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Biomedical subjects

W Wei

Publications and source records attributed to W Wei.

At least 19 recordsLinked to original sources

Pharyngolaryngoesophagectomy using the thoracoscopic approach.

BACKGROUND: Thoracoscopic mobilization of the esophagus for pharyngolaryngoesophagectomy allows dissection under direct vision, and therefore it potentially results in fewer complications than conventional transhiatal mobilization. In this article we report our experience with this approach. It was also hypothesized that a learning curve existed and that results have improved over time. PATIENTS AND METHODS: From July 1994 until January 2004, 57 patients underwent pharyngolaryngoesophagectomy in our institution. Intraoperative events and postoperative outcome were prospectively documented, and long-term follow-up data were also studied. Results were compared between the first 30 patients and the last 27 patients. RESULTS: There were no significant differences between the two groups with respect to the various clinicopathological characteristics. There was no difference in the median thoracoscopic time between the first 30 and last 27 patients at 90 and 75 min, respectively, p = 0.18. For the complete procedure there was significantly less blood loss in the later group; median (range) blood loss 700 (164-3000) ml versus 400 (100-1200) ml, p = 0.002. Overall pulmonary complications occurred in 12 patients (40%) in the first group versus 13 (48%) in the second group, p = 0.6. The incidence of atrial arrhythmia was also similar, affecting 6 (20%) patients and 3 (11%), respectively, p = 0.47. Hospital mortality rates were 13.3% and 7.4%, p = 0.67. Two-year survival rates were no different (46% versus 45% p = 0.85). CONCLUSIONS: Although, subjectively, operating skills have improved over time, better results in the second half of this series could not be demonstrated clearly, likely because the operating surgeons had prior extensive experience in esophageal and thoracoscopic procedures.

Adult↗

Preclinical and post-treatment changes in the HCC-associated serum proteome.

SELDI-based proteomic profiling of body fluids is currently in widespread use for cancer biomarker discovery. We have successfully used this technology for the diagnosis of hepatocellular carcinoma (HCC) in hepatitis C patients and now report its application to serial serum samples from 37 hepatitis C patients before development of HCC, with HCC and following radiofrequency ablation of the tumour. As with alpha-fetoprotein, an accepted biomarker for HCC, we hypothesised that HCC-associated proteomic features would 'return to normal' following successful treatment and the primary aim of our study was to test this hypothesis. Several SELDI peaks that changed significantly during HCC development were detected but they did not reverse following treatment. These data may be interpreted to suggest that the characteristic SELDI profile is not linearly related to tumour burden but may result from the progression of underlying liver disease or from the emergence of precancerous lesions. beta2-Microglobulin, a protein previously reported to be markedly elevated in patients with HCV related HCC, was also the most significantly HCC associated proteomic feature (m/z 11720) in this study.

Aged↗

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases.

CEACAM1, also known as biliary glycoprotein (BGP), CD66a, pp120 and C-CAM1, is a member of the CEA immunoglobulin superfamily. CEACAM1 is a putative tumor suppressor based on diminished expression in some solid neoplasms such as colorectal carcinoma. However, CEACAM1 is overexpressed in some tumors such as non-small cell lung cancer. To clarify the mechanism of action of this cell adhesion molecule, we studied thyroid carcinoma that has a spectrum of morphologies and variable behavior allowing separation of proliferation from invasion and metastasis. CEACAM1 is expressed in thyroid carcinoma cell lines derived from tumors that exhibit aggressive behavior. Introduction of CEACAM1 into endogenously deficient WRO cells resulted in reduced cell cycle progression associated with p21 upregulation and diminished Rb phosphorylation. Forced CEACAM1 expression enhanced cell-matrix adhesion and migration and promoted tumor invasiveness. Conversely, small interfering RNA (siRNA)-mediated downregulation of CEACAM1 expression in MRO cells accelerated cell cycle progression and significantly enhanced tumor size in xenografted mice. CEACAM1 is not appreciably expressed in normal thyroid tissue or benign thyroid tumors. In a human thyroid tissue array, CEACAM1 reactivity was associated with metastatic spread but not with increased tumor size. These findings identify CEACAM1 as a unique mediator that restricts tumor growth whereas increasing metastatic potential. Our data highlight a complex repertoire of actions providing a putative mechanism underlying the spectrum of biologic behaviors associated with thyroid cancer.

Adenocarcinoma, Follicular↗

A novel acoustic window for trans-oesophageal echocardiography by using a saline-filled endotracheal balloon.

BACKGROUND: The main structures anterior to the trachea are frequently poorly visualized by trans-oesophageal echocardiography (TEE) because of the tracheal air column. We studied a new acoustic window for TEE imaging of large vessels anterior to the trachea by using a saline-filled endotracheal balloon. METHODS: Cardiac surgery patients were studied. After ventilation was discontinued at the beginning of cardiopulmonary bypass, a saline-filled latex balloon was inserted into the trachea through the tracheal tube. The structures anterior to the trachea were imaged with and without the endotracheal balloon. TEE images of the proximal aortic arch and innominate artery were classified into three grades according to the quality of images: 1, vessel not visible; 2, part of vessel wall visible; 3, entire vessel wall visible. Grade 3 was categorized as good visualization while grades 1 and 2 were categorized as inadequate. TEE images with and without balloon were compared using the Mann-Whitney U-test and Chi-square analysis. P<0.05 was considered statistically significant. RESULTS: In 20 patients, 84% had good visualization of proximal aortic arch with presence of endotracheal balloon compared with 11% without (P<0.001). A total of 94% had good visualization of the proximal innominate artery with presence of endotracheal balloon compared with 0% without (P<0.001). CONCLUSIONS: A new 'TEE trans-tracheal acoustic window' was established by usage of a saline-filled endotracheal balloon. This window partially eliminates the TEE blind zone and provides improved visualization of the proximal aortic arch and innominate artery.

Adult↗

Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion cast study.

Autosomal-dominant polycystic kidney disease (ADPKD) accounts for about 10% of all cases of chronic renal failure requiring dialysis. The disease is characterized by proliferation of renal epithelial cells and formation of cysts that expand over years and replace the normal parenchyma of the kidney. As the cysts grow, the volume of the kidney can increase by more than 10-fold, implying that remodeling and expansion of the vasculature must occur to provide oxygenation and nutrition to the cyst cells. Our previous studies support the notion that there is angiogenesis in ADPKD. We report here results from resin casting of ADPKD kidneys vasculature. In this study, the corrosion-casting method was used in conjunction with scanning electron microscopy to study the vascular architecture and the evidence for angiogenesis in ADPKD kidneys. We found a well-defined vascular network around the cysts forming a 'vascular capsule' somewhat similar to that described in avascular leiomyomata. We also found that the normal vascular architecture is lost and replaced by an assortment of capillaries of larger size than those in the normal kidney, mixed with flattened and spiral arterioles, damaged glomeruli, and atresic venules, indicative of regression of the microvasculature. In the same areas, there was capillary sprouting, considered the hallmark of angiogenesis. The present study documents regression changes of the vasculature and confirms the existence of angiogenesis in ADPKD kidneys, and suggests the use of inhibitors of angiogenesis as a possible avenue for the treatment of the disease.

Adult↗

Mu opioid receptor-effector coupling and trafficking in dorsal root ganglia neurons.

Morphine induces profound analgesic tolerance in vivo despite inducing little internalization of the mu opioid receptor (muOR). Previously proposed explanations suggest that this lack of internalization could either lead to prolonged signaling and associated compensatory changes in downstream signaling systems, or that the receptor is unable to recycle and resensitize and so loses efficacy, either mechanism resulting in tolerance. We therefore examined, in cultured neurons, the relationship between muOR internalization and desensitization in response to two agonists, D-Ala2, N-MePhe4, Gly5-ol-enkephalin (DAMGO) and morphine. In addition, we studied the chimeric mu/delta opioid receptor (mu/ partial differentialOR) which could affect internalization and desensitization in neurons. Dorsal root ganglia neurons from muOR knockout mice were transduced with an adenovirus expressing either receptor and their respective internalization, desensitization and trafficking profiles determined. Both receptors desensitized equally, measured by Ca2+ current inhibition, during the first 5 min of agonist exposure to DAMGO or morphine treatment, although the mu/partial differentialOR desensitized more extensively. Such rapid desensitization was unrelated to internalization as DAMGO, but not morphine, internalized both receptors after 20 min. In response to DAMGO the mu/partial differentialOR internalized more rapidly than the muOR and was trafficked through Rab4-positive endosomes and lysosomal-associated membrane protein-1-labeled lysosomes whereas the muOR was trafficked through Rab4 and Rab11-positive endosomes. Chronic desensitization of the Ca2+ current response, after 24 h of morphine or DAMGO incubation, was seen in the DAMGO, but not morphine-treated, muOR-expressing cells. Such persistence of signaling after chronic morphine treatment suggests that compensation of downstream signaling systems, rather than loss of efficacy due to poor receptor recycling, is a more likely mechanism of morphine tolerance in vivo. In contrast to the muOR, the mu/partial differentialOR showed equivalent desensitization whether morphine or DAMGO treated, but internalized further with DAMGO than morphine. Such ligand-independent desensitization could be a result of the observed higher rate of synthesis and degradation of this chimeric receptor.

Analgesics, Opioid↗

Correlated expression of gfp and Bt cry1Ac gene facilitates quantification of transgenic hybridization between Brassicas.

Gene flow from transgenic oilseed rape (BRASSICA NAPUS) might not be avoidable, thus, it is important to detect and quantify hybridization events with its relatives in real time. Data are presented showing the correlation between genetically linked green fluorescent protein (GFP) with BACILLUS THURINGIENSIS (Bt) CRY1AC gene expression in hybrids formed between transgenic B. NAPUS "Westar" and a wild Chinese accession of wild mustard (B. JUNCEA) and hybridization between transgenic B. NAPUS and a conspecific Chinese landrace oilseed rape. Hybrids were obtained either by spontaneous hybridization in the field or by hand-crossing in a greenhouse. In all cases, transgenic hybrids were selected by GFP fluorescence among seedlings originating from seeds harvested from B. JUNCEA and the Chinese oilseed rape plants. Transgenicity was confirmed by PCR detection of transgenes. GFP fluorescence was easily and rapidly detected in the hybrids under greenhouse and field conditions. Results showed that both GFP fluorescence and Bt protein synthesis decreased as either plant or leaf aged, and GFP fluorescence intensity was closely correlated with Bt protein concentration during the entire vegetative lifetime in hybrids. These findings allow the use of GFP fluorescence as an accurate tool to detect gene-flow in time in the field and to conveniently estimate BT CRY1AC expression in hybrids on-the-plant.

Bacillus thuringiensis Toxins↗

Subtype IV of the BK polyomavirus is prevalent in East Asia.

BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney. Using either serological or genotyping methods, BKV isolates have been classified into four subtypes (I-IV), with subtype I mainly detected in all countries studied so far. To elucidate the subtype of BKV prevalent in East Asia, we examined BKV-positive urine samples collected from immunocompetent elderly patients in Mongolia, Northeast China, Northwest China, Southeast China, Southwest China, Vietnam and Japan. The 287-bp typing region of the viral genome in each of these samples was PCR-amplified and sequenced, and a phylogenetic tree was constructed. According to the tree, BKV isolates in East Asia were unambiguously classified into subtype I or IV (subtypes II and III were not detected). In Japan, subtype I was mainly detected and subtype IV was rare, whereas in the other regions subtype IV was detected frequently, at rates ranging from 24 to 100%. Thus, East Asia (excluding Japan) is a region in which subtype-IV BKV is prevalent, a finding that requires the view of the geographic distribution of BKV subtypes to be revised. Furthermore, we present evidence that the immunological states of urine donors do not affect the pattern of BKV subtypes.

BK Virus↗

Identification of serum biomarkers for colon cancer by proteomic analysis.

Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. Early detection greatly improves prognosis; however, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their applicability. No serum-based test is currently of sufficient sensitivity or specificity for widespread use. In the best currently available blood test, carcinoembryonic antigen exhibits low sensitivity and specificity particularly in the setting of early disease. Hence, there is great need for new biomarkers for early detection of CRC. We have used surface-enhanced laser desorbtion/ionisation (SELDI) to investigate the serum proteome of 62 CRC patients and 31 noncancer subjects. We have identified proteins (complement C3a des-arg, alpha1-antitrypsin and transferrin) with diagnostic potential. Artificial neural networks trained using only the intensities of the SELDI peaks corresponding to identified proteins were able to classify the patients used in this study with 95% sensitivity and 91% specificity.

Adenocarcinoma↗

Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis.

Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a 'blind' test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73-99%) and 86% specificity (95% CI 65-95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (P<0.001) and were identified as kappa and lambda immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC.

Amino Acid Sequence↗

Survival and initial chromatid breakage in normal and tumour cells exposed in vitro to gamma rays and carbon ions at the HIRFL.

Human hepatoma and normal liver cells were irradiated with (12)C(6+) ion beams (linear energy transfer (LET) = 96 keV microm(-1)) and gamma-rays at the Heavy Ion Research Facility in Lanzhou (HIRFL). The numbers and types of chromatid breaks were detected using the premature chromosome condensation technique. Irradiation with (12)C(6+) ions produced a majority of isochromatid break types, while chromatid breaks were dominant for irradiation with gamma-rays. Experimental results showed that the initial level of chromatid breaks is clearly related to the absorbed dose from (12)C(6+) ions and gamma-rays. The (12)C(6+) ions are relatively more effective at inducing initial chromatid breaks when compared with the gamma-rays. A relative biological effectiveness (RBE) of about 2.5 resulted for the induction of initial chromatid breaks by (12)C(6+) ions relative to gamma-rays in both cell lines.

Carbon↗

Characterization of carotenoid hydroxylase gene promoter in Haematococcus pluvialis.

Astaxanthin, a high-value ketocarotenoid is mainly used in fish aquaculture. It also has potential in human health due to its higher antioxidant capacity than beta-carotene and vitamin E. The unicellular green alga Haematococcus pluvialis is known to accumulate astaxanthin in response to environmental stresses, such as high light intensity and salt stress. Carotenoid hydroxylase plays a key role in astaxanthin biosynthesis in H. pluvialis. In this paper, we report the characterization of a promoter-like region (-378 to -22 bp) of carotenoid hydroxylase gene by cloning, sequence analysis and functional verification of its 919 bp 5'-flanking region in H. pluvialis. The 5'-flanking region was characterized using micro-particle bombardment method and transient expression of LacZ reporter gene. Results of sequence analysis showed that the 5'-flanking region might have putative cis-acting elements, such as ABA (abscisic acid)-responsive element (ABRE), C-repeat/dehydration responsive element (C-repeat/DRE), ethylene-responsive element (ERE), heat-shock element (HSE), wound-responsive element (WUN-motif), gibberellin-responsive element (P-box), MYB-binding site (MBS) etc., except for typical TATA and CCAAT boxes. Results of 5' deletions construct and beta-galactosidase assays revealed that a highest promoter-like region might exist from -378 to -22 bp and some negative regulatory elements might lie in the region from -919 to -378 bp. Results of site-directed mutagenesis of a putative C-repeat/DRE and an ABRE-like motif in the promoter-like region (-378 to -22 bp) indicated that the putative C-repeat/DRE and ABRE-like motif might be important for expression of carotenoid hydroxylase gene.

Base Sequence↗

Randomised clinical trial investigating the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction.

OBJECTIVE: To investigate the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction. PATIENTS AND METHODS: One hundred and sixty-two consecutive patients who had suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene were randomised into two groups, a control group (treated conservatively, n=82) and a contrast group (treated with combined administration of octreotide and methylglucamine diatrizoate, n=80). A laparotomy was performed in both the two groups if symptoms of strangulation developed or the obstruction did not resolve spontaneously after 72 h. RESULTS: Statistically significant rapid reduction in pain score, lower amount of nasogastric drainage, shorter hospital stay, lower operative rate and lower postoperative morbidity were observed in the contrast group. Among the non-operative patients, earlier passage of stool and gas, earlier first oral intake and shorter duration of nasogastric tube placement were significantly more frequently observed in the contrast group. No difference in the rate of readmission was found between the two groups. CONCLUSIONS: Combined administration of octreotide and methylglucamine diatrizoate accelerates resolution of small bowel obstruction by a specific therapeutic effect and is safe for the older persons.

Aged↗

Crustal rheology of the Himalaya and Southern Tibet inferred from magnetotelluric data.

The Cenozoic collision between the Indian and Asian continents formed the Tibetan plateau, beginning about 70 million years ago. Since this time, at least 1,400 km of convergence has been accommodated by a combination of underthrusting of Indian and Asian lithosphere, crustal shortening, horizontal extrusion and lithospheric delamination. Rocks exposed in the Himalaya show evidence of crustal melting and are thought to have been exhumed by rapid erosion and climatically forced crustal flow. Magnetotelluric data can be used to image subsurface electrical resistivity, a parameter sensitive to the presence of interconnected fluids in the host rock matrix, even at low volume fractions. Here we present magnetotelluric data from the Tibetan-Himalayan orogen from 77 degrees E to 92 degrees E, which show that low resistivity, interpreted as a partially molten layer, is present along at least 1,000 km of the southern margin of the Tibetan plateau. The inferred low viscosity of this layer is consistent with the development of climatically forced crustal flow in Southern Tibet.

Journal Article↗

Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen-induced arthritis.

OBJECTIVE AND DESIGN: To investigate the therapeutic effects and mechanisms of total glucosides of paeony (TGP), an effective compound of Chinese traditional herbal medicine (CTM), on collagen -induced arthritis (CIA) in rats. MATERIALS: CIA was induced in male Sprague-Dawley rats immunized with chicken type II collagen in Freund's complete adjuvant. TREATMENT: TGP (25, 50, 100 mg/kg/d) was orally administered to rats from day 14 to 28 after immunization. METHODS: Arthritis was evaluated by hind paw swelling, polyarthritis index, and histological examination. Activities of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) were determined and the ultrastructure of synoviocytes was observed. The proliferation and the production of vascular epidermal growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 1 (MMP-1) and MMP-3 in fibroblast-like synoviocytes (FLS) were detected. RESULTS: The administration of TGP (25, 50, 100 mg/kg, ig x 14 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The ultrastructure of synoviocytes from CIA rats was changed, and the level of IL-1 and TNF alpha produced by macrophage-like synoviocytes (MLS) from CIA rats was elevated. TGP (50, 100 mg/kg, ig x 14 days) inhibited above changes significantly. The MLS supernatants of CIA rats induced more cell proliferation and more production of VEGF, bFGF, MMP-1 and MMP-3 in FLS of CIA than those supernatants from CIA rats treated with TGP (50, 100 mg/kg, ig x 14 days). CONCLUSION: These results indicate that TGP exerts a suppressive effect on joint destruction in rat CIA. The therapeutic effect of TGP could be associated with its ability to ameliorate the secretion and metabolism of synoviocytes and to inhibit the abnormal proliferation and VEGF, bFGF, MMP-1 and MMP-3 production by FLS.

Animals↗

Cell-based gene therapy experiments in murine experimental autoimmune encephalomyelitis.

With the ultimate goal of developing a novel treatment for multiple sclerosis (MS), we have developed a cell-based gene therapy protocol for the treatment of murine experimental autoimmune encephalomyelitis (EAE), a powerful animal model for MS. We have determined that transduced fibroblasts secreting encephalogenic epitopes, when injected into mice with EAE, cause a striking abrogation of disease. Both myelin basic protein (MBP) and proteolipid protein mini-gene constructs expressed in syngeneic fibroblast cells were capable of ameliorating ongoing EAE induced by MBP protein. These experiments are crucial since they suggest that not all encephalogenic epitopes need be secreted for the control of disease. We also demonstrate the success of this protocol when transduced syngeneic, and most importantly, allogeneic cells are sequestered within an implantable chamber. Furthermore, we find that through modifying antigen expression by changing the signal sequence of the mini-gene construct, we were able to significantly reduce the dose of cells required for treatment. These improvements to the mini-gene delivery system are critical for the eventual translation of our protocol to the clinic.

Amino Acid Sequence↗