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Biomedical subjects

T Nguyen

Publications and source records attributed to T Nguyen.

At least 217 records · Page 12Linked to original sources

[Acute type B aortic dissection: prognosis after initial conservative treatment and predictive factors for a complicated course].

OBJECTIVE: Today there is still debate concerning the optimal mode of treatment for type B dissection of the aorta. Controversies are mainly due to discordant results regarding survival following medical or surgical treatment. We assessed the early and long-term outcome of acute dissection of the descending aorta after initial conservative treatment. METHODS: Between 1980 and 1995, 225 patients were hospitalized in the medical or surgical department of our institution with the diagnosis of acute type B aortic dissection. 38 patients (16.8%) underwent replacement of the descending aorta within the first week after hospital admission. Primary indications for immediate surgery were rupturing aneurysm in 15 patients, extensive dilatation of the descending aorta in 13, distal malperfusion in 8, and pseudocoarctation syndrome with uncontrollable hypertension in 2. All other patients (n = 187) underwent primary conservative treatment in the intensive care unit, which included appropriate antihypertensive medication. RESULTS: Hospital mortality during and after initial conservative treatment was 17.6% (33/187 patients). Main causes of death were rupture in 14 patients, intestinal malperfusion in 13 and cardiac failure in 3, whereas in 3 patients the cause of death could not be determined. Nine additional patients had to be referred for early surgery during the initial hospitalization because of contained rupture (n = 4), rapidly increasing size of the aorta (n = 2) and suspected intestinal ischemia (n = 3). Hospital mortality after early surgery was 21% (8/38 patients) for the overall time period. After hospital discharge from the initial acute dissection, surgery for chronic dissection was performed in 47 patients, mainly because of expanding descending aortic aneurysm. Hospital mortality was 8% in these patients (4/47). Actuarial survival rates after primary conservative therapy were 76 +/- 5% and 50 +/- 7% after 5 and 8 years respectively. CONCLUSION: Currently, surgery for acute type B dissection is limited to patients with rupturing disease, distal malperfusion or uncontrollable hypertension and pains. Despite aggressive antihypertensive treatment, hospital mortality after primary conservative treatment is still high and a substantial proportion of patients requires surgery during initial hospitalization. Although conservative treatment is recommended in most uncomplicated type B aortic dissections, early surgery should be considered in the following situations: younger patients with 5 cm diameter of the aorta at initial evaluation, as well as those with Marfan syndrome, patients with limited false aneurysm or retrograde dissection into the aortic arch, and those with poor medical compliance or uncontrollable proximal hypertension. Radiographic follow-up for an indefinite period may allow detection of potential late complications and proper planning of elective operations when indicated.

Acute Disease↗

Development of tricalcium phosphate/amylopectin paste combined with recombinant human transforming growth factor beta 1 as a bone defect filler.

Tricalcium phosphate (TCP) was combined with amylopectin to form a deliverable carrier paste for recombinant human transforming growth factor beta 1 (rhTGF-beta 1) intended for bone repair applications. Approximately 80% of rhTGF-beta 1 was released from the carrier within 24 h following in vitro incubation in serum. Full biological activity was maintained, suggesting the growth factor was stable in this formulation before and after in vitro release. In vivo efficacy also was assessed, in comparison to a sham control group and a placebo-treated group, using a rabbit unilateral segmental defect model (1 cm). Radiographs of defect sites taken at scheduled intervals and the mechanical testing of treated limbs at 56 days demonstrated a higher incidence of radiographic bone union, in concert with a stronger torque strength, in the rhTGF-beta 1-treated group compared to the placebo group. The short duration of the study and the fact that the model used was not a critical defect may account for the lack of superiority of the rhTGF-beta 1-treated group over the healing of the sham control. The in vivo pharmacokinetics of the growth factor evaluated in the same rabbit model suggested that rhTGF-beta 1 persisted intact at the defect site for more than 21 days. Gamma imaging and radioactivity recovery at defects administered to [131I]- and [125I]-labeled rhTGF-beta 1, respectively, estimated the half-life of rhTGF-beta 1 eliminated from the applied site to be 4-6 days. The present report substantiates the potential of rhTGF-beta 1 and its carrier for treatment of bone defects.

Amylopectin↗

Cloning and expression of a chicken alpha-amylase gene.

We have isolated and sequenced a genomic clone for a pancreatic alpha-amylase gene (amy) of the chicken (Gallus gallus). The gene is interrupted by nine introns, spans over 4 kb, and encodes a protein (AMY) of 512 aa that is 83% identical to the human pancreatic alpha-amylase enzyme. Southern blot analysis of chicken DNA revealed two distinct pancreatic amy loci. In addition, we have generated a cDNA from chicken pancreatic RNA corresponding to the coding sequence of the genomic clone. The cDNA was inserted into a yeast expression vector, and the resulting construct used to transform Saccharomyces cerevisiae cells. Transformed yeast cells synthesized and secreted active AMY enzyme, and the gel migration pattern of the alpha-amylase produced by the yeast cells was identical to that of the native chicken enzyme.

Amino Acid Sequence↗

Leukotriene C4 secretion from normal murine mast cells by a probenecid-sensitive and multidrug resistance-associated protein-independent mechanism.

P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are members of the superfamily of ATP-binding cassette transporter proteins. Because the ATP-dependent export system has been implicated in the release of leukotriene C4 (LTC4), we examined the roles of P-gp and MRP in the release of LTC4 from normal murine mast cells (MC-9). We have previously shown that MC-9 cells express P-gp at the level of protein and mRNA. In the present study, MRP expression in MC-9 cells was examined at the protein level by anti-MRP Ab, using flow cytometry and at the level of mRNA by PCR and Northern blot analyses. MC-9 cells were stimulated with calcium ionophore A23187 for 15 min in the presence or the absence of various concentrations of cyclosporin A (CsA) and its nonimmunosuppressive analogue CsA-1, which are known to inhibit P-gp efflux function, or in the presence or the absence of probenecid, an organic ion transport inhibitor that appears to inhibit MRP-mediated transport function. Culture supernatants were collected, and LTC4 was measured by ELISA assay. CsA and CsA-1 had no effect on LTC4 secretion from MC-9 cells, suggesting that P-gp is not involved in LTC4 release from MC-9 cells. In contrast, probenecid, in a concentration-dependent manner, inhibited LTC4 secretion from MC-9 cells without inhibiting its synthesis. However, MC-9 lacked MRP at both the protein and mRNA levels. These data suggest that LTC4 is secreted by normal mast cells by a probenecid-sensitive mechanism that is independent of MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family.

The SWI2/SNF2 gene family has been implicated in a wide variety of processes, involving regulation of DNA structure and chromatin configuration, mitotic chromosome segregation, and DNA repair. Here we report the characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily. Zbu1 was isolated in this study by its affinity for a site in the myosin light chain 1/3 enhancer. The protein has single-stranded DNA-dependent ATPase activity, includes seven helicase motifs, and a RING finger motif that is shared exclusively by the RAD5, spRAD8, and RAD16 family members. During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neonatal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain. In adult human tissues, alternatively spliced Zbu1 transcripts are ubiquitous with highest expression in these tissues. Gene expression is also dramatically induced in human tumor lines and in Li-Fraumeni fibroblast cultures, suggesting that it is aberrantly regulated in malignant cells. The developmental profile of Zbu1 gene expression and the association of the protein with a tissue-specific transcriptional regulatory element distinguish it from other members of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product.

Adenosine Triphosphatases↗

Cloning and chromosomal mapping of four putative novel human G-protein-coupled receptor genes.

We report the discovery of four novel human putative G-protein-coupled receptor (GPCR) genes. Gene GPR20 was isolated by amplifying genomic DNA with oligos based on the opioid and somatostatin related receptor genes and subsequent screening of a genomic library. Also, using our customized search procedure of a database of expressed sequence tags (dbEST), cDNA sequences that partially encoded novel GPCRs were identified. These cDNA fragments were obtained and used to screen a genomic library to isolate the full-length coding region of the genes. This resulted in the isolation of genes GPR21, GPR22 and GPR23. The four encoded receptors share significant identity to each other and to other members of the receptor family. Northern blot analysis revealed expression of GPR20 and GPR22 in several human brain regions while GPR20 expression was detected also in liver. Fluorescence in situ hybridization (FISH) was used to map GPR20 to chromosome 8q, region 24.3-24.2, GPR21 to chromosome 9, region q33, GPR22 to chromosome 7, region q22-q31.1, and GPR23 to chromosome X, region q13-q21.1.

Amino Acid Sequence↗

Discovery of a novel human G protein-coupled receptor gene (GPR25) located on chromosome 1.

We amplified human genomic DNA by the polymerase chain reaction (PCR) using oligonucleotides based on the primary sequence of the genes encoding the somatostatin receptors (SSTR) and the somatostatin-like receptor gene SLC-1. One resultant DNA fragment was used to screen a genomic DNA library resulting in the isolation of a gene, GPR25, encoding an additional member of the G protein-coupled receptor family (GPCR). GPR25 is intronless throughout its open reading frame (ORF) and encodes a protein of 360 amino acids. The receptor encoded by GPR25 shares highest identity to the receptor encoded by GPR15, angiotensin II type 1A receptor, and somatostatin receptor 5. Northern analysis found no transcripts expressed in liver or any of the 12 brain regions analyzed. Fluorescence in situ hybridization analysis localized GPR25 to chromosome 1q32.1.

Amino Acid Sequence↗

Synthesis and chiroptical properties of a novel C2-symmetric binaphthyl phosphortriamide ("chiral HMPA").

By use of an asymmetric Ullmann coupling involving chiral naphthalene oxazolines 1, the title compounds were prepared in good yields and with high diastereoselectivity. Hydrolysis of the binaphthyl oxazolines 2 led to the di-aldehydes 5, which were transformed into the azepine derivative, 6. The latter was treated with the appropriate phosphoryl halide to access the chiral HMPA systems 7 and 9. The CD spectra of the chiral azepine 6 and the chiral phosphoramides 7 and 9 were measured and showed a strong positive CD couplet near 225 nm, consistent with the P axial chirality (S configuration). Semi-empirical CNDO/S molecular orbital calculations of the CD spectrum of 6 satisfactorily reproduced the major features of the observed spectrum.

Circular Dichroism↗

Identification and characterization of the Cecropin antibacterial protein gene locus in Drosophila virilis.

Cecropin is a type of antibacterial peptide that is synthesized in response to infection and has been characterized in many insect species and one mammal. The Cecropin locus of Drosophila melanogaster also contains the gene Andropin, which has been identified only in this species and encodes a male-specific antibacterial peptide. As a first step in studying the molecular evolution of the cecropin and andropin genes among Drosophila species, we have isolated genomic clones that cover the Cecropin locus in Drosophila virilis. The cloned region totals approximately 25 kb, within which a 9-kb fragment contains four cecropin genes and one pseudogene. All four genes have a high level of sequence homology to D. melanogaster Cecropin, about 80% identity in the coding regions, and the intron positions are conserved. As in D. melanogaster and other insects, kappa B-related cis-regulatory elements are found upstream of these cecropin genes. An Andropin-related sequence was not identified in D. virilis; however, genome Southern hybridizations suggest that Andropin-related sequences are present in at least the melanogaster species subgroup. Analysis of 19 insect cecropin genes identifies a common ancestral Cecropin before the divergence of Diptera and Lepidoptera. In addition, D. melanogaster and D. virilis can be identified by monophyletic clades for Cecropin. In contrast, the Lepidopteran species show polyphyletic relationships for duplicated cecropin genes.

Amino Acid Sequence↗

Urea and protein metabolism in burned children: effect of dietary protein intake.

The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and skin protein synthesis rates to dietary protein intake (1.15 to 2.92 g/kg/d) was assessed in children with 20% to 40% total body surface area burn injury using a primed continuous infusion of 15N2-urea and L-13C6-phenylalanine. Plasma urea concentration, production, and excretion rates increased with dietary protein intake without evidence of approaching maximum plateau values. There was no consistent evidence of urea recycling in these subjects (urea production = excretion) at any level of protein intake. The rate of appearance (Ra) of phenylalanine (an index of whole-body protein breakdown) and rate of muscle protein synthesis were independent of dietary protein, whereas there was a significant increase in skin protein synthesis with higher protein intake. We conclude that there seems to be little benefit of high protein intake on whole-body protein breakdown and muscle protein synthesis rates in these burn patients, although high-protein diets may enhance wound healing.

Adolescent↗

Retinoic acid regulation of the VIP and PACAP autocrine ligand and receptor system in human neuroblastoma cell lines.

Neuroendocrine tumors, neuroblastoma in particular, commonly express the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) and their receptors. Retinoic acid (RA) has been shown to induce differentiation of neuroblastoma cell lines, possibly by augmenting or interfering with neuropeptide autocrine loops. We sought to determine which receptor gene subtypes are expressed in selected human neuroblastoma cell lines (SH-SY5Y, IMR-32, and LA-N-5), and the effect of RA on the VIP/PACAP ligand/receptor system. Expression of both PACAP1 and VIP1/PACAP2 receptor genes was detected by Northern analysis, which characteristically encode Type I (PACAP-preferring), and Type II (bivalent VIP/PACAP) receptors, respectively. Binding experiments carried out on IMR-32 cells, using 125I VIP and 125I PACAP-27 as tracers, corroborated that both receptor subtypes were expressed. In contrast to RA upregulation of VIP binding (confirmed here in IMR-32 cells), levels of both receptor mRNAs were reduced after RA treatment. VIP mRNA in each cell line was increased by RA, whereas PACAP mRNA, detected in IMR-32 cells only, was reduced. The studies indicate that several components of the VIP/PACAP autocrine system are regulated in neuroblastoma cell lines during RA differentiation.

Autocrine Communication↗

Retinal dopamine in the recovery from experimental myopia.

PURPOSE: To address further a possible role for retinal dopamine in postnatal eye growth, we studied the response of retinal dopamine in eyes of chicks recovering from myopia. METHODS: Newborn chicks either received a unilateral translucent goggle to induce form deprivation myopia or were reared with unimpaired visual input. The goggle was removed from half of the chicks on day 7. Myopic, recovering and control never-goggled chicks were studied on days 7, 9 and 14. Eyes were enucleated postmortem and measured in axial and equatorial dimensions with calipers. Retinal levels of dopamine and its principal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were assayed by high performance liquid chromatography with electrochemical detection. RESULTS: Compared to contralateral and control eyes, retinas of goggled eyes at each time point had reduced levels of dopamine and DOPAC and a lowered calculated DOPAC/dopamine ratio, an index of dopamine metabolism. In eyes recovering from myopia, all biochemical parameters showed prominent increases by 2 days after goggle removal and had reached the level of both contralateral eyes and control eyes by one week after goggle removal. As evidence of a contralateral effect, the retinas of open eyes of chicks wearing a unilateral goggle demonstrated equal dopamine levels but reduced DOPAC compared to eyes of never-goggled chicks. CONCLUSION: An early rise and eventual normalization of retinal dopamine, DOPAC and the DOPAC/dopamine ratio correlate with recovery from myopia. Combined with recent results from lens rearing experiments, these findings suggest that dopaminergic amacrine cells may participate in visually guided eye growth regulation and not just in the myopia response to visual form deprivation. The retinal biochemical alteration in eyes contralateral to a goggle identifies a previously unappreciated binocular interaction in the chick.

3,4-Dihydroxyphenylacetic Acid↗

Protective immunity against respiratory syncytial virus in early life after murine maternal or neonatal vaccination with the recombinant G fusion protein BBG2Na.

Maternal and neonatal immunization were evaluated for their capacity to induce protective immunity against respiratory syncytial virus (RSV) lower respiratory tract infections in early life. Murine models were studied by use of a novel recombinant vaccine candidate, designated BBG2Na, which was derived in part from the RSV (Long) G protein. Maternal immunization resulted in the passive transfer of high levels of RSV-A antibodies to the offspring, which protected them from RSV challenge for up to 14 weeks. Indeed, protection correlated with the detection of RSV antibodies in the serum. Neonatal immunization with BBG2Na induced significant antibody responses even in the first week of life. Most importantly, these neonatal responses were not inhibited by the presence of RSV maternal antibodies. Consequently, the combination of maternal and neonatal immunization with BBG2Na resulted in the continual presence of protective levels of antibodies in the offspring.

Animals↗

Daily changes in plasma and amniotic fluid prolactin during the last third of pregnancy in the baboon.

Alterations in plasma and amniotic fluid prolactin (PRL) levels have not been previously described in the pregnant baboon. In addition, PRL increases dramatically in response to estrogens and thus might be a good marker for expression of estrogen's biologic action. Therefore, the purpose of this study was to characterize the changes in plasma and amniotic fluid PRL with advancing gestational age and assess whether there was a correlation between plasma estradiol and PRL levels. A tethered pregnant baboon model was utilized for these studies. Blood was collected from five animals every day at 0900-1000 h (AM value) and 1800 h (PM value) from 125 to 135 days of pregnancy until delivery. Amniotic fluid was collected every day in the morning. Samples were analyzed by RIA for PRL, estradiol, and progesterone. PRL did not change with advancing gestational age. However, PRL showed a significant diurnal variation, with the PM values significantly higher (p < 0.05) than the AM values. In contrast to findings for PRL, AM values for estradiol and progesterone were on average higher that PM values (p < 0.05). A significant correlation was observed between the log10 estradiol (AM+PM) and log10 PRL (AM) from the following day (r = 0.52; p < 0.05). Finally, amniotic fluid PRL was present in high concentrations (200-400 ng/ml) but did not vary with gestational age. In conclusion, PRL, estradiol, and progesterone show distinct diurnal variations during the last one-third of pregnancy in the baboon. In addition, plasma PRL is positively correlated with estradiol.

Amniotic Fluid↗

Effect of ethanol on pancreatic interstitial pH and blood flow in cats with chronic pancreatitis.

OBJECTIVE: The objective of this study was to investigate the effects of ethanol on pancreatic blood flow and interstitial pH in chronic pancreatitis. BACKGROUND: Ethanol is known to contribute to the development of both acute and chronic pancreatitis. However, it is unclear how ethanol precipitates episodes of acute pancreatic inflammation in the setting of chronic pancreatitis. In a model of chronic pancreatitis in cats, it is known that pancreatic blood flow is abnormally low and decreases further after ethanol ingestion. Because it is possible that this reduction in blood flow might be damaging to the pancreas, we investigated the effects of ethanol on pancreatic interstitial pH, an index of pancreatic ischemia. METHODS: In normal cats and cats with obstructive chronic pancreatitis, pancreatic blood flow and interstitial pH were measured using the hydrogen gas clearance technique and pH microelectrode, respectively. RESULTS: In normal cats, intragastric, but not intravenous, ethanol reduced both pancreatic blood flow by 62% (p < 0.05) and interstitial pH (7.38 +/- 0.03 to 7.20 +/- 0.03, p < 0.05). In cats with chronic pancreatitis in which basal pancreatic blood flow was already only 60% of normal flow, both intragastric and intravenous ethanol decreased both pancreatic blood flow (intragastric, 40% decrease, p < 0.05; intravenous, 34% decrease, p < 0.05) and interstitial pH (intragastric, 7.24 +/- 0.04 to 7.08 +/- 0.04, p < 0.05; intravenous 7.20 +/- 0.08 to 7.07 +/- 0.07, p < 0.05). CONCLUSIONS: This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. These findings may explain the pathogenesis of bouts of acute pancreatic inflammation after ethanol ingestion in the setting of chronic disease.

Animals↗

A twin study of polycystic ovary syndrome and lipids.

Our objective was to assess the relative contribution of genetic and environmental factors (particularly androgens) on circulating levels of lipid fractions and to determine the effect, if any, of polycystic ovary syndrome (PCOS) on lipid fractions. The study was carried out in the outpatient clinic of the Royal Hospital for Women, Paddington, Sydney, Australia. A group of 19 monozygotic (MZ) and 15 dizygotic (DZ) twin pairs was identified from the National Twin Register. Ultrasound clinical and biochemical parameters were used to define polycystic ovaries. Serum androgen and lipid fractions were also measured. Eleven pairs of twins (five MZ, six DZ) were scan discordant (i.e. one twin had polycystic ovaries and the co-twin did not). Serum levels of the lipoprotein fractions in twins with polycystic ovaries were not significantly different from the levels found for their co-twins with normal ovaries. There were no significant correlations between androgen-related hormones and any of the lipid measurements. Body mass index (BMI) was positively correlated with triglycerides and lipoprotein (a), and negatively correlated with high-density lipoprotein cholesterol (HDL-C). Sex hormone-binding globulin (SHBG) levels were negatively correlated with triglycerides and lipoprotein (a) and positively associated with HDL-C. Fasting insulin levels were significantly correlated with triglycerides and negatively with HDL-C. The MZ intraclass correlation exceeded that of the DZ twin pairs for all the lipid variables measured. The heritability estimates for lipoprotein (a), apolipoprotein B, total cholesterol and HDL-C were 0.95, 0.56, 0.48 and 0.54, respectively. However, the intraclass correlation coefficient for triglycerides was not significantly different between MZ and DZ twins, but maximum likelihood analysis indicated that at least 10% of the variance of the circulating triglyceride concentration is determined by genetic factors. We conclude that twins discordant for the PCOS do not have significantly different lipid fractions.

Adolescent↗

Bilateral rudimentary first ribs as a cause of thoracic outlet syndrome.

First rib abnormalities are an uncommon cause of thoracic outlet syndrome. Cervical ribs are a much more frequent source of thoracic outlet syndrome, and in more than 95% of these patients, the symptoms are neurologic, not vascular. Rudimentary first ribs, however, uncommonly produce exclusively neurologic symptoms and usually manifest with vascular pathology. This article reviews a case of a patient with bilateral extensively neurologic thoracic outlet syndrome symptoms arising from bilateral rudimentary first ribs. The symptoms, pathologic features, and treatment, as well as an algorithm for working up patients with thoracic outlet syndrome, are discussed. Bilateral transaxillary first rib resection was curative in this patient and is the treatment of choice for either neurologic or vascular manifestations of thoracic outlet syndrome associated with rudimentary first ribs.

Female↗