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T Nguyen

Publications and source records attributed to T Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intracellular pathways regulating ciliary beating of rat brain ependymal cells.

1. The mammalian brain ventricles are lined with ciliated ependymal cells. As yet little is known about the mechanisms by which neurotransmitters regulate cilia beat frequency (CBF). 2. Application of 5-HT to ependymal cells in cultured rat brainstem slices caused CBF to increase. 5-HT had an EC50 of 30 microM and at 100 microM attained a near-maximal CBF increase of 52.7 +/- 4.1 % (mean +/- s.d.) (n = 8). 3. Bathing slices in Ca2+-free solution markedly reduced the 5-HT-mediated increase in CBF. Fluorescence measurements revealed that 5-HT caused a marked transient elevation in cytosolic Ca2+ ([Ca2+]c) that then slowly decreased to a plateau level. Analysis showed that the [Ca2+]c transient was due to release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores; the plateau was probably due to extracellular Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. 4. Application of ATP caused a sustained decrease in CBF. ATP had an EC50 of about 50 microM and 100 microM ATP resulted in a maximal 57.5 +/- 6.5 % (n = 12) decrease in CBF. The ATP-induced decrease in CBF was unaffected by lowering extracellular [Ca2+], and no changes in [Ca2+]c were observed. Exposure of ependymal cells to forskolin caused a decrease in CBF. Ciliated ependymal cells loaded with caged cAMP exhibited a 54.3 +/- 7.5 % (n = 9) decrease in CBF following uncaging. These results suggest that ATP reduces CBF by a Ca2+-independent cAMP-mediated pathway. 5. Application of 5-HT and adenosine-5'-O-3-thiotriphosphate (ATP-gamma-S) to acutely isolated ciliated ependymal cells resulted in CBF responses similar to those of ependymal cells in cultured slices suggesting that these neurotransmitters act directly on these cells. 6. The opposite response of ciliated ependymal cells to 5-HT and ATP provides a novel mechanism for their active involvement in central nervous system signalling.

Adenosine Triphosphate↗
PubMed2001

Resolution of bronchial hyperresponsiveness and pulmonary inflammation is associated with IL-3 and tissue leukocyte apoptosis.

We have used two models of murine pulmonary inflammation to investigate the signals responsible for the resolution of bronchial hyperresponsiveness (BHR). Both protocols involved two sensitizations with OVA followed by serial aerosolized challenge with OVA. We determined that administration of the second sensitization by aerosol (model A) was associated with a transient response, whereas administration by the i.p. route (model B) induced a sustained response, in the form of BHR and eosinophilia. This difference in kinetics was due solely to the route of the second Ag administration and was not associated with Ag dose or adjuvant. Differences in kinetics of lung eosinophilia/BHR were shown to be independent of IgE levels and IL-4 or IL-5. However, IL-3 levels in model A closely correlated with the rate of leukocyte clearance by apoptosis and were observed concomitant with a decline in BHR. Blockage of IL-3 in model B increased leukocyte apoptosis but reduced tissue eosinophilia and BHR. The use of mouse models in which a single different administration of allergen is associated with a failure/success to resolve inflammation and BHR by 72 h postchallenge indicates a link between IL-3 production, leukocyte apoptosis, and BHR responses.

Animals↗
PubMed2001

Identification of four novel human G protein-coupled receptors expressed in the brain.

We report the discovery and tissue distributions of four novel human genes, GPR61, GPR62, GPR63 and GPR77, all of which encode G protein-coupled receptors (GPCRs). GPR61 was discovered in a search of the patent literature which retrieved a rabbit DNA sequence partially encoding a novel GPCR. This sequence was used to obtain a full-length human cDNA encoding GPR61, a receptor of 417 amino acid length. A search of the GenBank genomic sequence databases revealed three previously unrecognized intronless genes encoding the orphan GPCrs (oGPCRs) GPR62, GPR63 and GPR77, with respective amino acid lengths of 368, 419 and 337. Sequence analysis revealed that GPR61 and GPR62, and a published orphan receptor p47MNR, shared the highest level of identities to each other, ranging from 36 to 45% in the transmembrane (TM) domains. Together, these three oGPCRs appear to comprise a novel subfamily of GPCRs, most closely related to the serotonin 5-HT(6) receptor. Sequence analysis of GPR63 and GPR77 revealed highest sequence identities in the TM regions with the oGPCR PSP24 (58%) and the anaphylatoxin C5a receptor (49%) respectively. Tissue distribution analyses detected the expression of all four novel genes in the human brain. GPR61 mRNA expression was detected in the caudate, putamen and thalamus of human brain, with a more widespread expression pattern in rat brain, with mRNA signals in areas of the cortex, hippocampus, thalamus, hypothalamus and midbrain. GPR62 mRNA expression was detected in the basal forebrain, frontal cortex, caudate, putamen, thalamus and hippocampus. GPR63 mRNA expression was detected in the frontal cortex, with lower levels in the thalamus, caudate, hypothalamus and midbrain. Analysis of GPR77 mRNA expression revealed signals in the frontal cortex, hippocampus and hypothalamus with high transcript levels in the liver.

Animals↗
PubMed2001

Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection.

Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201-restricted CTL response is directed towards the epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This epitope is targeted by 75% of HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide-major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201-positive subjects with acute HIV-1 infection (P = 2 x 10(-6)), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates.

Acute Disease↗
PubMed2001

Promoting early detection of breast cancer among Vietnamese-American women. Results of a controlled trial.

BACKGROUND: Although breast cancer is the second most common cancer among Vietnamese-American women, previous research has shown that they are less likely to have ever had, and to be more often overdue for, clinical breast examinations (CBE) and mammograms than women in the general population. METHODS: Over a 2.5-year period, the following intervention activities were targeted at both Vietnamese women and physicians in Alameda County, California: neighborhood-based educational activities; dissemination of health education materials; a media campaign; and continuing medical education seminars for physicians. Women in Los Angeles and Orange Counties served as controls. Preintervention telephone interviews were conducted with 384 randomly selected Vietnamese women in the intervention community and 404 women in the control community in 1996, and post-test intervention interviews were conducted with 405 and 402 women, respectively, in 1998. RESULTS: Multiple logistic regression analyses of postintervention surveys showed the intervention community women at posttest were no more likely to recognize, receive, plan, or be up-to-date for CBE or mammograms than women in the control community. However, women who reported greater exposure to the various intervention elements were significantly more likely to have heard of, have had, and to plan CBE and mammograms than women with less exposure. CONCLUSIONS: Although the effect on the women in the intervention group was not significant, the intervention did have a modest positive impact on women who had more exposure to it.

Adult↗
PubMed2001

Residual DNA quantification in clinical batches of BBG2Na, a recombinant subunit vaccine against human respiratory syncytial virus.

BBG2Na, a well-defined recombinant protein produced in Escherichia coli, is a promising human respiratory syncytial virus subunit vaccine candidate. This study describes the quantification of residual DNA in large scale batches used in phase I to III clinical trials. Two different analytical methods were developed and applied on five different final bulks of Drug Substance and their associated in process control samples, namely a chemiluminescent hybridisation assay and the total DNA Threshold System assay. These two complementary methods demonstrated the clearance of residual DNA during the downstream purification process. The amount of residual DNA found in the final bulks was below 20 pg of DNA per 300 microg BBG2Na, the highest tested clinical dose of antigen. This is very low level of residual DNA for a recombinant subunit vaccine produced in a bacteria and contribute to make for BBG2Na a well-characterised biopharmaceutical. This study also provides data concerning the validation of the hybridisation dot blot assay and the total DNA Threshold(trade mark)assay.

Clinical Trials as Topic↗
PubMed2001

Recent developments in microvascular angina.

Microvascular angina (Syndrome X) is an extremely heterogeneous clinical entity that is the product of genetic, coronary microvascular, metabolic, and clinical factors, which combine together to produce distinct cardiac manifestations and complications. The interactions of these abnormalities remain poorly understood. The diagnosis is considered in patients with anginal symptoms and no epicardial coronary narrowing. Therapy is also problematic, with beta-blockers as first-line pharmacotherapy followed by angiotensin-converting enzyme inhibitors and calcium channel blockers.

Adrenergic beta-Antagonists↗
PubMed2001

Does neuropeptide Y contribute to the anorectic action of amylin?

Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which amylin exerts its anorectic effect is controversial. This study investigated the acute effect of amylin on food intake induced by NPY, and the effect of chronic amylin administration on food intake and body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv) cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5 nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin-treated rats showed a significant reduction in body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to weight loss.

Amyloid↗
PubMed2001

Tissue-specific expression of an anti-proliferative hybrid transgene from the human smooth muscle alpha-actin promoter suppresses smooth muscle cell proliferation and neointima formation.

The retinoblastoma protein (Rb), a key regulator of cell cycle progression, can bind the transcription factor E2F converting it from a positive transcriptional factor capable of driving cells into S phase into a negative complex which arrests cells in G1. We have created a potent transcriptional repressor of E2F-dependent transcription by fusing the C-terminal fragment of Rb (p56) to the DNA and DP1-binding domains of E2F. Because the expression of E2F/56 fusion protein from a constitutive promoter was incompatible with virus growth, adenovirus constructs were prepared where transgenes were expressed from a fragment of the smooth muscle alpha-actin (SMA) promoter. Immunoblot and beta-galactosidase staining demonstrated smooth muscle-specific expression of this transcriptional element in vitro. The SMA-p56 and SMA-E2F/p56 adenoviral constructs also induced G0/G1 cell cycle arrest specifically in smooth muscle cells. Following administration to rat tissues, the SMA-beta-galactosidase construct exhibited expression in balloon-injured carotid arteries, but not in liver, bladder or skeletal muscle. Local delivery of the SMA-E2F/p56 adenoviral construct to balloon-injured carotid arteries inhibited intimal hyperplasia. Our results demonstrate that local delivery of the SMA-E2F/p56 adenoviral construct can limit intimal hyperplasia in balloon-injured vessels, while avoiding toxicity that could occur from the dissemination and expression of the viral transgene.

Actins↗
PubMed2001

Prediction of energy expenditure in a whole body indirect calorimeter at both low and high levels of physical activity.

OBJECTIVES: In studies that involve the use of a room calorimeter, 24 h energy intake is often larger than 24 h energy expenditure (24 h EE) because of a decrease in activity energy expenditure due to the confined space. This positive energy balance can have large consequences for the interpretation of substrate balances. The objective of this study was to develop a method for predicting an individual's 24 h EE in a room calorimeter at both low (1.4xRMR) and high (1.8xRMR) levels of physical activity. METHODS: Two methods are presented that predict an individual's 24 h EE in a metabolic chamber. The first method was based on three components: (1) a 30 min measurement of resting metabolic rate (RMR) using a ventilated hood system; (2) measurement of exercise energy expenditure during 10 min of treadmill walking; and (3) estimation of free-living energy expenditure using a tri-axial motion sensor. Using these measurements we calculated the amount of treadmill time needed for each individual in order to obtain a total 24 h EE at either a low (1.4xRMR) or a high (1.8xRMR) level of physical activity. We also developed a method to predict total 24 h EE during the chamber stay by using the energy expenditure values for the different levels of activity as measured during the hours already spent in the chamber. This would provide us with a tool to adjust the exercise time and/or energy intake during the chamber stay. RESULTS: Method 1: there was no significant difference in expected and measured 24 h EE under either low (9.35+/-0.56 vs 9.51+/-0.47 MJ/day; measured vs predicted) or high activity conditions (13.41+/-0.74 vs 13.97+/-0.78 MJ/day; measured vs predicted). Method 2: the developed algorithm predicted 24 h EE for 97.6+/-4.0% of the final value at 3 h into the test day, and for 98.6+/-3.7% at 7 h into the test day. CONCLUSION: Both methods provide accurate prediction of energy expenditure in a room calorimeter at both high and low levels of physical activity. It equally shows that it is possible to accurately predict total 24 h EE from energy expenditure values obtained at 3 and 7 h into the study.

Adaptation, Physiological↗
PubMed2001

The regulation of FasL expression during activation-induced cell death (AICD).

Activation-induced cell death (AICD), a Fas ligand (FasL)-dependent pathway, is important for maintaining T-cell homeostasis. Interleukin-2 (IL-2), an enhancer of AICD, can also enhance FasL expression. However, we show that the level of FasL or FLIP protein did not correlate with the susceptibility to AICD. Some T cells expressed high levels of FasL yet failed to undergo AICD, while others expressed little FasL and were sensitive. AICD susceptibility did not correlate with the kinetics of FasL up-regulation or down-regulation. The down-regulation of FasL can be mediated by a metalloprotease. However, we describe an alternative mechanism for the loss of FasL by endocytosis. Endocytosis inhibitors such as cytochalasins, sodium azide, deoxyglucose, or low temperatures prevented the loss of FasL. KB8301, a metalloprotease inhibitor had no effect on the loss of FasL or AICD in the T cells. Enhancing FasL expression was not crucial for AICD and the down-regulation of FasL proceeded via endocytosis.

Animals↗
PubMed2001

NF-kappaB is involved in the survival of cerebellar granule neurons: association of IkappaBbeta [correction of Ikappabeta] phosphorylation with cell survival.

The NF-kappaB transcription factor consists of dimeric complexes belonging to the Rel family, which include p50, p52, p65 (RelA), RelB and c-Rel. NF-kappaB activity is tightly controlled by IkappaB proteins which bind to NF-kappaB preventing its translocation to the nucleus. Activation of NF-kappaB is most often mediated by IkappaB degradation, which permits NF-kappaB to enter the nucleus. We investigated the role of NF-kappaB in the survival of cerebellar granule neurons. We found that survival of these neurons in high potassium medium is blocked by three separate inhibitors of NF-kappaB activity: SN-50, N-tosyl-L-phenylalanine chloromethyl ketone and pyrrolidinedithiocarbamate, indicating that NF-kappaB is required for neuronal survival. Gel-shift assays reveal three complexes that bind to the NF-kappaB binding site in high potassium medium. Switching these cultures to low potassium medium, a stimulus that leads to apoptotic death, causes a reduction in the level of the largest complex, which contains p65. Overexpression of p65 by transfection inhibits low potassium-induced apoptosis, whereas overexpression of IkappaBalpha promotes apoptosis even in high potassium medium. Surprisingly, however, neither the level of endogenous p65 nor that of IkappaBalpha and IkappaBbeta is altered by low potassium treatment. Similarly, no changes are seen in the nuclear or cytoplasmic levels of p50, p52, RelB and c-Rel. Phosphorylation of p65, which can lead to its activation, is unchanged. Phosphorylation of IkappaBbeta is, however, reduced by low potassium treatment. Besides being necessary for high potassium-mediated neuronal survival, NF-kappaB is also involved in the survival-promoting effects of IGF-1 and cAMP as judged by the ability of SN-50 to inhibit the actions of these survival factors and the ability of these factors to inhibit the low potassium-induced alterations in the DNA-binding activity of NF-kappaB. Taken together, our results show that NF-kappaB may represent a point of convergence in the signaling pathways activated by different survival factors and that uncommon mechanisms might be involved in NF-kappaB-mediated survival of cerebellar granule neurons.

Animals↗
PubMed2001

The ChromaGen contact lens system: colour vision test results and subjective responses.

The ChromaGen lens system is designed to enhance colour perception in colour vision deficiency (CVD). To investigate its efficacy, 14 CVD subjects were prescribed ChromaGen contact lenses. Colour vision tests (Ishihara, Farnsworth Munsell D-15, Farnsworth Lantern) were administered at baseline, lens dispensing, and after a 2-week lens-wearing trial during which subjective responses were recorded daily using visual analogue scales. ChromaGen lenses significantly reduced ishihara error rates (p < 0.001; ANOVA), particularly for deutan subjects. There was also a significant reduction in errors (p < 0.005) on the D-15 test. Conversely, lens wear had no significant effect on Farnsworth Lantern test performance. Subjectively, subjects reported enhanced colour perception, but poor vision in dim light. Judgement of distance and motion were only slightly affected. We conclude that ChromaGen lenses may enhance subjective colour experience and assist in certain colour-related tasks, but are not indicated as an aid for CVD in occupations with colour vision-related restrictions.

Adolescent↗
PubMed2001

Helicobacter pylori induces apoptosis in human epithelial gastric cells by stress activated protein kinase pathway.

BACKGROUND: The pathway by which Helicobacter pylori induces apoptosis in gastric epithelial cells is not known. The aim of this study was to determine whether H. pylori-induced apoptosis is associated with SAPK/JNK activity in human gastric cancer KATO III cells. MATERIALS AND METHODS: H. pylori VacA toxin positive strain was incubated with KATO III cells for 0.5, 1, 2 or 24 hours. The SAPK/JNK protein was harvested from the KATO III cell lysate by precipitation with a C-jun fusion protein and its activity was measured by C-jun phosphorylation utilizing transblotting and phosphoserine antibody. Cellular apoptosis was demonstrated by DNA fragmentation. In addition, cell growth in coculture with H. pylori was determined over 72 hours. RESULTS: H. pylori significantly stimulated SAPK/JNK activity in KATO III cells with a peak at the 0.5 hour time point (3.6-fold vs. control, p <.05), but a return to basal levels by 2 hours. In addition, significant DNA fragmentation was observed after 24 hours in these cells but not in the control KATO III cells. Cell growth was inhibited in a dose dependent fashion in coculture with H. pylori. CONCLUSION: These results show that H. pylori triggers an increase in apoptosis in KATO III cells as reflected by DNA fragmentation. This effect was preceded and correlated with an increase in SAPK/JNK activity suggesting that the H. pylori-induced apoptosis in human gastric epithelial cells may be mediated by the SAPK/JNK pathway.

Apoptosis↗
PubMed2001

Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy.

OBJECTIVE: To define both auditory nerve and cochlear receptor functions in subjects with auditory neuropathy (AN). DESIGN: We tested 33 AN subjects (66 ears) and compared them with 21 healthy subjects (28 ears). In AN subjects, the average pure-tone (1, 2, and 4 kHz) threshold loss was 57 dB HL. Click stimuli were used to elicit transient evoked otoacoustic emissions (TEOAEs), cochlear microphonics (CMs), and auditory brain stem responses (ABRs). Both cochlear and ABR potentials were recorded from surface electrodes (vertex-ipsilateral mastoid) using averaging procedures. The amplitudes and latencies of CMs and ABRs and the amplitude of the TEOAEs were analyzed. RESULTS: CM amplitudes recorded from normal ears decreased as a function of subject age. CMs recorded from AN subjects fell within the normal age-adjusted range in 60% of the subjects and were >2 SEEs (standard error of estimate) above the age-adjusted normal regression in 40% of the subjects. TEOAEs were absent in 19 (30%) AN ears (bilaterally in eight, and unilaterally in three subjects) and were present in 44 ears. In AN subjects, correlations among CM amplitude, TEOAE amplitude, and pure-tone average thresholds were not significantly related. CM amplitudes were not significantly different whether TEOAEs or ABRs were present or absent. The ABR was present in 21% of AN subjects and consisted of a low-amplitude Wave V without a preceding Wave I. Measures of CM amplitude and PTA hearing loss were not significantly different in those AN ears with a preserved ABR compared with ears with absent ABRs. Summating potentials to transient click stimuli were of small amplitude (<0.1 microV) and detectable in approximately 50% of the AN and healthy control subjects limiting formal analysis of summating potentials. CONCLUSIONS: In a significant proportion of AN subjects, we found abnormalities of cochlear receptor function, including elevated CM amplitudes and absence of TEOAEs. These two abnormalities occurred independently of each other. A low amplitude Wave V of the ABR was found in approximately one-fifth of AN subjects, evidence that neural synchrony can be partially preserved in some subjects with this disorder.

Adolescent↗
PubMed2001

Synchronous gastric adenocarcinomas in a patient with Meckel's diverticulum.

Meckel's diverticulum, which is the most common congenital anomaly of the gastrointestinal tract, occurs when the vitelline duct persists past the 7th week of gestation. Although complications may occur in 8% to 22% of patients with Meckel's diverticula, adenocarcinoma is very uncommon. We describe a patient with early gastric cancer who was incidentally found to have a superficial adenocarcinoma arising from ectopic gastric mucosa within a Meckel's diverticulum. To the best of our knowledge, synchronous gastric adenocarcinoma in a patient with Meckel's diverticulum has not been previously reported.

Adenocarcinoma↗
PubMed2001

Analysis of the cat eye syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere.

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R, ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny are CECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 and CECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located approximately 1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.

Abnormalities, Multiple↗