Search PubMed⌕ Search

Biomedical subjects

M Nguyen

Publications and source records attributed to M Nguyen.

At least 91 records · Page 5Linked to original sources
PubMed1999

Infection of barley protoplasts with rice hoja blanca tenuivirus. Brief report.

A barley protoplast system has been established that supports replication of Rice hoja blanca tenuivirus (RHBV). Following polyethylene glycol-mediated RHBV inoculation of barley protoplasts, newly synthesized viral RNAs and proteins could be detected. Time course analyses revealed de novo synthesis of genome length viral RNA4, as well as subgenomic-sized RNA4 molecules of both polarities. Two proteins, N and NS4, encoded by viral complementary RNA3 and viral RNA4 respectively, were detected by Western immunoblot analysis. The barley protoplast system thus constitutes a promising tool for in vivo studies of the sequential steps involved in the multiplication cycle of RHBV.

Hordeum↗
PubMed1999

Prediction by maternal risk factors of neonatal intensive care admissions: evaluation of >59,000 women in national managed care programs.

OBJECTIVE: Managed care plans have adopted risk assessment tools as part of pregnancy disease state management strategies to assist in reducing poor pregnancy outcomes and related costs. We evaluated the relationships of maternal risk factors to determine which pregnancy risk factors were associated with neonatal intensive care unit (levels II and III) admission. STUDY DESIGN: Risk assessments were performed through perinatal telephone interviews of nurses with 59, 861 pregnant women during 1996 and 1997 calendar years as part of managed care maternity risk screening and education programs. A series of 3 interviews was conducted, at 17 weeks and 28 weeks average gestational age and at 2 weeks post partum. Univariate chi(2) analysis was performed on >50 historical and pregnancy risk factors to determine the associations with neonatal intensive care unit admission. Significant factors were included in a stepwise logistic regression model. Receiver operating curves were generated for the use of significant factors in a risk scoring system in the prediction of neonatal intensive care unit admission, and the percentages of neonatal intensive care unit days attributable to significant risk factors were calculated. RESULTS: Among the participants most women (90%) had their prenatal visit during the first trimester. The mean maternal age was 30.2 +/- 5.2 years, with 74% of women reportedly of white ethnicity, 86% married, and 44.3% primigravid. The mean gestational age at birth decreased with increasing number of fetuses from singletons to quadruplets. The chi(2) analysis identified 26 significant risk factors associated with neonatal intensive care unit admission. Of these, 14 remained significant by logistic regression. Multiple gestation, preterm premature rupture of membranes, diabetes, abruptio placentae, pregnancy-induced hypertension, and preterm labor were independently associated with at least a 3-fold risk of neonatal intensive care unit admission. A modeled risk scoring system that used these and other significant factors was poorly predictive of neonatal intensive care unit admission. However, an analysis of neonatal intensive care unit length of stay attributable to significant risk factors concluded that 19% of all neonatal intensive care unit days in this population were associated with multiple gestations. Furthermore, 85% of neonatal intensive care unit days were the result of infant lengths of stay >/=1 week. CONCLUSION: This analysis of a managed care population showed similar risk factors to those traditionally associated with neonatal intensive care unit admission. Although many of these risk factors are not preventable, identification of neonatal intensive care unit admission risks with a screening program may be of use for focusing interventions, and earlier identification of these factors may allow maximum impact of interventions. Importantly, a reduction in the incidence of higher-order multiple gestations might help to reduce neonatal intensive care unit admissions and costs.

Adult↗
PubMed1999

Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice.

Platelet activation is characterized by shape change, induction of fibrinogen receptor expression and release of granular contents, leading to aggregation and plug formation. While this response is essential for hemostasis, it is also important in the pathogenesis of a broad spectrum of diseases, including myocardial infarction, stroke and unstable angina. Adenosine 5'-diphosphate (ADP) induces platelet aggregation, but the mechanism for this has not been established, and the relative contribution of ADP in hemostasis and the development of arterial thrombosis is poorly understood. We show here that the purinoceptor P2Y1 is required for platelet shape change in response to ADP and is also a principal receptor mediating ADP-induced platelet aggregation. Activation of P2Y1 resulted in increased intracellular calcium but no alteration in cyclic adenosine monophosphate (cAMP) levels. P2Y1-deficient platelets partially aggregated at higher ADP concentrations, and the lack of P2Y1 did not alter the ability of ADP to inhibit cAMP, indicating that platelets express at least one additional ADP receptor. In vivo, the lack of P2Y1 expression increased bleeding time and protected from collagen- and ADP-induced thromboembolism. These findings support the hypothesis that the ATP receptor P2Y1 is a principal receptor mediating both physiologic and pathological ADP-induced processes in platelets.

Adenosine Diphosphate↗
PubMed1999

Substance P antagonists: the next breakthrough in treating depression?

Several lines of evidence implicate the neuropeptide substance P in depression, either in the pathogenesis or as a novel target for amelioration of symptoms. NK1 (substance P) receptor antagonists have been reported to have antidepressant-like actions in animal models. The first clinical trial of an NK1 antagonist showed promising results. A second trial, using a more potent compound, is underway. If the clinical trials show that NK1 (substance P) antagonism represents a well-tolerated, distinct mechanism for antidepressant activity, novel antidepressant agents will emerge as mono- or adjunct-therapy.

Animals↗
PubMed1999

Place code for pitch: a necessary revision.

It is widely believed that the location of the cochlear excitation maximum, which has been shown by Békésy to depend on sound frequency and move from the cochlear apex to its base as the frequency increases, is a code for subjective pitch. The pitch of a tone is known to be practically independent of sound intensity. If the location does determine the pitch, it too must remain invariant. At the 1990 meeting of the Collegium held in Basel, however, the first author reported compelling indirect evidence indicating that this may not be true. It suggested that, at least in the mid-portion of the cochlea, the most important for speech frequencies, the maximum moves toward the cochlear base as sound intensity is increased. We now have a direct verification of this inference. Recording alternating Hensen's cell potentials at two or three second-turn locations of each of several Mongolian gerbil cochleas, we observed that the maximum response produced by a single tone moved substantially toward the cochlear base as sound intensity increased. For example, an intensity increment of only 10 dB caused the maximum to move by about 0.225 mm. Since Hensen's cells are known to reflect closely the excitation pattern of the outer hair cells, similar to that of the inner hair cells, the discovery makes it impossible for the cochlear excitation maximum to be an adequate code for pitch. We observed, on the other hand, that the apical excitation cut-off did not depend on sound intensity. Every cochlear location investigated had its invariant characteristic cut-off frequency. It is possible, therefore, that the cut-off location provides the place code for pitch. These findings may have profound consequences for our understanding of auditory mechanisms as well as for the technology of cochlear implants.

Acoustic Stimulation↗
PubMed1999

Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis.

OBJECTIVE: To observe the longitudinal changes in growth, and associated Doppler measurements, of the fetal circulation in pregnancies with a normal outcome and those complicated by pre-eclampsia, birth of a small for gestational age baby, or a combination of these complications. METHODS: Two hundred and ninety-two women had serial ultrasound scans performed from the 24th week of pregnancy. Measurements obtained included: the abdominal circumference, umbilical artery pulsatility index, the middle cerebral artery pulsatility index and time-averaged velocity, and the thoracic aorta pulsatility index and time-averaged velocity. Outcome measures included the birth of a small for gestational age infant, pre-eclampsia or a combination of these complications. RESULTS: One hundred and sixty-seven pregnancies ended in the normal birth of an appropriately grown infant at term, while 105 had a complicated outcome. They were divided into three categories: preeclampsia only (i.e. with the birth of an appropriately grown fetus, n = 13); small for gestational age only with no evidence of pre-eclampsia, n = 55; and pre-eclampsia complicated by the birth of a small for gestational age infant, n = 37. The group with pre-eclampsia complicated by small for gestational age was closest in characteristics to true clinical intrauterine growth restriction. A reduction in the abdominal circumference mirrored a rise in the umbilical artery pulsatility index and preceded changes in the middle cerebral artery and thoracic aorta. The greatest degree of change in the fetal circulation was observed during the three weeks preceding delivery. Ratios of the values obtained from the fetal and umbilical circulation demonstrated the greatest deviation from normal. CONCLUSIONS: A reduction in fetal growth velocity preceded changes observed in the fetal circulation. Ratios of the fetal Doppler parameters provided the clearest evidence of deterioration in the fetal condition. The information provided may be of use in the diagnosis and management of the growth-restricted fetus.

Female↗
PubMed1999

Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures.

Restitution, the lateral migration of cells over an intact basement membrane, maintains mucosal integrity. We studied the regulation of migration and proliferation of enzyme-dispersed canine oxyntic mucosa cells in primary culture. Confluent monolayers were wounded and cultured in serum-free medium, and cells migrating into the wound were counted. [3H]thymidine incorporation into DNA was studied using subconfluent cultures. Considerable migration occurred in untreated monolayers; however, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I), two trefoil peptides, and interleukin (IL)-1beta further enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-alpha- or IL-1beta-stimulated migration, but not the response to trefoil peptide, bFGF, or IGF-I. Exogenous TGF-beta inhibited cell proliferation but did not alter migration. Immunoneutralization with anti-TGF-beta blocked the response to exogenous TGF-beta and produced a small enhancement of basal thymidine incorporation but did not attenuate basal or TGF-alpha-stimulated migration. In conclusion, endogenous EGFR ligands regulate proliferation and migration. TGF-beta inhibits mitogenesis; it did not upregulate migration in these cultures. Although bFGF, IGF-I, and IL-1beta enhance gastric epithelial migration, only IL-1beta acted in a TGF-alpha-dependent fashion.

Animals↗
PubMed1999

Identification of specific EP receptors responsible for the hemodynamic effects of PGE2.

To identify the E-prostanoid (EP) receptors that mediate the hemodynamic actions of PGE2, we studied acute vascular responses to infusions of PGE2 using lines of mice in which each of four EP receptors (EP1 through EP4) have been disrupted by gene targeting. In mixed groups of males and females, vasodepressor responses after infusions of PGE2 were significantly diminished in the EP2 -/- and EP4 -/- lines but not in the EP1 -/- or EP3 -/- lines. Because the actions of other hormonal systems that regulate blood pressure differ between sexes, we compared the roles of individual EP receptors in males and females. We found that the relative contribution of each EP-receptor subclass was strikingly different in males from that in females. In females, the EP2 and EP4 receptors, which signal by stimulating adenylate cyclase, mediate the major portion of the vasodepressor response to PGE2. In males, the EP2 receptor has a modest effect, but most of the vasodepressor effect is mediated by the phospholipase C-coupled EP1 receptor. Finally, in male mice, the EP3 receptor actively opposes the vasodepressor actions of PGE2. Thus the hemodynamic actions of PGE2 are mediated through complex interactions of several EP-receptor subtypes, and the role of individual EP receptors differs dramatically in males from that in females. These differences may contribute to sexual dimorphism of blood pressure regulation.

Animals↗
PubMed1999

The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight.

Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor-/- mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor-/- mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor-/- mice maintained normal body weight well into adult life. In addition, each of the two receptor-/- strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long-term maintenance of body weight.

Animals↗
PubMed1999

Thrombin rapidly and efficiently activates gelatinase A in human microvascular endothelial cells via a mechanism independent of active MT1 matrix metalloproteinase.

Thrombin has been shown previously to activate gelatinase A in human umbilical vein endothelial cells. The activation is thought to be mediated by membrane-type 1 matrix metalloproteinase (MT1-MMP) on the cell surface, which generates the 62-kd intermediate and the 59-kd fully active forms. We used microvascular endothelial cells derived from human neonatal foreskin to investigate the mechanism of gelatinase A activation by thrombin. Gelatinase A was measured using zymography. Whereas activation by PMA generated both the 62-kd intermediate and the 59-kd fully active forms of gelatinase A after 24 hours, activation by thrombin produced only the 59-kd species rapidly (within 2 hours). Four findings indicate that MT1-MMP was not involved in thrombin-induced activation: (1) there was no up-regulation of MT1-MMP after 2 hours stimulation by thrombin, even though there was activation of gelatinase A; (2) the 62-kd intermediate species was never detected in response to thrombin; (3) tissue inhibitor of matrix metalloproteinase-2 completely prevented gelatinase A activation induced by PMA but not by thrombin; and (4) the metalloproteinase inhibitor 1,10-phenanthroline did not inhibit thrombin-induced activation. Together, these data demonstrate that activation of gelatinase A by thrombin is different from PMA and operating via a pathway independent of MT1-MMP. The ability of thrombin to rapidly and efficiently activate gelatinase A is likely to be a major contributing factor to its potent angiogenic activity.

Cell Membrane↗
PubMed1999

Requirement for total hip arthroplasty: an outcome measure of hip osteoarthritis?

OBJECTIVE: To assess if total hip arthroplasty (THA) is a valid outcome measure of hip osteoarthritis (OA), in respect to clinical and radiological assessments. METHODS: A prospective 3 year study of patients who had painful hip OA with an initial radiographic joint space width > or =1 mm at the narrowest point. Dependent variable was THA. Patient data including body mass index, OA structural severity by radiograph, OA symptomatic severity (pain, function), and OA localization were recorded at entry. Pelvic radiographs were obtained before THA, when available, and once yearly during the study. RESULTS: During the study 106 of 506 patients underwent THA. Risk was estimated (Kaplan-Meier method) to be 8+/-1, 16+/-2, and 23+/-2% after 1, 2, and 3 years, respectively. Factors predisposing to requirement for surgery were: age > or =70 years, female sex, superolateral migration of the femoral head, joint space width <2 mm, Kellgren-Lawrence grade > or =3, pain (visual analog scale) > or =50 mm, and Lequesne index > or =10 with a relative risk of 1.65, 1.71, 1.96, 1.85, 1.89, 1.86, and 2.59, respectively. Mean change in joint space width was 0.22+/-0.50 vs 0.97+/-1.35 mm/year in patients without and with THA, respectively (p<0.0001). Changes in radiological joint space width during the first year were highly predictive of requirement for THA during the 2 following years (risk of 5, 13, 25, and 79% in patients with a radiological joint space width worsening during the first year of 0, < or =25, >25 and < or =50, and >50%, respectively). CONCLUSION: These data suggest that THA could be considered as a valid outcome measure in OA. However, further studies should be conducted in other countries with different health care systems to evaluate the inter-country reliability of this measurement.

Aged↗
PubMed1999

Arthroscopic evaluation of post-traumatic patellofemoral chondropathy.

OBJECTIVE: To evaluate clinically and arthroscopically post-traumatic patellofemoral chondropathy. METHODS: Fifty-nine patients with post-traumatic patellofemoral chondropathy were included in a cross sectional study and 46 of them completed a 6 month longitudinal study. Evaluation of the disease, performed once in the cross sectional study and twice (at entry and after 6 months) in the longitudinal study, included clinical and arthroscopic variables evaluating disease activity and severity. Arthroscopy was performed under local anesthesia in an outpatient procedure using a small arthroscope. Chondropathy was evaluated by the overall assessment of the investigator using a visual analog scale, and by the Société Française d'Arthroscopie (SFA) scoring system (SFA score: 0-100). Synovitis was assessed by the "synovitis score," which represents a composite index taking into account intensity, extent and location of synovial abnormalities. RESULTS: In the cross sectional study, severity of chondropathy correlated with age, body mass index, disease duration, functional impairment (Lequesne's index and maximum number of steps descended), patellofemoral crepitus on active motion, limitation of flexion, and presence and amount of synovitis. Knee effusion correlated with the presence of synovitis, but no correlation was found between pain or functional impairment and presence or amount of synovitis. In the longitudinal study, no statistically significant change in chondropathy was observed after 6 months followup despite a statistically significant improvement in pain, function, and knee effusion after this period. However, a statistically significant correlation was found between the progression of patellofemoral chondropathy and the presence and amount of synovitis at baseline. Synovitis was present at baseline in 10 patients. Changes in SFA scores were 1.2 +/- 1.6 and -0.1 +/- 1.0 in the groups of patients with and without synovitis, respectively (p = 0.0062). CONCLUSION: These data suggest that synovitis might have a deleterious effect on the evolution of post-traumatic patellofemoral chondropathy or might be a marker for active cartilage breakdown.

Adult↗
PubMed1999

Different patterns of angiogenesis in sarcomas and carcinomas.

Solid tumors depend on angiogenesis for growth and metastasis. It has been shown that blood vessel density, as determined by counting the number of capillaries in clustered bursts, is a significant prognostic factor in carcinomas. It is unclear, however, whether vessel density is a prognostic factor in sarcomas. In this study, we examined angiogenesis in sarcomas of various grades and compared their vascular patterns to those of carcinomas. Microvessels were identified by von Willebrand factor staining. The matrix of multiple sarcoma and breast carcinoma specimens were extracted and subjected to Western analysis of various angiogenic factors and inhibitors. Metalloproteinase inhibitor presence was also determined by in situ hybridization. In breast carcinomas, capillaries were clustered in bursts within the stroma of the tumor, whereas the sarcoma capillaries were homogeneously distributed in the tumor stroma. Random blood vessel density per high power field in sarcomas did not correlate with patient prognosis. The matrix of sarcomas and carcinomas contained both angiogenic stimulators and inhibitors. Tissue inhibitor of metalloproteinase-1 was found predominantly in fibroblasts and myofibroblasts in the matrix of carcinoma specimens. The difference in the pattern of angiogenesis in sarcomas and carcinomas may be attributable to the presence of fibroblasts and myofibroblasts in carcinomas, resulting in the compartmentalization of bursts of angiogenic factors. The homogeneous appearance of vessel density in sarcomas observed in the present study would be the consequence of the influence of a single compartment.

Angiogenesis Inhibitors↗
PubMed1998

E1A-induced processing of procaspase-8 can occur independently of FADD and is inhibited by Bcl-2.

Expression of the 243-residue form of the adenovirus E1A protein in the absence of other viral proteins triggers apoptosis by a pathway that requires p53. This pathway includes processing and activation of initiator procaspase-8, redistribution of cytochrome c, and activation of procaspase-3. Bcl-2 functions at or upstream of procaspase-8 processing to inhibit all of these events and prevent cell death. This contrasts with the anti-apoptotic influence of Bcl-2 family proteins in the cell death pathway induced by Fas ligand or tumor necrosis factor (TNF), in which Bcl-2 typically acts downstream of Fas/TNFR1-mediated activation of caspase-8. Moreover, E1A induces procaspase-8 processing and cell death in cells deleted of FADD, an adaptor protein critical for Fas/TNFR1 activation of caspase-8. The results indicate that E1A is capable of activating caspase-8 by a Bcl-2-inhibitable pathway that does not involve autocrine stimulation of FADD-dependent death receptor pathways.

Adenovirus E1A Proteins↗
PubMed1998

Modulation of the vascular smooth muscle angiotensin subtype 2 (AT2) receptor by angiotensin II.

The angiotensin subtype 2 (AT2) receptor is scarce in most adult vascular tissues except after injury. Since angiotensin II (AngII) is released upon injury, we examined the possibility that AngII governs AT2 receptor expression in smooth muscle cells (SMC). A polyclonal antiserum, raised to a peptide corresponding to the AT2 receptor C-terminus, recognized a approximately 45-kDa protein after transfection of cos-7 cells with AT2 receptor cDNA. Detection of a approximately 65-kDa band in extracts of SMC indicated that the AT2 receptor was glycosylated. Treatment of SMCs with AngII increased AT2 receptor levels fourfold over 24 h. This response was abrogated by losartan, but not by PD123319, indicating AT1 receptor involvement. AngII-dependent increases in AT2 receptor levels were also prevented by LY294002, an inhibitor of phosphatidyinositol 3-kinase, but not by rapamycin. These results indicate AngII influences AT2 receptor expression through the AT1 receptor via a signaling pathway that includes PI3K.

Angiotensin II↗
PubMed1998

Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors, SAX and TKV.

Graded activity of the DPP signaling pathway is critical for specification of dorsal embryonic cell fates in Drosophila. We present evidence that a second BMP ligand, SCW, potentiates DPP activity. Using dominant-negative forms of the type I receptors SAX and TKV, we demonstrate that SAX mediates the SCW signal, while TKV is required for both DPP and SCW activity. We find that while DPP/TKV signaling is obligatorily required, SCW/SAX activity is necessary but not sufficient for dorsal patterning. SAX and TKV act synergistically, suggesting a mechanism for integration of the SCW and DPP signals. Further, we show that the extracellular protein SOG can antagonize SCW, thus limiting its ability to augment DPP signaling in a graded manner.

Animals↗
PubMed1998

Regulated targeting of BAX to mitochondria.

The proapoptotic protein BAX contains a single predicted transmembrane domain at its COOH terminus. In unstimulated cells, BAX is located in the cytosol and in peripheral association with intracellular membranes including mitochondria, but inserts into mitochondrial membranes after a death signal. This failure to insert into mitochondrial membrane in the absence of a death signal correlates with repression of the transmembrane signal-anchor function of BAX by the NH2-terminal domain. Targeting can be instated by deleting the domain or by replacing the BAX transmembrane segment with that of BCL-2. In stimulated cells, the contribution of the NH2 terminus of BAX correlates with further exposure of this domain after membrane insertion of the protein. The peptidyl caspase inhibitor zVAD-fmk partly blocks the stimulated mitochondrial membrane insertion of BAX in vivo, which is consistent with the ability of apoptotic cell extracts to support mitochondrial targeting of BAX in vitro, dependent on activation of caspase(s). Taken together, our results suggest that regulated targeting of BAX to mitochondria in response to a death signal is mediated by discrete domains within the BAX polypeptide. The contribution of one or more caspases may reflect an initiation and/or amplification of this regulated targeting.

Amino Acid Chloromethyl Ketones↗