Search PubMed⌕ Search

Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 649 records · Page 36Linked to original sources
PubMed1997

ACE inhibitors promote nitric oxide accumulation to modulate myocardial oxygen consumption.

BACKGROUND: ACE inhibitors potentiate kinin-nitric oxide (NO)-dependent coronary vascular dilation, and NO can modulate myocardial oxygen consumption. Whether ACE inhibitors also affect myocardial O2 consumption has not been established. METHODS AND RESULTS: Production of nitrite, a metabolite of NO in aqueous solution, in coronary microvessels and O2 consumption in myocardium were quantified with the use of in vitro tissue preparations, the Greiss reaction, and a Clark-type O2 electrode. In coronary microvessels, kininogen (the precursor of kinin; 10 micrograms/mL) and three ACE inhibitors (captopril, enalaprilat, or ramiprilat; 10(-8) mol/L) increased nitrite production from 76 +/- 6 to 173 +/- 15, 123 +/- 12, 125 +/- 12, and 153 +/- 12 pmol/mg, respectively (all P < .05). In myocardium, kininogen (10 micrograms/mL) and captopril, enalaprilat, or ramiprilat (10(-4) mol/L) reduced cardiac O2 consumption by 41 +/- 2%, 19 +/- 3%, 25 +/- 2%, and 35 +/- 2%, respectively. The changes in both nitrite release and O2 consumption in vitro were blocked by N omega-nitro-L-arginine methyl ester or N omega-nitro-L-arginine, inhibitors of endogenous NO formation. The effects were also blocked by HOE 140, which blocks the bradykinin B2-kinin receptor, and serine protease inhibitors, which inhibit local kinin formation. CONCLUSIONS: Our data indicate that stimulation of local kinin formation by use of a precursor for kinin formation or inhibition of kinin degradation by use of ACE inhibitors increases NO formation and is important in the control of cardiac O2 consumption. Vasodilation and control of myocardial O2 consumption by NO may contribute importantly to the therapeutic actions of ACE inhibitors in cardiac disease states.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effectiveness of extreme discordant sib pairs to detect oligogenic disease loci.

A method for the genomic screening of quantitative traits using extreme discordant sib pairs (EDSPs) has recently been described by Risch and Zhang [1995; 1996]. For many models relevant to common, genetically complex diseases, EDSPs are the most powerful siblings for detecting linkage. Thus, if such siblings can be identified and collected, powerful studies with reasonable genotyping budgets can be conducted. Using a subset of the GAW10 data, we have simulated a genomic screen using EDSPs. From the 4,780 total families in the first 20 replicates of 239 families, there were 100, 104, 155, 107, and 180 EDSP families for Q1, Q2, Q3, Q4, and Q5, respectively. EDSP data were analyzed for each trait using a modified version of MAPMAKER/SIBS capable of handling extreme discordant sib pairs. Four regions, one for Q1, one for Q2, and two for Q4, were able to exceed a threshold for linkage corresponding to a 0.001 pointwise significance level. In three cases, maximum lod score (MLS) peaks occurred within 3.8 cM of a major gene. In the fourth case, the MLS peak occurred 28.4 cM from a major gene. Omission of parents and an alternative definition of EDSP were also investigated.

Chromosome Mapping↗
PubMed1997

Absolute configurational assignment of self-organizing asymmetric tripodal ligand-metal complexes.

The solution configuration of labile coordination complexes may be difficult to determine, even in cases in which the solid state structure is known. We have previously synthesized a series of chiral ligands which form pseudo-C3-symmetric complexes with ZnII and CuII salts that possess an available electrophilic coordination site. Molecular modeling of ZnII complexes of the chiral ligand N,N-bis[(2-quinolyl)methyl]-1-(2-pyridyl)ethanamine (alpha-MeBQPA) showed that the spatial arrangement of the heterocyclic arms is controlled by a substituent on one methylene arm, resulting in the adoption of an enantiomeric conformation displaying a propeller-like asymmetry. In this paper we report the application of the exciton chirality method to the determination of the conformation of asymmetric metal-ligand complexes in solution. There is a good correlation between the predicted and the observed Cotton effects, demonstrating that the geometry in solution closely resembles that predicted by computational simulations and those obtained by X-ray crystallographic studies of metal complexes with racemic and enantiomerically pure ligands. The X-ray crystallographic structure of the first optically pure complex in this series is reported.

Circular Dichroism↗
PubMed1997

The complete mitochondrial DNA sequence of the white rhinoceros, Ceratotherium simum, and comparison with the mtDNA sequence of the Indian rhinoceros, Rhinoceros unicornis.

The complete nucleotide sequence of the mitochondrial genome of the white rhinoceros, Ceratotherium simum, was determined. The length of the reported sequence is 16,832 nucleotides. This length can vary, however, due to pronounced heteroplasmy caused by differing numbers of a repetitive motif (5'-CG-CATATACA-3') in the control region. The 16,832 nucleotide sequence presented here is the longest version of the molecule and contains 35 copies of this motif. Comparison between the complete mitochondrial sequences of the white and the Indian (Rhinoceros unicornis) rhinoceroses allowed an estimate of the date of the basal evolutionary divergence among extant rhinoceroses. The calculation suggested that this divergence took place approximately 27 million years before present.

Animals↗
PubMed1997

Autodirected insertion: preinserted VDAC channels greatly shorten the delay to the insertion of new channels.

VDAC, a mitochondrial outer membrane channel, has the ability to catalyze and direct the insertion of other VDAC channels into planar phospholipid membranes. The spontaneous rate of insertion of detergent-solubilized VDAC channels into phospholipid membranes is estimated to be 1.5 x 10(-5) channels min-1 micron-2. VDAC channels already in the membrane can increase this rate by a factor of 10(9). The presence of 5 M urea on the opposite side of the membrane increases this 10-fold to 4.5 x 10(5) channels min-1 microns-2. Similar but weaker effects are observed with Triton X100 addition (10(-3)% (v/v)). These agents are not acting on uninserted channels because they do not affect the delay from sample addition to first insertion. Under the chosen conditions, this delay is long (240 s) without preinserted channels. However, the presence of a few VDAC channels in the membrane reduces this delay to 14 s, close to the diffusion limit. Therefore, urea and Triton, added to the side of the membrane opposite that to which the VDAC sample was added, likely increase the flexibility of the VDAC channels in the membrane, allowing them to be more efficient catalysts for VDAC insertion. There are obvious implications for membrane protein insertion and targeting.

Cell Membrane↗
PubMed1997

Studies on the precursors of strong mutagen [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone]MX by chlorination of fractions from different waters.

The strong mutagen, [3-chloro-4-(dichloromethyl)-5-hydroxy- 2(5H)-furanone] MX, was found to be one of the most potent mutagens in drinking water. In this study, dissolved organic matters from river water and lake water were separated into several compound classes by sorbtion on a series of resin absorbents. After chlorine treatment of the fractions, MX was determined with GC/MS in the selected ion monitoring mode. Humic substances produced more MX on a TOC-basis than other fractions and contributed more to MX formation in the chlorinated natural waters. Some phenols were detected in the oxidation products of humic substances and therefore formation of MX may occur when some phenolic precursor structures in humic substances are treated with chlorine.

Absorption↗
PubMed1997

Cross-sensitization between phencyclidine and (-) but not (+) pentazocine.

Repeated administration of psychomotor stimulants such as amphetamine and cocaine, and psychotomimetics such as phencyclidine, produce progressively enhanced behavioral effects, a phenomenon known as behavioral sensitization. Little is known about the effects of repeated treatment with sigma ligands on locomotor activity. The present research determined the psychomotor stimulant effects of the sigma ligand (+)pentazocine and its enantiomer; and investigated whether reciprocal cross-sensitization occurs between them and PCP-induced locomotor activity and ambulation. Adult female Sprague-Dawley rats were used. Total locomotor activity and ambulation were assessed with an automated photoelectric system. Acute (+) or (-)pentazocine given IP produced slight but insignificant locomotor stimulant effects. Repeated administration of (+)pentazocine failed to produce behavioral sensitization. However, four repeated injections of (-)pentazocine or PCP produced behavioral sensitization. (-)Pentazocine sensitized rats showed cross-sensitization to PCP-induced locomotion and ambulation. Furthermore, PCP sensitized rats showed cross-sensitization to (-)pentazocine-induced locomotion and ambulation. These findings suggest that (+) and (-)pentazocine act at different receptor sites. (-)Pentazocine is more similar to PCP in producing locomotor stimulant effects.

Animals↗
PubMed1997

NMDA receptor antagonist MK-801 selectively impairs learning of the contiguity of the conditioned stimulus and unconditioned stimulus in goldfish.

Previous experiments have shown that administration of intracranial MK-801 blocks learning of classical fear conditioning in goldfish. The impairment of learning was decreased when fish received limited pretraining, suggesting that only the early phase of conditioning may be sensitive to disruption by MK-801. The present studies investigated the possibility that classical conditioning in goldfish consists of two successive phases and that only the initial phase depends critically on N-methyl-D-aspartate receptor function. A series of experiments showed that the anterograde amnestic effect of MK-801 is decreased or eliminated when fish received pretraining consisting of 6 or 12 conditioning trials, respectively. MK-801-sensitive learning is inferred to be completed within 12 trials. The neural mechanism of the learning which occurs during the later trials is manifestly insensitive of MK-801. Furthermore, MK-801 impaired learning when fish received pretraining consisting of six pseudoconditioning trials. The results indicate that MK-801-sensitive learning is associative or depends on the contiguity of the conditioned stimulus (CS) and unconditioned stimulus (US) and that MK-801 selectively impairs learning of the CS-US contiguity.

Animals↗
PubMed1997

nNOS and Ca2+ influx in rat pancreatic acinar and submandibular salivary gland cells.

Regulation of agonist-activated Ca2+ influx by the NOS pathway through generation of cGMP is being found in an increasing number of cell types. In the present work, we examined the role of the NOS pathway in agonist-evoked [Ca2+]i oscillations and attempted to identify the NOS isoform most likely to regulate Ca2+ influx. For this, we first show that two Ca(2+)-mobilizing agonists acting on pancreatic acinar cells, bombesin (BS) and the cholecystokinin analog CCK-JMV-180 (CCKJ), evokes different type of [Ca2+]i oscillations. The BS-evoked [Ca2+]i oscillations rapidly became acutely dependent on the presence of extracellular Ca2+, whereas the CCKJ-evoked oscillations continue for long periods of time in the absence of Ca2+ influx. This differential behavior allowed us to isolate Ca2+ influx and study its regulation while controlling for non specific effects on all other Ca2+ transporting events involved in generating [Ca2+]i oscillations. Inhibitors of selective steps in the NOS pathway inhibited agonist-induced cGMP production. The inhibitors were then used to show that scavenging NO with reduced hemoglobin, inhibition of guanylyl cyclase with 1H-[1,2,4] oxadiazolo[4,3-a] quinoxaline-1-one (ODQ) and inhibition of protein kinase G with Rp-8-pCPT-cGMPS inhibited [Ca2+]i oscillations evoked by BS but not those evoked by CCKJ. These findings were extended to duct and acinar cells of the SMG. In these cells, Ca(2+)-mobilizing agonists stimulate large Ca2+ influx, which was inhibited by all inhibitors of the NOS pathway. Western blot analysis and immunolocalization revealed that the cells did not express iNOS, eNOS was expressed only in blood vessels and capillaries whereas nNOS was expressed at high levels next to the plasma membrane of all cells. Accordingly, the nNOS inhibitor 7-nitroindazole (7-NI) inhibited BS- but not CCKJ-evoked [Ca2+]i oscillations and Ca2+ influx into SMG acinar and duct cells. Thus, together, our findings favor nNOS as the isoform activated by the Ca2+ released from internal stores to generate cGMP and regulate Ca2+ influx.

Animals↗
PubMed1997

Differential sensitivities to hyperbaric oxygen of lymphocyte subpopulations of normal and autoimmune mice.

We studied the effect of exposure to hyperbaric oxygen (HBO): 2.8 atm absolute 100% oxygen for 4 h daily over 3-7 days, on the immune system of normal (BALB/c and MRL- +/+) and autoimmune MRL-lpr/lpr) mice. In HBO exposed BALB/c mice, we observed a remarkable decrease in the cell population of the spleen and thymus. We found that the sensitivity to HBO varied among subpopulations of lymphocytes. For example, CD4+ CD8+ double positive cells in the thymus and B220+ B cells in the spleen were more sensitive than CD4+ or CD8+ single positive T cells in the thymus, and Thy-1+ T cells in the spleen, respectively. Accordingly, despite the decrease in total cell number in the spleen, the proliferative response of T cells from the spleen to Con A was not impaired in the HBO exposed mice. Exposure of MRL-lpr/lpr mice to HBO caused a marked reduction of weight and cell population of the otherwise enlarged spleen and lymph nodes, and amongst others of percentages of B220+Thy-1+ double positive abnormal cells. These results suggest the HBO therapy may be applicable for the treatment of some autoimmune diseases.

Animals↗
PubMed1997

A simple and efficient method for purification of prawn baculovirus DNA.

A new method for isolation of prawn baculovirus and subsequent extraction of viral DNA was developed. No density gradient centrifugation, ultracentrifugation or phenol-chloroform extraction steps were involved. Phenylmethylsulfonyl fluoride (PMSF) was used to prevent proteinase degradation, DNase and RNase were used to degrade prawn DNA and RNA respectively. The nucleocapsid was a bacilliform virion, about 58 62 nm in width and 300-350 nm in length as observed by transmission electron microscopy. Intact viral DNA was obtained by lysing nucleocapsids with guanidine hydrochloride and degrading protein with proteinase K. As the viral DNA was digested with restriction endonuclease and separated by electrophoresis, restriction fragments were clearly shown on the agarose gel. The size of the DNA was estimated approximately to be 290 kb. The virus which appeared to be a prawn baculovirus was named prawn white spot baculovirus (PWSBV) due to the white spots which appeared on the inside surface of the crust of infected prawns.

Animals↗
PubMed1997

Environmental and occupational determinants of blood pressure in rural communities in China.

PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community-based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self-reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population.

Adolescent↗
PubMed1997

Linking genes and environmental exposure: why China presents special opportunities.

The Human Genome Project will have an enormous impact on our ability to study and understand human disease by providing maps of human genes. However, many of the most prevalent human diseases result from the complex interaction of numerous genes. Even with the use of a catalogue of human genes, the task of analyzing complex genetic and environmental interactions involved in the common human disorders will be formidable. Due to its demographic specificities and large size, the Chinese population offers a unique resource for the study of human genetics and the ability to capitalize upon the recent revolution in biotechnology. Reasons that China provides an exceptional population for genetic studies of complex diseases include: (i) the resource of 1.3 billion people makes obtaining a large number of subjects with rare (and common) diseases possible; (ii) relative genetic homogeneity in many regions has been preserved; (iii) stratification is distinct; (iv) urban/rural and geographic contrasts, both in environmental factors and disease occurrence, are quite marked; (v) family members tend to stay congregated; and (vi) epidemiologic study is cost-beneficial.

China↗