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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 37 records · Page 2Linked to original sources

Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats.

RATIONALE AND OBJECTIVE: Alcohol and tobacco are often co-abused in humans and previous studies found that nicotine increases alcohol consumption in rats. Here, we studied whether nicotine would reinstate alcohol-taking behavior in drug-free rats and whether this effect would be enhanced by prior exposure to nicotine during alcohol self-administration training. METHODS: Rats were trained to press a lever for alcohol (12% w/v, 1 h/day), and following stable alcohol intake groups of rats ( n=11-12) were given daily vehicle or nicotine (0.2, 0.4 or 0.8 mg/kg, SC) injections just prior to the self-administration sessions for 10 days. Rats were then given 6 days of alcohol self-administration in the absence of nicotine and an additional 5-10 drug-free days during which lever presses were not reinforced (extinction). Subsequently, rats were tested for reinstatement of alcohol seeking following exposure to priming injections of vehicle or nicotine (0.4 mg/kg, SC). RESULTS: Nicotine increased alcohol self-administration in a dose- and time-dependent manner over the 10-day period. Nicotine also reinstated alcohol seeking after extinction of the alcohol-reinforced behavior, and this effect was strongly enhanced by prior nicotine exposure. CONCLUSIONS: The present data extend previous studies on the effect of nicotine on alcohol self-administration, and further indicate that nicotine is an effective stimulus for reinstatement of alcohol seeking during drug-free periods.

Alcohol Drinking↗

The Meta-Cognitive Beliefs Questionnaire: development of a measure of obsessional beliefs.

A 67 item self-report questionnaire called the Meta-Cognitive Beliefs Questionnaire (MCBQ) was developed to assess endorsement of beliefs about the importance of control and negative consequences associated with unwanted, ego-dystonic intrusive thoughts, images and impulses. The MCBQ and a battery of questionnaires that assessed symptoms and cognitions of worry, obsessive-compulsive disorder, anxiety, and depression were administered to large samples of undergraduate students. Beliefs about control of intrusive thoughts and perceived negative consequences due to uncontrolled mental intrusions had a unique significant relationship with obsessions, and to a lesser extent, worry. These findings are consistent with current cognitive behavioral theories that suggest an important role for meta-cognitive beliefs in the pathogenesis of obsessions.

Adult↗

Anti-hyperglycemic effects of ginseng: comparison between root and berry.

Previous studies demonstrated that both ginseng root and ginseng berry possess anti-diabetic activity. However, a direct comparison between the root and the berry under the same experimental conditions has not been conducted. In the present study, we compared anti-hyperglycemic effect between Panax ginseng root and Panax ginseng berry in ob/ob mice, which exhibit profound obesity and hyperglycemia that phenotypically resemble human type-2 diabetes. We observed that ob/ob mice had high baseline glucose levels (195 mg/dl). Ginseng root extract (150 mg/kg body wt.) and ginseng berry extract (150 mg/kg body wt.) significantly decreased fasting blood glucose to 143 +/- 9.3 mg/dl and 150 +/- 9.5 mg/dl on day 5, respectively (both P < 0.01 compared with the vehicle). On day 12, although fasting blood glucose level did not continue to decrease in the root group (155 +/- 12.7 mg/dl), the berry group became normoglycemic (129 +/- 7.3 mg/dl; P < 0.01). We further evaluated glucose tolerance using the intraperitoneal glucose tolerance test. On day 0, basal hyperglycemia was exacerbated by intraperitoneal glucose load, and failed to return to baseline after 120 min. After 12 days of treatment with ginseng root extract (150 mg/kg body wt.), the area under the curve (AUC) showed some decrease (9.6%). However, after 12 days of treatment with ginseng berry extract (150 mg/kg body wt.), overall glucose exposure improved significantly, and the AUC decreased 31.0% (P < 0.01). In addition, we observed that body weight did not change significantly after ginseng root extract (150 mg/kg body wt.) treatment, but the same concentration of ginseng berry extract significantly decreased body weight (P < 0.01). These data suggest that, compared to ginseng root, ginseng berry exhibits more potent anti-hyperglycemic activity, and only ginseng berry shows marked anti-obesity effects in ob/ob mice.

Animals↗

Fenoldopam mesylate blocks reductions in renal plasma flow after radiocontrast dye infusion: a pilot trial in the prevention of contrast nephropathy.

BACKGROUND: Radiocontrast nephropathy (RCN) is a common source of acute renal failure in hospitalized patients and is associated with increased morbidity and mortality rates. Fenoldopam mesylate is a dopamine A1 receptor agonist that augments renal plasma flow (RPF) in patients with normotensive and hypertensive conditions. To determine whether fenoldopam mesylate attenuates reductions in RPF after contrast infusion, we conducted a double-blind, randomized, placebo-controlled pilot trial of fenoldopam mesylate in patients who underwent contrast angiography. METHODS: Fifty-one patients with chronic renal insufficiency (creatinine level, 2.0-5.0 mg/dL) who were undergoing contrast angiography were screened, and 45 patients were randomized to receive normal saline solution (1/2 NS) or 1/2 NS plus fenoldopam mesylate at 0.1 microg/kg/min at lease 1 hour before infusion with contrast dye. Serum creatinine level was measured at baseline and at 24, 48, and 72 hours after angiography. The primary endpoint was change in RPF 1 hour after contrast infusion. The secondary endpoint was incidence of RCN, defined as a 0.5 mg/dL or a 25% rise in serum creatinine level at 48 hours. RESULTS: RPF at 1 hour after angiography was 15.8% above baseline in the fenoldopam mesylate group compared with 33.2% below baseline in the 1/2 NS group (P <.05). The incidence rate of RCN at 48 hours was 41.0% in the 1/2 NS group versus 21% in the fenoldopam mesylate group (P =.148). Among patients with diabetes, the incidence rate of RCN tended to be higher in the 1/2 NS group compared with the fenoldopam mesylate group (64% vs 33%; P =.14). The peak serum creatinine level at 72 hours after contrast infusion was significantly higher at in the 1/2 NS group (creatinine level, 3.6 +/- 1.0 mg/dL) compared with the fenoldopam mesylate group (creatinine level, 2.8 +/- 0.35 mg/dL; P <.05). RPF was significantly (P <.0001) reduced in patients with RCN compared with patients in whom RCN did not develop. CONCLUSION: The results of this pilot trial suggest that fenoldopam mesylate is a promising prophylactic agent for RCN and that larger multicenter trials should be conducted to prove its efficacy.

Acute Kidney Injury↗

Study of adaptive mutations in Salmonella typhimurium by using a super-repressing mutant of a trans regulatory gene purR.

Salmonella typhimurium purR encodes a transcriptional repressor regulating gene expression of de novo purine nucleotide biosynthesis. It represses purD gene transcription by binding to the 16-base pair purD operator (PUR box). A S. typhimurium strain carrying a super-repressing mutant of purR, purR(s), has been used as an experimental system to study adaptive mutation. Escherichia coli lac genes were genetically engineered into S. typhimurium chromosome and repressed by purR(s) so that they could be used as an indicator of adaptive mutations in purR(s) or in the purD operator. Mutations in purR(s) or in the purD operator accumulated when the mutant strain was placed on a minimal lactose plate supplemented with 10 microg/ml of adenine during prolonged incubation. These specific mutations reverted the mutant strain from lac(-) to lac(+) phenotype. The lac(+) strains were categorized into the early- and late-arising mutants according to the time for colony appearance. Our genetic studies indicate that (i) Poisson distributed mutations accumulated in the chromosomal regulatory gene purR or the purD operator in very slowly dividing cells under selection; (ii) after about 8 days of selection, the frequency of mutations in purD operator reached the high value of about two mutations per 10(8) cells; (iii) the mutational spectrum in the purD operator during growth was not significantly different from that during selection; (iv) defects in mutL or mutS appeared to have a stronger effect on growth-dependent mutations than on adaptive mutations.

Adaptation, Physiological↗

Comparison of results of percutaneous balloon mitral commissurotomy in patients aged > or = 65 years with those in patients aged < 65 years.

Percutaneous balloon mitral commissurotomy (PBMC) is now first-line therapy in patients with symptomatic mitral stenosis (MS) and favorable valve morphology. Unfortunately, the outcome of Medicare-aged patients undergoing this procedure has not previously been defined. The results of PBMC in 55 patients > or = 65 years old (71 +/- 6 years) with moderate or severe MS were compared with 268 younger patients (47 +/- 10). Preprocedural New York Heart Association functional class and pulmonary pressures did not differ. The older patients had higher blood pressure, were more likely to be in atrial fibrillation and had higher valve scores (9.9 +/- 2.5 vs 8.6 +/- 2.2, p = 0.001). Procedural success was higher in the younger group (71% vs 55%, p = 0.013), with a greater increase in mitral valve area. Complications were similar in both groups and there were no periprocedural deaths. At 6 months a significant improvement in function class was seen in both groups. Restenosis, as assessed by serial echocardiography, occurred at a rate of 0.06 cm(2)/year in both groups, and functional class remained unchanged over 3 years. Event-free survival was similar at 48 months: 76% in the younger group and 69% in the older group. Our data thus demonstrates that PBMC can be safely performed in the Medicare-aged population. Despite less acute success in the older population, complication rates do not differ and decrement in valve area over time occurs at a similar rate. Functional class remains improved and event-free survival over 4 years appears similar in both groups. PBMC should thus be offered to patients with MS and suitable anatomy regardless of their age.

Adult↗

Efficient silicon light-emitting diodes.

Considerable effort is being expended on the development of efficient silicon light-emitting devices compatible with silicon-based integrated circuit technology. Although several approaches are being explored, all presently suffer from low emission efficiencies, with values in the 0.01-0.1% range regarded as high. Here we report a large increase in silicon light-emitting diode power conversion efficiency to values above 1% near room temperature-close to the values of representative direct bandgap emitters of a little more than a decade ago. Our devices are based on normally weak one- and two-phonon assisted sub-bandgap light-emission processes. Their design takes advantage of the reciprocity between light absorption and emission by maximizing absorption at relevant sub-bandgap wavelengths while reducing the scope for parasitic non-radiative recombination within the diode. Each feature individually is shown to improve the emission efficiency by a factor of ten, which accounts for the improvement by a factor of one hundred on the efficiency of baseline devices.

Journal Article↗

Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells.

Sensitivity to glucocorticoid (GC)-evoked apoptosis in lymphoid cell lines correlates closely with GC-mediated suppression of c-Myc expression. To establish a functional role for c-Myc in GC-mediated apoptosis, we have stably expressed MycER(TM), the human c-Myc protein fused to the modified ligand-binding domain of the murine estrogen receptor alpha, in GC-sensitive CEM-C7-14 cells. In CEM-C7-14 cells, MycER(TM) constitutively imparts c-Myc functions. Cells expressing MycER(TM) (C7-MycER(TM)) exhibited a marked reduction in cell death after 72 h in 100 nM dexamethasone (Dex), with 10-20-fold more viable cells when compared to the parental CEM-C7-14 clone. General GC responsiveness was not compromised, as evidenced by Dex-mediated suppression of endogenous c-Myc and cyclin D3, and induction of c-Jun and the glucocorticoid receptor. MycER(TM) also blunted Dex-mediated upregulation of p27(kipI) and suppression of the Myc target p53. In comparison to parental CEM-C7-14 cells, Dex-evoked DNA strand breaks were negligible and caspase activation was delayed, but the extent of G1 cell cycle arrest was similar in C7-MycER(TM) cells. Myc-ER(TM) did not result in permanent, complete resistance to GC however, and the GC-treated cells eventually died, indicative of redundant or interactive mechanisms in the GC-evoked lytic response of lymphoid cells. Our results emphasize the importance of c-Myc suppression in GC-evoked apoptosis of CEM-C7-14 cells.

Antineoplastic Agents, Hormonal↗

Indium-cadmium-oxide films having exceptional electrical conductivity and optical transparency: clues for optimizing transparent conductors.

Materials with high electrical conductivity and optical transparency are needed for future flat panel display, solar energy, and other opto-electronic technologies. In(x)Cd(1-x)O films having a simple cubic microstructure have been grown on amorphous glass substrates by a straightforward chemical vapor deposition process. The x = 0.05 film conductivity of 17,000 S/cm, carrier mobility of 70 cm2/Vs, and visible region optical transparency window considerably exceed the corresponding parameters for commercial indium-tin oxide. Ab initio electronic structure calculations reveal small conduction electron effective masses, a dramatic shift of the CdO band gap with doping, and a conduction band hybridization gap caused by extensive Cd 5s + In 5s mixing.

Journal Article↗

[The therapy of transverse tibial bone transport and vessel regeneration operation on thromboangitis obliterans].

OBJECTIVE: To treat thromboangiitis obliterans by the way of transverse tibial bone transport and vessel regeneration operation. METHODS: a longitudinal osteotomy in the middle tibial bone (120 mm long, 20 mm wide) was prepared and then a bone external fixator which was able to move bone block was fixed. 5 days after the operation, the bone block was moved 1 mm transversely each day until the bone block was moved to 22 mm. Two months after the operation, the bone external fixator was removed. RESULTS: From the beginning of the bone transprort, the symptoms of cool sensation of leg, the tingling of foot, and the intermittent claudication became better and disappeared gradually. 25 days after the operation, it was proved that the rich vessels surrounding the bone block which was moved had been formed by the angiography. Before the operation the middle and the small vessels beneath the arteriae poplitea disappeared. CONCLUSION: the result acquired from the animal experiment was as same as the result acquired from the clinica practice. Today, this method is the most effective one to treat the peripheral chronic artery obliterations.

Blood Vessels↗

Transient expression of wild-type or biologically inactive telomerase allows the formation of artificial telomeres in mortal human cells.

Telomere seeding, the formation of artificial telomeres, has been routinely successful in immortalized but not normal human cells. We compared seeding efficiencies in preimmortal and immortal SV40-transformed cells using plasmid telomeres with T(2)AG(3) tracts of 1600 and 3200 bp. Seeding occurred only in immortal cells, indicating that transformed preimmortal cells behave like normal cells vis à vis formation of new telomeres and that T-antigen inhibition of cellular checkpoints is insufficient to allow seeding. Telomerase is active in immortal but not preimmortal cells, which do not express the reverse transcriptase hTERT. Upon transient expression of hTERT, seeds with 1600 bp of T(2)AG(3) formed telomeres in preimmortal cells. Comparable seeding efficiencies were obtained with wild-type hTERT or the HA-tagged protein that is catalytically active but unable to maintain endogenous telomeres. No seeding occurred with catalytically inactive hTERT. Given that telomerase expression was transient and that longer seeds did not form telomeres in the absence of the enzyme, seeding may not be elicited merely by elongation of telomeric sequences. We propose that modification of the telomeric terminus by telomerase may contribute to telomere seeding by leading to formation of a structure that impedes rejoining of this terminus with chromosomal sequences.

Blotting, Western↗

Molecular cloning and characterization of a novel mouse epidermal differentiation gene and its promoter.

The transcription factor E2F1 is an important regulator of cell proliferation, apoptosis, and differentiation. A novel mouse gene (Eig3) was originally identified as up-regulated in E2F1-overexpressing keratinocytes by the rapid analysis of gene expression technique. An apparently full-length cDNA and a 2.8-kb genomic fragment containing the entire gene have been cloned. Sequence comparisons suggest that Eig3 is homologous to a human epidermal differentiation gene, XP5, and belongs to a family of at least 10 murine genes that are related to the small proline-rich genes involved in skin differentiation. Eig3 was expressed in adult mouse stomach and epidermis and overexpressed in keratinocytes transgenic for E2F1 or E2F4, but not in c-myc transgenics. Interestingly, Eig3 expression was highly increased in mouse skin papillomas but not in squamous carcinomas. Since there is no E2F consensus binding sequence in the promoter or first intron of Eig3, E2F regulation may be indirect.

Amino Acid Sequence↗

Mg-dependent, Zn-ATPase: enzymatic characteristics, ion specificities and tissue distribution.

Mucosal crude microsomes, prepared from proximal rat small intestine, exhibited significant Mg-dependent, Zn-ATPase activity; Vmax = 23 micromoles Pi/mg protein/hr, Km = 160 nm, and Hill Coefficient, n = 1.5. Partial purification (approximately 10-fold) was achieved by detergent extraction, and centrifugation through 250 mm sucrose: Vmax = 268 units, Km = 1 nm, and n = 6. In partially purified preparations, the assay was linear with time to 60 min, and with protein concentration to 1 microg/300 microl. Activities at pH 8 and 8.5 were higher than at pH 7.2. The ATP Km was 0.7 mm, with an optimal ATP/Mg ratio of approximately 2. Ca elicited ATPase activity but did not augment the Zn-dependent activity. In partially purified preparations, the homologous salts of Co, Cd, Cu, and Mn exhibited no detectable activity. Vanadate inhibition studies yielded two component kinetics with a Ki of 12 microm for the first component, and 96 microm for the second component, in partially purified preparations. Tissue distribution analyses revealed gradients of activity. In the proximal half of the small intestine, Mg/Zn activity increased progressively from crypt to villus tip. In long axis studies, this activity decreased progressively from proximal to distal small bowel.

Adenosine Triphosphatases↗

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗

Protective effects of selenium against mercury toxicity in cultured Atlantic spotted dolphin (Stenella plagiodon) renal cells.

Marine mammals are known for their low susceptibility to mercury toxicity, and selenium may play a role in this protection against mercury intoxication. To gain insight into mechanisms by which selenium might inhibit mercury toxicity in cetacean cells, we investigated the effects of sodium selenite on cell proliferation and cell death (including apoptosis, oncosis, and necrosis) of control and mercuric chloride-treated Atlantic spotted dolphin renal cells (Sp1K cells). Concurrent exposure to 80 microM Na2SeO3 provided full protection against the decrease in cell proliferation induced by 20 microM HgCl2. Pretreatment with Na2SeO3 increased the protective effects of selenium administered later in conjunction with mercury, but pretreatment alone did not provide protection against mercury given alone. Furthermore, Na2SeO3 administered after the exposure to HgCl2 did not protect cells. These data suggest that the coexistence of Na2SeO3 and HgCl2 was essential for the protective effects of Na2SeO3 against the toxicity of HgCl2 in Sp1K cells, and may involve selenium-mercury binding. This is supported by the results of an experiment in which earlier premixed mercury and selenium solutions were less cytotoxic than freshly mixed solutions. Furthermore, HgCl2 induced apoptosis in Sp1K cells, as revealed by nuclear specific dye (7-AAD) incorporation and cell flow cytometry, and this was prevented by the concurrent exposure to Na2SeO3. Inhibition of mercury-induced apoptosis in marine mammal cells, provided by selenium, may contribute to the in vivo protection. This study is the first report that addresses the mechanism of mercury-selenium antagonism in cultured cetacean cells at the cellular level.

Animals↗

Further evidence for a bipolar risk gene on chromosome 12q24 suggested by investigation of haplotype sharing and allelic association in patients from the Faroe Islands.

A number of studies have strongly suggested a susceptibility locus for bipolar affective disorder on chromosome 12q24. The present study investigates for a shared chromosomal segment among distantly related patients with bipolar affective disorder from the Faroe Islands, using 17 microsatellite markers covering 24 cM in the previously suggested region on chromosome 12q24. D12S342 showed possible allelic association to bipolar affective disorder (P-value using CLUMP below 0.01). Increased sharing among cases of two-marker haplotypes were suggested at D12S1614--D12S342 (P-values using CLUMP below 0.01), and D12S2075--D12S1675 (P-values using CLUMP around 0.001). The region of most interest is around 6 cM and bounded by markers D12S1614 and D12S1675 as suggested by the interesting two-marker haplotypes. This area contains the minimum interesting region between D12S342 and D12S1658 suggested by the previously reported haplotypes in the two Danish families with bipolar affective disorder.

Bipolar Disorder↗