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Biomedical subjects

Y Xiao

Publications and source records attributed to Y Xiao.

At least 37 records · Page 2Linked to original sources

Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana.

A neurotoxin, named hainantoxin-IV, was purified from the venom of the spider Selenocosmia hainana. The amino acid sequence was determined by Edman degradation, revealing it to be a 35-residue polypeptide amidated at its C terminal and including three disulfide bridges: Cys2-Cys17, Cys9-Cys24, and Cys16-Cys31 assigned by partial reduction and sequence analysis. Hainantoxin-IV shares 80% sequence identity with huwentoxin-IV from the spider S. huwena, a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels, suggesting that hainantoxin-IV adopts an inhibitor cystine knot structural motif like huwentoin-IV. Under whole-cell voltage-clamp conditions, this toxin has no effect on tetrodotoxin-resistant voltage-gated sodium channels in adult rat dorsal root ganglion neurons, while it blocks TTX-S sodium channels in a manner similar to huwentoxin-IV, and the actions of both toxins on sodium currents are very similar to that of tetrodotoxin. Thus, they define a new family of spider toxins affecting sodium channels.

Amino Acid Sequence↗

COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer.

BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized histomorphologically by progressive development of fibrosis and atrophy of the pancreatic parenchyma. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin (TSP) family of extracellular glycoproteins that is expressed in CP tissues. In the present study, we characterized COMP mRNA and protein expression in the normal pancreas, chronic pancreatitis, and pancreatic cancer tissues. METHODS: 15 normal pancreatic tissues, 14 CP tissues and 14 pancreatic cancer tissues were analyzed by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. RESULTS: COMP mRNA and protein were detected at moderate to high levels in chronic pancreatitis tissues, at moderate levels in pancreatic cancer tissues, but at low levels in normal pancreatic tissues and in four pancreatic cancer cell lines. COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. COMP protein was also present in the fibrotic tissue in CP. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. CONCLUSION: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this gene in the course of acinar cell degeneration and dedifferentiation. COMP might thus serve as a marker for tissue destruction and disease activity in CP.

Adolescent↗

Tissue engineering for bone regeneration using differentiated alveolar bone cells in collagen scaffolds.

Regeneration of osseous defects by a tissue-engineering approach provides a novel means of treatment utilizing cell biology, materials science, and molecular biology. In this study the concept of tissue engineering was tested with collagen type I matrices seeded with cells with osteogenic potential and implanted into sites where osseous damage had occurred. Explant cultures of cells from human alveolar bone and gingiva were established. When seeded into a three-dimensional type I collagen-based scaffold, the bone-derived cells maintained their osteoblastic phenotype as monitored by mRNA and protein levels of the bone-related proteins including bone sialoprotein, osteocalcin, osteopontin, bone morphogenetic proteins 2 and 4, and alkaline phosphatase. These in vitro-developed matrices were implanted into critical-size bone defects in skulls of immunodeficient (SCID) mice. Wound healing was monitored for up to 4 weeks. When measured by microdensitometry the bone density within defects filled with osteoblast-derived matrix was significantly higher compared with defects filled with either collagen scaffold alone or collagen scaffold impregnated with gingival fibroblasts. New bone formation was found at all the sites treated with the osteoblast-derived matrix at 28 days, whereas no obvious new bone formation was identified at the same time point in the control groups. In situ hybridization for the human-specific Alu gene sequence indicated that the newly formed bone tissue resulted from both transplanted human osteoblasts and endogenous mesenchymal stem cells. The results indicate that cells derived from human alveolar bone can be incorporated into bioengineered scaffolds and synthesize a matrix, which on implantation can induce new bone formation.

Alveolar Process↗

Variation in needle longevity of Pinus tabulaeformis forests at different geographic scales.

Needle longevity of conifer species is known to increase with latitude, but little is known about intraspecific variation and associated factors within a location. Chinese pine (Pinus tabulaeformis Carr.) forests were investigated to identify patterns of needle longevity at seven sites with distinctive climatic conditions along a latitudinal gradient (33-38 degrees N) in Shaanxi province, northwest China. A demographic approach was used to quantify needle longevity as an index of entire foliage population adjusted to needle-age-specific mortality rates. There were significant differences in needle longevity of Chinese pine stands across sites and across sample plots within a site. Individual tree needle longevity ranged from 0.62 to 3.75 years for 276 samples across sites. Needle longevity increased with latitude (R2 = 0.40, P < 0.0001), but decreased with mean January temperature (R2 = 0.63, P < 0.0001). Foliage retention of Chinese pine stands at the regional level was generally associated with climatic variability, indicating that variation in needle longevity was primarily an environmental acclimation to low temperature in winter. Stand characteristics were closely associated with needle longevity at three sites located within the same climatic zone. Needle longevity was positively correlated with tree age (R2 = 0.48, P < 0.0001) and stand density (R2 = 0.26, P = 0.0015) at Huanglong and Huangling, respectively, whereas it was negatively associated with total tree height at Zhidan (R2 = 0.50, P < 0.0001). It is concluded that, at the stand and individual tree level, intraspecific variation in needle longevity is most likely a result of adaptation to patchy microsite environments.

China↗

Video techniques and data compared with observation in emergency trauma care.

Video recording is underused in improving patient safety and understanding performance shaping factors in patient care. We report our experience of using video recording techniques in a trauma centre, including how to gain cooperation of clinicians for video recording of their workplace performance, identify strengths of video compared with observation, and suggest processes for consent and maintenance of confidentiality of video records. Video records are a rich source of data for documenting clinician performance which reveal safety and systems issues not identified by observation. Emergency procedures and video records of critical events identified patient safety, clinical, quality assurance, systems failures, and ergonomic issues. Video recording is a powerful feedback and training tool and provides a reusable record of events that can be repeatedly reviewed and used as research data. It allows expanded analyses of time critical events, trauma resuscitation, anaesthesia, and surgical tasks. To overcome some of the key obstacles in deploying video recording techniques, researchers should (1) develop trust with video recorded subjects, (2) obtain clinician participation for introduction of a new protocol or line of investigation, (3) report aggregated video recorded data and use clinician reviews for feedback on covert processes and cognitive analyses, and (4) involve multidisciplinary experts in medicine and nursing.

Feedback↗

Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate. AIMS: In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs. MATERIALS AND METHODS: 15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls. RESULTS: CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues. CONCLUSION: These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.

Adolescent↗

Internationalization of the animal science undergraduate curriculum: a survey of its current status, barriers to its implementation and its value.

The goal of this project was to identify the current level at which internationalization has been adopted as a theme in the North American animal science curriculum and to identify its value and the barriers to its implementation. We surveyed animal, dairy, and poultry science departments across Canada and the United States. One hundred twenty-four surveys were mailed and 60% were returned. Associations between aspects of internationalization and student outcomes (admission to veterinary and graduate schools and starting salaries) were examined. Although administrators strongly believed internationalization had value, implementation was limited. The most common practices included international content in core animal science classes, advising, international internships, and participation of faculty in international scholarly activities. Few departments have incorporated internationalization into their mission statements or developed a specific international-themed class, scholarships devoted to international activities, or roles for international students. Few departments reported participation of students in international programs. Barriers included finances and limited commitment from higher administration. Student outcomes were positively associated with faculty size, percentage of international faculty, the ratio of international students to the total student population, international content in core animal science classes, a specific international-themed class, availability of international internships, and exchange of class material internationally via the Internet. Departments that did not offer international opportunities had a negative association (r = -0.79) with starting salary, but these relationships may not be causal. Alternatively, progressive departments may attract and retain exceptional students. The analysis indicated an awareness of the value of international programs, positive impacts in student outcomes, and financial barriers to implementation.

Agriculture↗

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat.

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell-cell and cell-matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cells infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell-cell and cell-matrix interactions, while syndecan-2 showed a predilection to associate with cell-matrix interactions during hard tissue formation.

Alveolar Process↗

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Biopsy, Needle↗

Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors.

Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding regions have been reported in cancer. The mechanisms that generate such mutations and the importance of mtDNA mutations in tumor development are still not clear. Here we present the identification of a specific and highly polymorphic homopolymeric C stretch (D310), located within the displacement (D) loop, as a mutational hotspot in primary tumors. Twenty-two % of the 247 primary tumors analyzed harbored somatic deletions/insertions at this mononucleotide repeat. Moreover, these alterations were also present in head and neck preneoplastic lesions. We further characterized the D310 variants that appeared in the lung and head and neck tumors. Most of the somatic alterations found in tumors showed deletion/insertions of 1- or 2-bp generating D310 variants identical to constitutive polymorphisms described previously. Sequencing analysis of individual clones from lymphocytes revealed that patients with D310 mutations in the tumors had statistically significant higher levels of D310 heteroplasmy (more than one length variant) in the lymphocyte mtDNA as compared with the patients without D310 mutations in the tumor mtDNA. On the basis of our observations, we propose a model in which D310 alterations are already present in normal cells and achieve homoplasmy in the tumor through a restriction/amplification event attributable to random genetic drift and clonal expansion.

Carcinoma, Squamous Cell↗

Assessment of lung cancer response after nonoperative therapy: tumor diameter, bidimensional product, and volume. A serial CT scan-based study.

PURPOSE: Tumor response after nonoperative lung cancer therapy is traditionally evaluated by bidimensional measurement of maximum tumor diameters. The purpose of this analysis is to investigate whether tumor largest dimension (based on RECIST [Response Evaluation Criteria In Solid Tumors]), bidimensional tumor product, and volume correlate with each other in evaluating tumors of patients with locally advanced non-small-cell lung cancer (NSCLC). In addition, the pace of locally advanced NSCLC volumetric response over time, as well as the prognostic value of tumor size, was assessed in this report with software-assisted evaluation of sequential tumor measurement. METHODS AND MATERIALS: Patients with locally advanced NSCLC treated with thoracic radiotherapy (RT) with or without chemotherapy were included, if the following were available: a pretreatment computed tomography (CT) simulation and at least two follow-up diagnostic thoracic CT scans taken at our institution after 1996 that were available in Dicom format for electronic transfer of images from diagnostic radiology to a computer terminal with commercial statistics software (AcQsim/CMS Focus). Primary lung tumor and grossly involved lymph nodes were contoured manually on pre-RT axial images and on all follow-up CT scans. Tumor/lymph node largest dimensions, bidimensional products (BP), and volumes were measured using the same software. Data were presented as percent change in volume or unidimensional and bidimensional measurements, with the CT simulation measurements serving as baseline. RESULTS: A total of 22 patients were evaluated. The median thoracic RT dose was 62.4 Gy (range: 50.0-69.6), and all patients had a Karnofsky performance status > or =80. Chemotherapy (mostly carboplatin/paclitaxel) was given to 17 patients. Nineteen patients had Stage III NSCLC; 1 patient was in Stage I, 1 was in Stage IV, and 1 was recurrent. A total of 107 thoracic CT scans (22 pretreatment and 85 follow-up), averaging 4.9 scans per patient, were analyzed. Tumors reached the smallest volume at a median of 11.0 months from RT completion in all patients, 8.5 months in patients who subsequently failed locally (n = 8), and 11.9 months in those who did not fail locally. Failure rates were as follows: in-field, 36% (8/22); intrathoracic (lung nodules, effusion, pleura), 55% (12/22); and distant, 50% (11/22). Eleven patients are still alive, 4 free of disease. Overall median survival time (MST) is 27.3 months. The median initial tumor volume was 88.0 cc (range: 3.8-218) for all patients; median BP was 33.0 cm(2) (range: 3.1-112.1), and median tumor largest dimension was 7.6 cm (range: 2.2-13.5). The MST of patients with initial tumor volume < or =63.0 cc (n = 9) was >53.0 months and of those with tumor volume > 63.0 cc was 17.3 months. The MST of patients (n = 6) with initial bidimensional tumor product < or =16 cm(2) was >53.0 months and of those with tumor product >16 cm(2) was 17.3 months. The MST of patients with largest initial dimension < or =4 cm was >53.1 months and of those with largest dimension > 4 cm was 25.0 months. At 24 months, 79% of patients with a tumor volume < or =124.0 cc (n = 18) had locally controlled tumors, vs. 0% of patients with tumor volumes >124.0 cc. At the same time point, 93% of patients with BP < or =40 cm(2) were locally controlled, vs. 0% of those with BP > 40 cm(2); 100% of patients with tumor dimensions < or =7.5 cm were locally controlled, vs. 40% of those with dimensions >7.5 cm. The partial responses in our series (assessed as the best response obtained during observation period) were as follows: 4 patients assessed based on either dimension only, product only, or volume only; 15 partial responses based on dimension or product; 16 partial responses based on volume alone; 3 cases of no tumor response, based on dimension or product; and 2 cases based on tumor volume alone. That represents good to excellent agreement among all three methods of measurement. CONCLUSIONS: (1) The response of locally advanced NSCLC to nonoperative therapy is a slow process, with tumor volumes reaching their nadir several months after treatment. (2) Smaller initial tumor size, as measured by largest tumor dimension, bidimensional product, or tumor volume, is associated with better local control and survival than larger initial measurements. (3) Any of the three tumor measurements (largest dimension, bidimensional product, or volume) can be used as a reliable tool in assessing lung cancer response to nonoperative therapy. This confirms further the validity of RECIST and does not suggest that tumor volume is significantly superior for response evaluation.

Aged↗

Epitope-vaccine as a new strategy against HIV-1 mutation.

An effective vaccine is urgently needed to stop AIDS-epidemic. Up to now none of the candidate HIV-vaccines has been developed to prevent HIV-1 infection. A few neutralizing antibodies against HIV-1 enveloping proteins proved to be highly effective to neutralize different strains in vitro. Unfortunately, these antibodies are rare in infected humans, and have never yet been raised by a vaccine. The multiple sequential and antigenic variability of HIV-1 led to unprecedented difficulties in development of effective vaccines and anti-viral drugs. More and more experimental evidences indicated that HIV-1 mutants resulted in immune evasion may be a grave challenge for conventional strategy to prepare effective vaccines. We suggested that epitope-vaccine could be a new strategy to induce high levels of neutralizing antibodies with predefined epitope-specificity against HIV-1. Several candidate epitope-vaccines including mono-epitope-vaccine, multi-epitope-vaccine, epitope-vaccines in combination, were prepared and systematically studied in animal experiments. These studies provided experimental evidences that epitope-vaccine could be a new strategy to develop effective vaccines for prevention and immunotherapy against viral infection of HIV-l or other viruses.

AIDS Vaccines↗

An investigation of a model of percentage depth dose for irregularly shaped fields.

A significant component of the total dose delivered to tumor and surrounding tissue during a radiation treatment arises from the scattering of the primary beam. Accounting for this component accurately and efficiently is a necessity. In this study we investigate a method for calculating the phantom-scatter contributions to the total dose by simple summation of scatter dose from a set of individual triangles that span an irregular field. The calculation of phantom scatter is based on a two-parameter model, which is applicable to regions where electron equilibrium is established. The two physical parameters are the dose-averaged linear attenuation coefficient and the beam-hardening coefficient. The advantage of this model is that it is a natural method when an irregular field is shaped by a multi-leaf collimator (MLC). Accuracy is not compromised by the triangulation since the irregular field is defined by the straight edges of the MLC leaves. The model predicts the percent depth dose with acceptable accuracy for any arbitrary shape of fields. We report on results for 6- and 18-MV photon beams and for a number of irregularly shaped fields.

Electrons↗

Analytical method for yrast line states in interacting Bose-Eeinstein condensates.

We propose a method to investigate the energy eigenvalue problem and corresponding yrast line for harmonically trapped interacting N-boson systems. This method is particularly simple and effective to obtain the explicit analytical expressions of low-L energy eigenstates with L denoting systems' total angular momentum but with an arbitrarily large N. We have derived the explicit analytical results for L = 0,1,....,9 and discussed the yrast line for these low- L energy eigenstates.

Journal Article↗

N- and C-domains of HIV-1 gp41: mutation, structure and functions.

Recent studies demonstrated that the N- and C-domains of HIV-1 gp41 is involved in virus-mediated membrane fusion resulting in HIV-entry into the target cells. Up to now, viral mutation baffled many scientists to develop effective vaccines and drugs against HIV-1. To acquire more information of mutation of gp41 and to reveal the relationship of structure and function of the N- and C-domains, we compared and analyzed amino acid sequences of the gp41 ectodomain (aa 512-681) of 862 isolates from most HIV-1 clades (including A, B, C, D, E, F, G, H, I, J and O clades). A consensus sequence of the ectodomain with the highest frequency emerging on each position is constituted. The fusion domain and the N-domain belong to the most conserved regions in gp41, and most variable residues assemble partial to the C terminal of gp41. The hydrophobicity of each position is also calculated. The a and d positions in the N-domain for maintaining stabilization of the trimeric coiled coil interactions are highly conservative, and the e and g positions in the C-domain to retain the interaction show also highly conservative. The strange high conservation of the c residues may have an implication in the coiled coil structure. The highly conserved residues form the lining of the hydrophobic cavity and the deep cavity is an ideal target for small molecular inhibitors. On the C-terminal of the C-domain there is a highly conserved segment GIVQQQ. They are intimately involved in forming the three interfaces between neighboring helices. The function of the N- and C-domains, such as binding to the potential cellular receptor and inducing protective activities, are also discussed. These studies on the mutation, structure and functions of the N- and C-domains suggested that both domains become a new focus to develop effective vaccine and antiviral drugs in the new strategies.

Amino Acid Sequence↗