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T Phan

Publications and source records attributed to T Phan.

At least 37 records · Page 2Linked to original sources
PubMed2000

ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1.

ATF6, a member of the leucine zipper protein family, can constitutively induce the promoter of glucose-regulated protein (grp) genes through activation of the endoplasmic reticulum (ER) stress element (ERSE). To understand the mechanism of grp78 induction by ATF6 in cells subjected to ER calcium depletion stress mediated by thapsigargin (Tg) treatment, we discovered that ATF6 itself undergoes Tg stress-induced changes. In nonstressed cells, ATF6, which contains a putative short transmembrane domain, is primarily associated with the perinuclear region. Upon Tg stress, the ATF6 protein level dropped initially but quickly recovered with the additional appearance of a faster-migrating form. This new form of ATF6 was recovered as soluble nuclear protein by biochemical fractionation, correlating with enhanced nuclear localization of ATF6 as revealed by immunofluorescence. Optimal ATF6 stimulation requires at least two copies of the ERSE and the integrity of the tripartite structure of the ERSE. Of primary importance is a functional NF-Y complex and a high-affinity NF-Y binding site that confers selectivity among different ERSEs for ATF6 inducibility. In addition, we showed that YY1 interacts with ATF6 and in Tg-treated cells can enhance ATF6 activity. The ERSE stimulatory activity of ATF6 exhibits properties distinct from those of human Ire1p, an upstream regulator of the mammalian unfolded protein response. The requirement for a high-affinity NF-Y site for ATF6 but not human Ire1p activity suggests that they stimulate the ERSE through diverse pathways.

3T3 Cells↗
PubMed2000

TGF-(beta)1 maintains hematopoietic immaturity by a reversible negative control of cell cycle and induces CD34 antigen up-modulation.

Somatic stem cells are largely quiescent in spite of their considerable proliferative potential. Transforming growth factor-(beta)1 (TGF-(beta)1) appears to be a good candidate for controlling this quiescence. Indeed, various mutations in the TGF-beta signalling pathway are responsible for neoplasic proliferation of primitive stem/progenitor cells in human tissues of various origins. In hemopoietic single cell culture assays, blocking autocrine and endogeneous TGF-(beta)1 triggers the cell cycling of high proliferative potential undifferenciated stem/progenitor cells. However, it has never been demonstrated whether TGF-(beta)1 has an apoptotic effect or a differentiating effect on these primitive cells, as already described for more mature cells. Using single cell experiments both in liquid or semi-solid culture assays and dye tracking experiments by flow cytometry, we demonstrate that low, physiological concentrations of TGF-(beta)1, which specifically maintain primitive human hemopoietic stem/progenitor cells in quiescence, have a reversible effect and do not induce apoptosis. We moreover demonstrate that these low concentrations prevent the rapid loss of the mucin-like protein CD34, a most common marker of immature hematopoietic stem/progenitor cells, which is progressively lost during differentiation. TGF-(beta)1 not only up-modulated the CD34 antigen before S phase entry but also maintained a high level of CD34 expression on cells which had escaped cell cycle inhibition, suggesting that proliferation inhibition and differentiation control by TGF-(beta)1 may be independent. These data provide additional evidence that TGF-(beta)1 acts as a key physiological factor ensuring the maintenance of a stem cell reserve.

Antigens, CD34↗
PubMed1999

Protein kinase A is a negative regulator of renal branching morphogenesis and modulates inhibitory and stimulatory bone morphogenetic proteins.

Protein kinase A (PKA) regulates morphogenetic responses to bone morphogenetic proteins (BMPs) during embryogenesis. However, the mechanisms by which PKA regulates BMP function are unknown. During kidney development, BMP-2 and high doses of BMP-7 inhibit branching morphogenesis, whereas low doses of BMP-7 are stimulatory (Piscione, T. D., Yager, T. D., Gupta, I. R., Grinfeld, B., Pei, Y., Attisano, L., Wrana, J. L., and Rosenblum, N. D. (1997) Am. J. Physiol. 273, F961-F975). We examined the interactions between PKA and these BMPs in embryonic kidney explants and in the mouse inner medullary collecting duct-3 model of collecting duct morphogenesis. H-89, an inhibitor of PKA, stimulated branching morphogenesis and enhanced the stimulatory effect of low doses of BMP-7 on tubule formation. Furthermore, H-89 rescued the inhibition of tubulogenesis by BMP-2 (or high doses of BMP-7) by attenuating BMP-2-induced collecting duct apoptosis. In contrast, 8-bromo-cAMP, an activator of PKA, inhibited tubule formation and attenuated the stimulatory effects of low doses of BMP-7. To determine mechanisms underlying the interdependence of BMP signaling and PKA activity, we examined the effect of PKA on the known signaling events in the BMP-2-dependent Smad1 signaling pathway and the effect of BMP-2 on PKA activity. PKA did not induce endogenous Smad1 phosphorylation, Smad1-Smad4 complex formation, or Smad1 nuclear translocation. In contrast, BMP-2 increased endogenous PKA activity and induced phosphorylation of the PKA effector, cAMP-response element-binding protein, in a PKA-dependent manner. We conclude that BMP-2 induces activation of PKA and that PKA regulates the effects of BMPs on collecting duct morphogenesis without activating the known signaling events in the BMP-2-dependent Smad1 signaling pathway.

Animals↗
PubMed1999

Anterior chest wall pain in postpartum costochondritis.

Costochondritis is a common diagnosis in patients with anterior chest wall pain in whom serious disease has been excluded. The diagnosis is usually made on clinical grounds, because laboratory and imaging investigations usually provide little information. The authors describe a young woman with postpartum costochondritis and discuss the role of bone scintigraphy in confirming the clinical diagnosis.

Adult↗
PubMed1998

Detection and Identification of Base Alterations Within the Region of Factor V Leiden by Fluorescent Melting Curves.

Background: Factor V Leiden (G1691A) is a common cause of inherited thrombosis. In fluorescent melting curve analysis, the Leiden mutation is distinguished from the wild-type by a decrease in melting temperature (Tm) of a wild-type probe. Because Tm depends on the type and position of the mismatch, other base alterations, such as the recently described base alteration A1692C, should be distinguishable from the true Leiden mutation. Methods and Results: Of 2,100 samples tested for the factor V Leiden mutation using a wild-type probe, 200 heterozygous or homozygous mutant samples were further tested using a Leiden probe. The Tm of the A1692C base alteration was 1.5 degrees C greater than the Leiden mutation with the wild-type probe and 8 degrees C less with the Leiden probe. One sample was heterozygous for a new base alteration G1689A with a Tm 0.8 degrees C greater than the Leiden mutation with the wild-type probe, and 10 degrees C less with the Leiden probe. Tm estimates from fluorescence melting curve analysis have intra-assay standard deviations of approximately 0.1 degrees C. Conclusions: Fluorescence melting curve analysis can distinguish between sequence alterations with Tms differing by less than 1 degrees C. This is the first demonstration of a widely applicable technique that can significantly increase the specificity of hybridization techniques without the need for sequencing.

Journal Article↗
PubMed1997

Phosphodiesterase I, a novel adhesion molecule and/or cytokine involved in oligodendrocyte function.

One of the more complex developmental processes occurring postnatally in the CNS is the formation of the myelin sheath by oligodendrocytes. To examine the molecular events that take place during myelination, we isolated oligodendrocyte-derived cDNA clones, one of which (p421.HB) represents a putative alternatively spliced isoform of rat brain-specific phosphodiesterase I (PD-Ialpha) and a species homolog of the human cytokine autotaxin. Analysis of the structural composition of the p421.HB/PD-Ialpha protein suggests a transmembrane-bound ectoenzyme, which, in addition to the phosphodiesterase-active site contains presumed cell recognition and Ca2+-binding domains. Consequently, it may be involved in extracellular signaling events. Expression of p421.HB/PD-Ialpha is enriched in brain and spinal cord, where its mRNA can be detected in oligodendrocytes and in cells of the choroid plexus. Expression in the brain increases during development with an intermediate peak of expression around the time of active myelination and maximal expression in the adult. We have identified four presumably alternatively spliced isoforms, two of which appear to be CNS-specific. Decreased levels of p421.HB/PD-Ialpha mRNA in the dysmyelinating mouse mutant jimpy, but not shiverer, suggest a role for p421.HB/PD-Ialpha during active myelination and/or late stages of oligodendrocyte differentiation. Furthermore, p421.HB/PD-Ialpha mRNA levels were reduced in the CNS at onset of clinical symptoms in experimental autoimmune encephalomyelitis. These data together implicate the importance of p421.HB/PD-Ialpha in oligodendrocyte function, possibly through cell-cell and/or cell-extracellular matrix recognition.

Animals↗
PubMed1997

Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat hippocampus.

It is known that opioid peptides acting on opioid receptors can modulate hippocampal synaptic functions. Although a novel member of the opioid receptor family, ORL1 receptors, that displays high-sequence homology with classical opioid receptors is abundant in the hippocampus, little is known regarding its role in synaptic function. The present study was designed to investigate whether activation of the ORL1 receptor by its natural ligand, orphanin FQ, could modulate synaptic transmission and synaptic plasticity in the hippocampus. The actions of orphanin FQ in the CA1 and dentate gyrus were examined by field potential recordings in response to stimulation of Schaffer collaterals and perforant path, respectively. Our results showed that orphanin FQ, but not the inactive analog des-Phe1-orphanin FQ, reduced both the slope of the excitatory postsynaptic potentials and population spike amplitude. The inhibitory effect of orphanin FQ is dose dependent and probably involves a presynaptic mechanism, as suggested by the significantly increased paired-pulse facilitation evoked in the presence of orphanin FQ. In addition, orphanin FQ was found to inhibit the induction of long-term potentiation at the Schaffer collateral-CA1 synapse. These results demonstrate that orphanin FQ can function as an inhibitory modulator regulating synaptic transmission and synaptic plasticity in the hippocampus, suggesting that activation of ORL1 receptors may play an important role in synaptic plasticity involved in learning and memory.

Amino Acid Sequence↗
PubMed1997

Inositol phosphate metabolism during myocardial ischemia.

Inositol phosphate release in intact heart in response to norepinephrine involves primarily release of inositol(1,4)bisphosphate (Ins(1,4)P2) rather than inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) but Ins(1,4,5)P3 release predominates under conditions of post-ischemic reperfusion. In the current study, effects of myocardial ischemia on inositol phosphate responses were examined. Global myocardial ischemia in rat ventricle caused a reduction in the content of [3H]Ins(1,4)P3 (70-90%) and [3H]Ins(1,4,5)P3 (46%) and altered the pattern of norepinephrine stimulation such that increases in [3H]Ins(1,4,5)P3 were observed. Simulated ischemia in isolated right atria or isolated ventricular myocytes (P alpha 2 16-20 mmHg. pH 6.7. KCl 10 mM) produced similar changes. Reduction in O2 in the absence of other changes reduced the content of [3H]Ins (1,4)P2 (79%) in right atria whereas hypoxia and reduced pH were required to alter the [3H]Ins(1,4,5)P3 response. Progressive reduction in atrial ATP content using metabolic inhibitors caused a parallel decrease in [3H]Ins(1,4,5)P3 content (r = 0.96) without affecting [3H]Ins(1,4)P2 or the isomers of InsP1, showing that levels of Ins(1,4)P2 and Ins(1,4,5)P3 are regulated differently in the heart. These findings show that effects of ischemia on inositol phosphates in heart are complex and multifactorial, with Ins(1,4)P2 being affected under more moderately ischemic conditions than required for alterations in Ins(1,4,5)P3. These studies also demonstrate that ischemia produces similar effects on the release and metabolism of inositol phosphates in heart regardless of the ischemic model or the myocardial preparation used.

Adenosine Triphosphate↗
PubMed1997

The influence of culture on psychiatric assessment: the Vietnamese refugee.

The influence of culture on psychiatric diagnostic assessments remains controversial. The authors outline differences between the emic approach to assessment, which is informed by ethnographic concepts of the centrality of culture in shaping the psyche and its expressions, and the etic approach, which downplays cultural effects and focuses on the universal elements in manifestations of psychological distress. Based on the experience of assessing Vietnamese refugees in Australia, the authors explore semantic, contextual, and conceptual factors that may impede the psychiatric assessment of patients from other cultures. Areas of misinterpretation are illustrated using examples from the Vietnamese language. The authors discuss how variations in politicohistorical experiences within ethnic populations may result in differences in the modes of expressing and understanding mental illness. Recognition of the tension between etic and emic perspectives allows the clinician to draw on the most useful elements of each in assessing and treating individual patients.

Cross-Cultural Comparison↗
PubMed1997

Satisfaction of Vietnamese patients and their families with refugee and mainstream mental health services.

OBJECTIVE: The study examined levels of satisfaction with mainstream mental health services and specialized mental health services for refugees among Vietnamese psychiatric patients and their relatives. Demographic, diagnostic, symptomatic, and service-related issues that might influence satisfaction were investigated. METHODS: Eighty-six Vietnamese patients were identified from case notes of mainstream inpatient services (N = 31), mainstream community services (N = 7), and a specialized refugee treatment unit (N = 48). During an interview, a scale measuring satisfaction with treatment as well as measures of anxiety, depression, and posttraumatic stress disorder was administered to them. A modified satisfaction scale was administered to 56 relatives. RESULTS: Patients and relatives were, on average, moderately satisfied with treatment. Patients expressed greater satisfaction with the specialized treatment unit for refugees than with mainstream services, a finding that was not influenced by diagnostic differences or symptom levels at the time patients responded. Further analyses controlling for multiple comparisons revealed that the extent of the information provided and the ease of negotiating changes in treatment were the most salient variables in distinguishing satisfaction levels across the two types of treatment centers. Patients' fluency in English and their relatives' level of education were inversely associated with satisfaction scores, tentatively suggesting that the greater the ability of patients and their families to evaluate services, the less likely they were to express satisfaction with treatment. CONCLUSIONS: Specialized mental health services for refugees may be more acceptable to refugee populations than their mainstream counterparts, perhaps because better communication with patients and their families is possible in the specialized services. Patients and families who are in a position to evaluate services fully are more likely to be critical of treatments offered.

Acculturation↗
PubMed1996

Mutations in the B2 bradykinin receptor reveal a different pattern of contacts for peptidic agonists and peptidic antagonists.

The B2 bradykinin receptor, a seven-helix transmembrane receptor, binds the inflammatory mediator bradykinin (BK) and the structurally related peptide antagonist HOE-140. The binding of HOE-140 and the binding of bradykinin are mutually exclusive and competitive. Fifty-four site-specific receptor mutations were made. BK's affinity is reduced 2200-fold by F261A, 490-fold by T265A, 60-fold by D286A, and 3-10-fold by N200A, D268A, and Q290A. In contrast, HOE-140 affinity is reduced less than 7-fold by F254A, F261A, Y297A, and Q262A. The almost complete discordance of mutations that affect BK binding versus HOE-140 binding is surprising, but it was paralleled by the effect of single changes in BK and HOE-140. [Ala9]BK and [Ala6]BK are reduced in receptor binding affinity 27,000- and 150-fold, respectively, while [Ala9]HOE-140 affinity is reduced 7-fold and [Ala6]HOE-140 affinity is unchanged. NMR spectroscopy of all of the peptidic analogs of BK or HOE-140 revealed a beta-turn at the C terminus. Models of the receptor-ligand complex suggested that bradykinin is bound partially inside the helical bundle of the receptor with the amino terminus emerging from the extracellular side of helical bundle. In these models a salt bridge occurs between Arg9 and Asp286; the models also place Phe8 in a hydrophobic pocket midway through the transmembrane region. Models of HOE-140 binding to the receptor place its beta-turn one alpha-helical turn deeper and closer to helix 7 and helix 1 as compared with bradykinin-receptor complex models.

Adrenergic beta-Antagonists↗
PubMed1995

Peripheral neuropathy associated with simvastatin.

Four patients are described who developed sensorimotor neuropathy while being treated with simvastatin and had complete or partial resolution of clinical abnormalities after withdrawal of treatment. In one case onset was within days of commencing treatment, but in two cases symptoms did not develop for two years. The electrophysiological and pathological features of the neuropathy were those of axonal degeneration. Clinical evidence of proximal and distal weakness and muscle fasciculations and persistent abnormalities of sensory conduction after recovery suggest the possibility of toxic damage to anterior horn cells and dorsal root ganglia. Thirty eight other cases with symptoms suggestive of peripheral neuropathy have been reported to the Australian Adverse Drug Reactions Advisory Committee, 22 of whom recovered after cessation of treatment; in five cases there was recurrence after re-exposure to the drug. Simvastatin should be considered among the causes of peripheral neuropathy, and the drug should be withdrawn if patients receiving it develop muscle weakness or sensory disturbances.

Adult↗
PubMed1995

Conditionally immortalized oligodendrocyte cell lines migrate to different brain regions and elaborate 'myelin-like' membranes after transplantation into neonatal shiverer mouse brains.

Five immortalized oligodendrocyte cell lines, representing a spectrum of different stages of oligodendrocyte maturation, were transplanted into neonatal shiverer mouse brains and examined for their ability to survive, multiply, and migrate in vivo. Each of the cell lines migrated to different regions of the brain with remarkable consistency when injected into the mouse forebrain, suggesting that the cells might be responding to different environmental cues present in the neonatal mouse brain. These results are consistent with the fact that cells at different stages in the oligodendrocyte lineage probably possess different sets of surface molecules and receptors. Significant differences were also observed in the survival and proliferation of the lines examined, even when the lines tested had quite similar in vitro phenotypes. Interestingly, the cell line with the most mature in vitro phenotype, N20.1, appeared to elaborate membranous processes when transplanted into the brain, reminiscent of oligodendrocytes ensheathing axonal segments. The experiments suggest that these immortalized cells could be useful models to study the cellular and molecular mechanisms involved in the development, maturation and possibly formation of myelin by oligodendrocytes in the mammalian brain.

Animals↗
PubMed1994

Murine oligodendroglial cells express nerve growth factor.

The studies reported here present evidence for the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) by an oligodendroglial cell line and of NGF by oligodendrocytes in mouse primary culture. An immortalized oligodendroglial cell line (N19) expressing markers for immature oligodendrocytes stimulated PC12 cells to elaborate processes. Polymerase chain reaction analysis with degenerate primers indicated that the N19 cells expressed the mRNAs for the neurotrophic factors NGF and BDNF. Northern blot analysis confirmed that the N19 cells expressed the 1.3-kb NGF mRNA and the 1.4- and 4-kb BDNF mRNAs. In situ hybridization histochemistry identified the presence of NGF mRNAs in 9-day primary oligodendroglial cultures. Combined immunocytochemistry and in situ hybridization histochemistry colocalized NGF mRNA within primary cultured cells that immunostained for the oligodendrocyte marker galactocerebroside (GC). Double-immunofluorescence analysis also colocalized NGF protein within GC+ cells and within A2B5+ cells, a marker for oligodendrocyte progenitors. These results show that oligodendroglia and their precursor cells can express the neurotrophic factor NGF. They suggest that cells in the oligodendrocyte lineage may play an active role in neurite extension through fiber tracts in addition to myelination.

Animals↗
PubMed1994

Pharmacologic enhancement of random skin flap survival by prostaglandin E2.

This study evaluated the effect of prostaglandin E2 on skin flap survival in the porcine model. Dorsal random skin flaps on hypopigmented 15- to 25-kg pigs were used. Prostaglandin E2 (10 ng/kg per minute) was infused for 2 days prior to surgery and continued during the 7-day postoperative period. Mean flap survival was 52.58% +/- 3.62% for the control group and 68.51% +/- 3.34% for the experimental group (P < .05). A moderate correlation existed between prostaglandin E2 serum levels and flap viability. A strong correlation was noted between red blood cell flexibility and the amount of flap survival (r = .86). As red blood cell flexibility increased, the survival percentage also increased. Although prostaglandin E2 reduced adenosine diphosphate-induced platelet aggregation from a baseline of 86.08% +/- 8.33% to 54.61% +/- 17.21%, no correlation was noted between the amount of platelet aggregation and percent flap survival (r = .52).

Animals↗
PubMed1994

Long-term pretreatment with pentoxifylline increases random skin flap survival.

Optimizing survival of random skin flaps is essential to ensure successful rehabilitation of patients in whom flap reconstruction is necessary. This study tested the hypothesis that pentoxifylline improves random skin flap survival in porcine dorsal flank flaps when administered for at least 2 weeks preoperatively. Specific aims included establishing the mechanisms by which pentoxifylline enhanced survival. Treatment with pentoxifylline (25 mg/kg per day) for 14 days before surgery and for 7 days thereafter significantly increased mean flap survival to 73.2% +/- 4.5% compared with mean flap survival of 49.6% +/- 2.2% in untreated pigs. Increased flap survival was associated with a parallel increase in red blood cell flexibility. Plasma concentration of pentoxifylline ranged from 92.9 to 122.7 ng/mL but did not correlate directly with the improved flap survival. Likewise, pentoxifylline decreased platelet aggregation; there was a trend toward increased flap survival in those pigs with the least amount of aggregation. Thus, pentoxifylline improves random flap survival but only after a sufficient pretreatment period of at least 14 days.

Animals↗