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Biomedical subjects

X Yang

Publications and source records attributed to X Yang.

At least 91 records · Page 5Linked to original sources
PubMed2003

Inhibitors of the complement system currently in development for cardiovascular disease.

Controlled activation of the complement system is critical to the host-defense response of the immune system. Activated complement is responsible for the stimulation of a localized protective inflammatory response to either invading microorganisms or foreign molecules (toxins). However, the autologous activation of the complement system can have devastating consequences on many organ systems. This review discusses the various pathways involved in the activation of the complement system and the multiple levels of control established within the body to regulate activation. It also focuses on the role of complement activation in cardiovascular disease, especially myocardial ischemia and reperfusion injury as well as in cardiopulmonary bypass procedures. Lastly, this review also provides a comprehensive overview of both biologically derived proteins and chemically developed inhibitors of the complement system that range from those that are currently in the discovery stage to those that are in clinical development as novel therapeutic agents.

Animals↗
PubMed2003

Response of early-weaned pigs to an enterotoxigenic Escherichia coli (K88) challenge when fed diets containing spray-dried porcine plasma or pea protein isolate plus egg yolk antibody.

Enterotoxigenic E. coli (ETEC) infection and resulting scours is a major problem for young pigs, especially when purified plant proteins are fed rather than spray-dried porcine plasma (SDPP). The effect of supplementing a pea protein isolate (PPI)-based diet with egg yolk antibodies (EYA) from laying hens immunized with ETEC K88 antigen on piglet performance, incidence of scours, and gut histology was studied in a 14-d trial. Ninety-six 10-d-old weaned pigs were assigned to five dietary treatments in a completely randomized design to give six replicate pens per treatment. The treatments were PPI without EYA (PPI-EYA), PPI with EYA (PPI+EYA), SDPP without EYA (SDPP-EYA), SDPP with EYA (SDPP+EYA), or a combination of PPI and SDPP (PPI+SDPP). Diets were formulated to similar nutrient levels and provided for ad libitum intake. Blood from all pigs was taken on d 0, 7, and 14 for determining plasma urea N (PUN). On d 7, pigs were orally challenged with 6 mL of 10(10) cfu/ mL ETEC K88. Piglets were weighed on d 7 and 14. On d 7, 8, and 14, four pigs per treatment were sacrificed to study the histology of the small intestine. Weekly feed intake, BW changes, and gain:feed were determined. Fecal swabs from 10 pigs per treatment were taken for a PCR test to detect K88 E. coli. Feed efficiency over the 14-d period was not affected (P > 0.78) by dietary treatment. Mean ADFI on an as-fed basis was lower (P < 0.002) in piglets fed PPI-EYA (64.3 g/d) compared with PPI+EYA (94.8 g/d) or SDPP (102 g/d) during wk 1. Piglets fed PPI-EYA tend to have a lower (P < 0.026) overall ADG (84 g/d) than those fed PPI+EYA (123 g/d) or SDPP (127 g/d) (P < 0.006)-based diets. Although scours was evident in all groups of pigs 6 h after the challenge, most of the piglets fed EYA- or SDPP-containing diets recovered 10 to 72 h postchallenge, whereas those fed PPI-EYA continued to have severe diarrhea, resulting in 33% mortality. The PCR results showed that a greater (P < 0.01) percentage of piglets fed PPI-EYA compared with those fed SDPP- or EYA-containing diets continued to shed ETEC K88 at the end of the 14-d study. Piglets fed PPI-EYA had shorter villi (P < 0.01), higher intestinal pH (P < 0.013), and higher PUN (P < 0.05) than those fed the SDPP- or EYA-containing diets during the entire 14-d study. It was concluded that specific EYA and SDPP could provide passive control of ETEC infection and potentially improve feed intake and weight gain in young pigs fed PPI.

Animal Feed↗
PubMed2002

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians.

AIMS/HYPOTHESIS: We carried out global transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. This approach also complemented the ongoing genomic linkage analyses to identify genes linked to insulin resistance and diabetes in Pima Indians. METHODS: We compared gene expression profiles of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians using oligonucleotide arrays consisting of about 40,600 transcripts of known genes and expressed sequence tags, and analysed the results with the Wilcoxon rank sum test. We verified the mRNA expression of ten differentially (best-ranked) and ten similarly (worst-ranked) genes using quantitative Real Time PCR. RESULTS: There were 185 differentially expressed transcripts by the rank sum test. The differential expressions of two out of the ten best-ranked genes were confirmed and the similar expressions of all ten worst-ranked genes were reproduced. CONCLUSION/INTERPRETATION: Of the 185 differentially expressed transcripts, 20 per cent were true positives and some could generate new hypotheses about the aetiology or pathophysiology of insulin resistance. Furthermore, differentially expressed genes in chromosomal regions with linkage to diabetes and insulin resistance serve as new diabetes susceptibility genes.

Adult↗
PubMed2002

Photodynamic therapy with photofrin reduces invasiveness of malignant human glioma cells.

In this study we investigated the influence of Photofrin-based photodynamic therapy (PDT) on the migration of two human glioma cell lines in vitro. U87 and U25ln tumour cells were treated with Photofrin at various doses and subjected to a fixed optical (632 nm) dose of 100 mJ/cm(2). Photofrin cytotoxicity was determined using MTT and colony forming assays. Using a matrigel artificial basement membrane migration assay, we demonstrated that low doses of subcytotoxic PDT treatment, such as PDT with 2.5 micro g/ml Photofrin on U87 cells and 1 micro g/ml on U25ln cells, significantly ( p<0.001) inhibited in vitro migration of both cell lines. Furthermore, in a qualitative spheroid confrontation assay, subcytotoxic PDT of co-cultures between tumour spheroids and brain aggregates resulted in an absence of progressive tumour invasion and destruction of the brain aggregate. In conclusion, our data indicate that low-dose subcytotoxic PDT with Photofrin significantly inhibits invasiveness of U87 and U25ln cells.

Animals↗
PubMed2002

Effect of lipase treatment on the biocompatibility of microbial polyhydroxyalkanoates.

Films made from microbial polyesters polyhydroxybutyrate (PHB) and poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) were treated by lipases and NaOH solution. The change of the polyester biocompatibility was evaluated by inoculating mouse fibroblast cell line L929 on films of PHB, PHBHHx and their blends. Polylactic acid (PLA) was used as a control. It was found that untreated PHB and PLA films gave a poor support to the growth of L929 cells, viable cell density ranged from 0.1x10(4}) to 0.7x10(4) per ml only. While films of pure PHBHHx and PHB blended with PHBHHx showed improved biocompatibility, viable cell density observed increased from 9.6x10(2) to 6x10(4) on blended films of PHB/PHBHHx in ratios of 0.9/0.1 to 0/1, respectively. This result showed PHBHHx has a better biocompatibility compared with PHB. Films of PHB, PLA and the blends treated with lipases and 1 N NaOH, respectively, showed an improved ability to support cell growth. Biocompatibility of PHB was approximately the same as PLA after the treatment, while PHBHHx and its dominant blends showed improved biocompatibility compared with PLA. The sensitivity of the treatments was reduced when PHBHHx content increased in the PHB/PHBHHx blends. All three lipase treatments demonstrated more biocompatibility increase on all the films compared with the results of NaOH treatment. Scanning electron microscopy showed that PHB films changed its surface from multi-porous to rough non-porous after the lipase or NaOH treatment. While PHBHHx films showed little change after these treatments. The results showed that the polyester surface morphology played an important role in affecting cell attachment and growth on these materials.

Journal Article↗
PubMed2002

Reproductive characteristics of cloned heifers derived from adult somatic cells.

This study examined the onset of puberty, follicular dynamics, reproductive hormone profiles, and ability to maintain pregnancy in cloned heifers produced by somatic cell nuclear transfer. Four adult somatic cell-cloned heifers, derived from a 13-yr-old Holstein cow, were compared to 4 individual age- and weight-matched heifers produced by artificial insemination (AI). From 7 to 9 mo of age, jugular venous blood samples were collected twice weekly, and from 10 to 11 or 12 mo of age, blood sampling was carried out every other day. After the heifers reached puberty (defined as the first of 3 consecutive blood samples with peripheral plasma progesterone concentrations of >1 ng/ml), ultrasound examination of ovaries and jugular plasma sample collection were carried out daily for 1 estrous cycle. Cloned heifers reached puberty later than controls (mean +/- SEM, 314.7 +/- 9.6 vs. 272 +/- 4.4 days and 336.7 +/- 13 vs. 302.8 +/- 4.5 kg for clones and controls, respectively; P < 0.05). However, cloned and control heifers were not different in estrous cycle length, ovulatory follicle diameter, number of follicular waves, or profiles of hormonal changes (LH, FSH, estradiol, and progesterone). Three of the 4 clones and all 4 control heifers became pregnant after AI. These results demonstrate that clones from an aged adult have normal reproductive development.

Aging↗
PubMed2002

Evidence from mitochondrial DNA that head lice and body lice of humans (Phthiraptera: Pediculidae) are conspecific.

The specific status of the head and body lice of humans has been debated for more than 200 yr. To clarify the specific status of head and body lice, we sequenced 524 base pairs (bp) of the cytochrome oxidase I (COI) gene of 28 head and 28 body lice from nine countries. Ten haplotypes that differed by 1-5 bp at 11 nucleotide positions were identified. A phylogeny of these sequences indicates that these head and body lice are not from reciprocally monophyletic lineages. Indeed, head and body lice share three of the 10 haplotypes we found. F(ST) values and exact tests of haplotype frequencies showed significant differences between head and body lice. However, the same tests also showed significant differences among lice from different countries. Indeed, more of the variation in haplotype frequencies was explained by differences among lice from different countries than by differences between head and body lice. Our results indicate the following: (1) head and body lice do not represent reciprocally monophyletic lineages and are conspecific; (2) gene flow among populations of lice from different countries is limited; and (3) frequencies of COI haplotypes can be used to study maternal gene flow among populations of head and body lice and thus transmission of lice among their human hosts.

Animals↗
PubMed2002

Structurally distinct membrane-associated and soluble forms of GH-binding protein in the mouse.

It has previously been shown that the large increase in GH-binding capacity of mouse liver microsomes during pregnancy is due largely to an increase in the amount of GH-binding protein (GHBP), with a more modest increase in GH receptor (GHR). Here we show that mouse liver GHBP is predominantly present as a membrane-associated protein structurally distinct from the soluble form of GHBP present in serum. Liver GHBP is associated with both intracellular membranes and the plasma membrane. Membrane-associated GHBP and soluble GHBP appear to be identical polypeptides distinguished by the addition of different N-glycans to asparagine residues. The pattern of release of GHBP from membranes by various treatments indicates that GHBP associates with membranes through noncovalent interactions with one or more membrane protein, but not with GHR. Covalent crosslinking provides evidence for several GHBP-associated membrane polypeptides, with molecular masses ranging from 58 kDa to over 200 kDa. These studies in the mouse and similar studies in the rat suggest that GHBP is an important cell-surface receptor for GH in the liver of these species. We postulate that an arginine-glycine-aspartic acid sequence found on rat and mouse GHBP but absent in other species is responsible for the association of GHBP with the plasma membrane by binding to one or more integrins on the surface of liver cells.

Animals↗
PubMed2002

Autoimmunity to the M(r) 32,000 subunit of replication protein A in breast cancer.

PURPOSE: We sought to identify autoantigens recognized by antibodies in breast cancer patient sera with potential diagnostic or prognostic significance. EXPERIMENTAL DESIGN: Serum from a female breast cancer patient exhibiting a high titer antinuclear antibody was used to screen a HeLa cDNA expression library, leading to the cloning of a cDNA for the M(r) 32,000 subunit of replication protein A (RPA32). RPA32 expression and localization were assayed in autologous tumor by monoclonal antibody staining. A specific ELISA using recombinant protein was used to screen sera from 801 breast cancer patients and 65 controls. RESULTS: A relationship between anti-replication protein A (RPA) antibodies and the ductal breast carcinoma of the proband was suggested by overexpression and aberrant localization of RPA32 in tumor cells as compared with surrounding normal ductal tissue and by the presence of anti-RPA32 antibodies before the diagnosis. The prevalence of anti-RPA32 antibodies was significantly higher (P < 0.01) among breast cancer patients (87 of 801 patients) than among noncancer controls (0 of 65 controls). Similarly, anti-RPA32 antibodies were present in 4 of 39 patients with intraductal in situ carcinoma. No associations were found between anti-RPA antibodies and survival, occurrence of a second tumor, metastases, or antibodies to p53. Reactivity to RPA32 also was detected in sera from 3 of 47 patients with other cancers. CONCLUSIONS: In view of the central role of RPA in DNA replication, recombination, and repair, we suggest that autoimmunity to RPA32 may reflect molecular changes involved in the process of tumorigenesis. The finding of antibodies to RPA32 before diagnosis and their prevalence in in situ carcinoma suggest that they are potentially useful markers of early disease.

Antigens, Neoplasm↗
PubMed2001

Computational characterization of substrate binding and catalysis in S-adenosylhomocysteine hydrolase.

S-Adenosylhomocysteine (AdoHcy) hydrolase catalyzes the reversible hydrolysis of AdoHcy to adenosine (Ado) and homocysteine (Hcy), playing an essential role in modulating the cellular Hcy levels and regulating activities of a host of methyltransferases in eukaryotic cells. This enzyme exists in an open conformation (active site unoccupied) and a closed conformation (active site occupied with substrate or inhibitor) [Turner, M. A., Yang, X., Yin, D., Kuczera, K., Borchardt, R. T., and Howell, P. L. (2000) Cell Biochem. Biophys. 33, 101-125]. To investigate the binding of natural substrates during catalysis, the computational docking program AutoDock (with confirming calculations using CHARMM) was used to predict the binding modes of various substrates or inhibitors with the closed and open forms of AdoHcy hydrolase. The results have revealed that the interaction between a substrate and the open form of the enzyme is nonspecific, whereas the binding of the substrate in the closed form is highly specific with the adenine moiety of a substrate as the main recognition factor. Residues Thr57, Glu59, Glu156, Gln181, Lys186, Asp190, Met351, and His35 are involved in substrate binding, which is consistent with the crystal structure. His55 in the docked model appears to participate in the elimination of water from Ado through the interaction with the 5'-OH group of Ado. In the same reaction, Asp131 removes a proton from the 4' position of the substrate after the oxidation-reduction reaction in the enzyme. To identify the residues that bind the Hcy moiety, AdoHcy was docked to the closed form of AdoHcy hydrolase. The Hcy tail is predicted to interact with His55, Cys79, Asn80, Asp131, Asp134, and Leu344 in a strained conformation, which may lower the reaction barrier and enhance the catalysis rate.

Adenosine↗
PubMed2001

Fabrication of layer-by-layer deposited multilayer films containing DNA and its interaction with methyl green.

Multilayer films were fabricated by layer-by-layer electrostatic deposition techniques between poly(diallyldimethylammonium chloride) (PDDA) and calf thymus DNA (CT DNA) on glassy carbon and quartz substrates. Electrochemical impedance spectroscopy (EIS), Fourier transform infrared (FTIR) spectroscopy and UV-vis spectroscopy demonstrated the uniform assembly of PDDA/DNA multilayer films, and X-ray photoelectron spectroscopy confirmed the elemental composition of the films. Moreover, the interaction of DNA in PDDA/DNA films with methyl green was investigated by UV-vis spectroscopy and circular dichroism (CD).

Animals↗
PubMed2001

Single rotational product propensity in the photodissociation of HOD.

Photodissociation of HOD from the B state has been studied using the high resolution rydberg "tagging" time-of-flight (TOF) technique. The TOF spectra show an unusually strong population (approximately 50%) for a single rotational state for the OD (A(2)Sigma, upsilon = 0) fragments. Through theoretical studies, this phenomenon, which we have labeled the "single rotational product propensity," is attributed to a dynamically constrained threshold effect in the photodissociation of the HOD molecule on the B state.

Journal Article↗
PubMed2001

Extremely rotationally excited OH from water (HOD) photodissociation through conical intersection.

Photodissociation of HOD from the B state has been studied using the Rydberg "tagging" time-of-flight technique. Experimental results indicate that extreme rotational excitation in the OH(X,v = 0) product ( N up to 50 or so) is produced through the conical intersection dissociation pathway such that some of the OH product states lie above the O((3)P)+H dissociation limit, which are supported only through large centrifugal barriers. The population distribution for OH(X,v = 0) also shows an alternation with N, similar to that observed for H(2)O that is attributed to dynamical interference. The tunneling rates of these extremely rotationally excited OH molecules are also analyzed.

Journal Article↗
PubMed2001

Bulk-like features in the photoemission spectra of hydrated doubly charged anion clusters.

We produced gaseous hydrated clusters of sulfate and oxalate anions [SO4(2-)-(H2O)n and C2O4(2-)(H2O)n, where n = 4 to 40]. Photoelectron spectra of these clusters revealed that the solute dianions were in the center of the water cluster, (H2O)n. For small clusters, these spectra were characteristic of the respective solutes, but beyond the first solvation shell (n approximately 12), features in the spectra from the solutes were diminished and a new feature from ionization of water emerged, analogous to bulk aqueous solutions. For large clusters with dimensions greater than 1 nanometer, the solute photoemission features disappeared and the spectra were dominated by the ionization of water as the solvent coverage increased. A smooth transition from gas-phase clusters to behavior of electrolyte solutions was clearly revealed, and the large solvated clusters can be used as molecular models to investigate the photophysics and chemistry of aqueous electrolyte solutions.

Journal Article↗
PubMed2001

Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway.

RpoS and RpoN are two alternative sigma factors typically associated with general stress responses in bacteria. To date, there has been no experimental evidence that RpoS and RpoN can directly control the expression of one another. Herein, using a combined strategy of gene disruption and genetic complementation targeting rpoN and rpoS in Borrelia burgdorferi strain 297, we describe a regulatory network for B. burgdorferi. In this network, RpoN controls the expression of RpoS, which, in turn, governs the expression of two important membrane lipoproteins, outer surface protein C and decorin-binding protein A, and likely other proteins of B. burgdorferi. Our findings provide a foundation for elucidating further key regulatory networks that potentially impact many aspects of B. burgdorferi's parasitic strategy, host range, and virulence expression.

Antigens, Bacterial↗
PubMed2001

Ultrafast time-resolved soft x-ray photoelectron spectroscopy of dissociating Br2.

The dissociation of excited state Br2 is probed with the novel technique of ultrafast soft x-ray photoelectron spectroscopy. Excited Br2 molecules are prepared in the dissociative (1)Pi(u) state with 80 fs, 400 nm pulses, and a series of photoelectron spectra are obtained during dissociation with pulses of soft x-ray light (47 nm, 26.4 eV, 250 fs). The formation of Br atoms is readily detected and the data support an extremely fast dissociation time for Br2 on the order of 40 fs. Amplitudes of the pump-probe features reveal that the ionization cross section of atomic Br at 47 nm is approximately 40 times larger than that of Br2.

Journal Article↗
PubMed2001

Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) is an enzyme that catalyzes the incorporation of biotin into apo-carboxylases, and its deficiency causes biotin-responsive multiple carboxylase deficiency. The reported sequences of cDNA for human HLCS from liver, lymphocyte, and KG-1 myeloid cell lines differ at their 5' regions. To elucidate variations of the human HLCS mRNA and longer 5' cDNA ends, we performed screening of the human liver cDNA library and rapid amplification of the cDNA ends (RACE). Our results suggest the existence of three types of HLCS mRNA that start at different exons. The first type starts at exon 1, and the second type starts at exon 3, and both are found in various human tissues. The third type, corresponding to the cDNA from the KG-1 cell, starts at exon 2 of the HLCS gene. Various splicing patterns from exons 3-6 were also observed. None of the variations of cDNA found created a new initiation codon. Mutation screening from exons 6-14, therefore, was sufficient to detect amino acid changes in HLCS in patients. Our direct sequencing strategy for screening mutations in the HLCS gene revealed mutations in five Japanese patients and seven non-Japanese patients. Our analyses involving 12 Japanese and 13 non-Japanese patients and studies by others indicate that (1) there is no panethnically prevalent mutation; (2) the Arg508Trp, Gly581Ser, and Val550Met mutations are found in both Japanese and non-Japanese populations; (3) the IVS10+5G-->A mutation is predominant and probably a founder mutation in European patients; (4) the 655-656insA, Leu237Pro, and 780delG mutations are unique in Japanese patients; (5) the spectrum of the mutations in the HLCS gene may vary substantially among different ethnic groups.

Base Sequence↗