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Biomedical subjects

S Xia

Publications and source records attributed to S Xia.

At least 19 recordsLinked to original sources

Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial.

BACKGROUND: Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis. AIM: To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis. METHOD: A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points. RESULTS: No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine. CONCLUSIONS: Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.

Adolescent↗

Bioavailability and therapeutic activity of alicaforsen (ISIS 2302) administered as a rectal retention enema to subjects with active ulcerative colitis.

BACKGROUND: Alicaforsen is a phosphorothioate-modified antisense oligodeoxynucleotide designed to sequence-specifically reduce intercellular adhesion molecule 1 messenger RNA levels. AIMS: To determine the systemic and local bioavailability of alicaforsen, and its activity when administered as a once daily enema in subjects with active ulcerative colitis. METHODS An open-label study was conducted to assess the relative absorption (local and systemic pharmacokinetics) and pharmacologic activity of alicaforsen enema in subjects with active ulcerative colitis. Fifteen subjects received nightly enemas of alicaforsen (240 mg) for a treatment period of 6 weeks. Alicaforsen concentrations in plasma and colonic tissue biopsies were determined. Disease activity index and multiple measurements including endoscopy were used to assess alicaforsen activity in these subjects. RESULTS: Plasma concentrations of parent alicaforsen represented < 0.6% mean bioavailability when compared with historical intravenous area under the plasma concentration-time curves. Concentrations of the intact oligonucleotide in mucosal colonic tissue biopsies were orders of magnitude higher than those observed in plasma. A 46% reduction in mean Disease Activity Index and 33% rate of remission as defined by complete mucosal healing were observed at the end of treatment. Conclusion These data confirm that alicaforsen enema provides local treatment for a local disease with little meaningful systemic exposure.

Absorption↗

A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis.

BACKGROUND: Alicaforsen is an antisense oligonucleotide designed to inhibit expression of human intercellular adhesion molecule 1. Previous clinical studies have demonstrated activity of alicaforsen enema in ulcerative colitis and pouchitis. AIM: To determine the minimally effective dosing regimen of alicaforsen enema in subjects with mild to moderate left-sided ulcerative colitis. METHODS: Randomized, placebo-controlled, double-blind, two-dose ranging multicentre study. One hundred and twelve subjects were equally randomized to receive one of four alicaforsen enema regimens or placebo daily for 6 weeks. Primary end point was Disease Activity Index at week 6. Secondary end points included evaluation of clinical improvement, relapse rates and durability of response. Analysis of data were performed on the intent-to-treat population. RESULTS: No significant difference was observed between treatment arms and placebo in the primary end point. A prolonged reduction in mean% Disease Activity Index relative to baseline was observed in the daily 240 mg alicaforsen enema treatment arm in comparison with placebo from week 18 (51% vs. 18%, P=0.04) to week 30 (50% vs. 11%, P=0.03). CONCLUSIONS: Alicaforsen enema was safe and well tolerated at all doses studied. The durability of the response to alicaforsen enema treatment may suggests a disease-modifying effect.

Adult↗

Erk pathway inhibitor U0126 induces gamma-globin expression in erythroid cells.

Fetal hemoglobin (HbF) induction is an effective approach to improve clinical symptoms in sickle cell disease. Understanding molecular mechanisms for gamma-gene re-activation will aid efforts to design lead compounds. A potential inhibitory role for the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway in gamma-gene expression has been suggested recently. Therefore, we determined the ability of U0126, a selective inhibitor of MEK1/2 the upstream activators of ERK, to re-activate gamma-globin expression. K562 stable lines over-expressing constitutively active MEK1 were established. A significant increase in ERK phosphorylation was observed and gamma-gene expression was silenced concomitantly, however U0126 attenuated this effect. Studies in human erythroid progenitors confirmed the ability of U0126 to induce HbF. Cellular mechanisms for the inhibitory role of ERK signaling in drug-mediated HbF induction will be discussed.

Blotting, Western↗

[Androgen receptor isoforms expression and its novel cDNA cloning in human prostate].

OBJECTIVE: To investigate the androgen receptor isoforms expression and its novel eDNA cloning in prostate tissue. METHODS: The tissue from a case of benign prostatic hyperplasia (BPH) was analyzed by high resolution isoelectric focusing (IEF) technique and molecular biological technique of cDNA cloning was used to determine its AR isoforms expression and genes of AR isoforms. RESULTS: From the prostatic specimen, three types of AR isoforms were detected with pI values of 6.5, 6.0 and 5.3 respectively. A novel AR subtype cDNA cloning, named as PHAR-1 and including 1 913 nucleotides was isolated from the same BPH tissue. The GenBank accession number for the nucleotide sequence of this AR cDNA was BankIT372205 AF324243. The comparison between PHAR-1 and AR nucleotide sequence registered in GenBank showed that 961 nucleotides in three part of nucleotide sequence were the same, while the other 952 nucleotides were different. CONCLUSION: These three AR isoforms may originate from the same gene. The results may be important for the study of BPH, or prostatic growth. It is also valuable in the field of pharmacotherapy for treatment of BPH and prostatic cancer.

DNA, Complementary↗

Lymphogenous cyst-vein shunt in the management of chylothorax and chylorrhea.

A 36 year-old woman developed marked lymphedema and chylous cysts of the lower abdominal wall, groin, labia, accompanied by chylorrhea. After cyst excision and transplantation of the greater omentum, a left chylothorax occurred. After thoracic duct ligation and left pleurodesis, pleural effusion recurred and worsened. Lymphangioscintigraphy and conventional lymphography suggested that undrained enlarged retroperitoneal lymphatics in the right iliac fossa had disrupted and lymph had leaked into the left chest from the right iliac fossa. Treatment by a lymphatic cyst-vein anastomosis redirected excess chylous lymph into the blood circulation and chylothorax initially remitted. Several years later with recurrence of chylorrhea, the anastomosis was found to be occluded. After a second operative connection between a lymphogenous cyst and the greater saphenous vein, chylorrhea subsided and chylothorax has remitted for more than 4 years.

Abdominal Muscles↗

[Determination of deoxyribonucleic acid with rosaniline by a resonance light scattering method].

The resonance light scattering (RLS) spectra of Rosaniline with DNA have been studied. The RLS of Rosaniline is greatly enhanced by DNA in pH range of 10.5-10.8. There is a resonance light scattering peak ofat 485 nm, and the enhanced intensity of RLS at this wavelength is proportional to the concentration of DNA. The linear range of the calibration graph is 0-1.00 mg.L-1 with the correlation coefficient of 0.9980. The detection limit is 14.2 ng.mL-1. The relative standard deviation(n = 10) was within 2.1%. This method is simple, rapid and has been applied to the determination of DNA in mixed samples with satisfactory results.

Attention↗

[Luminescence dependence upon concentration and temperature in YPO4:Pr3+].

Under selective excitation 3P0 state of Pr3+ ion in YPO4, the emission spectra and fluorescence decay curves are measured at different concentrations and temperatures. The origin of the spectral line located at 613.2 nm has been discussed and assigned to be the 1D2 (gamma 3)-->3H4 (gamma 5) transition. The different concentration dependence of emission intensities of levels 3P0 and 1D2 has been studied. Using static model, the fluorescence decay curve of 1D2 level is fitted, and the result shows that the cross-relaxation caused by the interaction of dipole-quadrupole between adjacent Pr3+ ions results in the concentration quenching.

Attention↗

[The synthesis, Raman, FTIR spectra and characteristic of Rb(NTO).(H2O)].

A new coordination compound of Rb(NTO).(H2O) were synthesized by reaction of NTO water solution with Rb2CO3. The composition of this compound was defined by elemental analysis of C, H and N and quantitative analysis of Rb. The structure and properties were characterized by FTIR spectra Raman spectra, and X-ray powder defferaction, and the different bonds formed. In the molecule of Rb(NTO).(H2O) has been tried to discuss.

English Abstract↗

[Determination of deoxyribonucleic acid with neutral red by resonance light scattering method].

The method is based on the enhancement effect of the resonance light scattering (RLS) due to the long range assembly of neutral red (NR) on the molecular surface of DNA. The RLS of NR is greatly enhanced by DNA in the pH range of 5.0-7.0. The enhanced intensity of RLS at 335.0 nm is proportional to the concentration of DNA in the range 0-600 ng.mL-1. The detection limit is 12.8 ng.mL-1. This method is simple, rapid and has been applied to the determination of DNA in mixed samples with satisfactory results.

Animals↗

[In-situ FTIR spectroscopic studies of electro oxidation of ethanol in alkaline media at a nm-Pt/GC electrode].

The electro-oxidation of ethanol on a nm-Pt/GC electrode in alkaline solutions was investigated by using cyclic Voltammetry and in-situ FTIR spectroscopy. The results demonstrated that the main product of ethanol oxidation was CH3COO-, only small quantity of CH3CHO was determined simultaneously. In contrast with the dual path reaction mechanism for the oxidation of ethanol in acid media, the oxidation of ethanol in alkaline media was revealed via the intermediate process of dissociative adsorption.

English Abstract↗

[In situ FTIRS studies of CO2 reduction on thin film alloy electrodes].

The nanometer thin film alloy electrode (Sb-Pb-Pt/GC) was prepared by electrochemical methods. Excellent catalytic effect was observed on these film alloy material in the electro-reduction of carbon dioxide (CO2). The reduction can take place at potentials as high as -0.4 V. The oxidation of reduced products of CO2 on Sb-Pb-Pt/GC yielded current peaks at arrowed -0.08, 0.2 and 0.3 V, while the oxidation of reduction products on a nm-Pt/GC electrode gave rise a current peak near 0.4 V. The in situ FTIR spectroscopic studies confirmed at a molecule level that the products of CO2 reduction on Sb-Pb-Pt/GC are mainly organic acid and alcoholic compounds, while on a nm-Pt/GC electrode the production of CO2 is mainly CO species.

Alloys↗

Developmental expression of an amn(+) transgene rescues the mutant memory defect of amnesiac adults.

The Drosophila memory gene amnesiac (amn) has been proposed to encode a neuropeptide protein, which includes regions homologous to vertebrate pituitary adenylyl cyclase-activating peptide (PACAP; Feany and Quinn, 1995). Definitive experiments to link this gene to memory formation, however, have not yet been accomplished (Kandel and Abel, 1995). The experiments described here demonstrate that the putative amn transcript is involved in adult memory formation. With the use of a UAS-amn(+) transgene, we show complete rescue of memory defects in amn(28A), a mutant allele caused by the insertion of a GAL4 enhancer trap transposon (Moore et al., 1998). Study of the amn(28A) reporter reveals widespread expression in the adult brain but also enriched expression in the embryonic and larval nervous systems. To begin addressing the temporal requirement of amn in memory, we asked whether the memory defects could be rescued by restricting transgenic expression to the adult stage. A heat-shock regimen shown previously to rescue fully the amn ethanol sensitivity defect (Moore et al., 1998) failed to rescue the memory defect. These results, coupled with previous genetic and anatomical studies, suggest that adult memory formation and ethanol sensitivity have different temporal and spatial requirements for amn.

Aging↗

Regional distribution in human of a novel aortic collagen-associated microfibrillar protein.

We have reported two hypothetical proteins of human aorta, based on sequences cloned from a cDNA library constructed from mRNAs purified from the adventitia. These sequences have immunoglobulin-kappa (IgK)-like domains, and we have shown that microfibrils of the aortic adventia are immunoreactive with antibodies against IgK. The present study was performed to characterize more specifically the regional distribution in human of one of these proteins in particular and the distribution of matrix proteins with IgK-like motifs in general. An antibody was raised in rabbit against a synthetic peptide based on a unique sequence in one of the hypothetical proteins (NPSNRVTPQKNFP), which has not been reported in the sequence of any other known protein. This antibody and a rabbit anti-human IgK antibody were used as first antibodies in the staining reactions. A monoclonal mouse anti-smooth muscle cell alpha-actin antibody was also used. Immunoreactivity with the sequence-specific antibody was limited to the aorta and large vessels. Adventitial microfibrillar staining was more conspicuous in the abdominal aorta than in the thoracic aorta and in the internal iliac than in the external iliac artery. The immunoreactive protein was associated with fibroblasts and not smooth muscle cells. Immunoreactivity coated the collagen fibers diffusely, while elastin fibers were not stained. Further studies using antibodies against IgK demonstrated immunoreactivity of collagen and fibroblasts in a variety of tissues: spleen, ovary, testicle, cervix, prostate, skin, and breast (but not brain). Immunoglobulin motifs may be a feature of matrix proteins produced by fibroblasts in many tissues, but the first motif that we identified from a cDNA library of aortic adventitia appears to be specific to aorta and large vessels.

Amino Acid Sequence↗

Regional distribution in the mouse of proteins homologous to artery-specific antigenic proteins (ASAPs).

We have reported the sequences of four novel proteins derived from extracts of human aortic tissue and a cDNA library from human aortic adventitia. These proteins are immunoreactive with serum immunoglobulins from patients with abdominal aortic aneurysms (AAA), and they have homologies of amino acid sequence with microfibrillar proteins of connective tissue. We are reporting separately that two of these proteins are artery-specific antigenic proteins (ASAPs) in man. The present work investigates the regional distribution of these two proteins (AAAP-40 and MatCAM-1) in mouse (E-beta-b). Antibodies were raised in rabbit against polypeptides encoding novel amino acid sequences, unique to these proteins (e.g., not reported in GenBank). Immunohistochemical studies with these two specific antibodies show conspicuous immunoreactivity of collagen-associated microfibrils in the aortic adventitia of the murine abdominal and thoracic aorta. Immunoreactive peptides were not present in brain, muscle, or kidney. These findings support the hypothesis that proteins occur in the mouse that are homologous to a unique family of aortic microfibrillar proteins in man.

Actin Cytoskeleton↗

[Changes of the activities of ET-1 in the serum and BALF of ILD patients and their clinical significance].

OBJECTIVE: To evaluate the roles of the Endothelin-1 (ET-1) in pathogenesis of the patients with interstitial lung disease (ILD). METHODS: The ET-1 activities in the serum and BALF from 10 patients with sarcoidosis, 7 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects non-smokers were determined using the radio-immunoassay. RESULTS: In the activities of ET-1 in the serum and BALF in the patients with sarcoiosis (62 +/- 29 and 17.0 +/- 2.4) ng/L and in the IPF (77 +/- 71 and 10 +/- 3) ng/L. was higher than those in the normal control subjects (20 +/- 8 and 4.0 +/- 0.6) ng/L. The activities of ET-1 in serum was negative correlated with PaO2 (r = -0.538, P < 0.01). The level of ET-1 in the BALF of the patient was positive correlated with total cells in BALF (r = 0.649, P < 0.01). The levels of ET-1 in the BALF in the sarcoidosis was positive correlated with the percentage of lymphocyte (r = 0.712, P < 0.01) but in patients with IPF was positive correlated with the percentage of neutrophil (r = 0.813, P < 0.01). CONCLUSIONS: ET-1 might play an important role in pathogenic of the patients with sarcoidosis and IPF. The levels of ET-1 can act as the markers of activity of disease.

Adult↗

[A prevalence study on hepatitis C infection in 4,055 healthy children of Beijing].

OBJECTIVE: To understand the prevalence of hepatitis C (HC) infection in children of urban Beijing. METHODS: Serum antibodies against hepatitis C virus (anti-HCV) and HCV RNA were determined with enzyme-linked immunosorbent assay (ELISA) in 4 055 healthy children under 14 years of age living in four urban districts of Beijing. RESULTS: Fourteen children were positive for anti-HCV, and four of them were positive for HCV RNA as well, with a prevalence of HCV infection of 0.35%. There was no significant difference in prevalence of HCV infection between children living in different districts and by sex and age. However, very significant difference in prevalence of HCV infection between children with history of blood transfusion and injection of human blood-derived globulin and those without it. The parents of 14 children with positive anti-HCV were all negative for it. CONCLUSION: Blood-borne transmission still was the main route for HCV infection in children.

Adolescent↗