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Biomedical subjects

G Wu

Publications and source records attributed to G Wu.

At least 37 records · Page 2Linked to original sources

Effect of lifestyle exposures on sperm aneuploidy.

Lifestyle exposures including cigarette smoke, alcohol, and caffeine have all been studied in relationship to male reproductive health. Over the years the focus has primarily been on semen quality and/or fertility. More recently, literature evaluating direct adverse effects of lifestyle exposures on sperm chromosomes and chromatin has grown due to concern that induced damage could be transmitted to offspring causing transgenerational health effects. In this paper we present a new analysis that summarizes published studies of smoking effects on sperm chromosome number and demonstrates a statistically significant increase in sperm disomy among smokers compared to nonsmokers (P < 0.001). In addition, new data on the effect of alcohol intake on sperm chromosome number are presented showing a rate ratio of 1.38 (95% CI 1.2, 1.6) for XY frequency in sperm of alcohol drinkers compared to nondrinkers.

Aneuploidy↗

Changes in weight and composition in various tissues of pregnant gilts and their nutritional implications.

The objectives of this study were to characterize the quantitative changes in various body tissues of high-lean type gilts during gestation and to determine the protein needs of pregnant gilts based on changes in tissue contents. Thirty-five gilts (158.2 +/- 8.3 kg) were housed in individual gestation crates with six unbred gilts randomly selected and slaughtered to provide data for d 0 of gestation. The remaining gilts were bred and assigned randomly to one of six slaughter groups: d 45, 60, 75, 90, 102, and 112. Gilts were fed 2 kg (as-fed basis) of gestation diet daily (3.1 Mcal/kg of ME and 0.56% lysine). Carcass soft tissue, bone, gastrointestinal tract, spleen, pancreas, kidney, liver, uterus, fetus, mammary gland, and the remaining viscera were separated and weighed. Carcass soft tissue, liver, remaining viscera, uterus, and gastrointestinal tract were ground, freeze-dried, and analyzed for composition. Body weights of the gilts increased quadratically (P < 0.001) during gestation. Weights of carcass soft tissue and uterus, including placenta, increased linearly (P < 0.001) during gestation. Weights of individual fetuses, fetal litters, individual mammary glands, and the entire mammary glands increased cubically (P < 0.001) during gestation. Crude protein in carcass soft tissue increased cubically (P < 0.01), whereas DM and ether extract (EE) in carcass soft tissue increased linearly (P < 0.01). The DM, CP, and EE in the entire mammary glands increased quadratically (P < 0.001) during gestation. The DM, CP, and EE in fetal litter increased cubically (P < 0.01) as gestation progressed. The accretion rates of the conceptus, fetal litter, individual fetus, individual mammary gland, and CP in fetal litter differed (P < 0.05) before and after d 70 of gestation. The CP daily gain from all maternal and fetal tissues was 40 and 103 g/d before and after d 70 of gestation, respectively, suggesting that pregnant gilts may require different quantities of dietary protein during gestation. Based on the maintenance requirement, maternal tissue gain, and conceptus gain, pregnant gilts require 6.8 and 15.3 g/d of true ileal-digestible lysine (or 147 and 330 g/d of true ileal-digestible protein) before and after d 70 of gestation, respectively, to support their true biological needs.

Animal Feed↗

BMS-201620: a selective beta 3 agonist.

A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.

Adrenergic beta-3 Receptor Agonists↗

Ventral brainstem enterogenous cyst: an unusual location.

Enterogenous cysts mostly locate in the spinal canal and have only rarely been reported in an intracranial site. We report a case of enterogenous cyst in the ventral to brainstem. The 45-year-old woman presented with paroxysmal headache and diplopia. A CT scan and MRI revealed a cystic clival mass from midbrain to medulla. Subtotal resection was performed using a sub-temporal approach and the patient made a good recovery. Pathological examination revealed that the lesion was a typical enterogenous cyst.

Brain Diseases↗

Inhomogeneous electronic structure probed by spin-echo experiments in the electron doped high-Tc superconductor Pr1.85Ce0.15CuO4-y.

63Cu nuclear magnetic resonance spin-echo decay rate (T-12) measurements are reported for the normal and superconducting states of a single crystal of Pr(1.85)Ce(0.15)CuO(4-y) in a magnetic field B(0)=9 T over the temperature range 2<T<200 K. The spin-echo decay rate is temperature dependent for T<55 K and has a substantial dependence on the radio frequency (rf) pulse parameters below T approximately 25 K. This dependence indicates that T-12 is strongly effected by a local magnetic field distribution that can be modified by the rf pulses, including ones that are not at the nuclear Larmor frequency. The low-temperature results are consistent with the formation of a static inhomogeneous electronic structure that couples to the rf fields of the pulses.

Journal Article↗

GNB3 gene C825T and ACE gene I/D polymorphisms in essential hypertension in a Kazakh genetic isolate.

The Kazakh inhabitants living in Barkol pasture of northeast China belong to a genetic isolate characterized by ethnically homogeneous and a communal pastoral lifestyle. To investigate whether the polymorphisms in the G-protein beta-3 subunit (GNB3) gene and angiotensin-converting enzyme (ACE) gene are associated with essential hypertension (EH), we carried out a case-control study of 290 hypertensive subjects and 244 normotensive (NT) controls randomly selected from Kazakh populations of Barkol. A previous medical history of diabetes and hypertension, and body mass index (BMI) was recorded. Plasma glucose, triglyceride, and cholesterol were measured. The insertion/deletion (I/D) polymorphism of the ACE gene and the C825T polymorphism of the GNB3 gene were determined by the polymerase chain reaction (PCR) technique. The distributions of genotypes and alleles for the two polymorphisms did not differ significantly between the case and control populations, and odds ratio of EH related to the ACE gene D allele and GNB3 gene T allele was not significantly different from 1.0. Logistic regression analysis shows the variation at the GNB3 and ACE did not have any statistically significant synergistic effect on blood pressure (BP). Stratification of NT and untreated hypertensives according to I/D polymorphism of ACE gene and C825T polymorphism of GNB3 gene disclosed no significant difference across genotypes with respect to BMI, glucose, triglyceride, cholesterol, systolic and diastolic BP. In conclusion, the polymorphisms in the GNB3 gene and ACE gene, solely or combined, did not confer a significantly increased risk for the development of EH in the Kazakh isolate of northeast China.

Adult↗

Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population.

Two polymorphisms, apolipoprotein A5 (APOA5) -1131T>C and apolipoprotein C3 (APOC3) -482C>T, were examined in a healthy Chinese group. Analysis of covariance (ancova) showed that both -1131T>C and -482C>T minor alleles were associated with triglyceride (TG)-raising effects (p < 0.001 and p = 0.012, respectively) after adjustment of sex, age, and body mass index (BMI). Moreover, -1131T>C minor alleles were also found to be associated with total cholesterol (TC)-raising effects (p = 0.045). However, the relationship between -482C>T minor alleles and TC-raising effects was not observed after adjustment of sex, age, and BMI. By contrast, significant inverse associations were noted between minor alleles (-1131T>C and -482C>T) and high-density lipoprotein cholesterol (HDL-C) concentrations (p = 0.021 and p = 0.021, respectively). Linear regression analysis showed that the effects of -1131T>C and -482C>T polymorphisms on TG and HDL-C (0.001 and 0.008; 0.041 and 0.005, respectively) are independent and additive and that -1131T>C can seriously affect the levels of TG (0.001 vs 0.008). The additive effect of the two polymorphisms was confirmed further by haplotype analysis. Our results strongly support that the two single nucleotide polymorphisms, -1131T>C in APOA5 and -482C>T in APOC3, are related to the levels of serum TG and HDL-C and those of other several lipids and lipoproteins in the Chinese population.

Apolipoprotein A-V↗

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.

Primary erythermalgia is a rare autosomal dominant disease characterised by intermittent burning pain with redness and heat in the extremities. A previous study established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q, but the causative gene was not identified. We performed linkage analysis in a Chinese family with primary erythermalgia, and screened the mutations in the two candidate genes, SCN9A and GCA, in the family and a sporadic patient. Linkage analysis yielded a maximum lod score of 2.11 for both markers D2S2370 and D2S2330. Based on critical recombination events in two patients in the family, we further limited the genetic region to 5.98 cM between D2S2370 and D2S2345. We then identified two missense mutations in SCN9A in the family (T2573A) and the sporadic patient (T2543C). Our data suggest that mutations in SCN9A cause primary erythermalgia. SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation.

Base Sequence↗

N-Acetylglucosamine- an osmotic slute for peritoneal dialysis without inducing hyperinsulinemia.

METHODS: N-Acetylglucosamine (NAG) was compared to glucose as an osmotic solute during peritoneal dialysis in rats. The effect of the tested solutes on blood glucose and insulin levels during dialysis was evaluated. RESULTS: During 6-hour exchange with NAG (220 mmol/l) solution, the dialysate volume was higher than in rats dialyzed with fluid containing glucose (220 mmol/l; GLU: 34.5 +/- 1.7 vs. 32.8 +/- 1.1 ml, respectively; p < 0.05). The peritoneal permeability to protein (D/S x 1,000) was lower in the NAG group (9.7 +/- 2.5 vs. 16.3 +/- 5.6 in GLU; p < 0.02). Dialysis with GLU-based solution resulted in hyperglycemia up to 180 +/- 39 mg/dl; in the NAG group the increase in the blood glucose level was moderate (up to 91 +/- 9 mg/dl; p < 0.001). Dialysis with GLU fluid caused an increase in blood insulin level by 53.2 +/- 62.4 pmol/l, whereas the insulin blood concentration in NAG-treated animals was increased by 5.0 +/- 5.4 pmol/l (p < 0.001). CONCLUSIONS: NAG is more effective than GLU osmotic solute during peritoneal dialysis and it reduces peritoneal permeability to protein. Dialysis with NAG results in lower hyperglycemia and hyperinsulinemia, both effects are favorable in diabetic peritoneal dialysis patients.

Acetylglucosamine↗

Growth and compositional changes of fetal tissues in pigs.

Three hundred twenty fetuses were obtained from 33 pregnant gilts (Camborough-22, Pig Improvement Co.) to determine rates of nutrient deposition in fetal tissues and to estimate nutrient requirements for fetal growth. Pregnant gilts were fed an equal amount of a gestation diet (2.0 kg/d; as-fed basis), and were slaughtered at d 0, 45, 60, 75, 90, 102, or 110 of gestation (n = 3 to 6 per day). Fetuses were dissected into carcass and individual tissues (including gastrointestinal tract, liver, lung, heart, kidney, spleen [> or = d 75]), and partial placental collection was made for chemical analysis. Fetal tissues were weighed and analyzed for DM, ash, CP, and crude fat. Regression equations were obtained to explain the weight and compositional changes of individual tissues during gestation. Weights of the fetus, carcass, gastrointestinal tract, liver, heart, lung, and kidney increased cubically (P < 0.001), whereas brain weight increased linearly (P < 0.001) as gestation progressed. Fetal protein and fat contents increased quadratically (P < 0.001) as gestation progressed (R2 = 0.906 and 0.904, respectively). Changes in fetal protein and fat contents fit a multiphasic regression that consisted of two linear equations (P < 0.001, R2 = 0.988 and P < 0.001, R2 = 0.983, respectively), indicating that protein and fat growth accelerated after d 69 of gestation. Fetal protein and fat accretions were 0.25 and 0.06 g/d (P < 0.001) before d 69 of gestation, and increased to 4.63 and 1.09 g/d (P < 0.001) after d 69 of gestation. Protein needs for tissue protein gains increased 19-fold after d 69 of gestation. Results of this study indicate that the growth of the fetus and fetal tissues occurs at different rates during gestation and support the practice of a two-phase feeding strategy (before and after approximately d 70 of gestation) for pregnant gilts.

Animal Feed↗

Genomic characterization of Rim2/Hipa elements reveals a CACTA-like transposon superfamily with unique features in the rice genome.

The availability of huge amounts of rice genome sequence now permits large-scale analysis of the structure and molecular characteristics of the previously identified transposase-encoding Rim2 (also called Hipa) element, which is transcriptionally activated by infection with the fungal pathogen Magnaporthe grisea and by treatment with the corresponding fungal elicitor. Based on genomic cloning and data mining from 230 Mb of rice genome sequence, 347 Rim2 elements, with an average size of 5.8 kb, were identified. This indicates that an estimated total of 600-700 Rim2 elements are present in the whole genome. Rim2 insertions occur non-randomly on the chromosomes, as visualized by fluorescence in situ hybridization. The elements harbor 16-bp terminal inverted repeats with the core sequence CACTG, 16-bp sub-terminal repeats, internal variable regions, 3-bp target sequence duplications in the flanking regions, and genes coding for Rim2 proteins (the putative transposase) and hydroxyproline-rich glycoproteins. High levels of insertion into genic regions are observed for members of this family, and the transposition history of the family can be deduced from the high level of shared sequences and analysis of repeat target sites of the elements. Phylogenetic analysis indicates that the putative RIM2 proteins fall into a subgroup distinct from the TNP2-like subgroup of transposases. Southern hybridization with genomic DNA from monocotyledonous and dicotyledonous plants demonstrates that the RIM2-coding sequence is unique to the Oryza genome. Our results demonstrate that the Rim2 elements from rice belong to a distinct superfamily of CACTA-like elements with evolutionary diversity.

Amino Acid Sequence↗

Chromosomal abnormalities in Day-6, in vitro-produced pig embryos.

A cytogenetic study was undertaken to quantify, by chromosomal karyotyping, the incidence and type of chromosomal abnormalities present in Day-6 in vitro-produced (IVP) porcine embryos. Morphologically normal Day-6 blastocysts (n=318) were fixed and grouped into six classes according to the number of total cells (from < or =20 to 61-70). Of 248 embryos suitable for analysis, 97 (39.1%) displayed chromosomal abnormalities. The abnormalities included haploidy (9.3%), polyploidy (71.1%) and mixoploidy (19.6%). Within polyploid embryos, triploidy and tetraploidy showed the highest incidence (56.5 and 27.5%, respectively); among mixoploid embryos, diploid-triploid embryos (2n/3n) were prevalent (36.8%). Overall, the mean cell number was 34.3 +/- 12.1 and the mitotic index was 8.6 +/- 6.1. Chromosomally abnormal embryos had fewer (P<0.01) total cells compared to normal (2n) embryos (31.8 +/- 1.3 versus 35.9 +/- 1.0). In addition, the incidence of polyploidy decreased as the number of cells increased, while that of mixoploidy did not differ. These data indicate that polyploidy affects a large percentage of IVP porcine embryos capable of developing to blastocysts and the incidence of chromosomal abnormalities is much higher than that reported previously in in vivo embryos in this species. Given the ability of morphologically normal embryos with an abnormal chromosome complement to undergo preimplantation development in vitro, and the inability to identify blastocysts with abnormal karyotype without cytogenetic analysis, careful consideration should be given to factors affecting ploidy of IVP embryos, especially the incidence of polyspermic fertilization, when evaluating criteria of a porcine in vitro embryo production scheme.

Animals↗

Enhanced intracellular availability and survival of hammerhead ribozymes increases target ablation in a cellular model of osteogenesis imperfecta.

Antisense hammerhead ribozymes have the capability to cleave complementary RNA in a sequence-dependent manner. In osteogenesis imperfecta, a genetic disorder of connective tissue, mutant collagen type I has been shown to participate in but not sustain formation of the triple helix. Selective ablation of mutant collagen gene transcript could potentially remove the mutant gene product and reverse the dominant-negative effect exerted by the abnormal protein. In earlier studies we showed that the hammerhead ribozyme Col1A1Rz547 selectively cleaved a mutant Col1A1 gene transcript in a murine calvarial osteoblast cell line. In order to test the possible therapeutic efficacy of this approach, a dramatic downregulation of the mutant transcript must be achieved, a function directly related to high steady-state level of intracellular ribozyme. We report significantly enhanced expression of Col1A1Rz547 by vaccinia T7 polymerase following infection with an attenuated T7-pol vaccinia virus as shown both by the intracellular level of the ribozyme and the cleavage of the mutant Col1A1 gene transcript. We also describe the engineering of a multimeric ribozyme construct comprising eight subunits, which can self-cleave to monomers. These studies suggest the potential use of multimeric ribozymes expressed by a vaccinia-based system in the therapy of a variety of disorders.

Animals↗

Effect of iron sucrose on human peritoneal mesothelial cells.

BACKGROUND: Iron supplementation is often required in uraemic patients with anaemia. Peritoneal cavity was proposed as an alternative intravenous route for iron infusion in patients treated with peritoneal dialysis. We studied the effect of iron sucrose (Venofer) on the function of human peritoneal mesothelial cells maintained in in vitro culture. MATERIALS AND METHODS: In in vitro experiments on human peritoneal, the mesothelial effect of elemental iron (in conc. 0.0001-1 mg mL-1) present in Venofer on their viability, growth and synthesis of IL-6 was studied. Additionally we evaluated with a fluorescent probe (2',7'-dichlorodihydro-fluorescein diacatate) generation of reactive oxygen species in cells exposed to iron sucrose. We also measured accumulation of iron in the cytoplasm of mesothelial cells after their in vitro exposure to Venofer. RESULTS: In in vitro conditions iron induces a dose-dependent inhibition of viability of the mesothelial cells as reflected by inhibition of the cells growth by 34% at Fe 0.1 mg mL-1 vs. control (P < 0.05) increased release of lactate dehydrogenase (LDH) from the cytosol: 67.1 +/- 30.3 mU mL-1 at Fe 1 mg mL-1 vs. 7.9 +/- 6.4 in control group (P < 0.001), and reduced synthesis of IL-6: 209 +/- 378 pg mg-1 cell protein at Fe 1 mg mL-1 vs. 38674 +/- 4146 pg mg-1 cell protein in controls (P < 0.001). Cytotoxicity of iron towards mesothelial cells was enhanced in vitro when it was tested in presence of the dialysis fluid. Iron used in vitro at concentration 0.0001 mg mL-1 and greater induces generation of oxygen-derived free radicals in mesothelial cells. Furthermore, iron is taken by these cells and stored in their cytosol, resulting in stimulation of the intracellular generation of free radicals. CONCLUSIONS: We conclude that iron used in the form of iron sucrose is cytotoxic to human peritoneal mesothelial cells. Accumulation of iron sucrose within cytoplasm of these cells may lead to induction of its chronic cytotoxic effect.

Cell Division↗

Transient third nerve palsy in a young patient with intracranial arteriovenous malformation.

PURPOSE: To describe a patient with transient third nerve palsy as the possible presenting sign of intracranial arteriovenous malformation. METHOD: Case report. RESULT: A 24-year-old female presented to ophthalmic casualty with sudden onset binocular diplopia and was diagnosed to have right sided partial third nerve palsy. Within 30 hours the third nerve palsy had recovered completely. A MRI scan and subsequent carotid angiogram revealed a large, high flow, trans-cortical Spetzler-Martin grade 4 arteriovenous malformation. The feeder vessel of the AVM originated from the right middle cerebral artery. Superficial venous drainage was via the superficial middle cerebral vein to the right transverse sinus. The deep venous drainage was via thalamostriate veins into markedly dilated internal cerebral vein and vein of Galen (Great cerebral vein). Venous reflux was noted around the midbrain from the vein of Galen. CONCLUSIONS: Transient third nerve palsy may rarely occur secondary to intracranial arteriovenous malformation. Ophthalmologists should consider neuroimaging in the investigations for transient cases of III nerve palsy in young patients.

Adult↗