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M Bui

Publications and source records attributed to M Bui.

At least 19 recordsLinked to original sources
PubMed2001

Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia.

The hereditary spastic paraplegias (HSPs; Strümpell-Lorrain syndrome, MIM number 18260) are a diverse class of disorders characterized by insidiously progressive lower-extremity spastic weakness (reviewed in refs. 1-3). Eight autosomal dominant HSP (ADHSP) loci have been identified, the most frequent of which is that linked to the SPG4 locus on chromosome 2p22 (found in approximately 42%), followed by that linked to the SPG3A locus on chromosome 14q11-q21 (in approximately 9%). Only SPG4 has been identified as a causative gene in ADHSP. Its protein (spastin) is predicted to participate in the assembly or function of nuclear protein complexes. Here we report the identification of mutations in a newly identified GTPase gene, SPG3A, in ADHSP affected individuals.

Amino Acid Sequence↗
PubMed2000

Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins.

The protein kinase inhibitor H7 blocks influenza virus replication, inhibits production of the matrix protein (M1), and leads to a retention of the viral ribonucleoproteins (vRNPs) in the nucleus at late times of infection (K. Martin and A. Helenius, Cell 67:117-130, 1991). We show here that production of assembled vRNPs occurs normally in H7-treated cells, and we have used H7 as a biochemical tool to trap vRNPs in the nucleus. When H7 was removed from the cells, vRNP export was specifically induced in a CHO cell line stably expressing recombinant M1. Similarly, fusion of cells expressing recombinant M1 from a Semliki Forest virus vector allowed nuclear export of vRNPs. However, export was not rescued when H7 was present in the cells, implying an additional role for phosphorylation in this process. The viral NS2 protein was undetectable in these systems. We conclude that influenza virus M1 is required to induce vRNP nuclear export but that cellular phosphorylation is an additional factor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study.

Hypercholesterolemia, a significant cardiovascular risk factor, is prevalent in the American population. Many drugs lower circulating cholesterol levels, but they are not infrequently associated with severe side effects. Accordingly, natural means to lower cholesterol levels safely would be welcomed. We examined 40 hypercholesterolemic subjects (total cholesterol 210-300 mg/dL) in a randomized, double-blind, placebo-controlled study. The four groups of ten subjects received either placebo bid, chromium polynicotinate (Cr) 200 microg bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and GSE at the same dosage bid. Over two months, the average percent change +/- SEM in the total cholesterol from baseline among groups was: placebo -3.5% +/- 4, GSE -2.5% +/- 2, Cr -10% +/- 5, and combination -16.5% +/- 3. The decrease in the last group was significantly different from placebo (p < 0.01). The major decrease in cholesterol concentration was in the LDL levels: placebo -3.0% +/- 4, GSE -1.0% +/- 2.0, Cr -14% +/- 4.0, and the combination -20% +/- 6.0. Again, the combination of Cr and GSE significantly decreased LDL when compared to placebo (p<0.01). HDL levels essentially did not change among the groups. Also, there was no significant difference in the triglyceride concentrations among the groups; and no statistically significant differences were seen in the levels of autoantibodies to oxidized LDL (Ox-LDL). However, the trend was for the two groups receiving GSE to have greater decreases in the latter parameter, i.e., -30.7% and -44.0% in the GSE and combined groups in contrast to -17.3% and -10.4% in the placebo and chromium groups. We determined the number of subjects in each group who decreased autoantibodies to oxidized LDL greater than 50% over eight weeks and found these ratios among groups: placebo = 2/9, Cr = 1/10, GSE = 6/10, and combined = 3/8. Thus, 50% of subjects (9/18) receiving GSE had a greater than 50% decrease in autoantibodies compared to 16% (3/19) in the two groups not receiving GSE. No significant changes occurred in the levels of circulating homocysteine and blood pressure among the four groups. We conclude that a combination of Cr and GSE can decrease total cholesterol and LDL levels significantly. Furthermore, there was a trend to decrease the circulating autoantibodies to oxidized LDL in the two groups receiving GSE.

Analysis of Variance↗
PubMed1999

An ecological study of determinants of coronary heart disease rates: a comparison of Czech, Bavarian and Israeli men.

BACKGROUND: The large differences in cardiovascular disease rates between Eastern and Western Europe have largely developed over the last few decades, and are only partly explained by classical risk factors. This study was set up to identify other potential determinants of these differences. METHODS: This was an ecological study comparing random samples of men aged 45-64 years selected from three cities representing populations with different rates of cardiovascular mortality: Pardubice (Czech Republic), Augsburg (Bavaria, Germany), and Jerusalem (Israel). In total, 191 (response rate 70%), 153 (70%) and 162 (62%) men, respectively, participated. All centres followed the same study protocol. Lifestyle, anthropometry and biochemical risk factors were assessed by identical questionnaires, standardized medical examination, and central analyses of fasting blood samples. RESULTS: The mortality rates in the study populations, as well as the prevalence of coronary heart disease in study samples, were highest in Czech, intermediate in Bavarian and low in Israeli men. This pattern was replicated across the three samples by mean blood pressure (P < 0.001), cigarette smoking (not significant), triglycerides (P < 0.05), fibrinogen or D-dimer levels (P < 0.05). On the other hand, the prevalence of diabetes and obesity were similar; total and high density lipoprotein (HDL)-cholesterol, apolipoprotein B, lipoprotein (Lp(a)) and glucose did not differ between Czech and Bavarian men; and Czechs had particularly low levels of serum insulin and factor VIIc. Israelis had low fasting glucose and total cholesterol, as well as HDL-cholesterol levels and a high Lp(a) (each P < 0.001) compared with the two other samples. Striking differences were found for plasma homocysteine (10.5 in Czechs versus 8.9 mumol/l in Bavarians, P < 0.001) and for alpha-carotene (geometric mean in Czechs 16, Bavarians 21 and Israelis 30 micrograms/l), beta-carotene (60, 110 and 102 micrograms/l), and lycopene (84, 177 and 223 micrograms/l), respectively; all P-values < 0.001). Adjustment for obesity or smoking did not change these estimates. There were no differences in the levels of tocopherol and retinol. CONCLUSIONS: Czech men had high levels of blood pressure, triglycerides, fibrinogen and D-dimer but many other traditional risk factors, as well as indicators of metabolic disorders and vitamins A and E, did not differ between the study samples. The low levels of carotenoids and high concentrations of homocysteine in Czech men seem to reflect their low dietary intakes of fruit and vegetables. The results provide indirect support for the importance of dietary factors in the East-West morbidity and mortality divide.

Aged↗
PubMed1998

Differences between plasma and adipose tissue biomarkers of carotenoids and tocopherols.

Biomarkers of dietary exposure or nutritional status are sought actively to overcome limitations of traditional dietary methodology. We compared plasma and adipose tissue biomarkers for carotenoids and tocopherols. The data consisted of samples from 91 men and 122 women, ages 45-70 years, from the control group of the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC) Study. Pearson correlations between plasma and adipose tissue measurements for beta-carotene, lycopene, and alpha-tocopherol adjusted for smoking status displayed low, although significant, correlations of 0.39, 0.24, and 0.39, respectively. The correlation was further stratified by sex. After being corrected for measurement error using deattenuation factors obtained from a reproducibility study, the stratified correlation coefficients were as high as 0.80 for beta-carotene in men, 0.62 for lycopene in women, and 0.52 for alpha-tocopherol in women. In addition, plasma and adipose tissue measurements from the myocardial infarction (MI) subset of the EURAMIC study population were used to evaluate the odds of MI, adjusting for confounders. We found that the concentration of lycopene in plasma was not positively associated significantly with MI (odds ratio, 1.78; P = 0.26). Adipose tissue lycopene, in contrast to reports elsewhere on the total population, showed an inverse association with MI (odds ratio, 0.62; P = 0.15). These results suggest that plasma and adipose carotenoids represent different markers for nutritional status and cannot be used interchangeably in epidemiological and dietary validation studies.

Adipose Tissue↗
PubMed1996

Membrane association of influenza virus matrix protein does not require specific hydrophobic domains or the viral glycoproteins.

The matrix protein of influenza virus is a major structural component of the virion which is generally believed to bridge between the membrane envelope and the ribonucleocapsid core. To investigate the interaction of M1 with cellular membranes in the absence of other influenza proteins, we examined its distribution by subcellular fractionation after expression in HeLa cells. Approximately 81 to 88% of M1 protein, expressed without other viral proteins, was soluble, whereas the remaining 12 to 19% was tightly associated with membranes. Conditions known to release peripherally associated membrane proteins did not detach M1 proteins from isolated membranes, suggesting that the fraction of M1 bound to membranes behaves as an integral protein. Coexpression of M1 with hemagglutinin or neuraminidase did not alter the extent of membrane association of M1 protein, indicating that there is no strong interaction between M1 and the cytoplasmic tails of the viral glycoproteins. Additional attempts were made to identify membrane binding domains in M1 protein. Mutants constructed with mutations in the four hydrophobic regions thought to be responsible for membrane association still exhibited the same levels of membrane association as that observed with wild-type matrix protein. Therefore, specific hydrophobic domains are apparently not required for membrane binding.

Animals↗
PubMed1996

Modulation of Ca2+ and Na+ transport by taurine in heart and vascular smooth muscle.

Using the whole-cell voltage clamp technique, taurine was found to affect different types of various ionic currents including T and L-type Ca2+ currents, slow Na+ and fast Na+ currents as well as the delayed outward K+ current. Also, in normal situations, taurine had no effect on the Na(+)-Ca2+ exchange current. The effect of taurine on the different types of ionic currents appears to depend on [Ca2+]o and [Ca2+]i and may also vary according to the tissue or cell type studied. Using standard Ca2+ imaging techniques, short-term exposure (10 to 20 min) of single heart cells and aortic vascular smooth muscle cells was found to increase total intracellular free Ca2+ in a dose-dependent manner. However, using 3-dimensional Ca2+ and Na+ imaging techniques, long-term exposure of heart and vascular smooth muscle cells to taurine was found to decrease both nuclear and cytosolic Ca2+ without significantly changing either nuclear or cytosolic Na+ levels. Long-term exposure to taurine was found to prevent cytosolic and nuclear increases of Ca2+ induced by permanent depolarization of heart cells with high [K+]o. This preventive effect of taurine on nuclear Ca2+ overload was associated with an increase of both cytosolic and nuclear free Na+. Thus, the effect of long-term exposure to taurine on intranuclear Ca2+ overload in heart cells seems to be mediated via stimulation of sarcolemma and nuclear Ca2+ outflow through the Na(+)-Ca2+ exchanger.

Animals↗
PubMed1996

Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins.

Influenza virus enters its host cell by receptor-mediated endocytosis followed by acid-activated membrane fusion in endosomes. The viral ribonucleoprotein particles (vRNPs) delivered into the cytosol then dissociate from the matrix protein, M1, and from each other, after which they are individually imported into the nucleus via the nuclear pores. For some time, it has been believed that the low pH in endosomes may, in some way, trigger the capsid disassembly events necessary for nuclear transport. This report provides direct evidence that the association of M1 with vRNPs is sensitive to mildly acidic pH within the infected cell. Recombinant M1, expressed in cultured cells, was found to associate with vRNPs and inhibit their nuclear import. Brief acidification of the cytosolic compartment eliminated the interfering activity and allowed the incoming vRNPs to enter the nucleus. Newly assembled progeny M1-vRNP complexes in the cytosol of infected cells were also dissociated by brief acidification. Acidic pH was thus found to serve as a switch that allowed M1 to carry out its multiple functions in the uncoating, nuclear transport, and assembly of vRNPs.

Animals↗
PubMed1996

Nuclear trafficking of influenza virus ribonuleoproteins in heterokaryons.

The influenza virus nucleoprotein (NP), matrix protein (M1), and ribonucleoproteins (vRNPs) undergo regulated nuclear import and export during infection. Their trafficking was analyzed by using interspecies heterokaryons containing nuclei from infected and uninfected cells. Under normal conditions, it was demonstrated that the vRNPs which were assembled in the nucleus and transported to the cytosol were prevented from reimport into the nucleus. To be import competent, they must first assemble into virions and enter by the endosomal entry pathway. In influenza virus mutant ts51, in which M1 is defective, direct reimport took place but was inhibited by heterologous expression of wild-type M1. These data confirm M1's role as the inhibitor of premature nuclear import and as the main regulator of nuclear transport of vRNPs. In addition to this vRNP shuttling, M1 also shuttled between the nucleus and the cytoplasm in ts51-infected cells. When NP was expressed in the absence of virus infection, it was also found to be a shuttling protein.

Animals↗
PubMed1996

Modulation of cardiac cell Ca2+ currents by PAF.

Using the whole-cell voltage clamp technique, PAF was found to stimulate T- and L-type Ca2+ currents in a dose dependent manner in both human and chick ventricular single cells. However, PAF had no effect on either the fast sodium current or the delayed outward K+ current in these heart cells. The effect of PAF on both Ca2+ currents was blocked by the PAF receptor antagonist WEB2170. Treatment of single ventricular cells with Pertussis toxin (PTX) prevented stimulation of T- and L-type calcium currents by PAF. These results suggest that there are functional PAF receptors in both human and chick ventricular cells. The stimulation of both types of Ca2+ currents seems to be mediated via a PTX sensitive G-protein.

Animals↗
PubMed1995

ET-1 stimulates Ca2+ currents in cardiac cells.

Using the whole-cell voltage-clamp technique, endothelin (ET-1) was found to stimulate T- and L-type Ca2+ currents in a dose-dependent manner in both human and chick ventricular single cells. However, ET-1 had no effect on both the fast sodium current and the delayed outward K+ current in these cells. The effect of ET-1 on both Ca2+ currents was blocked by the ET(A) receptor antagonist BQ123. Treatment of single ventricular cells with pertussis toxin (PTX) prevented stimulation of T- and L-type calcium currents by ET-1. These results suggest that there are functional ET(A) receptors in both human and chick ventricular cells. The stimulation of both types of Ca2+ currents appears to be mediated by a PTX-sensitive G-protein.

Animals↗
PubMed1991

Forearm blood flow response to posture change in the very old: non-invasive measurement by venous occlusion plethysmography.

Little is known about the peripheral vascular response to posture change in very elderly people who are vulnerable to the development of orthostatic hypotension. This is due, in part, to the risks of currently utilized invasive vascular monitoring techniques in the elderly population. We studied the forearm vascular response to active standing in 18 healthy young, 10 healthy old, and 19 impaired elderly subjects, using the non-invasive technique of venous occlusion plethysmography. In six subjects this technique was compared to duplex doppler ultrasonography for the measurement of postural changes in forearm blood flow. Forearm blood flow changes determined by venous occlusion plethysmography were 11% larger than doppler measurements, but the two methods strongly correlated (r = 0.90, P less than .001). Mean forearm vascular resistance increased to a significantly greater extent at 1 minute of standing in young subjects than in both groups of old, although the response was quite variable in all groups. Two healthy elderly (20%) and eight impaired elderly (40%) subjects had unexpected forearm vasodilatation at 1 minute of standing. By 3 minutes, forearm vascular resistance had increased by similar amounts in all three groups of subjects. Five impaired elderly and no healthy young or healthy old subjects had orthostatic hypotension, defined as greater than or equal to 10 mm Hg decline in mean arterial blood pressure at 1 or 3 minutes of standing. Forearm vascular resistance changes did not correlate with blood pressure response to standing. Thus, forearm vascular response to 1 minute of active standing is attenuated in many elderly subjects. This abnormality may impair adaptation to orthostatic stress in advanced age.

Adult↗
PubMed1985

[Not Available].

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Academies and Institutes↗
PubMed1975

[Not Available].

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History, Ancient↗
PubMedDate not supplied

Stem cell genes in androgen-independent prostate cancer.

Despite recent advances in the detection and treatment of early stage prostate cancer, there remains little effective therapy for patients with locally advanced and/or metastatic disease. Although the majority of patients with advanced disease respond initially to androgen ablation therapy, most go on to develop androgen-independent tumors that are inevitably fatal. Therefore, understanding the mechanisms by which a hormone-sensitive tumor escapes hormonal control is critical to the development of effective therapeutic modalities. The study of the differentiation pathways of normal and abnormal prostate growth has led to the development of a stem cell model for prostate cancer [1-3]. Recent work discussed in this commentary suggests that prostate tumors resist apoptosis and proliferate by adopting features of normal prostatic stem/progenitor cells. Basal cells, the putative stem/progenitor cells of the prostate, possess the phenotype of androgen-independence as do most advanced prostate cancers. Therefore, the study of basal cells may prove critical to understanding prostate carcinogenesis and to the development of novel strategies for preventing and managing prostate cancer.

Androgens↗