Inhibin B, activin A, and follistatin and the pathogenesis of polycystic ovary syndrome.
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Activins↗
Biomedical subjects
Y G Chen
Publications and source records attributed to Y G Chen.
Effects of artificial liver support system on patients with acute or chronic liver failure.
AIMS: Acute on chronic liver failure (AoCLF) is associated with a high mortality rate. Artificial liver support system (ALSS) is useful to bridge patients with liver failure to liver transplantation or to regenerate their own livers. The aims of this prospective study were to investigate the effects of ALSS on clinical manifestations, liver function, and 30-day survival to probe the factors related to mortality in patients with AoCLF. METHODS: In this study, 338 enrolled patients with AoCLF who received ALSS treatment for 1 to 8 sessions, were compared with 312 patients treated with conventional medications. RESULTS: Clinical manifestations and liver functions were significantly improved, namely, decreased levels of serum transaminases, total bilirubin, and bile acid, as well as increased levels of serum albumin following ALSS treatment. The 30-day survival rates of the patients who received ALSS versus controls were 47.9% versus 34.6%, respectively (P = .01). The MELD score and the stage of hepatic encephalopathy were highly associated with mortality (P < .001), but the sessions of ALSS showed a positive relation to the 30-day survival (P < .05). CONCLUSIONS: ALSS appears to be efficacious and safe for the treatment of patients with AoCLF. Both model for end-stage liver disease (MELD) score and hepatic encephalopathy are useful to predict the mortality of patients.
Adolescent↗
Anti-carcinogenic and anti-metastatic properties of indole-3-carbinol in prostate cancer.
Indole-3-carbinol (I3C), a compound present as glucobracissin in cruciferous vegetables has anticancer activities which is in line with some of the epidemiological evidence that suggests a beneficial effect of consumption of cruciferous vegetables on cancer incidence and progression. The precise target of indole-3-carbinol has not been determined. We examined the effect of I3C on prostate cancer in a well-defined R3327 model using Copenhagen rats and the transplantable cell line, MAT-LyLu. This cell line derived from a tumor in Copenhagen rats is androgen independent and metastasizes to the lung and lymph nodes. Tumors were induced in Copenhagen rats by injecting MAT-LyLu subcutaneously and the animals treated with I3C that was administered either intraperitoneally or intravenously, in order to achieve maximal systemic exposure. This was a departure from the traditional chemopreventive route of indole-3-carbinol where the compound was incorporated in the diet. Our results indicate that I3C inhibited the incidence, growth and metastases of MAT-LyLu cells and both i.p. and i.v. injections of I3C were equally effective. Statistical analysis (Kaplan-Meier curves) clearly indicates a tumor-free and overall survival benefit as a result of treatment with I3C. These studies show for the first time that I3C in an injectible form has anti-prostate cancer activity.
Animals↗
Toxic effects of aminophenols on aquatic life using the zebrafish embryo test and the comet assay.
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Aminophenols↗
Induction of heat shock protein gp96 by immune cytokines.
Cytokines play a major role in regulating both humoral and cell-mediated immune responses. Recent advances in our understanding of cell-mediated immune responses have focused on the antigen presentation machinery and the proteins in the endoplasmic reticulum (ER). These proteins help the formation and stabilization of the major histocompatibility complex (MHC)-peptide interaction. A 96-kDa, ER-resident glycoprotein (gp96) is being evaluated as a therapeutic agent in cancer because of its ability to associate with a vast number of cellular peptides irrespective of size or sequence. Because the antigen presentation complex is assembled in the ER and a number of ER-resident proteins are modulated by cytokines, it is important to examine the regulation of gp96 in response to immune cytokines interferon gamma (IFN-gamma), and interleukin 2 (IL-2). Defects in signaling pathway in either of the cytokines can result in suboptimal immune response. We examined the effect of the cytokines IFN-gamma and IL-2 on the induction of gp96 in different cancer cell lines and examined the induction of DNA-binding proteins that recognize gamma interferon-activating sequence (GAS), present in the promoter region of gp96. The induction of GAS binding protein correlated with the induction of STAT 1 protein, a transcriptional regulator and mediator of IFN-gamma-mediated gene expression. The use of cytokines in inducing gp96 levels may have significance in maintaining high levels of gp96 for a sustained immune response.
Animals↗
Peptide mimotopes of oncoproteins as therapeutic agents in breast cancer.
Generation of an immune response to oncoproteins can lead to a cancer specific protective immunity. Several such oncoproteins are being examined as tumor targets with mixed results. We are evaluating the clinical utility of synthetic peptides that would mimic the antigen immunologically and elicit a tumor specific immune response. HER-2/neu, an oncoprotein whose expression in breast cancer is associated with poor prognosis, lower disease free-survival and a propensity for metastases was chosen as a model. Antibodies, Ab2, Ab4 and Ab5 directed towards the extracellular domain of HER-2/neu were reacted to peptides from two synthetic phage display peptide libraries, LX-8 (12-mer peptide library containing disulfide bridge) and X-15 (linear 15-mer). The isolated peptides were sequenced and characterized for ability to produce high titer antibodies and cross-reactivity. The peptides isolated did not show any sequence homology to protein databases but did show a hierarchy of immunogenic epitopes. Antibodies generated against peptides selected against the same antibody Ab2 or Ab4 showed affinity variation. Phages selected against Ab2 were also able to compete with binding of Ab2 to HER-2/neu. These results validate our hypothesis that synthetic peptides that mimic the antigenic epitope of oncoprotein can be generated and their clinical utility rests on devising a screening mechanism to identify peptides that can elicit an immune response directed to the oncoprotein and if possible its antigenic variants.
Animals↗
Multiple molecular targets of indole-3-carbinol, a chemopreventive anti-estrogen in breast cancer.
The mechanism of action of the anti-estrogen indole-3-carbinol (I3C), present in cruciferous vegetables, is being examined in our laboratory with a view to promote the use of this naturally occurring chemopreventive as an alternative to synthetic anti-estrogens in human breast cancer. Our previous results clearly demonstrated that despite its low affinity for the estrogen receptor (ER), I3C abrogated estradiol-mediated cellular and biochemical effects in estradiol-responsive cells and tissues. In an earlier report, we identified ER phosphorylation as one of the targets of I3C, and in this communication we describe the consequence of inhibition of ER phosphorylation. Estradiol-induced DNA-binding proteins that bound to several DNA-responsive elements were inhibited by I3C and this effect was not at the level of DNA-protein physical interaction as inclusion of I3C in vitro in the reaction mix did not affect the binding. We analyzed the spectrum of genes induced by estradiol and modulated and/or intercepted by I3C. Our results conclude that although estradiol-mediated functions are affected by I3C, its biochemical targets are multiple and some of these may be modulated by the oligomeric products of I3C.
Anticarcinogenic Agents↗
A cDNA from human bone marrow encoding a protein exhibiting homology to the ATP1gamma1/PLM/MAT8 family of transmembrane proteins.
A cDNA clone, IWU-1, was cloned from human bone marrow. Its putative open reading frame encoded a protein of 115 amino acids with a calculated molecular mass of 12.9 kDa. The deduced amino acid sequence exhibited high homology (>68%) to members of the ATP1gamma1/PLM/MAT8 family of single transmembrane proteins, primarily in the region containing the putative transmembrane domain. The sequence at the amino-terminal side exhibited high homology (>61%) to the cytoplasmic region of the angiotensin II type 1 receptors.
Amino Acid Sequence↗
Effects of pathway and neuronal aging on the specificity of motor axon regeneration.
Youth is a strong predictor of functional recovery after peripheral nerve repair, while adulthood is commonly associated with poor outcome. Identification of the factors responsible for this difference could form the basis for strategies to improve regeneration in adults. Preferential reinnervation of motor pathways by motor axons (PMR) occurs strongly in young rats, but is often absent in older animals, and thus parallels the overall trend for superior results in young individuals. These experiments evaluate the individual contributions of peripheral nerve age and motoneuron age to the decline in regeneration specificity (PMR) which accompanies the aging process. The femoral nerves of young and old Lewis rats were removed as inverted "Y" grafts from the femoral trunk proximally to the terminal muscle and cutaneous branches distally. These grafts were transferred from (1) old to young, (2) young to old, (3) old to old, and (4) young to young bilaterally in 10 individuals per group. After 8 weeks of regeneration, reinnervation of cutaneous and muscle branches was assessed by dual labeling with HRP and Fluoro-Gold. Motor neuron regeneration was random in old to old (mean muscle branch (M) = 159, mean cutaneous branch (C) = 168), but PMR was seen when young pathways were used in old animals (M = 163, C = 116). PMR was vigorous when either type of graft was used in young animals (young graft, M = 218, C = 134; old graft, M = 204, C = 127). In this model, motoneuron age appears to be the primary determinant of specificity. However, the pathway also makes significant contributions, as shown by the ability of young pathways to generate specificity in old animals. Manipulation of graft Schwann cell behavior might therefore be an appropriate strategy to improve outcome in older individuals.
Age Factors↗
Compounds from Kadsura ananosma.
The 18-(13-->12 beta)-abeo-lanostene triterpenoid acid, ananosic acid A (1), and the dibenzocyclooctadiene lignan, ananosin A (2), were isolated from the stem bark of Kadsura ananosma. Their structures were elucidated by extensive spectral studies and the structure of 1 was confirmed by single crystal X-ray diffraction analysis.
Crystallography, X-Ray↗
Triterpenoid acids from Schisandra propinqua with cytotoxic effect on rat luteal cells and human decidual cells in vitro.
Three triterpenoid acids, nigranoic acid (1), manwuweizic acid (2), schisandronic acid (3), and other four compounds were isolated from the stems of Schisandra propinqua. Compounds 1 and 2 showed significant cytotoxic effect against human decidual cells and rat luteal cells in vitro.
Animals↗
The TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
The type I TGF beta receptor (T beta R-I) is activated by phosphorylation of the GS region, a conserved juxtamembrane segment located just N-terminal to the kinase domain. We have studied the molecular mechanism of receptor activation using a homogeneously tetraphosphorylated form of T beta R-I, prepared using protein semisynthesis. Phosphorylation of the GS region dramatically enhances the specificity of T beta R-I for the critical C-terminal serines of Smad2. In addition, tetraphosphorylated T beta R-I is bound specifically by Smad2 in a phosphorylation-dependent manner and is no longer recognized by the inhibitory protein FKBP12. Thus, phosphorylation activates T beta R-I by switching the GS region from a binding site for an inhibitor into a binding surface for substrate. Our observations suggest that phosphoserine/phosphothreonine-dependent localization is a key feature of the T beta R-I/Smad activation process.
Activin Receptors, Type I↗
[New progress of serial analysis of gene expression].
As an efficient tool that has been developed recently, serial analysis of gene expression (SAGE) allows the qualitative and quantitative analysis of a large number of transcripts. It can define the transcripts at relatively low levels and characterize the genomic expression near completion. In addition, it provides insights into the timely and orderly expression of genes by comparing the profiles constructed for a pair of cells that are kept at different conditions, thus identifying a set of novel genes. In this review, the newest progress of SAGE's application and research is mentioned in details with its original method and principle outlined.
Animals↗
[Studies on chemical constituents of Schisandra propinqua (Wall.) Hook. f. et Thoms].
OBJECTIVE: To isolate and characterize compounds from the stems of Schisandra propinqua. METHOD: Extracting with solvent, isolating by column chromatography and identifying by the spectroscopic methods. RESULT: Six dibenzocyclooctadiene lignans were isolated and identified as tigloylgomisin P(1), angeloylgomisin O(2), angeloylisogomisin O(3), kadsulignan L(4), (+/-) 5,8-epoxyl-6, 7-dimethyl-2',3',2",3"-dimethylenedioxy-4', 1"-dimethyl-1,2:3,4-dibenzo-1, 3-cyclooctadiene(5) and wuweizisu C(6). CONCLUSION: Compounds 4 and 5 were the first two dibenzocyclooctadiene lignans with an 6,9-epoxy bridge cycle discovered in the genus Schisandra. The others were originally isolated from S. propinqua.
Cyclooctanes↗
[Studies on chemical constituents of Stellera chamejasma L].
OBJECTIVE: Isolate and identify the bioactive compounds from the root of Stellera chamejasma. METHOD: The compounds were extracted with solvents, isolated by column chromatography and identified by spectroscopic methods. RESULT: Seven compounds were isolated and identified as umbelliferone(1); daphnoretin (2); 2,6-dimethoxyl p-benzoquinone(3); (-)-eudesmin(4); (+)-matairesinol(5); lirioresinol B(6) and daucosterol(7). CONCLUSION: Compounds 3, 4 and 5 were isolated from the plant for the first time.
Furans↗
Expression of mPer1 and mPer2, two mammalian clock genes, in murine bone marrow.
Although circadian variations in hematopoiesis have been well documented, the molecular mechanism of the circadian rhythms remains elusive. To determine if a clock system exists in bone marrow to mediate the circadian rhythms, we analyzed the expression of mPer1 and mPer2, both mouse homologues of the Drosophila period gene and known regulators of the clock system, in murine bone marrow by relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). We demonstrated that both genes were expressed in bone marrow. Furthermore, the expression patterns of mPer1 and mPer2 in total bone marrow cells exhibited two peaks over a 24-h period. In contrast, the expression patterns of these two genes in the Gr-1-positive cells isolated from bone marrow mainly contributed to one of the two peaks. These results indicate that a clock system exists in bone marrow and suggest that the circadian rhythms in bone marrow are lineage- and/or differentiation stage-dependent.
Analysis of Variance↗
Engagement of bone morphogenetic protein type IB receptor and Smad1 signaling by anti-Müllerian hormone and its type II receptor.
Anti-Müllerian hormone induces the regression of fetal Müllerian ducts and inhibits the transcription of gonadal steroidogenic enzymes. It belongs to the transforming growth factor-beta family whose members signal through a pair of serine/threonine kinase receptors and Smad effectors. Only the anti-Müllerian hormone type II receptor has been identified. Our goal was to determine whether anti-Müllerian hormone could share a type I receptor with another family member. Co-immunoprecipitation of known type I receptors with anti-Müllerian hormone type II receptor clearly showed that the bone morphogenetic protein type IB receptor was the only cloned type I receptor interacting in a ligand-dependent manner with this type II receptor. Anti-Müllerian hormone also activates the bone morphogenetic protein-specific Smad1 pathway and the XVent2 reporter gene, an anti-Müllerian hormone type II receptor-dependent effect abrogated by a dominant negative version of bone morphogenetic protein type IB receptor. Reverse amplification experiments showed that bone morphogenetic protein type IB receptor is co-expressed with anti-Müllerian hormone type II receptor in most anti-Müllerian hormone target tissues. Our data support a model in which a ligand, anti-Müllerian hormone, gains access to a shared type I receptor and Smad1 system through a highly restricted type II receptor.
Animals↗
Controlling TGF-beta signaling.
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Animals↗