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Biomedical subjects

Z Tang

Publications and source records attributed to Z Tang.

At least 37 records · Page 2Linked to original sources

Identification of a novel activation domain in the Notch-responsive transcription factor CSL.

CSL is the primary target of the Notch signaling pathway in mammalian cells. It is a DNA binding protein that generally represses transcription in the absence of Notch signaling and activates transcription upon formation of a ternary complex with NICD, the protease-generated intracellular domain of NOTCH: Previous mapping experiments identified the central third of CSL as both necessary and sufficient for DNA binding and activation by NOTCH: Here we show that CSL promotes transcription in 293T cells in the absence of added NICD and that this activity requires both the central domain plus the C-terminal third of the protein. Evidence is presented that argues against a contribution of endogenous NICD and instead supports the possibility that distinct coactivators may directly stimulate the activity of CSL in a cell type-specific manner. This conclusion supports a recent finding that Drosophila CSL (Suppressor of Hairless) can also mediate transcriptional activation in the absence of NOTCH:

3T3 Cells↗

[Expression rates of three angiogenic factors in hepatocellular carcinoma and their relation with microvessel density and portal vein tumor thrombosis].

OBJECTIVE: To investigate the expression rates of the three angiogenic factors-basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) in hepatocellular carcinoma (HCC) and to investigate the relation of their expression rates to the microvessel density (MVD) of the tumor and to the formation of portal vein tumor thrombus (PVTT). METHODS: Immunohistochemical staining was conducted on 61specimens of hepatic cell carcinoma removed in operation. RESULTS: The expression rates of dFGF, VEGF, and PD-ECGF in HCC tissue were 45.9%, 75.4% and 70.5% respectively. The incidence rates of PVTT while all of the 3 angiogenic factor were negatively expressed, one of them was positively expressed, two of them were positively expressed, and all of them were positively expressed were 16.7%, 25.0%, 54.2% and 63.2% respectively (P < 0.05, test for trend). The MVD counts in HCC tissue in the above-mentioned four conditions were 99 +/- 56, 113 +/- 27, 140 +/- 347 and 194 +/- 52 respectively (P < 0.001, ANOVA test). CONCLUSION: As the number of positively expressed angiogenic factors in HCC tissue increases, the angiogenic capability of the tumor enhances greatly, and the incidence rate of PVTT increases too.

Adult↗

Craniosynostosis and related limb anomalies.

Many genetically determined craniosynostosis syndromes feature limb anomalies, implying that pathways of cranial suture and limb morphogenesis share some identical components. Identification of heterozygous mutations in FGFR1, FGFR2, FGFR3, TWIST and MSX2 in craniosynostosis has focused particular attention on these genes. Here we explore two themes: use of clinical/molecular analysis to provide new clues to pathophysiology and the contrasting effects of loss- and gain-of-function mutations. Apert syndrome is a severe craniosynostosis/syndactyly disorder usually caused by specific substitutions (Ser252Trp or Pro253Arg) in FGFR2. The relative severity of cranial and limb malformations varies in opposite directions for the two mutations, suggesting that these phenotypes arise by different mechanisms. Clinical and biochemical evidence supports a model in which alternative splice forms of FGFR2 mediate these distinct effects. Pro-->Arg substitutions equivalent the Pro253Arg/FGFR2 mutation occur in both FGFR1 and FGFR3, and are also associated with craniosynostosis. This suggests a common pathological mechanism, whereby enhanced affinity for a limited repertoire of tissue-specific ligand(s) excessively prolongs signalling in the cranial suture. The first MSX2 mutation in craniosynostosis was described in 1993 but this remains the only example. We have recently identified three MSX2 mutations associated with a different cranial phenotype, parietal foramina. DNA binding studies show that the craniosynostosis and parietal foramina arise from gain and loss of function, respectively.

Acrocephalosyndactylia↗

Formation of binary alloy cluster ions from group-14 elements and cobalt and comparison with solid-state alloys.

By using laser ablation on mixtures of transition metal cobalt and group-14 elements, binary alloy cluster anions were produced while no binary alloy cluster cations were detected, and the homocluster cations of group-14 elements appeared at very low abundance. The differences between clustering abilities of germanium, tin and lead with cobalt are described, and the chemical bonds in the binary alloy cluster anions appear to indicate a transition from covalent to metal bonds. The cluster anion [CoPb10](-) appears in very high abundance (magic number), and an endohedral structure is proposed for this cluster. The cluster anion [CoPb12](-), also representing a magic number, probably has an icosahedral structure. Compared with solid-state Co/Ge binary alloys, the compositions of most binary alloy cluster anions are germanium-rich, in which the covalent bonds are predominant.

Journal Article↗

BCL-1 rearrangement in acute lymphocytic leukemia and its clinical significance.

BCL-1 rearrangement (BCL-1/IgH gene rearrangement) in acute lymphocytic leukemia and its clinical significance was investigated. In 38 patients with acute lymphocytic leukemia (ALL), the genomic DNA of mononuclear cells isolated from peripheral blood and bone marrow was amplified by using hemi-nested polymerase chain reaction (PCR) technique and the expression of cyclin D1 protein of mononuclear cells was detected by using immunohistochemical method. Ten patients with acute granulocytic leukemia, 2 with chronic granulocytic leukemia and 10 with normal bone marrow served as control group. The results showed that BCL-1 rearrangement was detectable in 3 of 38 ALL patients (7.9%) and cyclin D1 protein positive expression was detected in 4 ALL patients (10.5%). Three ALL patients with BCL-1 rearrangement were all B-cell leukemia (B-ALL) and accompanied by cyclin D1 protein expression. No BCL-1/IgH rearrangement or cyclin D1 protein expression was detected in 12 patients with granulocytic leukemia and 10 cases of normal bone marrow. Leukocyte counts in peripheral blood of B-ALL patients with BCL-1 rearrangement and (or) cyclin D1 protein expression were significantly increased and the patients had bad reaction to chemotherapy. It was concluded that: 1) BCL-1/IgH gene rearrangement were detected in acute B lymphocytic leukemia; 2) B-ALL patients with BCL-1 rearrangement and (or) cyclin D1 protein expression had poor prognosis.

Adolescent↗

Mutation and overexpression of the beta-catenin gene may play an important role in primary hepatocellular carcinoma among Chinese people.

AIM: To study the role of beta-catenin gene mutation and expression in hepatocellular carcinogenesis. METHOD: Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, and four normal liver tissues were analyzed. Subcellular distribution of beta-catenin was examined by immunohistochemistry staining. Mutation and semiquantitative expression of beta-catenin gene exon 3 mRNA were detected by RT-PCR-SSCP and in situ hybridization. RESULT: Immunohistochemistry showed that all normal liver tissues and para-cancerous tissues examined showed membranous-type staining for beta-catenin protein, frequently with weak expression in the cytoplasm, but no beta-catenin accumulation in nuclei was found; while in liver cancer, 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. On SSCP, 15 cases (44.1%) of HCC altogether displayed three kinds of characteristic mutational mobility shifts. No abnormal shifting bands were found in tissues from normal liver or para-cancerous area. The beta-catenin gene exon 3 mRNA expression index of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to beta-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of paracancerous tissues and normal liver tissues. CONCLUSION: beta-catenin gene mutation and overexpression may have a critical role in malignant progression of hepatic carcinogenesis among Chinese people.

Carcinoma, Hepatocellular↗

Metabolism and functions of highly unsaturated fatty acids: an update.

This review briefly examines the recent progress in knowledge about the synthesis and degradation of highly unsaturated fatty acids (HUFA) and their functions. Following the cloning of mammalian Delta6-desaturase (D6D), the D6D mRNA was found in many tissues, including adult brain, maternal organs, and fetal tissue, suggesting an active synthesis of HUFA in these tissues. The cloning also confirmed the long-postulated hypothesis that the same pathway is followed in n-6 and n-3 HUFA synthesis. Dietary n-6 and n-3 HUFA both induce fatty acid oxidation enzymes in peroxisomes when compared to their respective precursor polyunsaturated fatty acids. This suggests that peroxisomes may be the primary site of HUFA degradation when HUFA are supplied in excess from the diet. Peroxisome proliferators strongly induce the enzymes for the HUFA synthesis. The mechanism of this induction is currently unknown. Recent studies revealed new HUFA functions that are not mediated by eicosanoids. These functions include endocytosis/exocytosis, ion-channel modulation, DNA polymerase inhibition, and regulation of gene expression. These new discoveries will enable us to re-examine the underlying mechanisms for the classical symptoms of essential fatty acid deficiency as well as vitamin E deficiency. Progress has also been made in understanding the mechanism by which dietary HUFA reduce body fat deposition. One mechanism is induction of genes for fatty acid oxidation, which is mediated by peroxisome proliferator-activated receptor-alpha. Another likely mechanism is that HUFA suppress genes for fatty acid synthesis by reducing both mRNA and protein maturation of sterol regulatory element binding protein-1.

Animals↗

Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis.

Notch signaling plays an important role in cell-fate specification in multicellular organisms by regulating cell-cell communication. The Drosophila deltex gene encodes a modulator of the Notch pathway that has been shown to interact physically with the Ankyrin repeats of Notch. We isolated four distinct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse Deltex2 (MDTX2), mouse Deltex2DeltaE (MDTX2DeltaE), and mouse Deltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a high degree of similarity to Drosophila Deltex and its human homolog, DTX1 throughout their lengths, even though they possess distinct structural features. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and in the thymus, overlapping with those of mouse Notch1. In mammalian tissue culture cells, overexpression of any of the four mouse deltex homologs suppressed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein, in a manner similar to suppression by an activated form of human Notch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the expression of myogenin, one of the myogenic transcriptional factors; this was also similar to a previously reported activity of constitutively activated Notch. Furthermore, misexpression of any of the MDTX genes in Xenopus embryos resulted in an expansion of the region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, our results suggest that these mouse deltex homologs are involved in vertebrate Notch signaling and regulation of neurogenesis.

Amino Acid Sequence↗

Synthesis and biodistribution of a new 99mTc nitrido complex for brain imaging.

Bis(N-isobutyl-dithiocarbamato) nitrido technetium-99m complex [99mTcN(IBDTC)2] (IBDTC: N-isobutyl dithiocarbamato) was synthesized by the reduction of 99mTcO4- into [99mTc = N]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of sodium N-isobutyl dithiocarbamate dihydrate. The radiochemical purity of the complex was over 90% as measured by thin layer chromatography. It was stable over 6h at room temperature. Its partition coefficient indicated that it is a good lipophilic complex. Biodistribution in mice demonstrated that the complex accumulated in the brain with high uptake and good retention. The brain uptake (ID%/g) was 6.22, 5.45 and 3.88 and the brain/blood ratio was 1.51, 2.24, 1.84 at 5, 30 and 60 min post-injection, respectively. These results suggest potential usefulness of the complex as a brain perfusion imaging agent.

Animals↗

Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1.

The mitotic checkpoint blocks the activation of the anaphase-promoting complex (APC) until all sister chromatids have achieved bipolar attachment to the spindle. A checkpoint complex containing BubR1 and Bub3 has been purified from mitotic human cells. Upon checkpoint activation, the BubR1-Bub3 complex interacts with Cdc20. In the absence of Mad2, BubR1 inhibits the activity of APC by blocking the binding of Cdc20 to APC. Surprisingly, the kinase activity of BubR1 is not required for the inhibition of APCCdc20. BubR1 also prevents the activation of APCCdc20 in Xenopus egg extracts, and restores the mitotic arrest in Cdc20-overexpressing cells treated with nocodazole. Because BubR1 also interacts with the mitotic motor CENP-E, the ability of BubR1 to inhibit APC may be regulated by kinetochore tension or occupancy.

Animals↗

Comparison of blood counts in venous, fingertip and arterial blood and their measurement variation.

We compared routine blood pictures in venous, fingertip and arterial blood and their measurement variation. A pair of venous and fingertip blood samples were simultaneously collected from 24 volunteers, and another pair of venous and arterial samples from another 12 volunteers. The volunteers were healthy adults, aged 20-22 years, with males and females in equal numbers. Three aliquots of blood were taken from each person for three measurements of blood counts, including haemoglobin concentration and haematocrit, using an automatic haematology analyser. Compared to arterial blood, there was a significant increase of erythrocyte count (2.7%) and haematocrit (3.1%) in the venous blood. The total and large leucocyte counts were significantly higher (9.2% and 12.6%, respectively) in the fingertip blood than in the venous blood. There were a decreasing number of leucocytes in the fingertip blood with repeated sampling. The intermeasurement variation for total leucocyte or haemoglobin measurement was significantly larger as measured with the fingertip blood or arterial blood than with the venous blood. The intermeasurement coefficients of variation of haemoglobin (1.3%) and small leucocyte ratio or platelet (approximately 4.0%) measurements with venous and arterial blood were the smallest and largest, respectively. Volume of arterial plasma was diminished by 2-3% after microcirculation. Elevation of total leucocyte count in the fingertip blood was mainly due to the increase of granulocytes. Measurement with venous blood was of better precision than with fingertip or arterial blood.

Adult↗

Changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction.

PURPOSE: This study investigated the changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction. MATERIALS AND METHODS: Bilateral mandibular corticotomies were performed in 8 goats. The mandibles in 6 goats were lengthened 10 mm using a custom-made distractor with 2 different rates of distraction (1 mm/d [n = 3] and 2 mm/d [n = 3]); the other 2 nondistracted mandibles served as a control. The goats with distracted mandibles were killed at 2 weeks after completion of distraction. The inferior alveolar nerve specimens from all animals were harvested and processed for histologic and ultrastructural evaluation. RESULTS: The mandibles were lengthened successfully in the distracted animals. Morphologic changes in the inferior alveolar nerves were observed when compared with the nondistracted controls. Moreover, signs of nerve degeneration, such as demyelination, axonal swelling, axoplasmic darking, and decrease in the number of axons, were more extensive and prominent in those nerves distracted at a rate of 2 mm/d. CONCLUSIONS: Degenerative changes in the inferior alveolar nerve occur after mandibular lengthening by distraction osteogenesis. The distraction rate of 1 mm/d appears to be tolerable and safe for the inferior alveolar nerve, but rapid distraction may cause serious degeneration.

Animals↗

APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.

In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. With the use of a baculoviral expression system, we have reconstituted the ubiquitin ligase activity of human APC. In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. However, the minimal APC2/11 ubiquitin ligase module does not possess substrate specificity, because it also ubiquitinates the destruction box deletion mutants of securin and cyclin B1. Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. Zn(2+)-binding and mutagenesis experiments indicate that APC11 binds Zn(2+) at a 1:3 M ratio. Unlike the two Zn(2+) ions of the canonical RING-finger motif, the third Zn(2+) ion of APC11 is not essential for its ligase activity. Surprisingly, with Ubc4 as the E2 enzyme, Zn(2+) ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn(2+) ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis.

Amino Acid Sequence↗

Single nucleotide polymorphisms (SNPs) assay using reversible association and dispersion of DNA-linked colloidal nanoparticles.

The amphiphilic copolymer consisting of oligodeoxyribonucleotide (ODN; dT12) as the hydrophilic part and thermo-responsive poly(N-isopropylacrylamide) (polyNIPAAm) as the hydrophobic part was prepared. The copolymers formed DNA-linked colloidal nanoparticles above the phase transition temperature of polyNIPAAm part. The nanoparticles aggregated rapidly when the complementary ODN (dA12) was added into the dispersion. In contrast, they kept dispersed in the absence of the complementary ODN and in the presence of the point-mutated ODN ((dA6)dT(dA5)). These distinct phenomena may be applied for an oligonucleotides discrimination system in gene diagnosis.

Acrylic Resins↗

Oxygen effects on glucose meter measurements with glucose dehydrogenase- and oxidase-based test strips for point-of-care testing.

OBJECTIVES: To determine the effects of different oxygen tensions (Po2) on glucose measurements with glucose dehydrogenase (GD)-based and glucose oxidase (GO)-based test strips, to quantitate changes in glucose measurements observed with different Po2 levels, and to discuss the potential risks of oxygen-derived glucose errors in critical care. DESIGN: Venous blood from healthy volunteers was tonometered to create different oxygen tensions simulating patient arterial Po2 levels. Venous blood from diabetic patients was exposed to air to alter oxygen tensions simulating changes in Po2 during sample handling. Whole-blood glucose measurements obtained from these samples with six glucose meters were compared with reference analyzer plasma glucose measurements. Glucose differences were plotted vs. different Po2 levels to identify error trends. Error tolerances were as follows: a) within +/-15 mg/dL of the reference measurement for glucose levels 100 mg/dL. SETTING AND SUBJECTS: Five healthy volunteers in the bench study and 11 diabetic patients in the clinical study. RESULTS: In the bench study, increases in Po2 levels decreased glucose measured with GO-based amperometric test strips, mainly at Po2 levels >100 torr. At nearly constant glucose concentrations, glucose meter systems showed large variations at low (39 torr) vs. high (396 torr) Po2 levels. Glucose measured with GD-based amperometric and GO-based photometric test strips generally were within error tolerances. In the clinical study, 31.6% (Precision PCx), 20.2% (Precision QID), and 23.0% (Glucometer Elite) of glucose measurements with GO-based amperometric test strips, 14.3% (SureStep) of glucose measurements with GO-based photometric test strips, and 4.6% (Accu-Chek Advantage H) and 5.9% (Accu-Chek Comfort Curve) of glucose measurements with GD-based amperometric test strips were out of the error tolerances. CONCLUSIONS: Different oxygen tensions do not significantly affect glucose measured with the GD-based amperometric test strips, and have minimal effect on GO-based photometric test strips. Increases in oxygen tension lowered glucose measured with GO-based amperometric test strips. We recommend that the effects of different oxygen tensions in blood samples on glucose measurements be minimized by using oxygen-independent test strips for point-of-care glucose testing in critically ill and other patients with high or unpredictable blood Po2 levels.

Blood Gas Analysis↗

Homeodomain leucine zipper proteins bind to the phosphate response domain of the soybean VspB tripartite promoter.

The soybean (Glycine max L. Merr. cv Williams 82) genes VspA and VspB encode vacuolar glycoprotein acid phosphatases that serve as vegetative storage proteins during seed fill and early stages of seedling growth. VspB expression is activated by jasmonates (JAs) and sugars and down-regulated by phosphate and auxin. Previous promoter studies demonstrated that VspB promoter sequences between -585 and -535 mediated responses to JA, and sequences between -535 and -401 mediated responses to sugars, phosphate, and auxin. In this study, the response domains were further delineated using transient expression of VspB promoter-beta-glucuronidase constructs in tobacco protoplasts. Sequences between -536 and -484 were identified as important for phosphate responses, whereas the region from -486 to -427 mediated sugar responses. Gel-shift and deoxyribonuclease-I footprinting assays revealed four DNA-binding sites between -611 and -451 of the soybean VspB promoter: one in the JA response domain, two in the phosphate response domain, and one binding site in the sugar response domain. The sequence CATTAATTAG present in the phosphate response domain binds soybean homeodomain leucine zipper proteins, suggesting a role for these transcription factors in phosphate-modulated gene expression.

Acid Phosphatase↗

Ultrasensitive optical DNA biosensor based on surface immobilization of molecular beacon by a bridge structure.

A novel biotinylated molecular beacon (MB) probe was developed to prepare a DNA biosensor using a bridge structure. MB was biotinylated at the quencher side of the stem and linked on a biotinylated glass cover slip through streptavidin, which acted as a bridge between MB and glass matrix. An efficient fluorescence microscope system was constructed to detect the fluorescence change caused by the conformation change of MB in the presence of complementary DNA target. The proposed biosensor was used to directly detect, in real-time, the target DNA molecules. The bridge immobilization method caused the proposed DNA biosensor to have a faster and more stable response. Under the optimal conditions, the newly developed DNA biosensor showed a linear response toward ssDNA in the range of 5-100 nM with a detection limit of 2 nM. It was interesting to note that the described biosensor was reproducible after being regenerated by urea.

Biosensing Techniques↗