes mellitus in France, the existing treatment used and the effect of this chronic disease on everyday life patterns of the diabetic population. A survey was undertaken by Lilly laboratories and SOFRES medical institute from November to December 1992, which involved randomly screening 20,000 french families. After the screening questionnaire was sent at to the 20,000 families, the following feedback was obtained: 996 patients have been identified. More than 80% of the patients (that is, 122 were insulin treated and a further 674 were identified as NIDDM) replied to the second self assessment questionnaire. It was possible to make an estimation of the prevalence of diabetes mellitus in France that is to say: 1.9% of the general population. The general practitioner makes the primary diagnosis in more than 80% of the cases, and treats 97% of the NIDDM patients and 74% of the insulin treated diabetic patients. The diabetic patients have an average of 8 consultations per year with their general practitioners and 3-4 consultations per year with the endocrinologist. Therapeutic management of the NIDDM patients is based mainly on diet (82%) alone or in association with drugs. 32% of patients primary treated by drugs and secondary by insulin are not satisfied with their glycemic control (vs 22% of IDDM patients and 15% of NIDDM patients). Less than 35% of diabetic women are current users of contraception. More than one third of children who were born from a diabetic mother had a birth weight above 4 kgs.

Adult↗

The magnetic resonance appearance of extraperitoneal bowel perforation: a case report.

The use of magnetic resonance imaging (MRI) for abdominal and gastrointestinal imaging has been quite limited, when compared to its utilization in other organ systems. We present an interesting case of extraperitoneal bowel perforation, which was diagnosed by magnetic resonance (MR). Extraperitoneal bowel perforation is frequently a confusing and difficult diagnosis to make. The multiplanar imaging capability and unique sensitivity of MR to fluid enabled a specific diagnosis to be made in this challenging case.

Abscess↗