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Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 469 records · Page 26Linked to original sources

[Effect of P(ET)CO(2) monitoring on cardiac function during hepatectomy].

OBJECTIVE: To investigate the relationship between end-tidal Pco2 (P(ET)CO(2)) and cardiac output (CO) during hepatectomy. METHOD: Swan-Ganz catheter was inserted into the right jugular vein of twenty-one patients undergoing hepatectomy to observe the hemodynamic parameters. Cardiac output (CO) was examined by thermodilution technique. Mechanical ventilation was performed after anaesthesia induction, and P(ET) CO(2) was monitored continuously. The relationship between CO and P(ET)CO(2) was analyzed. RESULTS: A strong positive correlation was found between P(ET)CO(2) and CO, r =0.90, P < 0.05. CONCLUSION: P(ET)CO(2) can be used as a predictor of CO. This technique is safe, simple and can be used in hemodynamic unstable patients during the major surgical procedure and in patient with poor cardiac function.

Cardiac Output↗

Molecular interactions and viral stability revealed by structural analyses of chemically treated cypovirus capsids.

Cytoplasmic polyhedrosis virus (CPV, genus Cypovirus) is a unique member of the family Reoviridae which lacks the outer protective shells that exist in all other members, yet exhibits unusual stability. We have analyzed the effects of different acidic, basic, detergent, and urea treatments on CPV capsids. The integrity of the CPV capsids was unaffected under high-pH conditions that disrupted the orthoreovirus inner core, consistent with its ability to maintain structural integrity in extremely alkaline environments during infection. However, it was sensitive to low pH, detergents, and urea, similarly to other viruses in this family. The three-dimensional structure comparisons by electron cryomicroscopy of the intact empty CPV capsid with the "spikeless" capsid whose turrets were removed by chemical treatments revealed the interaction footprint of the turret on the capsid shell. The observed structural changes associated with the removal of the turret suggest critical structural roles of the turret in maintaining capsid integrity in addition to its enzymatic activities.

Capsid↗

Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.

Haemophilus influenzae NadR protein (hiNadR) has been shown to be a bifunctional enzyme possessing both NMN adenylytransferase (NMNAT; EC ) and ribosylnicotinamide kinase (RNK; EC ) activities. Its function is essential for the growth and survival of H. influenzae and thus may present a new highly specific anti-infectious drug target. We have solved the crystal structure of hiNadR complexed with NAD using the selenomethionine MAD phasing method. The structure reveals the presence of two distinct domains. The N-terminal domain that hosts the NMNAT activity is closely related to archaeal NMNAT, whereas the C-terminal domain, which has been experimentally demonstrated to possess ribosylnicotinamide kinase activity, is structurally similar to yeast thymidylate kinase and several other P-loop-containing kinases. There appears to be no cross-talk between the two active sites. The bound NAD at the active site of the NMNAT domain reveals several critical interactions between NAD and the protein. There is also a second non-active-site NAD molecule associated with the C-terminal RNK domain that adopts a highly folded conformation with the nicotinamide ring stacking over the adenine base. Whereas the RNK domain of the hiNadR structure presented here is the first structural characterization of a ribosylnicotinamide kinase from any organism, the NMNAT domain of hiNadR defines yet another member of the pyridine nucleotide adenylyltransferase family.

Amino Acid Sequence↗

Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii pneumonia: using simulation modeling to inform clinical guidelines.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis. METHODS: A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/microL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/microL. Data were from randomized controlled trials and other published literature. RESULTS: For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/microL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY. CONCLUSIONS: Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/microL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone.

AIDS-Related Opportunistic Infections↗

Thoracoscopic discectomy and fusion in an animal model: safe and effective when segmental blood vessels are spared.

STUDY DESIGN: Disc-endplate excision and spine fusion were compared in animals randomly assigned to segmental vessel-spared and segmental vessel-ligated groups in an in vivo goat model of anterior spine discectomy and fusion using thoracoscopic techniques. OBJECTIVES: To compare safety and completeness of disc and endplate excision, and to perform a histologic and biomechanical comparison between fusion masses when the segmental vessels are spared and when they are ligated using thoracoscopic techniques. SUMMARY OFF BACKGROUND DATA: Because thoracoscopy is relatively new and technically demanding, many surgeons ligate the segmental blood vessels to enhance spine exposure and limit the risk of injury during discectomy and fusion. Although rare, spinal cord compromise secondary to segmental vessel ligation has been reported. METHODS: This study was divided into two phases. In Phase 1, 10 mature goats were randomly assigned to either the segmental vessel-ligated or the segmental vessel-spared group. Disc and endplate excision was performed at six consecutive thoracic levels in each animal (30 levels per group). The animals were killed, and the depth of disc excision was measured in the transverse and sagittal planes. The vertebral bodies then were separated through the disc space; photographic images of the endplates were digitized, and the area of endplate excision was calculated. In Phase 2, 12 mature goats were randomly assigned to the segmental vessel-ligated or vessel-spared group, and five noncontiguous thoracic segments were fused using autologous iliac crest graft. At 4 months the animals were killed, and the spines were harvested. At each disc level, the three-dimensional rotational and translational motions were analyzed and histomorphometric analysis was performed. RESULTS: Phase 1: Each animal survived the operative procedure, and no surgical complications occurred. No difference was found between vessel-ligated and vessel-spared groups in operative time (21.8 vs 22.7 minutes per disc), blood loss (97 vs 159 mL), or transverse (81% vs 74%) or sagittal (85% vs 85%) disc excision. The total area of endplate excision was 70% in the vessel-ligated group and 67% in the vessel-spared group (P > 0.1). Phase 2: Biomechanical testing demonstrated no difference in stiffness of the fused segments between the two groups in flexion-extension or axial rotation. However, greater flexibility in lateral bending was found in the specimens whose vessels were ligated (P < 0.05). The percentage of trabecular bone volume was similar between the two groups. CONCLUSIONS: The segmental vessels in the thoracic spine can be effectively spared without injury during disc excision and fusion. Although slightly more disc area was excised with ligation of the vessels, this was not statistically significant, and the fusion mass was similar between the two groups. Sparing the segmental vessels may provide blood supply that aids fusion mass, and the result may be greater spine stiffness in the coronal plane. Sparing the segmental vessels during thoracoscopic anterior disc excision and fusion can be safe. It should be considered in patients with a high risk for neurologic injury because of decreased spinal cord perfusion in revision surgery, severe kyphosis, congenital anomalies. Because the neurologic risk of vessel ligation has not been clearly established for idiopathic scoliosis, the surgeon will have to consider the risk-benefit ratio of adopting these methods when deciding not to ligate vessels in these patients.

Animals↗

UV-induced T-->C transition at a TT photoproduct site is dependent on Saccharomyces cerevisiae polymerase eta in vivo.

UV-induced reversion of the arg4-17 ochre allele in Saccharomyces cerevisiae is largely dependent on translesion polymerase eta (Rad30p), known to bypass cyclobutane-type TT dimers in an error-free fashion. arg4-17 locus reversion was predominantly due to T-->C transition of T127, the 3' T of a TT photoproduct site. This event was at least 20-fold reduced in a rad30 deletion mutant, irrespective of the status of nucleotide excision repair. These data correlate with known properties of 6-4 TT photoproducts and in vitro characteristics of polymerase eta and suggest that polymerase eta plays an important in vivo role in inserting G opposite the 3' T of 6-4 TT photoproducts at this site. Alternatively, an unprecedented error-prone processing of cyclobutane-type photoproducts at this site by polymerase eta must be assumed as the critical mechanism. Whereas photoreactivation results indeed hint at the latter possibility, a possible regulatory influence of reducing the overall UV damage load on the bypass probability of non-cyclobutane-type pyrimidine dimer photoproducts should not be dismissed.

Argininosuccinate Lyase↗

Gemini-induced columnar jointing in vitreous ice. Cryo-HRSEM as a tool for discovering new colloidal morphologies.

A gemini surfactant is able to promote columnar jointing in vitreous ice where long pillars, often of hexagonal cross section, are formed. This jointing is visible by cryo-high-resolution scanning electron microscopy (cryo-HRSEM), in which colloidal suspensions in bulk water are cooled rapidly in liquid ethane, thereby avoiding the potential artifacts with other types of EM. The jointing is proposed to arise from a new type of colloidal morphology where the surfactant self-assembles into hexagonal columns. Evidence for this mechanism comes from a cryo-HRSEM photo of an ice-free hexagonal "skeleton" composed of surfactant. Cryo-HRSEM, a method that is just beginning to realize its potential, would seem to have a promising future in the discovery of additional and as yet unimagined colloidal structures.

Journal Article↗

[Mitochondrial myopathy and mitochondrial encephalomyopathy].

OBJECTIVE: To investigate the symptomatic, biochemical, and pathological characteristics of mitochondrial myopathy and mitochondrial encephalomyopathy. METHODS: Physical examination, electromyography, electroencephalography, cranial CT or MRI, serum enzymological examination, and light microscopy and electron microscopy of muscle biopsy specimens were made among twenty-one in-patients with the diagnosis of mitochondrial myopathy and mitochondrial encephalopathy. All the patients were followed up for more than 5 years. RESULTS: Four patients died of lung infection, epilepticism or multiple organ failure 3, 4, 6, and 8 years after the onset of disease. One patient had already survived for 12 years. Among the 6 patients with the original diagnosis of mitochondrial myopathy, the diagnosis of two was changed as myoclonus epilepsy with ragged fiber (MERRF) 5 and 6 years after the onset. Among the seven patients whose disease was originally diagnosed as chronic progressive external ophthalmoplegia the diagnosis was changed as mitochondrial encephalomyopathy with lactic acidemia and stroke like episodes seven years after the onset. CONCLUSION: It is not difficult to diagnose mitochondrial myopathy and mitochondrial encephalomyopathy based on the symptomatical, biochemical, and pathological characteristics. However, the clinical manifestations of these diseases may change during the progress of the disease. Follow-up is highly recommended.

Adolescent↗

abf-1 and abf-2, ASABF-type antimicrobial peptide genes in Caenorhabditis elegans.

Two genes encoding the ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptide, abf-1 and abf-2, were identified in Caenorhabditis elegans. Recombinant ABF-2 exhibited potent microbicidal activity against Gram-positive and Gram-negative bacteria, and yeasts. The tissue-specific distribution estimated by immunofluorescence staining and transgenic analysis of a gfp fusion gene (where GFP corresponds to green fluorescent protein) suggested that ABF-2 contributes to surface defence in the pharynx. abf-1 contains a single intron at a conserved position, suggesting that asabf and abf originated from a common ancestor. Both transcripts for abf-1 and abf-2 were detected as two distinct forms, i.e. spliced leader (SL)1-trans-spliced with a long 5'-untranslated region (UTR) and SL-less with a short 5'-UTR. A polycistronic precursor RNA encoding ABF-1 and ABF-2 was detected, suggesting that these genes form an operon. An 'opportunistic operon' model for regulation of abf genes, including the generation of short SL-less transcripts, is proposed. In conclusion, C. elegans should have an immune defence system due to the antimicrobial peptides. C. elegans can be a novel model for innate immunity. Furthermore, the combination of biochemical identification in Ascaris suum and homologue hunting in C. elegans should be a powerful method of finding rapidly evolved proteins, such as some immune-related molecules in C. elegans.

Amino Acid Sequence↗

Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin.

Nicotinamide/nicotinate mononucleotide (NMN/ NaMN)adenylyltransferase (NMNAT) is an indispensable enzyme in the biosynthesis of NAD(+) and NADP(+). Human NMNAT displays unique dual substrate specificity toward both NMN and NaMN, thus flexible in participating in both de novo and salvage pathways of NAD synthesis. Human NMNAT also catalyzes the rate-limiting step of the metabolic conversion of the anticancer agent tiazofurin to its active form tiazofurin adenine dinucleotide (TAD). The tiazofurin resistance is mainly associated with the low NMNAT activity in the cell. We have solved the crystal structures of human NMNAT in complex with NAD, deamido-NAD, and a non-hydrolyzable TAD analogue beta-CH(2)-TAD. These complex structures delineate the broad substrate specificity of the enzyme toward both NMN and NaMN and reveal the structural mechanism for adenylation of tiazofurin nucleotide. The crystal structure of human NMNAT also shows that it forms a barrel-like hexamer with the predicted nuclear localization signal sequence located on the outside surface of the barrel, supporting its functional role of interacting with the nuclear transporting proteins. The results from the analytical ultracentrifugation studies are consistent with the formation of a hexamer in solution under certain conditions.

Amino Acid Sequence↗

Age-related bone mineral density, accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in chinese women.

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward's triangle [Ward's]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination ( R(2)) of the fitting curve were 0.398 to 0.612 ( p = 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20-24 years at Troc and Ward's, and the latest at the age of 40-44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward's (-66.2%) and the lowest at RU1/3 of the distal forearm (-31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 +/- 0.4% in those 30-39, 4.6 +/- 4.4% in those 40-49, 23.9 +/- 13.3% in those 50-59, 56.3 +/- 20.3% in those 60-69, 71.8 +/- 16.7% in those 70-79 and 83.2 +/- 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6-11.1% at the age of 40-49 and 36.5-40.6% at the age of 50-59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5-3.7% at the age of 40-49 and and 3.9-21.7% at the age of 50-59 years at the other skeletal sites (AP, FN, Troc, Ward's, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites ( p<0.001) at the age of 40-59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured.

Absorptiometry, Photon↗

Down-modulation of monocyte transendothelial migration and endothelial adhesion molecule expression by fibroblast growth factor: reversal by the anti-angiogenic agent SU6668.

Basic and acidic fibroblast growth factor (bFGF and aFGF, respectively) and vascular endothelial growth factor (VEGF) exert angiogenic actions and have a role in wound healing, inflammation, and tumor growth. Monocytes and endothelial cells are involved in these processes, but the effect of FGF and VEGF on monocyte-endothelial cell interactions has not been defined. We observed that monocyte adhesion to resting or cytokine (tumor necrosis factor-alpha or interleukin-1 alpha)-stimulated human umbilical vein endothelial cells (HUVECs) was markedly inhibited (40 to 65%) by culture (1 to 6 days) of HUVECs with aFGF or bFGF. Monocyte transendothelial migration induced by C5a and chemokines (MCP-1, SDF-1 alpha, RANTES, MIP-1 alpha) was also suppressed (by 50 to 75%) on bFGF-stimulated HUVECs. VEGF did not have these effects at the concentrations used (10 to 20 ng/ml), although like bFGF, it promoted HUVEC proliferation. Culture of HUVECs with bFGF and aFGF significantly down-regulated intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression on resting or tumor necrosis factor-alpha-stimulated HUVECs, but had no influence on platelet endothelial cell adhesion molecule (PECAM)-1 and VE-cadherin expression. bFGF also inhibited MCP-1 production by HUVECs. The inhibitory effects of bFGF on monocyte transendothelial migration and adhesion molecule expression were reversed by SU6668, an anti-angiogenic agent and bFGF receptor tyrosine kinase inhibitor. Our results suggest that bFGF and aFGF may suppress endothelial-dependent monocyte recruitment and thus have an anti-inflammatory action during angiogenesis in chronic inflammation but inhibit the immunoinflammatory tumor defense mechanism. However, SU6668 is an effective agent to prevent this down-regulatory action of bFGF on monocyte-endothelial cell interactions.

Angiogenesis Inhibitors↗

Subchondral defects in caprine femora augmented with in situ setting hydroxyapatite cement, polymethylmethacrylate, or autogenous bone graft: biomechanical and histomorphological analysis after two-years.

Juxta-articular defects pose significant challenges due to the high risk of fracture of the subchondral plate and articular cartilage. We evaluated the mechanical and histomorphological repair process of caprine subchondral femoral defects augmented with either a bioresorbable in situ setting hydroxyapatite cement (HAC), polymethylmethacrylate (PMMA), autogenous bone graft (AG), or left empty. Twelve-mm subchondral defects were made bilaterally in the medial femoral condyles of skeletally mature goats and augmented with a test material or left empty. Femurs were harvested at varying time periods out to 2 years and evaluated for subchondral stiffness and histomorphological indices. Several defects augmented using autograft or left empty sustained focal fracture of the subchondral plate. No HAC or PMMA augmented defects showed evidence of subchondral fracture. The HAC and PMMA augmented defects showed comparable stiffness at all time points. The mean volume fraction of HAC remaining within the defects progressively decreased from 96% at 24 h to 38% at 2 years. The new bone replacing the HAC appeared to have normal physiological architecture and orientation. In situ setting hydroxyapatite cement may be a viable alternative for the repair of subchondral defects with an important advantage that while undergoing gradual resorption and replacement with host bone, mechanical integrity of the skeletal defect is maintained.

Animals↗

Site-directed mutagenesis and functional analysis of an active site tryptophan of insect chitinase.

Chitinase is an enzyme used by insects to degrade the structural polysaccharide, chitin, during the molting process. Tryptophan 145 (W145) of Manduca sexta (tobacco hornworm) chitinase is a highly conserved residue found within a second conserved region of family 18 chitinases. It is located between aspartate 144 (D144) and glutamate 146 (E146), which are putative catalytic residues. The role of the active site residue, W145, in M. sexta chitinase catalysis was investigated by site-directed mutagenesis. W145 was mutated to phenylalanine (F), tyrosine (Y), isoleucine (I), histidine (H), and glycine (G). Wild-type and mutant forms of M. sexta chitinases were expressed in a baculovirus-insect cell line system. The chitinases secreted into the medium were purified and characterized by analyzing their catalytic activity and substrate or inhibitor binding properties. The wild-type chitinase was most active in the alkaline pH range. Several of the mutations resulted in a narrowing of the range of pH over which the enzyme hydrolyzed the polymeric substrate, CM-Chitin-RBV, predominantly on the alkaline side of the pH optimum curve. The range was reduced by about 1 pH unit for W145I and W145Y and by about 2 units for W145H and W145F. The W145G mutation was inactive. Therefore, the hydrophobicity of W145 appears to be critical for maintaining an abnormal pKa of a catalytic residue, which extends the activity further into the alkaline range. All of the mutant enzymes bound to chitin, suggesting that W145 was not essential for binding to chitin. However, the small difference in Km's of mutated enzymes compared to Km values of the wild-type chitinase towards both the oligomeric and polymeric substrates suggested that W145 is not essential for substrate binding but probably influences the ionization of a catalytically important group(s). The variations in kcat's among the mutated enzymes and the IC50 for the transition state inhibitor analog, allosamidin, indicate that W145 also influences formation of the transition state during catalysis.

Amino Acid Substitution↗

Transmission electron microscopy for the semi-conductor industry.

During the last 5 years, semi-conductor industry has dramatically enhanced the device performance by continuously introducing new technologies and aggressively scaling down the feature sizes. During the progress, transmission electron microscopy (TEM) has played a very important role in the process development, manufacture controlling, and failure analysis. On the other hand, the development of TEM techniques for the semi-conductor devices, especially the sample preparation technique, has changed the entire aspect of the TEM. TEM is no longer a name heard only in research institutes and universities. It becomes so important for semi-conductor industry that TEM are treated as the most reliable resource for process evaluation and failure analysis and that TEM images are often used as one of the most powerful evidence for the patent infringement trial. In this paper, the author reviews the great challenges that electron microscopist has been facing from the semi-conductor industry and presents TEM results that illustrate the utilization of various TEM techniques to meet the challenges. To emphasize the unique ability of TEM, application of the precision TEM technique is mentioned in detail. A new three-dimensional TEM technique is also discussed.

Journal Article↗

Crystal structures of E. coli nicotinate mononucleotide adenylyltransferase and its complex with deamido-NAD.

Nicotinamide/Nicotinate mononucleotide (NMN/NaMN) adenylyltransferase is an indispensable enzyme in both de novo biosynthesis and salvage of NAD+ and NADP+. In prokaryotes, it is absolutely required for cell survival, thus representing an attractive target for the development of new broad-spectrum antibacteria inhibitors. The crystal structures of E. coli NaMN adenylyltransferase (NMNAT) and its complex with deamido-NAD (NaAD) revealed that ligand binding causes large conformational changes in several loop regions around the active site. The enzyme specifically recognizes the deamidated pyridine nucleotide through interactions between nicotinate carboxylate with several protein main chain amides and a positive helix dipole. Comparison of E. coli NMNAT with those from archaeal organisms revealed extensive differences in the active site architecture, enzyme-ligand interaction mode, and bound dinucleotide conformations. The bacterial NaMN adenylyltransferase structures described here provide a foundation for structure-based design of specific inhibitors that may have therapeutic potential.

Amino Acid Sequence↗

Purification and characterization of acylation stimulating protein from porcine serum.

A method for purifying acylation stimulating protein (ASP) from porcine serum is described. The mRNA encoding ASP was cloned by reverse transcriptase-polymerase chain reaction which predicted a 76 residue peptide. Based on this sequence, we generated antisera to a C-terminal peptide (ASP(1-20)) which aided ASP purification. Identity of the purified protein was verified by N-terminal sequencing. The molecular mass of porcine ASP is 8926. Porcine ASP stimulated esterification of fatty acid into triacylglycerol in cultured human cells with potency similar to that of human ASP (twofold at 5 microM). Based on this evidence that ASP exists in porcine blood, and that it has acylation stimulating activity, we propose that ASP may play a role in regulation of energy storage in adipose tissue in the pig.

Amino Acid Sequence↗

Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis.

Desmoplastic small round cell tumor (DSRCT) is defined genetically by the chimeric fusion of the Ewing's sarcoma and Wilms' tumor genes, generating a novel transcription factor, EWS-WT1. By using cells with inducible EWS-WT1 to screen high-density microarrays, we identified BAIAP3 as a transcriptional target of the chimera. The BAIAP3 promoter is specifically bound in vivo by the (-KTS) isoform of EWS-WT1, consistent with its activation in reporter assays. BAIAP3 encodes a protein implicated in regulated exocytosis, which is colocalized with a secreted growth factor within cytoplasmic organelles. Ectopic expression of BAIAP3 in tumor cells dramatically enhances growth in low serum and colony formation in soft agar. BAIAP3 therefore encodes a transcriptional target of an oncogenic fusion protein that implicates the regulated exocytotic pathway in cancer cell proliferation.

Angiogenesis Inhibitors↗