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Biomedical subjects

C Wei

Publications and source records attributed to C Wei.

At least 19 recordsLinked to original sources
PubMed2007

COX-2 involvement in breast cancer metastasis to bone.

Cyclooxygenase-2 (COX-2) is expressed in 40% of human invasive breast cancers. Bone is the predominant site of metastasis in case of breast cancer. We investigated the role of COX-2 in a suitable mouse model of breast cancer metastasis to bone using the whole-body luciferase imaging of cancer cells. We provide several lines of evidence that COX-2 produced in breast cancer cells is important for bone metastasis in this model including (1) COX-2 transfection enhanced the bone metastasis of MDA-435S cells and (2) breast cancer cells isolated and cultured from the bone metastases produced significantly more prostaglandin E(2) (an important mediator of COX-2) than the parental injected cell populations of breast cancer cells. Next, we found that a COX-2 inhibitor, MF-tricyclic, inhibited bone metastasis caused by a bone-seeking clone both in prevention regimen (in which case mice started receiving MF-tricyclic 1 week before the injection of cancer cells) and in treatment regimen (in which case mice received MF-tricyclic after the development of bone metastasis). These studies indicate that COX-2 produced in breast cancer cells may be vital to the development of osteolytic bone metastases in patients with breast cancer, and that COX-2 inhibitors may be useful in halting this process.

Animals↗
PubMed2006

ENDO-GIA staplers for side-to-side anastomosis of veins.

OBJECTIVE: To study the application of ENDO-GIA staplers for the side-to-side anastomosis of veins. MATERIALS AND METHODS: An animal study was conducted. Five dogs received side-to-side anastomosis of allograft IVC by ENDO-GIA staplers (Group 1). In addition, five received the same operation with right renal vein reimplantation to allograft IVC (Group 2). Five dogs, receiving the same operation as in Group 1 using polypropylene sutures (control group, Group 3). An autopsy was performed if the dogs survived more than 8 weeks. RESULTS: The IVC anastomosis remained patent in four subjects (80%) for Group 1, in five subjects (100%) for Group 2 and in four subjects (80%) for Group 3. CONCLUSIONS: From the results of our experiment, ENDO-GIA staplers can be considered for use in the side-to-side anastomosis of large veins such as piggyback cavacaval side-to-side anastomosis in cadaveric orthotopic liver transplantation (OLT) or side-to-side splenorenal shunt in portal hypertension.

Anastomosis, Surgical↗
PubMed2006

Essential role of Ca2+ release channels in angiotensin II-induced Ca2+ oscillations and mesangial cell contraction.

The increased resistance of the glomerulus as a result of contractile dysfunction of mesangial cells (MCs) is associated with reduction of glomerular filtration rate and development of glomerulosclerosis. Evidences show MCs contraction changes with intracellular Ca(2+) concentration ([Ca(2+)](i)). Here, we explore the mechanism of angiotensin II (AngII)-induced Ca(2+) oscillations and MCs contraction. Primary MCs from 3-month-old and 28-month-old rats were used for detection of Ca(2+) oscillations and MC planar area with confocal microscopy. AngII could induce typical Ca(2+) oscillations and contraction of MCs. This process was abolished by thapsigargin, 2-aminoethoxydiphenyl borate, or 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine, and partially inhibited by ryanodine, but could not be inhibited in the absence of extracellular Ca(2+). Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate (InsP(3)) receptors displayed a strong colocalization, which may contribute to the amplification of Ca(2+) response. MLC(20) phosphorylation and MC planar area were associated with AngII-induced Ca(2+) oscillations. The frequency of Ca(2+) oscillations was dependent on the AngII concentration and correlated with the MCs' contractive extent, which could be attenuated by KN-93. The amplitude reduction of oscillations correlated with the decrease in aging-related contraction. In conclusion, [Ca(2+)](i) response of MCs to AngII is characterized by repetitive spikes through the following repetitive cycles: Ca(2+) release by phospholipase C -InsP(3) pathway, Ca(2+) amplification by Ca(2+)-activated RyRs and Ca(2+) reuptake by the endoplasmic reticulum. MCs contraction can be modulated by oscillations not only in an AngII-induced frequency-dependent mode but also in an aging-related, amplitude-dependent mode.

Angiotensin II↗
PubMed2004

Influence of light fleck and low light on foliar injury and physiological responses of two hybrid poplar clones to ozone.

Five-month old hybrid poplar clones NE388 and NE359 were exposed to square-wave 30, 55, and 80 ppb O(3) (8 h/day, 7 day/week) under constant high light (HL) and light fleck (LF) during 28 May-29 June 1999, and exposed to 30 and 55 ppb O(3) under HL, LF, and constant low light (LL) during 22 May-28 June 2000 within Continuously Stirred Tank Reactors (CSTR) in a greenhouse. Ramets of these two hybrid clones received similar total photosynthetically active radiation (PAR) within the LF and LL treatments. Visible foliar symptoms, leaf gas exchange, and growth were measured. More severe O(3) induced foliar symptoms were observed on ramets within the LF and LL treatments than within the HL treatment for both clones. The LF treatment resulted in significantly greater foliar injury than the LL treatment for NE388. The LF and LL treatments generally resulted in lower photosynthetic rates (Pn) for both clones, but did not affect stomatal conductance (g(wv)); therefore, the ratios of g(wv)/Pn and the O(3) uptake/Pn were greatest in plants grown under the LF treatment, followed by those grown under LL treatment; plants grown under HL had the lowest ratios of g(wv)/Pn and O(3) uptake/Pn. Greater ratios of g(wv)/Pn and O(3) uptake/Pn were consistently associated with more severe visible foliar symptoms. The negative impacts of the LF treatment on growth were greater than those of the LL treatment. Results indicate that not only the integral, but also the pattern of photo flux density, may affect carbon gain in plants. Increased foliar injury may be expected under light fleck conditions due to the limited repair capacity as a result of continuity of O(3) uptake while photosynthesis decreases under LL conditions.

Adaptation, Physiological↗
PubMed2004

Responses of hybrid poplar clones and red maple seedlings to ambient O(3) under differing light within a mixed hardwood forest.

The responses of ramets of hybrid poplar (Populus spp.) (HP) clones NE388 and NE359, and seedlings of red maple (Acer rubrum, L.) to ambient ozone (O(3)) were studied during May-September of 2000 and 2001 under natural forest conditions and differing natural sunlight exposures (sun, partial shade and full shade). Ambient O(3) concentrations at the study site reached hourly peaks of 109 and 98 ppb in 2000 and 2001, respectively. Monthly 12-h average O(3) concentrations ranged from 32.3 to 52.9 ppb. Weekly 12-h average photosynthetically active radiation (PAR) within the sun, partial shade and full shade plots ranged from 200 to 750, 50 to 180, and 25 to 75 micromol m(-2) s(-1), respectively. Ambient O(3) exposure induced visible foliar symptoms on HP NE388 and NE359 in both growing seasons, with more severe injury observed on NE388 than on NE359. Slight foliar symptoms were observed on red maple seedlings during the 2001 growing season. Percentage of total leaf area affected (%LAA) was positively correlated with cumulative O(3) exposures. More severe foliar injury was observed on plants grown within the full shade and partial shade plots than those observed on plants grown within the sun plot. Lower light availability within the partial shade and full shade plots significantly decreased net photosynthetic rate (Pn) and stomatal conductance (g(wv)). The reductions in Pn were greater than reductions in g(wv), which resulted in greater O(3) uptake per unit Pn in plants grown within the partial shade and full shade plots. Greater O(3) uptake per unit Pn was consistently associated with more severe visible foliar injury in all species and/or clones regardless of differences in shade tolerance. These studies suggest that plant physiological responses to O(3) exposure are likely complicated due to multiple factors under natural forest conditions.

Acer↗
PubMed2004

Genotype-phenotype correlations in Peutz-Jeghers syndrome.

BACKGROUND AND AIMS: Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder often caused by mutations in STK11. Time to onset of symptoms was characterised for a large collection of individuals with PJS who had been tested for STK11 mutations and genotype-phenotype correlations were evaluated. METHODS: We characterised mutations in 42 independent probands and also used a historical cohort design to study 51 individuals with Peutz-Jeghers syndrome who had completed self-administered questionnaires. RESULTS: Mutations were detected in 22/32 (69%) probands with PJS and 0/10 probands referred to rule out PJS. Real-time PCR analysis to quantitate DNA failed to detect any large deletions in PJS participants without STK11 mutations. The median time to onset for gastrointestinal symptoms or polypectomy was 13 years of age but showed a wide variability. Gastric polyps were frequent in PJS participants, with a median age at onset of 16 years. Individuals with missense mutations had a significantly later time to onset of first polypectomy (p = 0.04) and of other symptoms compared with those participants either with truncating mutations or no detectable mutation. CONCLUSION: STK11 mutation analysis should be restricted to individuals who meet PJS criteria or their close relatives. Direct sequencing of STK11 yields a high rate of point mutations in individuals who meet phenotypic PJS criteria. Individuals with missense mutations of STK11 typically had a later time to onset for PJS symptoms. The common occurrence of gastric polyps may facilitate chemopreventive studies for this disorder.

AMP-Activated Protein Kinase Kinases↗
PubMed2003

The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics.

The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

Animals↗
PubMed2003

Protecting the terminus: t-loops and telomere end-binding proteins.

Telomeric DNA is composed of a region of duplex telomeric tract followed by a single-strand overhang on the 3' G-rich strand. The DNA is packaged by proteins that associate directly with the single- and double-strand regions of the telomeric tract and by their associated proteins. This review discusses the evidence that G-strand overhangs are present on both ends of eukaryotic chromosomes and the steps needed to generate these overhangs. The overhangs are protected by specialized G-overhang-binding protein and/or invasion by the overhang of the duplex region of the telomeric tract to form a structure called a 't-loop'. The G-overhang-binding proteins identified from different species are described, and their properties compared. The data supporting the existence of t-loops at native telomeres is discussed, and the conditions required to promote their in vitro formation are presented.

Animals↗
PubMed2002

Genetic transformation of two species of orchid by biolistic bombardment.

We report here the transformation of two species of orchid, Dendrobium phalaenopsis and D. nobile,by biolistic bombardment. Calli or protocorm-like bodies (PLBs) were used as target explants. Gold particles (1.0 microm) coated with plasmid DNA (pCAMBIA1301) encoding an intron-containing beta-glucuronidase gene (gus-int) and a hygromycin phosphotransferase (hpt) gene were introduced into the PLBs or calli using the Bio-Rad PDS-1000/He Biolistic Particle Delivery System. Calli and PLBs were then chopped up and pre-cultured in 1/2-strength MS medium supplemented with 0.4 M mannitol for a 1-h osmoticum treatment before bombardment. Immediately after bombardment, the calli and PLBs were transferred to 1/2-strength MS medium without mannitol for recovery. Putatively transformed plantlets were obtained by selection and regeneration on medium supplemented with 30 mg/l hygromycin. The highest efficiency of transformation was obtained when selection was conducted at 2 days post-bombardment. For D. phalaenopsis and D. nobile, respectively, about 12% and 2% of the bombarded calli or PLBs produced independent transgenic plants. Integration and expression of the transgenes were confirmed by Southern hybridization and Northern hybridization. No nontransformed plants were regenerated, indicating a tight selection scheme. However, separate incorporation of the gus gene and the hpt gene was observed, and in one transgenic line the gus gene was integrated into the genome of the transgenic plant, but not expressed.

Biolistics↗
PubMed2001

Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1.

Dysregulation of imprinted genes on human chromosome 11p15 has been implicated in Beckwith-Wiedemann syndrome (BWS), an overgrowth syndrome associated with congenital malformations and tumor predisposition. The molecular basis of BWS is complex and heterogeneous. The syndrome is associated with alterations in two distinct imprinting domains on 11p15: a telomeric domain containing the H19 and IGF2 genes and a centromeric domain including the KCNQ1OT1 and CDKNIC genes. It has been postulated that disorders of imprinting in the telomeric domain are associated with overgrowth and cancer predisposition, whereas those in the centromeric domain involve malformations but not tumor development. In this study of 125 BWS cases, we confirm the association of tumors with constitutional defects in the 11p15 telomeric domain; six of 21 BWS cases with uniparental disomy (UPD) of 11p15 developed tumors and one of three of the rare BWS subtype with hypermethylation of the H19 gene developed tumors. Most importantly, we find that five of 32 individuals with BWS and imprinting defects in the centromeric domain developed embryonal tumors. Furthermore, the type of tumors observed in BWS cases with telomeric defects are different from those seen in BWS cases with defects limited to the centromeric domain. Whereas Wilms' tumor was the most frequent tumor seen in BWS cases with UPD for 11p15 or H19 hypermethylation, none of the embryonal tumors with imprinting defects at KCNQ1OT1 was a Wilms' tumor. This suggests that distinct tumor predisposition profiles result from dysregulation of the telomeric domain versus the centromeric domain and that these imprinting defects activate distinct genetic pathways for embryonal tumorigenesis.

Beckwith-Wiedemann Syndrome↗
PubMed2001

Nuclear antisense effects of neutral, anionic and cationic oligonucleotide analogs.

The antisense activity of oligomers with 2'-O-methyl (2'-O-Me) phosphorothioate, 2'-O-methoxyethyl (2'-O-MOE) phosphorothioate, morpholino and peptide nucleic acid (PNA) backbones was investigated using a splicing assay in which the modified oligonucleotides blocked aberrant and restored correct splicing of modified enhanced green fluorescent protein (EGFP) precursor to mRNA (pre-mRNA), generating properly translated EGFP. In this approach, antisense activity of each oligomer was directly proportional to up-regulation of the EGFP reporter. This provided a positive, quantitative readout for sequence-specific antisense effects of the oligomers in the nuclei of individual cells. Nuclear localization of fluorescent labeled oligomers confirmed validity of the functional assay. The results showed that the free uptake and the antisense efficacy of neutral morpholino derivatives and cationic PNA were much higher than that of negatively charged 2'-O-Me and 2'-O-MOE congeners. The effects of the PNA oligomers were observed to be dependent on the number of L-lysine (Lys) residues at the C-terminus. The experiments suggest that the PNA containing Lys was taken up by a mechanism similar to that of cell-penetrating homeodomain proteins and that the Lys tail enhanced intracellular accumulation of PNA oligomer without affecting its ability to reach and hybridize to the target sequence.

Anions↗
PubMed2001

CYP1A2 is expressed along with CYP1A1 in the human lung.

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S(9) fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S(9) fractions from the tissues catalyzed the bioactivation of benzo[a]pyrene (B[a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.

Animals↗
PubMed2001

Tumor necrosis factor-alpha induces coordinated changes in major histocompatibility class I presentation pathway, resulting in increased stability of class I complexes at the cell surface.

It is demonstrated that similar to interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) induces coordinated changes at different steps of the major histocompatibility complex (MHC) class I processing and presentation pathway in nonprofessional antigen-presenting cells (APCs). TNF-alpha up-regulates the expression of 3 catalytic immunoproteasome subunits--LMP2, LMP7, and MECL-1--the immunomodulatory proteasome activator PA28 alpha, the TAP1/TAP2 heterodimer, and the total pool of MHC class I heavy chain. It was also found that in TNF-alpha--treated cells, MHC class I molecules reconstitute more rapidly and have an increased average half-life at the cell surface. Biochemical changes induced by TNF-alpha in the MHC class I pathway were translated into increased sensitivity of TNF-alpha--treated targets to lysis by CD8(+) cytotoxic T cells, demonstrating improved presentation of at least certain endogenously processed MHC class I--restricted peptide epitopes. Significantly, it was demonstrated that the effects of TNF-alpha observed in this experimental system were not mediated through the induction of IFN-gamma. It appears to be likely that TNF-alpha--mediated effects on MHC class I processing and presentation do not involve any intermediate messengers. Collectively, these data demonstrate the existence of yet another biologic activity exerted by TNF-alpha, namely its capacity to act as a coordinated multi-step modulator of the MHC class I pathway of antigen processing and presentation. These results suggest that TNF-alpha may be useful when a concerted up-regulation of the MHC class I presentation machinery is required but cannot be achieved by IFN-gamma. (Blood. 2001;98:1108-1115)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction.

We report, to our knowledge, the first HIV type 1 (HIV-1) transgenic (Tg) rat. Expression of the transgene, consisting of an HIV-1 provirus with a functional deletion of gag and pol, is regulated by the viral long terminal repeat. Spliced and unspliced viral transcripts were expressed in lymph nodes, thymus, liver, kidney, and spleen, suggesting that Tat and Rev are functional. Viral proteins were identified in spleen tissue sections by immunohistochemistry and gp120 was present in splenic macrophages, T and B cells, and in serum. Clinical signs included wasting, mild to severe skin lesions, opaque cataracts, neurological signs, and respiratory difficulty. Histopathology included a selective loss of splenocytes within the periarterial lymphoid sheath, increased apoptosis of endothelial cells and splenocytes, follicular hyperplasia of the spleen, lymphocyte depletion of mesenteric lymph nodes, interstitial pneumonia, psoriatic skin lesions, and neurological, cardiac, and renal pathologies. Immunologically, delayed-type hypersensitivity response to keyhole limpet hemocyanin was diminished. By contrast, Ab titers and proliferative response to recall antigen (keyhole limpet hemocyanin) were normal. The HIV-1 Tg rat thus has many similarities to humans infected with HIV-1 in expression of viral genes, immune-response alterations, and pathologies resulting from infection. The HIV-1 Tg rat may provide a valuable model for some of the pathogenic manifestations of chronic HIV-1 diseases and could be useful in testing therapeutic regimens targeted to stages of viral replication subsequent to proviral integration.

Animals↗
PubMed2001

CYP1A2 is expressed along with CYP1A1 in the human lung.

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S9 fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S9 fractions from the tissues catalyzed the bioactivation of benzo[a]pyrene (B[a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.

Animals↗
PubMed2001

Expression of aminopeptidase N in bile canaliculi: a predictor of clinical outcome in biliary atresia and a potential tool to implicate the mechanism of biliary atresia.

BACKGROUND: Only a few studies on extrahepatic biliary atresia (BA) have reported that the morphological changes of bile canaliculi could predict the clinical outcome after portoenterostomy and provide differential diagnosis of neonatal jaundice. Aminopeptidase N (APN) is an ectoenzyme of bile canaliculi that is involved in bile secretion. In this study, we tried to see whether APN of bile canaliculi had a significant role in BA. PATIENTS AND METHODS: We used monoclonal antibody 9B2 to compare the expression of APN in livers with BA, neonatal hepatitis, and choledochal cysts, as well as in nontumorous portions of pediatric hepatic livers with tumors. The expression of APN in fetuses, preterm babies, and term neonates was also studied. RESULTS: A high degree of 9B2 expression in BA was closely related to poor outcome. Cholestasis in choledochal cysts, rather than neonatal hepatitis, made 9B2 expression stronger. Increasing expression of 9B2 from fetuses to neonates was noted and the degree of 9B2 expression was similar between term neonates and nontumorous portions of pediatric livers with tumors. Interestingly, some cases of BA had 9B2 expression like that of preterm babies. CONCLUSIONS: APN of bile canaliculi progressively develops from fetuses to neonates and is well developed in neonates. APN can be induced to stronger expression by obstructive jaundice. The amount of expression of APN of bile canaliculi in BA is a predictor of clinical outcome and may be a tool for implicating the mechanism of BA.

Antibodies, Monoclonal↗