Biomedical subjects

C Wu

Publications and source records attributed to C Wu.

At least 19 recordsLinked to original sources

PubMed2007

Ca2+ regulation in detrusor smooth muscle from ovine fetal bladder after in utero bladder outflow obstruction.

PURPOSE: We characterized intracellular Ca(2+) regulation in fetal bladders following outflow obstruction by examining the Ca(2+) response to agonists in smooth muscle cells. MATERIALS AND METHODS: Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery. Intracellular Ca(2+) in single smooth muscle cells isolated from the bladder wall was measured with epifluorescence microscopy using fura-2(AM) during exposure to agonists, such as carbachol and adenosine triphosphate, and to other activators, such as caffeine and KCl. RESULTS: Detrusor smooth muscle cells from obstructed bladders had resting intracellular Ca(2+) similar to that in sham operated controls. The maximal response to carbachol was decreased following obstruction (p <0.05). Construction of dose-response curves also demonstrated higher EC(50) (p <0.05). However, these changes were not mirrored by caffeine evoked Ca(2+) release, which was not significantly different between the obstruction group and sham operated controls. Kinetic analysis of carbachol transients further revealed an attenuated maximal rate of increase in obstructed bladders (p <0.01). The magnitude of intracellular Ca(2+) to purinergic neurotransmitter adenosine triphosphate was also found to be smaller in cells from obstructed bladders (p <0.05), although transmembrane influx by high K depolarization was not significantly affected. CONCLUSIONS: Muscarinic and purinergic pathways were down-regulated in fetal detrusor muscle following outflow obstruction. These major functional receptors appeared to be more susceptible to obstruction than other Ca(2+) regulators. Their impairment may contribute to the compromised contractile function seen in in utero bladder outflow obstruction.

Animals↗

PubMed2007

PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies.

Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory molecules, plays an important role in the regulations of the cellular and humoral immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies named 10E10 and 2H11 were successfully generated and further characterized. Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T lymphocytes, B lymphocytes and dendritic cells. Then, by using immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD-L1 was found in human gastric carcinoma specimens but not in normal or gastric adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1. Taken together, these results showed that the two functional mouse anti-human PD-L1 monoclonal antibodies we generated might be of great value for further exploration of the costimulatory molecule regulating network and immunointervention for tumor immunotherapy.

Animals↗

PubMed2006

Construction of a contig of BAC clones spanning the region of the apple scab avirulence gene AvrVg.

The ascomycete Venturia inaequalis, causal pathogen of apple scab, underlies a gene-for-gene relationship with its host plant apple (Malus spp.). 'Golden Delicious', one of the most common cultivated apples in the world, carries the ephemeral resistance gene Vg. Avirulence gene AvrVg, matching resistance gene Vg has recently been mapped on the V. inaequalis genome. In this paper, we present the construction of a BAC library from a V. inaequalis AvrVg isolate. The library is composed of 7680 clones, with an average insert size of 80kb. By hybridization, it has been estimated that the library contains six haploid genome equivalents. Thus the V. inaequalis genome can be predicted to be approximately 100Mb in size. A chromosome walk, starting from the marker VirQ5 co-segregating with AvrVg, has been performed using the BAC library. Twelve BAC clones were identified during four steps of the chromosome walking. The size of the resulting contig is approximately 330kb.

Ascomycota↗

PubMed2006

Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy.

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty-seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow-up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1-year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin-dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short-term safety and efficacy of this approach.

Adult↗

PubMed2006

T-type Ca2+ channels in non-vascular smooth muscles.

T-type Ca2+ current has been recorded in smooth muscle myocytes, and associated interstitial cells, isolated from the gastro-intestinal tract, urinary bladder, urethra, prostate gland, myometrium, vas deferens, lymphatic vessels and airways smooth muscle. By contrast, current through such channels has not been recorded from other tissues, such as the ureter. Whilst the properties of this Ca2+ current are similar in most of these cells, with respect to their voltage-dependence, ion selectivity and response to channel modulators, some differences have been recorded, most notably in the gastro-intestinal tract, and may demand a reappraisal of how a T-type Ca2+ current is characterised. The functions of such a current in different tissues remains uncertain. In most of smooth muscles discussed in this review, it is hypothesised that it underlies rhythmic or spontaneous electrical activity, especially in concert with other current-carrying systems, such as Ca2+-activated outward currents. Of equal interest is that the T-type Ca2+ channel may be a target for agents that modulate tissue function, especially in pathological conditions, or are the site of secondary effects of agents used in clinical medicine. For example, T-type Ca2+ channel modulators have been proposed to reduce overactive muscular activity in the gastro-intestinal or urinary tract, or function as tocolytic agents: and the action of volatile anaesthetics on them in airways smooth muscle requires consideration in their overall action.

Animals↗

PubMed2006

Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders.

Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca(2+) regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca(2+)](i) to adult cells and exhibited transient [Ca(2+)](i) increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by alpha,beta-methylene ATP; high-K-evoked [Ca(2+)](i) rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose-response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca(2+) release, P2X receptor-linked Ca(2+) entry, depolarisation-induced Ca(2+) rise via L-type Ca(2+) channels, Na(+)/Ca(2+) exchange and functional intracellular Ca(2+) stores are all operational in fetal bladder myocytes. Whilst most of Ca(2+) regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.

Adenosine Triphosphate↗

PubMed2006

Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease which was caused by a novel coronavirus (SARS-CoV). SARS has caused an outbreak in the world during 2003 and 2004, with 8098 individuals being infected and a death toll of 774 in 28 regions around the world. Specific humoral responses to viral infection remain unclear. OBJECTIVE: To analyse the antigenicity of the SARS-CoV genome and identify potential antigenic epitopes in the structural proteins. METHODS: Potential antigenic epitopes were identified in the structural proteins (nucleocapsid, membrane, spike, and small envelope proteins) and hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS-CoV. A peptide chip platform was created and the profiles of antibodies to these epitopes were investigated in 59 different SARS patients' sera obtained 6-103 days after the onset of the illness. Serial sera from five additional patients were also studied. RESULTS: Epitopes at the N-terminus of the membrane protein and the C-terminus of nucleocapsid protein elicited strong antibody responses. Epitopes on the spike protein were only moderately immunogenic but the effects were persistent. Antibodies were also detected for some putative proteins, noticeably the C-termini of SARS3a and SARS6. CONCLUSIONS: Important epitopes of the SARS-CoV genome that may serve as potential markers for the viral infection are identified. These specific antigenic sites may also be important for vaccine development against this new fatal infectious disease.

Antibodies, Viral↗

PubMed2006

The parvins.

The parvins are a family of proteins involved in linking integrins and associated proteins with intracellular pathways that regulate actin cytoskeletal dynamics and cell survival. Both alpha-parvin (PARVA) and beta-parvin (PARVB) localize to focal adhesions and function in cell adhesion, spreading, motility and survival through interactions with partners, such as integrin-linked kinase (ILK), paxillin, alpha-actinin and testicular kinase 1. A complex of PARVA with ILK and the LIM protein PINCH-1 is critical for cell survival in a variety of cells, including certain cancer cells, kidney podocytes and cardiac myocytes. While PARVA inhibits the activities of Rac1 and testicular kinase 1 and cell spreading, PARVB binds alphaPIX and alpha-actinin, and can promote cell spreading. In contrast to PARVA, PARVB inhibits ILK activity and reverses some of its oncogenic effects in cancer cells. This review focuses on the structure and function of the parvins and some possible roles in human diseases.

Actinin↗

PubMed2006

Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interference.

We compared antisense phosphorothioate oligonucleotides (PS-ODN) that target BCL-2 such as Genasense (G3139-PS), with other PS-ODN or phosphodiester-ODN (PO-ODN) in their relative capacity to induce apoptosis of chronic lymphocytic leukemia (CLL) B cells in vitro. Surprisingly, we found that thymidine-containing PS-ODN, but not PO-ODN, induced activation and apoptosis of CLL cells independent of BCL-2 antisense sequence or CpG motifs. All tested thimidine-containing PS-ODN, irrespective of their primary sequences, reduced the expression of Bcl-2 protein and increased the levels of the proapoptotic molecules p53, Bid, Bax in CLL cells. Apoptosis induced by thymidine-containing PS-ODN was preceded by cellular activation, could be blocked by the tyrosine-kinase inhibitor imatinib mesylate (Gleevec), and was dependent on ABL kinase. We conclude that thymidine-containing PS-ODN can activate CLL cells and induce apoptosis via a mechanism that is independent of BCL-2 gene interference or CpG motifs.

Amino Acid Chloromethyl Ketones↗

PubMed2006

Phagocytosis of apoptotic cells and immune regulation.

The termination of the apoptotic programme occurs in most cases via recognition and clearance by phagocytes, especially the professional phagocytes, such as macrophages and immature dendritic cells. Engulfed cells do not simply disappear from the midst of living tissues. The fine-defined presentation of yielded self-antigens to T cells is a central event in the induction or the maintenance of the peripheral immune tolerance to self. Conversely, abnormality in this pathway may contribute to the pathogenesis of systemic and organ-specific autoimmune diseases. We herein reviewed the relationship between phagocytosis of apoptotic cells and immune regulation, especially the effects of engulfed apoptotic cells on immune tolerance and autoimmune diseases.

Animals↗

PubMed2005

Phylogenetic analysis of snow sheep (Ovis nivicola) and closely related taxa.

Based on mitochondrial cytochrome b gene sequence analysis, the history of true sheep (Ovis) began approximately 3.12 million years ago (MYA). The evolution of Ovis resulted in three generally accepted genetic groups: Argaliforms, Moufloniforms, and Pachyceriforms. The Pachyceriforms of the subgenus Pachyceros comprise the thin-horn sheep Ovis nivicola (snow sheep), Ovis dalli (Dall and Stone sheep), and Ovis canadensis (Rocky Mountain and desert bighorn). North America wild sheep (O. canadensis and O. dalli) evolved separately from Eurasian wild sheep and diverged from each other about 1.41 MYA. Ancestral stock that gave rise to snow sheep, Moufloniforms, and Argaliforms occurred 2.3 MYA, which then gave rise to two different extant lines of snow sheep that diverged from each other about 1.96 MYA. The more recent nivicola line is genetically closer to the North American wild sheep and may represent a close association during the refugium when Alaska and Siberia were connected by the Bering land bridge. The earlier period of evolution of the Pachyceriforms suggests they may have first evolved in Eurasia, the oldest ancestor then giving rise to North American wild sheep, and that a canadensis-like ancestor most likely gave rise to nivicola. Cytogenetic analysis further validates that the standard diploid number for modern nivicola is 52.

Animals↗

PubMed2005

Interleukin-1alphabeta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain.

The pro-inflammatory cytokine interleukin-1 (IL-1) has been implicated in both inflammatory processes and nociceptive neurotransmission. To further investigate the role of IL-1 in different pain states, gene-disrupted mice lacking both IL-1alpha and IL-1beta genes (IL-1alphabeta (-/-)) were characterized in inflammatory, neuropathic, and post-operative pain models. IL-1alphabeta (-/-) mice showed normal sensorimotor function as measured by the rotorod assay compared to control mice (BALB/c). Acute and persistent formalin-induced nocifensive behaviors were reduced by 20% in IL-1alphabeta (-/-) mice as compared to control mice. IL-1alphabeta (-/-) mice also showed reduced inflammatory thermal and mechanical hyperalgesia compared to controls following the intraplantar administration of carrageenan or complete Freund's adjuvant (CFA). The duration of inflammatory hyperalgesia was shortened in IL-1alphabeta (-/-) mice versus controls in the CFA model. In contrast, deletion of IL-1alphabeta did not change the extent or the duration of post-operative pain developing after skin incision of the hind paw. Finally, time to onset, duration, and magnitude of mechanical allodynia were reduced in two models of neuropathic pain, spinal nerve L5-L6 ligation and chronic constriction injury of the sciatic nerve, in IL-1alphabeta (-/-) mice versus controls. These results demonstrate that IL-1alphabeta modulates both the generation and the maintenance of inflammatory and chronic neuropathic pain and that IL-1 may modulate nociceptive sensitivity to a greater extent in conditions of chronic as compared to acute pain.

Acute Disease↗

PubMed2005

A predictive approach to nutrient criteria.

Violation of a water quality standard triggers the need for a total maximum daily load (TMDL); this should result in actions that improve water quality, but sometimes at significant cost. If the standard is well-conceived, a designated-use statement characterizes societal values, and a criterion provides a measurable surrogate for designated use. This latter provision means that scientists measure the criterion and view violations of the criterion as equivalent to noncompliance with the designated use. However, if a criterion is not a good indicator of designated use, it is apt to result in misallocation of the limited resources for water quality improvement through the TMDL process. This concern provides the basis for our assessment of the national nutrient criteria strategy recently proposed by the U.S. EPA. We acquired data sets for four case studies (Lake Washington, Neuse River Estuary, San Francisco Bay, and Lake Mendota) and then used expert elicitation to quantify designated-use attainment for each case. Applying structural equation modeling, we identified good water quality criteria as the best predictors of the designated use elicited response variable. Further, we used the model to relate the level (concentration) of each criterion to the probability of compliance with the designated use; this provides decision-makers with an estimate of risk associated with the criterion level, facilitating the selection of appropriate water quality criteria.

Forecasting↗

PubMed2005

Intracellular Ca2+ regulation in a human prostate stromal cell culture.

AIMS: Prostate stromal cell cultures are used in vitro to study the cellular pathophysiology of benign prostatic hyperplasia (BPH), but their functional properties are poorly understood. This study characterized intracellular Ca2+ ([Ca2+]i) regulation in a cultured cell line in comparison to freshly isolated cells, as a background to understanding contractile regulation and cellular proliferation in this tissue. METHODS: Prostate stromal cells were isolated from either PrS6 cell cultures, with an extended life span by transfection with the SV40 T-antigen, tsA58-U19, or freshly obtained transition zone prostate samples, primary cells. [Ca2+]i was measured in vitro with the indicator Fura-2 by epifluorescence microscopy. RESULTS: Phenylephrine, high-K+, and caffeine induced Ca2+-transients in primary cells (resting [Ca2+]i 94 +/- 8 nM, n = 29; peak 193 +/- 26 nM, n = 19). In PrS6 cells resting [Ca2+]i was 96 +/- 8 nM (n = 78) and in 34 of these 78 cells, 30 microM phenylephrine increased [Ca2+]i to 296 +/- 28 nM. 5-methyl-urapidil (10-30 microM) inhibited this response in 10 of 16 cells. Spontaneous Ca2+-transients were also observed in 91% of phenylephrine-responsive cells, but in only 20% of non-responsive cells (P < 0.01). Ca2+-transients were also induced by high-K+ solution, and 20 mM caffeine. The latter abolished the response to subsequent phenylephrine application. Depletion of intracellular Ca2+ stores by caffeine or restoration from a Ca2+-free superfusate caused a substantial rise of [Ca2+]i. CONCLUSIONS: PrS6 prostate stromal cells express functional alpha1-adrenoceptors associated with spontaneous intracellular Ca2+-transients. They exhibit functional Ca2+ channels, intracellular Ca2+ stores, and Ca2+ entry induced by store depletion. Stromal cultures can therefore be used to characterize the cellular physiology of prostate stromal cell contraction and proliferation.

Adrenergic alpha-Agonists↗

PubMed2005

Estimating the mortality rate of hepatitis C using multiple data sources.

The New York State hospital discharge database and the multiple cause-of-death file were used to estimate the mortality rate of hepatitis C in New York State excluding New York City in 1997. The mortality rate with hepatitis C was severely underestimated when each data source was used alone. Applying the capture recapture method using the hospital discharge database and the multiple cause-of-death file appears to be an efficient method to estimate the mortality rate with hepatitis C.

Adult↗

PubMed2005

The phylogeny of Chinese indigenous pig breeds inferred from microsatellite markers.

A genetic study of 32 local Chinese, three foreign pig breeds [Duroc (DU), Landrace and Yorkshire], and two types of wild boar (Hainan and Dongbei wild boar) based on 34 microsatellite loci was carried out to clarify the phylogeny of Chinese indigenous pig breeds. The allele frequencies, effective numbers of alleles, and the average heterozygosity within populations were calculated. The results showed that the genetic variability of the Lingao pig was the largest, while the Jiaxing pig was the lowest. The greatest distance between domestic pigs was found between Shanggao and DU pig and the shortest was found between Wuzhishan and Lingao pig, respectively. A neighbour-joining tree constructed from Modified Cavalli-Sforza genetic distances divided Chinese pigs into two clusters; four subclusters were also identified. Our results only partly agree with the traditional types of classification and also provide a new relationship among Chinese local pig breeds. Our data also confirmed that Chinese pig breeds have a different origin from European/American breeds and can be utilized in programmes that aim to maintain Chinese indigenous pig breeds.

Alleles↗

PubMed2005

Effect of chlorine dioxide gas on fungi and mycotoxins associated with sick building syndrome.

The growth of indoor molds and their resulting products (e.g., spores and mycotoxins) can present health hazards for human beings. The efficacy of chlorine dioxide gas as a fumigation treatment for inactivating sick building syndrome-related fungi and their mycotoxins was evaluated. Filter papers (15 per organism) featuring growth of Stachybotrys chartarum, Chaetomium globosum, Penicillium chrysogenum, and Cladosporium cladosporioides were placed in gas chambers containing chlorine dioxide gas at either 500 or 1,000 ppm for 24 h. C. globosum was exposed to the gas both as colonies and as ascospores without asci and perithecia. After treatment, all organisms were tested for colony growth using an agar plating technique. Colonies of S. chartarum were also tested for toxicity using a yeast toxicity assay with a high specificity for trichothecene mycotoxins. Results showed that chlorine dioxide gas at both concentrations completely inactivated all organisms except for C. globosum colonies which were inactivated an average of 89%. More than 99% of ascospores of C. globosum were nonculturable. For all ascospore counts, mean test readings were lower than the controls (P < 0.001), indicating that some ascospores may also have been destroyed. Colonies of S. chartarum were still toxic after treatment. These data show that chlorine dioxide gas can be effective to a degree as a fumigant for the inactivation of certain fungal colonies, that the perithecia of C. globosum can play a slightly protective role for the ascospores and that S. chartarum, while affected by the fumigation treatment, still remains toxic.

Chaetomium↗

PubMed2005

Growth of Staphylococcus epidermidis in anaesthetic resuscitative drugs: implications for potential contamination.

This controlled laboratory study investigated the survival of Staphylococcus epidermidis (S. epidermidis) over a 24 hour period in four commonly drawn-up anaesthetic resuscitative drugs: suxamethonium, atropine, metaraminol and ephedrine. These drugs were prepared in typical therapeutic concentrations and then inoculated with S. epidermidis. Samples of the inoculated drug preparations were cultured on horse blood agar plates at 0, 2, 6, 12 and 24 hourly intervals and incubated for 24 hours. Colony counts were performed at the end of the incubation period. Suxamethonium, atropine and metaraminol all showed an inhibitory effect on colony counts within the first six hours. There was a more gradual decline of colony counts over a 24 hour period in the ephedrine solution. This decline was similar to that occurring in the normal saline. It is concluded that suxamethonium, atropine and metaraminol do not support the survival of the common skin contaminant, S. epidermidis over a 24 hour period.

Adjuvants, Anesthesia↗