Biomedical subjects

X Huang

Publications and source records attributed to X Huang.

At least 235 records · Page 13Linked to original sources

PubMed2000

Effect of interferon-alpha on CD20 antigen expression of B-cell chronic lymphocytic leukemia.

Chimeric CD20 monoclonal antibody as alternative therapy in relapsed low-grade non-Hodgkin's lymphoma (NHL) has produced responses in nearly 50% of patients. Augmenting CD20 expression on tumor cells and/or inducing its expression may increase the cell kill and effectiveness of antibody therapy. Peripheral blood lymphocytes from 19 patients with B-cell chronic lymphocytic leukemia (B-CLL) were incubated in vitro in the presence of interferon-alpha (IFN-alpha) (500 U/ml and 1,000 U/ml) for 24 and 72 hours. The effect on CD20 expression was studied by flow cytometry. The differences in the percentage positivity, the mean fluorescence intensity (MFI), and the product of percentage positivity and MFI were used to assess upregulation. There was a significant upregulation of CD20 expression on B cells seen at both concentrations after 24-hour priming (p < 0.01). B-CLL cells cultured for 72 hours in the presence of IFN-alpha also showed upregulation of CD20 expression; however, the degree of upregulation was much lower than that seen at 24 hours. There was no statistically significant increase in CD20 antigen expression on normal lymphocytes following cytokine exposure. These results suggest that IFN-alpha priming may augment the effectiveness of antibody therapy by directly upregulating CD20 antigen expression in addition to its indirect action through effector cells of the host.

Antigens, CD↗

PubMed2000

Alzheimer's disease, beta-amyloid protein and zinc.

Alzheimer's disease (AD) is characterized by amyloid deposits within the neocortical parenchyma and the cerebrovasculature. The main component of these predominantly extracellular collections, Abeta, which is normally a soluble component of all biological fluids, is cleaved out of a ubiquitously expressed parent protein, the amyloid protein precursor (APP), one of the type 1 integral membrane glycoproteins. Considerable evidence has indicated that there is zinc dyshomeostasis and abnormal cellular zinc mobilization in AD. We have characterized both APP and Abeta as copper/zinc metalloproteins. Zinc, copper and iron have recently been reported to be concentrated to 0.5 to 1 mmol/L in amyloid plaque. In vitro, rapid Abeta aggregation is mediated by Zn(II), promoted by the alpha-helical structure of Abeta, and is reversible with chelation. In addition, Abeta produces hydrogen peroxide in a Cu(II)/Fe(III)-dependent manner, and the hydrogen peroxide formation is quenched by Zn(II). Moreover, zinc preserves the nontoxic properties of Abeta. Although the zinc-binding proteins apolipoprotein E epsilon4 allele and alpha(2)-macroglobulin have been characterized as two genetic risk factors for AD, zinc exposure as a risk factor for AD has not been rigorously studied. Based on our findings, we envisage that zinc may serve twin roles by both initiating amyloid deposition and then being involved in mechanisms attempting to quench oxidative stress and neurotoxicity derived from the amyloid mass. Hence, it remains debatable whether zinc supplementation is beneficial or deleterious for AD until additional studies clarify the issue.

Alzheimer Disease↗

PubMed2000

1,4-Anthraquinone: an anticancer drug that blocks nucleoside transport, inhibits macromolecule synthesis, induces DNA fragmentation, and decreases the growth and viability of L1210 leukemic cells in the same nanomolar range as daunorubicin in vitro.

1,4-Anthraquinone (AQ) was synthesized and shown to prevent L1210 leukemic cells from synthesizing macromolecules and growing in vitro. In contrast, its dihydroxy-9,10anthraquinone precursor, quinizarin, was inactive. The antitumor activity of AQ was compared to that of daunorubicin (DAU), which is structurally different from AQ but also contains a quinone moiety. AQ is equipotent to DAU against L1210 tumor cell proliferation (IC50: 25 nM at day 2 and 9 nM at day 4) and viability (IC50: 100 nM at day 2 and 25 nM at day 4), suggesting that its cytostatic and cytotoxic activities are a combination of drug concentration and duration of drug exposure. Since AQ does not increase but rather decreases the mitotic index of L1210 cells at 24 h, it is not an antitubulin drug but might arrest early stages of cell cycle progression. Like DAU, a 1.5-3 h pretreatment with AQ is sufficient to inhibit the rates of DNA, RNA and protein syntheses (IC50: 2 microM) determined over 30-60 min periods of pulse-labeling in L1210 cells in vitro. In contrast to DAU, which is inactive, a 15 min pretreatment with AQ has the advantage of also inhibiting the cellular transport of both purine and pyrimidine nucleosides (IC50: 2.5 microM) over a 30 s period in vitro. Hence, AQ may prevent the incorporation [3H]thymidine into DNA because it rapidly blocks the uptake of these nucleosides by the tumor cells. After 24 h, AQ induces as much DNA cleavage as camptothecin and DAU, two anticancer drugs producing DNA strand breaks and known to, respectively, inhibit topoisomerase I and II activities. However, the concentration-dependent induction of DNA cleavage by AQ, which peaks at 1.6-4 microM and disappears at 10-25 microM, resembles that of DAU. The mechanism by which AQ induces DNA cleavage is inhibited by actinomycin D, cycloheximide and aurintricarboxylic acid, suggesting that AQ activates endonucleases and triggers apoptosis. The abilities of AQ to block nucleoside transport, inhibit DNA synthesis and induce DNA fragmentation are irreversible upon drug removal, suggesting that this compound may rapidly interact with various molecular targets in cell membranes and nuclei to disrupt the functions of nucleoside transporters and nucleic acids, and trigger long-lasting antitumor effects which persist after cessation of drug treatment. Because of its potency and dual effects on nucleoside transport and DNA cleavage, the use of bifunctional AQ with antileukemic activity in the nM range in vitro might provide a considerable advantage in polychemotherapy to potentiate the action of antimetabolites and sensitize multidrug-resistant tumor cells.

Animals↗

PubMed2000

Parallel genotyping of human SNPs using generic high-density oligonucleotide tag arrays.

Large scale human genetic studies require technologies for generating millions of genotypes with relative ease but also at a reasonable cost and with high accuracy. We describe a highly parallel method for genotyping single nucleotide polymorphisms (SNPs), using generic high-density oligonucleotide arrays that contain thousands of preselected 20-mer oligonucleotide tags. First, marker-specific primers are used in PCR amplifications of genomic regions containing SNPs. Second, the amplification products are used as templates in single base extension (SBE) reactions using chimeric primers with 3' complementarity to the specific SNP loci and 5' complementarity to specific probes, or tags, synthesized on the array. The SBE primers, terminating one base before the polymorphic site, are extended in the presence of labeled dideoxy NTPs, using a different label for each of the two SNP alleles, and hybridized to the tag array. Third, genotypes are deduced from the fluorescence intensity ratio of the two colors. This approach takes advantage of multiplexed sample preparation, hybridization, and analysis at each stage. We illustrate and test this method by genotyping 44 individuals for 142 human SNPs identified previously in 62 candidate hypertension genes. Because the hybridization results are quantitative, this method can also be used for allele-frequency estimation in pooled DNA samples.

Blood Pressure↗

PubMed2000

Potassium sodium tin selenide, K3NaSn3Se8

The title compound, tripotassium sodium tritin octaselenide, K(3)NaSn(3)Se(8), has a molecular (zero-dimensional) structure containing trimeric [Sn(3)Se(8)](4-) units which consist of three edge-sharing SnSe(4) tetrahedra. The [Sn(3)Se(8)](4-) anions and the tetrahedrally coordinated Na(+) cations are arranged in an alternating fashion along the c axis to form SiS(2)-like chains, which are then separated by eight-coordinate K(+) cations. The Sn-Se bond distances are normal, being in the range 2.477 (1)-2.612 (1) A.

Journal Article↗

PubMed2000

Tumor necrosis factor alpha stimulation of human Clara cell secretory protein production by human airway epithelial cells.

Clara cell secretory protein (CCSP) or uteroglobin/CC10 is a product of epithelial cells in a variety of organs including the lung. CCSP has anti-inflammatory properties and may act as an inhibitor of secretory phospholipase A2's. Tumor necrosis factor alpha (TNF-alpha) is capable of inducing the expression of gene products including a variety of cytokines and chemokines in the airway epithelium that may upregulate the airway inflammatory response. Therefore, it was of interest to determine whether this proinflammatory cytokine might also induce the production of a counterregulatory protein such as CCSP, which might modulate the inflammatory response in the airway. Normal human tracheobronchial epithelial cells in primary culture and a human bronchial epithelial cell line (BEAS-2B) were studied. CCSP mRNA levels in BEAS-2B cells were detected by ribonuclease protection assay. CCSP mRNA levels increased in response to TNF-alpha (20 ng/mL) stimulation after 8-36 h, with the peak increase at 18 h. Immunoblotting of CCSP released from BEAS-2B cells into the culture media demonstrated that TNF-alpha induced the synthesis and secretion of CCSP over 8 to 18 h. Similarly, TNF stimulated the release of CCSP from human tracheobronchial epithelial cells in primary culture at 8 and 18 h. The CCSP reporter gene including 801 bases 5' of the transcription start site did not increase transcriptional activity in response to TNF-alpha stimulation. A CCSP mRNA half-life assay indicated that TNF-alpha induced increases in CCSP mRNA at least in part at a posttranscriptional level. Therefore, TNF-alpha induces airway epithelial cell expression of human CCSP and may modulate airway inflammatory responses in this manner.

Animals↗

PubMed2000

Metal chelation as a potential therapy for Alzheimer's disease.

Alzheimer's disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer's disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetylcholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer's disease is linked to the characteristic neocortical amyloid-beta deposition, which may be mediated by abnormal metal interaction with A beta as well as metal-mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid-beta plaque formation. This paper reviews recent observations on the possible etiologic role of A beta deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer's disease therapeutics.

Alzheimer Disease↗

PubMed2000

Identification of the active site of HetR protease and its requirement for heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120.

HetR is a serine-type protease required for heterocyst differentiation in heterocystous cyanobacteria under conditions of nitrogen deprivation. We have identified the active Ser residue of HetR from Anabaena sp. strain PCC 7120 by site-specific mutagenesis. By changing the S152 residue to an Ala residue, the mutant protein cannot be labeled by Dansyl fluoride, a specific serine-type protein inhibitor. The mutant protein showed no autodegradation in vitro. The mutant hetR gene was introduced into Anabaena strain 884a, a hetR mutant. The resultant strain, Anabaena strain S152A, could not form heterocysts under conditions of nitrogen deprivation even though the up-regulation of the mutant hetR gene was induced upon removal of combined nitrogen. The Anabaena strain 216, which carries a mutant hetR gene encoding S179N HetR and could not form heterocysts, also produced HetR protein upon induction. Sequence comparison shows that Ser152 is conserved in all cyanobacterial HetR. Immunoblotting was used to study HetR induction in both the wild-type and mutant strains. The amount of mutant HetR in strain S152A and in strain 216 increased continuously for 24 h after nitrogen step-down, while the amount of HetR in wild-type cells reached a maximum level within 6 h after nitrogen step-down. Our results show the Ser152 is the active site of HetR. The protease activity is required for heterocyst differentiation and might be needed for repression of HetR overproduction under conditions of nitrogen deprivation.

Anabaena↗

PubMed2000

Normal development, wound healing, and adenovirus susceptibility in beta5-deficient mice.

Integrins have been shown to play important roles in embryonic development, wound healing, metastasis, and other biological processes. alphavbeta5 is a receptor for RGD-containing extracellular matrix proteins that has been suggested to be important in cutaneous wound healing and adenovirus infection. To examine the in vivo function of this receptor, we have generated mice lacking beta5 expression, using homologous recombination in embryonic stem cells. Mice homozygous for a null mutation of the beta5 subunit gene develop, grow, and reproduce normally. Keratinocytes harvested from beta5(-/-) mice demonstrate impaired migration on and adhesion to the alphavbeta5 ligand, vitronectin. However, the rate of healing of cutaneous wounds is not different in beta5(-/-) and beta5(+/+) mice. Furthermore, keratinocytes and airway epithelial cells obtained from null mice show adenovirus infection efficiency equal to that from wild-type mice. These data suggest that alphavbeta5 is not essential for normal development, reproduction, adenovirus infection, or the healing of cutaneous wounds.

Adenoviridae↗

PubMed2000

Impaired insulin-stimulated expression of the glycogen synthase gene in skeletal muscle of type 2 diabetic patients is acquired rather than inherited.

To examine whether defective muscle glycogen synthase (GYS1) expression is associated with impaired glycogen synthesis in type 2 diabetes and whether the defect is inherited or acquired, we measured GYS1 gene expression and enzyme activity in muscle biopsies taken before and after an insulin clamp in 12 monozygotic twin pairs discordant for type 2 diabetes and in 12 matched control subjects. The effect of insulin on GYS1 fractional activity, when expressed as the increment over the basal values, was significantly impaired in diabetic (15.7 +/- 3.3%; P < 0.01), but not in nondiabetic (23.7 +/- 1.8%; P = NS) twins compared with that in control subjects (28.1 +/- 2.3%). Insulin increased GYS1 messenger ribonucleic acid (mRNA) expression in control subjects (from 0.14 +/- 0.02 to 1.74 +/- 0.10 relative units; P < 0.01) and in nondiabetic (from 0.24 +/- 0.05 to 1.81 +/- 0.16 relative units; P < 0.01) and diabetic (from 0.20 +/- 0.07 to 1.08 + 0.14 relative units; P < 0.01) twins. The effect of insulin on GYS1 expression was, however, significantly reduced in the diabetic (P < 0.003), but not in the nondiabetic, twins compared with that in control subjects. The postclamp GYS1 mRNA levels correlated strongly with the hemoglobin A1c levels (r = -0.61; P < 0.001). Despite the decrease in postclamp GYS1 mRNA levels, the GYS1 protein levels were not decreased in the diabetic twins compared with those in the control subjects (2.10 +/- 0.46 vs. 2.10 +/- 0.34 relative units; P = NS). We conclude that 1) insulin stimulates GYS1 mRNA expression; and 2) impaired stimulation of GYS1 gene expression by insulin in patients with type 2 diabetes is acquired and most likely is secondary to chronic hyperglycemia.

Aged↗

PubMed2000

Assessing potential health risks from microcystin toxins in blue-green algae dietary supplements.

The presence of blue-green algae (BGA) toxins in surface waters used for drinking water sources and recreation is receiving increasing attention around the world as a public health concern. However, potential risks from exposure to these toxins in contaminated health food products that contain BGA have been largely ignored. BGA products are commonly consumed in the United States, Canada, and Europe for their putative beneficial effects, including increased energy and elevated mood. Many of these products contain Aphanizomenon flos-aquae, a BGA that is harvested from Upper Klamath Lake (UKL) in southern Oregon, where the growth of a toxic BGA, Microcystis aeruginosa, is a regular occurrence. M. aeruginosa produces compounds called microcystins, which are potent hepatotoxins and probable tumor promoters. Because M. aeruginosa coexists with A. flos-aquae, it can be collected inadvertently during the harvesting process, resulting in microcystin contamination of BGA products. In fall 1996, the Oregon Health Division learned that UKL was experiencing an extensive M. aeruginosa bloom, and an advisory was issued recommending against water contact. The advisory prompted calls from consumers of BGA products, who expressed concern about possible contamination of these products with microcystins. In response, the Oregon Health Division and the Oregon Department of Agriculture established a regulatory limit of 1 microg/g for microcystins in BGA-containing products and tested BGA products for the presence of microcystins. Microcystins were detected in 85 of 87 samples tested, with 63 samples (72%) containing concentrations > 1 microg/g. HPLC and ELISA tentatively identified microcystin-LR, the most toxic microcystin variant, as the predominant congener.

Bacterial Toxins↗

PubMed2000

Agricultural work-related injuries among farmers in Hubei, People's Republic of China.

OBJECTIVES: This population-based study evaluated patterns of and risk factors for, agricultural injuries among farmers in the People's Republic of China. METHODS: A multistage sample of 1500 Chinese farmers was selected from 14 villages. Face-to-face interviews with 1358 farmers were conducted between July 1997 and September 1997 (response rate = 91%). Agricultural work-related injuries that occurred in the previous 24 months and the associated factors were evaluated. RESULTS: A total of 33% of the farmers reported at least 1 work-related injury in the 24 months before the survey. Major external causes of the injuries were hand tools (50%), falls (26%), and heavy falling objects (10%). The statistically significant risk factors for injury were low family income, 1 to 6 school years of education, self-reported pesticide exposure, tension in relationships with neighbors, and stress in life. The most notable result was the relation between self-reported pesticide exposure and injury, with farmers with greater pesticide exposure at significantly greater risk for injury. CONCLUSIONS: The results of this study indicated that injuries occurring among Chinese farmers may have unique patterns and potential risk factors.

Accidents, Occupational↗

PubMed2000

Novel Single- and Double-Layer and Three-Dimensional Structures of Rare-Earth Metal Coordination Polymers: The Effect of Lanthanide Contraction and Acidity Control in Crystal Structure Formation.

Lanthanide atom sizes (the lanthanide contraction) directly control the type of structure formed by the coordination of a single multidentate ligand, 3,5-pyrazoledicarboxylic acid (H(3)pdc). Single-layer, double-layer ([Eu(2)(Hpdc)(3)(H(2)O)(6)], see picture), and three-dimensional networks were found. Control of the reaction pH plays a key role in the structure formation in this system.

Journal Article↗

PubMed2000

Cytogenetical diagnosis in paraffin-embedded fetoplacental tissue using comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a FISH-related technique used to assess global chromosomal aberrations in a variety of human tumours. Recently CGH has been applied to cytogenetic analysis of fresh frozen fetoplacental tissues. Here we report the application of CGH to paraffin-embedded placental samples. Ten samples from paraffin-embedded blocks of 6 control placentas and fetoplacental tissue from 10 aneuploidies, and 2 unbalanced aberrations were evaluated. Balanced karyotype profiles were obtained from samples of healthy placentas and all samples from the same placenta appeared to have similar confidence intervals. CGH analysis of four cases of trisomy 21, three cases of trisomy 18, one case of trisomy 13, one case of trisomy 15 and one case of trisomy 7 all showed overrepresentation of the respective trisomic chromosome. The CGH profile was also in accordance with the karyotyping of a case with isochromosome 21. The CGH profile of a case with der (2)t(2;6)(q37.3;q22.2) revealed partial trisomy for chromosome 6 between q21 and q27. CGH may be a useful adjunct in prenatal genetic diagnosis when retrospective diagnosis is needed from archival samples.

Chromosome Aberrations↗

PubMed2000

Intra-abdominal sound pressure levels during impulse noise exposure in sheep.

Ambient sound pressure levels (SPLs) created with intense blasts were compared with SPLs recorded in the abdomen of euthanized sheep. Hydrophones were placed in the abdominal cavity at locations referred to as proximal, medial, and distal with respect to a shock tube that created 169-dB peak SPL (pSPL). No differences in pSPL, duration, or rise time were found between recordings in air and at the intra-abdominal proximal position. Significant differences were noted in these variables when recordings in air were compared with recordings made at the medial and distal locations. Intra-abdominal pSPL varied by 20 dB depending on recording location.

Abdomen↗

PubMed2000

Chromosomal location of AFLP markers in common wheat utilizing nulli-tetrasomic stocks.

Amplified fragment length polymorphism (AFLP) markers with a total of 256 EcoRI + ANN - MseI + CNN primer combinations were investigated employing the common wheat cultivar Triticum aestivum 'Chinese Spring.' On average, 103 fragments per primer combination were amplified, ranging from a maximum of 226 fragments to a minimum of 18 fragments. The primer combinations E + AAA - M + CNN and E + ATT - M + CNN produced very few distinct fragments. By using 15 randomly chosen EcoRI + ANN - MseI + CNN primer combinations, 928 AFLP markers were allocated to wheat chromosomes, of which 131 were assigned to specific chromosome arms. These AFLP markers were locus-specific and randomly distributed on the different chromosomes. In addition, 6 and 41 AFLP markers were simultaneously absent in two nulli-tetrasomics (NTs) of both homoeologous and non-homoeologous groups, respectively, whereas additional fragments were detected in N1BT1A, N5AT5D, and N6BT6A lines.

Chromosome Mapping↗

PubMed2000

Copper catalyzed oxidation of Alzheimer Abeta.

Abeta derived from amyloid plaques of Alzheimer's disease-affected brain contain several oxidative posttranslational modifications. In this study we have characterized the amino acid content of human amyloid-derived Abeta and compared it with that of human synthetic Abeta subjected to metal-catalyzed oxidation. Human amyloid derived Abeta has an increased content of arginine (46%) and glutamate/glutamine residues (28%), but a decreased content of histidine residues (-32%) as compared to the expected amino acid content. Incubation of synthetic human Abeta with Cu(II), but not Fe(III), in the presence of H2O2 similarly induced a decrease in histidine residues (-79%), but also a decrease in tyrosine residues (-28%). Our results suggest that histidine and tyrosine are most vulnerable to metal mediated oxidative attack, consistent with our earlier findings that Cu coordinated via histidine residues is redox competent. Our results suggest that the loss of histidine residues in human amyloid-derived Abeta may be a result of Cu oxidation, and that unidentified post-translational mechanisms operate to modify other amino acids of Abeta in vivo.

Alzheimer Disease↗

PubMed2000

Effects of angiotensin II receptor blockade on hepatic fibrosis in rats.

OBJECTIVE: To investigate the effects of angiotensin II type 1 receptor blockade, losartan, on serum levels of components of extracellular matrix in experimental fibrotic rats. METHODS: Fifty male Spague-Dawley rats were separated into five groups (control, model, and 3 treatment groups). Excepting rats in control group, all rats were given subcutaneous injection of 40% carbon tetrachloride (once every 3 days for 6 weeks). Rats in 3 treatment groups were also given losartan of 10mg/kg, 5mg/kg, 2.5mg/kg daily for 6 weeks via gastrogavage, respectively. At the end of sixth week, all rats were sacrificed. Radioimmunoassay was performed to determine the serum levels of hyaluronic acid (HA), Laminin (LN), procollagen type III (PCIII) and collagen type IV. Van Giesion collagen staining was used to evaluate the extracellular matrix of the liver tissue. RESULTS: Compared with model group, losartan significantly reduced the serum levels of HA [from (911.66 +/- 345.49)microg/L to (425.05 +/- 115.80)microg/L], LN [from (209.87 +/- 91.57)microg/L to (83.56 +/- 22.12)microg/L, PCIII [from (31.82 +/- 6.90)microg/L to (22.78 +/- 8.38)microg/L] and collagen IV [from (54.09 +/- 19.81)microg/L to (30.51 +/- 12.39)microg/L] (P<0.05) and greatly attenuated the degree of liver fibrosis (P<0.05). CONCLUSION: Losartan can markedly reduce the serum levels of LN, HA, PCIII and collagen type IV of fibrotic rats induced by CCl(4) and greatly attenuate the degree of liver fibrosis.

Angiotensin Receptor Antagonists↗