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Biomedical subjects

C Cheng

Publications and source records attributed to C Cheng.

At least 19 recordsLinked to original sources

In vivo proliferation, migration and phenotypic changes of Schwann cells in the presence of myelinated fibers.

Following injury to a peripheral nerve, changes in the behavior of Schwann cells help to define the subsequent microenvironment for regeneration. Such changes, however, have almost exclusively been considered in the context of Wallerian degeneration distal to an injury, where loss of axonal contact or input is thought to be critical to the changes that occur. This supposition, however, may be incorrect in the proximal stumps where axons are still in contact with their cell bodies. In this work, we studied aspects of in vivo Schwann cell behavior after injury within the microenvironment of proximal stumps of transected rat sciatic nerves, where axons are preserved. In particular we studied this microenvironment proximal to the outgrowth zone, in an area containing intact myelinated fibers and a perineurial layer, by using double immunolabelling of Schwann cell markers and 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells. In normal sciatic nerve, Schwann cells were differentiated, in an orderly fashion, into those associated with unmyelinated fibers that labeled with glial fibrillary acidic protein (GFAP) and those associated with myelinated fibers that could be identified by individual axons and myelin sheaths. After sciatic nerve transection, there was rapid and early expansion in the population of GFAP-labeled cells in proximal stumps that was generated in part, by de novo expression of GFAP in Schwann cells of myelinated fibers. Schwann cells from this population also underwent proliferation, indicated by progressive rises in BrdU and GFAP double labeling. Finally, this Schwann cell pool also developed the property of migration, traveling to the distal outgrowth zone, but also with lateral penetration into the perineurium and epineurium, while in intimate contact with new axons. The findings suggest that other signals, in the injured proximal nerve stumps, beyond actual loss of axons, induce 'mature' Schwann cells of myelinated axons to dedifferentiate into those that up-regulated their GFAP expression, proliferate and migrate with axons.

Animals↗

Improved detection rate of prostate cancer using the 10-core biopsy strategy in Singapore.

OBJECTIVES: To evaluate if changing the biopsy regime to 10 cores might improve the positive predictive value (PPV) of elevated prostate-specific antigen [PSA, elevated range, 4 to 20 ng per ml, normal range, < 4 ng per ml] for the diagnosis of prostate carcinoma. METHODS: From February 2000 to April 2001, 191 patients, mean age 64 years [range, 38 to 85 yr], underwent transrectal ultrasound [TRUS] for either elevated PSA [elevated range, 4 to 20 ng per ml] and/or abnormal digital rectal examination [DRE]. A 10-core TRUS-guided biopsy of the prostate was performed. This included the standard sextant biopsy and two additional cores for each far lateral zone. RESULTS: Using this technique, 47 out of 191 patients [24.6%] had prostate cancer. The PPV for PSA levels of 4.1 to 10.0 ng per ml and 10.1 to 20.0 ng per ml were 19.3% and 35.4%, respectively. The lateral cores contributed 21.3% of the cancer cases, which would have been missed if only sextant biopsies were performed. CONCLUSIONS: With the 10-core biopsy method, the PPV for prostate cancer for patients with a PSA in the range of 4 to 20 ng per ml was in the range of 25%. This is significantly different from previous reports. The reason for this may be due to the adoption of a better, more uniform and systematic biopsy strategy for patients with elevated PSA, or it may be a true reflection of the current population incidence. Hence, this biopsy strategy is highly recommended.

Adult↗

Anaerobic sequencing batch reactor as initiating stage in complete pentachlorophenol biodegradation.

Biodegradation of pentachlorophenol (PCP) has been studied in a sequence of two completely mixed reactors. Investigation on the first anaerobic sequencing batch reactor (AnSBR) is discussed in detail in this paper. Key technological and microbiological features were studied: two different types of adaptation process of anaerobic sludge towards PCP detoxication; the influence of the sludge concentration upon the rate of PCP biodegradation; minimum retention time for PCP degradation in dependence on the PCP concentration; modeling of the PCP degradation process; effluent COD and SS concentrations; changes in the micro- and macrostructure of the sludge during acclimatization process.

Bacteria, Anaerobic↗

The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.

Cation channels in the DEG/ENaC family are proposed to detect cutaneous stimuli in mammals. We localized one such channel, DRASIC, in several different specialized sensory nerve endings of skin, suggesting it might participate in mechanosensation and/or acid-evoked nociception. Disrupting the mouse DRASIC gene altered sensory transduction in specific and distinct ways. Loss of DRASIC increased the sensitivity of mechanoreceptors detecting light touch, but it reduced the sensitivity of a mechanoreceptor responding to noxious pinch and decreased the response of acid- and noxious heat-sensitive nociceptors. The data suggest that DRASIC subunits participate in heteromultimeric channel complexes in sensory neurons. Moreover, in different cellular contexts, DRASIC may respond to mechanical stimuli or to low pH to mediate normal touch and pain sensation.

Acid Sensing Ion Channels↗

Cloning, expression and characterization of a novel human REPS1 gene.

Ral is a member of the small GTPase-binding protein (G protein) family, and plays an important role in the Ras-RalGDS signal transduction pathway. A series of recent findings reveal several important downstream target proteins of Ral, such as RalBP1, Reps1, and others. Here we report another binding partner for RalBP1, which we have isolated from the human fetal brain library. The human REPS1 protein shares 83% amino acid identity with the mouse Reps1 protein. Northern blot analysis shows that the REPS1 is expressed in a variety of tissues, with the strongest expression in the heart and testis.

Adult↗

Sterically stabilized polyplex: ligand-mediated activity.

Synthetic vectors have been considered as a safer and more versatile alternative to viral-based gene delivery systems. A variety of very simple synthetic vector systems, e.g., cationic lipid- and polymer-complexed plasmid DNA have activity in vivo but it appears to be mediated by non-specific electrostatic interactions limiting targeting. In order to avoid these problems, we designed a sterically stabilized layered colloidal system. The steric polymer coating reduces non-specific interactions. We have synthesized a PEG conjugate of PEI that complexes DNA to form small, stable colloids with a steric polymer coat on their surface. The polymer enhances colloidal stability and reduces non-specific binding and toxicity. It also renders the complex inactive presumably due to reduced binding. Ligands are then appended to the distal end of the steric polymer to restore cell binding and expression at target cells. We prepared conjugates with RGD peptide ligands appended to the distal end of the steric polymer. The resulting conjugates also form complexes but with ligands exposed on their surface restoring binding and activity. Labeled oligonucleotides and DNA were used to measure intracellular distribution. Oligonucleotides are found localized in the nucleus, whereas the labeled plasmid DNA remained in the cytoplasm. Import of plasmid DNA into the nucleus appears to be very inefficient yet sufficient for expression.

Chemical Phenomena↗

Peptide accumulations in proximal endbulbs of transected axons.

Axons proximal to a transection develop into enlarged, but presumed 'passive' endbulb structures. In previous studies, we observed that proximal stumps of transected sciatic nerves accumulate discrete and striking deposits of calcitonin gene-related peptide (CGRP) that have apparent direct and local actions on nearby microvessels. In this work, we provide evidence that CGRP, in the company of several additional peptides, are deposited through 'arrested' anterograde transport into axon endbulbs that develop after transection. In proximal stump tips of rat sciatic nerves transected 48 h earlier, CGRP accumulation colocalized with a label for neurofilament that was accentuated at axon tips, but was prevented by a concurrent more proximal sciatic section. Similarly, interruption of CGRP deposition eliminated its apparent actions on local microvessels following injury. CGRP accumulation was also observed in sural nerve proximal stump tips, indicating its presence in sensory axons despite the known declines in the sensory neuronal synthesis of CGRP that occur following axotomy. Peptide accumulation was not unique to CGRP, with a similar pattern of anterograde accumulation observed for substance P (SP), neuropeptide Y (NPY) and galanin. Deposited peptides and perhaps other axonal constituents in the milieu of a peripheral nerve injury may be associated with important local physiological actions in the regenerative microenvironment.

Animals↗

Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients.

One hundred and thirty three gastric cancer cases were investigated immunohistochemically to clarify the biological role of survivin in gastric cancer cells using a commercially available anti-survivin antibody (SURV11A). Five gastric cancer cell lines were employed to assess localization of survivin by reverse-transcription-polymerase chain reaction (RT-PCR) Southern blotting, Western blotting and immunofluorescence, signals being found in both nucleus and cytoplasm. Survivin nuclear staining of gastric cancer cells was evident in 109 of 133 cases (82.0%) and associated with a favorable prognosis, being an independent prognosticator on multivariate analysis. Survivin nuclear positivity also correlated with younger age and lower incidence of vessel cancer invasion. In contrast, survivin cytoplasmic positivity was noted in 117 cases (88.0%) and did not correlate with any factor of progression or prognosis. The results indicate that survivin is present in the majority of gastric cancer cells but a nuclear localization may play an important physiological role in hindering tumor progression.

Adult↗

Rearrangement with formamide extrusion in the electrospray mass spectra of aminoacylbenzylamines.

Several aminoacylbenzylamines and their analogs were synthesized and analyzed by electrospray ionization mass spectrometry together with high-resolution and tandem mass spectrometric techniques. Fragment ions ([M + H - CH3NO](+)) were observed and attributed to a transfer of the benzyl group to the N-terminal amino group, leading to elimination of formamide. The proposed mechanism is supported by accurate mass measurements, and by experiments on deuterium labeling and variations of functional groups.

Amino Acids↗

Characterization of Gac1p, a regulatory subunit of protein phosphatase type I involved in glycogen accumulation in Saccharomyces cerevisiae.

GAC1 and GLC7 encode regulatory and catalytic subunits, respectively, of a type 1 phosphatase (PP1) in Saccharomyces cerevisiae that controls glycogen synthesis by regulating the phosphorylation state of glycogen synthase (Gsy2p). To investigate the role of Gac1p in this process, a set of GAC1 deletions were tested for their ability to complement a gac1 null mutation and to associate with Glc7p and with Gsy2p. The N-terminal 93 amino acids of Gaclp are necessary and sufficient for the interaction with Glc7p, whereas a region spanning residues 130-502 is required for Gsy2p binding. Both domains are required for full activity in vivo, although the Glc7p-binding domain retains some residual activity and can alter the phosphorylase a phosphatase activity of Glc7p in vitro. Further mutational analysis showed that Val71 and Phe73 of Gaclp are necessary for binding to Glc7p, while Asn356 and Tyr357 of Gaclp are necessary for binding to Gsy2p. These results suggest that Gac1p targets PPI to its substrate Gsy2p and that Gac1p may alter the catalytic activity of PP . Our data also show that overexpression of Gac1p affects glucose repression and ion homeostasis, two additional targets of GLC7, suggesting that multiple regulatory subunits compete for Glc7p binding in vivo.

Amino Acid Substitution↗

Early postoperative oral feeding after colectomy: an analysis of factors that may predict failure.

BACKGROUND: Previous studies have shown that early postoperative oral feeding is feasible. Traditionally patients were fed when flatus or defecation documented the return of bowel function. This study was undertaken to determine factors that may preclude early feeding. METHODS: One hundred four successive patients underwent colorectal surgery from October 1999 to January 2001. Eighty-nine patients started an oral diet either on postoperative day 1 or 2. Their clinical outcomes were recorded prospectively. Fifteen of the 104 patients were excluded for small-bowel resection (5 patients), perioperative complications (5 patients), prior radiation (3 patients), and small-bowel obstruction (2 patients). A failure in postoperative feeding consisted of nausea, vomiting, or readmission. RESULTS: The mean age of our cohort was 65 years (range, 28-87 years). There were 45 male and 44 female patients. The mean postoperative hospital stay was 6 days (range, 3-13 days). The median American Society of Anesthesiology score was II (range, I-IV). The types of resection performed were right colectomy (27 patients), low anterior resection (26 patients), sigmoid resection (11 patients), abdominoperineal resection (8 patients), formation or closure of colostomy (7 patients), posterior pelvic exenteration (4 patients), total colectomy (3 patients), left colectomy (2 patients), and transverse colectomy (1 patient). Sixty-five patients (73%) tolerated early oral feeding. Of the 24 patients that did not, 16 had nausea or emesis, and 8 required readmission for postoperative complications (small-bowel obstruction [4 patients], wound dehiscence [1 patient], abdominal pain [1 patient], and anastomotic leak [2 patients]). Univariate analysis revealed that the use of volume expanders contributed to intolerance of early feeding. On multivariate analysis, blood loss during the operation was the only factor contributing to failure of early postoperative oral feeding. CONCLUSIONS: Early oral feeding is safe and feasible for postcolectomy patients with a history of colorectal neoplasms.

Adult↗

Is there a role for curative surgery for pelvic recurrence from rectal carcinoma in the presence of hydronephrosis?

BACKGROUND: The prognosis for patients with recurrent rectal adenocarcinoma is not uniformly fatal if one can safely and selectively reoperate on a subset of patients with resectable disease. Even with careful selection, many patients undergo exploratory laparotomy and do not have resectable disease. We have reported that the presence of hydronephrosis in the setting of recurrent rectal carcinoma portends a poor outcome because of invariable association with unresectable disease. The purpose of this study was to update our experience of patients presenting with unilateral or bilateral hydronephrosis and recurrent rectal cancer. METHODS: A retrospective chart review of 142 patients with recurrent rectal cancer evaluated at our institution from January 1989 to December 1999 was performed. RESULTS: Twenty-seven of 142 patients referred for the management of recurrent rectal cancer had unilateral or bilateral hydronephrosis. Fifteen (55%) of these patients had distant metastatic disease. Twelve patients (45%) with hydronephrosis and local recurrent disease on evaluation were analyzed. Six of the 12 patients underwent exploratory laparotomy, with none found to have resectable disease. Their mean survival after diagnosis of recurrent disease was 14 months. CONCLUSIONS: Based on our results, the presence of hydronephrosis (unilateral or bilateral) in recurrent rectal adenocarcinoma portends a survival equivalent to the presence of distant metastasis. Therefore, we do not believe potential curative surgery has a role for patients with locally recurrent rectal adenocarcinoma in the presence of hydronephrosis.

Adenocarcinoma↗

Optimizing the sterilization of PLGA scaffolds for use in tissue engineering.

There are few suitable techniques available to sterilize biodegradable polyester three-dimensional tissue engineering scaffolds because they are susceptible to degradation and/or morphological degeneration by high temperature and pressure. We used a novel polyllactide-co-glycolide) scaffold (Osteofoam) to determine the optimal sterilization procedure--i.e. a sterile product with minimal degradation and deformation. Initial studies, found that an argon plasma created at 100W for 4min was optimal for sterilizing Osteofoam scaffolds without affecting their morphology. The RFGD plasma sterilization method was compared to two well-established techniques--ethylene oxide (ETO) and gamma-irradiation (gamma)--which were in turn compared to disinfection in 70% ethanol. Disinfection in 70% ethanol serves as a useful control because it affects neither the morphology nor the molecular weight of the polymer: yet, ethanol is unsuitable as a sterilization method because it does not adequately eliminate hydrophilic viruses and bacterial spores. The three sterilization techniques, ETO, gamma and RFGD plasma, were compared in terms of their immediate and long-term effects on the dimensions, morphology, molecular weight and degradation profile of the scaffolds. Scaffolds shrank to 60% of their initial volume after ETO sterilization whereas their molecular weight (Mw) decreased by approximately 50% after gamma-irradiation. Thus, both ETO and gamma-irradiation posed immediate problems as sterilization techniques for 3-D biodegradable polyester scaffolds. During the in vitro degradation study, all sterilized samples showed advanced morphological and volume changes over time relative to ethanol (EtOH) disinfected samples, with the greatest changes observed for gamma-irradiated samples. ETO, RFGD plasma sterilized and EtOH disinfected samples showed similar changes in Mw and mass over the 8-week time frame. Overall, of the three sterilization techniques studied, RFGD plasma was the best.

Absorbable Implants↗

The NF-kappaB inhibitor diethyldithiocarbamate (DDTC) increases brain cell death in a transient middle cerebral artery occlusion model of ischemia.

A transient ischemic middle cerebral artery occlusion model of stroke was used to examine the role of the transcription factor NF-kappaB in cell death as measured by DNA fragmentation and infarction volume. The left middle cerebral artery was occluded for either 30 min or 2 h in rats. One set of animals was pretreated with diethyldithiocarbamate (DDTC), an inhibitor of NF-kappaB, 30 min prior to reperfusion. The animals were reperfused and allowed to survive for 2 or 7 days. DNA fragmentation was assayed by in situ end labeling in the stroke core and penumbral regions. Specific cortical and subcortical regions were measured using quantitative image analysis. DNA fragmentation was seen only on the ischemic side of the brains in all cases. Overall, the DDTC-treated groups showed significantly increased DNA fragmentation within the ischemic side compared to the saline control groups. DDTC treatment also caused an increase in stroke volume based on triphenyl tetrazolium chloride staining. Electrophoretic mobility shift assays showed NF-kappaB activation peaking 15 min following reperfusion and that this activation was blocked by the DDTC treatment. This study suggests that the use of NF-kappaB inhibitors to block cell death following stroke needs to be carefully examined because global inhibitors may not promote neuronal survival.

Animals↗

Simulation of biomass gasification with a hybrid neural network model.

Gasification of several types of biomass has been conducted in a fluidized bed gasifier at atmospheric pressure with steam as the fluidizing medium. In order to obtain the gasification profiles for each type of biomass, an artificial neural network model has been developed to simulate this gasification processes. Model-predicted gas production rates in this biomass gasification processes were consistent with the experimental data. Therefore, the gasification profiles generated by neural networks are considered to have properly reflected the real gasification process of a biomass. Gasification profiles identified by neural network suggest that gasification behavior of arboreal types of biomass is significantly different from that of herbaceous ones.

Biomass↗

Cloning and characterization of a novel human TEKTIN1 gene.

Tektins comprise a family of filament-forming proteins that are known to be coassembled with tubulins to form ciliary and flagellar microtubules. A new member of the tektin gene family was cloned from the human fetal brain cDNA library. We hence named it the human TEKTIN1 gene. TEKTIN1 cDNA consists of 1375 bp and has a putative open reading frame encoding 418 amino acids. The predicted protein is 48.3 kDa in size, and its amino acid sequence is 82% identical to that of the mouse, rat, and dog. One conserved peptide RPNVELCRD was observed at position number 323-331 of the amino acid sequence, which is a prominent feature of tektins and is likely to represent a functionally important protein domain. TEKTIN1 gene was mapped to the human chromosome 17 by BLAST search, and at least eight exons were found. Northern blot analysis indicated that TEKTIN1 was predominantly expressed in testis. By in-situ hybridization analysis, TEKTIN1 mRNA was localized to spermatocytes and round spermatids in the seminiferous tubules of the mouse testis, indicating that it may play a role in spermatogenesis.

Amino Acid Sequence↗

Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 genea from human fetal brain.

Short-chain dehydrogenases/reductases (SDR) constitute a large protein family of NAD(P)(H)-dependent oxidoreductase. They are defined by distinct, common sequence motifs and show a wide range of substrate specialisms. By large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a novel human SDR-type dehydrogenase/reductase gene named Dehydrogenase/reductase (SDR family) member 1 (DHRS1). The DHRS1 cDNA is 1411 base pair in length, encoding a 314-amino-acid polypeptide which has a SDR motif. Northern blot reveals two bands, of about 0.9 and 1.4 kb in size. These two forms are expressed in many tissues. The DHRS1 gene is localized on chromosome 14q21.3. It has 9 exons and spans 9.2 kb of the genomic DNA.

Amino Acid Sequence↗

A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues.

We report the cloning and characterization of a novel human hydroxysteroid dehydrogenase like gene (HSDL1) located on human chromosome 16q24.2. The HSDL1 cDNA is 3407 base pair in length, encoding a 309 amino acid polypeptide related to human 17beta-HSD3. Northern blot reveals that the HSDL1 is highly expressed in testis and ovary. In situ hybridization indicates that the expression of HSDL1 is predominantly increased in the prostate cancer tissue compared with the normal prostate tissue, which suggests that the gene expression is important to the arising of prostate cancer.

Amino Acid Sequence↗