Biomedical subjects

Hao Wang

Publications and source records attributed to Hao Wang.

At least 37 records · Page 2Linked to original sources

PubMed2007

Effects of continuous high-volume hemofiltration on experimental severe acute pancreatitis in pigs.

OBJECTIVE: To compare the effects of different doses of hemofiltration on severe acute pancreatitis (SAP) in pigs. METHODS: The animal model of SAP was produced by intraductal injection of sodium taurocholate and trypsin. Animals in group 1 served as SAP control. Animals in group 2 received (20 mL/kg per hour) continuous low-volume hemofiltration (LVHF), and animals in group 3 received (100 mL/kg per hour) continuous high-volume hemofiltration (HVHF) immediately after the induction of SAP. After the instrumentation of the animals by arterial and Swan-Ganz catheters, hemodynamic indexes were monitored intermittently at different times. The rectal temperature and the concentration of amylase and cytokines in serum were measured at the same time. RESULTS: The survival time of HVHF group was significantly prolonged (P < 0.01). The initial elevation of body temperature and the hypothermia in the late course of experiments were significantly ameliorated by HVHF (P < 0.01). Six hours after the induction of pancreatitis, the urine output of animals in HVHF group was obviously higher than that in control group (P < 0.05), which stayed behind 36 hours later (P < 0.05). The major hemodynamic finding was that pancreatitis-induced hypotension was significantly attenuated by HVHF (P < 0.01). The development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increase in CI, an attenuated decrease in systemic vascular resistance index. Plasma amylases in the HVHF group were significantly lower than those in control and LVHF groups (P < 0.01). The serum concentrations of cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 6, and IL-10 all decreased significantly in treatment groups (P < 0.01), and those of HVHF group were less significant than the HVHF group (P < 0.01). CONCLUSIONS: The HVHF was associated with a better hemodynamic profile, a less hyperkinetic state, and more prolonged survival than that of LVHF, which may result from the HVHF that can remove the inflammatory cytokines more efficiently.

Acute Disease↗

PubMed2006

Activation of SHP2 protein-tyrosine phosphatase increases HoxA10-induced repression of the genes encoding gp91(PHOX) and p67(PHOX).

The CYBB and NCF2 genes encode the phagocyte oxidase proteins gp91(PHOX) and p67(PHOX), respectively. These genes are transcribed after the promyelocyte stage of differentiation, and transcription continues until cell death. In undifferentiated myeloid cells, homologous cis-elements in the CYBB and NCF2 genes are repressed by the homeodomain transcription factor HoxA10. During cytokine-induced myelopoiesis, tyrosine phosphorylation of HoxA10 decreases binding affinity for the CYBB and NCF2 cis-elements. This abrogates HoxA10-induced transcriptional repression as differentiation proceeds. Therefore, mechanisms involved in differentiation stage-specific HoxA10 tyrosine phosphorylation are of interest because HoxA10 phosphorylation modulates myeloid-specific gene transcription. In this study, we found that HoxA10 is a substrate for SHP2 protein-tyrosine phosphatase in undifferentiated myeloid cells. In contrast, HoxA10 is a substrate for a constitutively active mutant form of SHP2 in both undifferentiated and differentiating myeloid cells. Expression of such SHP2 mutants results in persistent HoxA10 repression of CYBB and NCF2 transcription during myelopoiesis. Both HoxA10 overexpression and activating SHP2 mutations have been described in human myeloid malignancies. Therefore, our results suggest that these mutations could cooperate, leading to decreased myeloid-specific gene transcription and functional differentiation block in myeloid cells with both defects.

Animals↗

PubMed2006

Double-negative T cells, activated by xenoantigen, lyse autologous B and T cells using a perforin/granzyme-dependent, Fas-Fas ligand-independent pathway.

The ability to control the response of B cells is of particular interest in xenotransplantation as Ab-mediated hyperacute and acute xenograft rejection are major obstacles in achieving long-term graft survival. Regulatory T cells have been proven to play a very important role in the regulation of immune responses to self or non-self Ags. Previous studies have shown that TCRalphabeta+CD3+CD4-CD8- (double-negative (DN)) T cells possess an immune regulatory function, capable of controlling antidonor T cell responses in allo- and xenotransplantation through Fas-Fas ligand interaction. In this study, we investigated the possibility that xenoreactive DNT cells suppress B cells. We found that DNT cells generated from wild-type C57BL/6 mice expressed B220 and CD25 after rat Ag stimulation. These xenoreactive B220+CD25+ DNT cells lysed activated, but not naive, B and T cells. This killing, which took place through cell-cell contact, required participation of adhesion molecules. Our results indicate that Fas ligand, TGF-beta, TNF-alpha, and TCR-MHC recognition was not involved in DNT cell-mediated syngenic cell killing, but instead this killing was mediated by perforin and granzymes. The xenoreactive DNT cells expressed high levels of granzymes in comparison to allo- or xenoreactive CD8+ T cells. Adoptive transfer of DNT cells in combination with early immune suppression by immunosuppressive analog of 15-deoxyspergualin, LF15-0195, significantly prolonged rat heart graft survival to 62.1 +/- 13.9 days in mice recipients. In conclusion, this study suggests that xenoreactive DNT cells can control B and T cell responses in perforin/granzyme-dependent mechanisms. DNT cells may be valuable in controlling B and T cell responses in xenotransplantation.

Adoptive Transfer↗

PubMed2006

Chronic morphine exposure impairs short-term synaptic depression of geniculo-cortical visual pathway in vivo.

Chronic morphine exposure can induce addiction and affect synaptic plasticity, but the underlying neuronal mechanisms remain unknown. Two forms of short-term synaptic depression (paired-pulse depression (PPD) and frequency depression) were investigated in vivo in the geniculo-cortical visual pathway of morphine-treated and saline-treated (as control) adult rats. Acute exposure to morphine had no effect on paired-pulse synaptic depression and 10-40 Hz induced frequency synaptic depression. However, chronic morphine exposure reduced markedly the paired-pulse depression and frequency depression at 40 Hz. The effect of chronic morphine exposure on short-term synaptic plasticity in the geniculo-cortical visual pathway was sensitization given that morphine re-exposure further significantly reduced the short-term synaptic depression. Interestingly, the further reduction in short-term synaptic depression due to re-exposure of morphine was recovered to normal (control) levels at 3 to 6h after morphine re-exposure. These findings suggest that chronic morphine treatment could significantly degrade the short-term synaptic plasticity of geniculo-cortical visual pathway.

Action Potentials↗

PubMed2006

Experimental validation of predicted mammalian erythroid cis-regulatory modules.

Multiple alignments of genome sequences are helpful guides to functional analysis, but predicting cis-regulatory modules (CRMs) accurately from such alignments remains an elusive goal. We predict CRMs for mammalian genes expressed in red blood cells by combining two properties gleaned from aligned, noncoding genome sequences: a positive regulatory potential (RP) score, which detects similarity to patterns in alignments distinctive for regulatory regions, and conservation of a binding site motif for the essential erythroid transcription factor GATA-1. Within eight target loci, we tested 75 noncoding segments by reporter gene assays in transiently transfected human K562 cells and/or after site-directed integration into murine erythroleukemia cells. Segments with a high RP score and a conserved exact match to the binding site consensus are validated at a good rate (50%-100%, with rates increasing at higher RP), whereas segments with lower RP scores or nonconsensus binding motifs tend to be inactive. Active DNA segments were shown to be occupied by GATA-1 protein by chromatin immunoprecipitation, whereas sites predicted to be inactive were not occupied. We verify four previously known erythroid CRMs and identify 28 novel ones. Thus, high RP in combination with another feature of a CRM, such as a conserved transcription factor binding site, is a good predictor of functional CRMs. Genome-wide predictions based on RP and a large set of well-defined transcription factor binding sites are available through servers at http://www.bx.psu.edu/.

Amino Acid Motifs↗

PubMed2006

Preparation and photocatalytic properties of YVO4 nanopowders.

YVO(4) photocatalysts with different grain sizes were obtained by annealing the YVO(4) nanopowders synthesized via microwave irradiation. The products were characterized by X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), surface area and porosity analyzer, and ultraviolet-visible (UV-vis) spectrophotometer. Photocatalytic measurements showed that the YVO(4) nanopowders with grain size of about 5 nm possess superior photocatalytic properties in decolorization of methyl orange solution.

Azo Compounds↗

PubMed2006

Functional degradation of visual cortical cells in aged rats.

Functional degradation of mammalian visual cortex is associated with aging. It has been hypothesized that much of the decline might be mediated by a degradation of cortical inhibitory system during senescence. In the present work, we compared the properties of adaptation, onset latency and signal-to-noise ratio in primary visual cortex of young and old rats using extracellular single-unit techniques. The short-term synaptic plasticity of young and old rats was also studied using field potential recording techniques. We found significant increased adaptation, prolonged onset latency, lower signal-to-noise ratio and decreased short-term synaptic plasticity in aged rats. The results are in accordance with previously reported functional declines in old monkeys and old cats, indicating a universal mechanism of degradation in cortical function that accompanies old age in different mammalian species.

Adaptation, Physiological↗

PubMed2006

PKC-betaII sensitizes cardiac myofilaments to Ca2+ by phosphorylating troponin I on threonine-144.

Ventricular myocytes express Galphaq-coupled receptors that can mediate enhanced contractility by increasing the sensitivity of the contractile apparatus to Ca(2+). The precise mechanisms underlying this change have been difficult to define, in part because myofilament regulatory proteins contain multiple phosphorylation sites for protein kinase C (PKC), protein kinase A (PKA) and myosin light chain kinase (MLCK), with potentially opposing effects. MLCK increases whereas PKC and PKA have a strong tendency to decrease myofilament Ca(2+) sensitivity in myocardium. Here we show in mouse cardiac myocytes that PKC-betaII can increase Ca(2+) sensitivity of tension by a similar magnitude to MLCK but via a distinct mechanism. For PKC-betaII (32)P-incorporation occurred primarily into cardiac troponin I (cTnI) and functional effects were highly dependent upon mutations in phosphorylation sites of cTnI. Replacement of serines-23/24 (PKA sites) with alanine prevented cross-phosphorylation of these sites, reduced (32)P-incorporation into cTnI by half and resulted in myofilament Ca(2+) sensitization rather than desensitization in response to PKC-betaII. Replacement of three additional sites on cTnI, serines-43/45 and threonine-144, eliminated PKC-betaII-mediated Ca(2+) sensitization and the remaining (32)P-incorporation into cTnI. A preference for PKC-betaII phosphorylation of threonine-144 in the intact filament lattice was revealed by differential stable isotope labeling and supported by an analysis of peptide phosphorylation. The results suggest that threonine-144 within the critical inhibitory domain of cTnI represents a novel site of regulation of myofilament Ca(2+) sensitivity by PKC-betaII, with possible implications for chronically stressed or diseased hearts.

Actin Cytoskeleton↗

PubMed2006

Preliminary study on a potential antibacterial peptide derived from histone H2A in hemocytes of scallop Chlamys farreri.

Histone H2A is reported to participate in host defense response through producing novel antimicrobial peptides (AMPs) from its N-terminus in vertebrates and invertebrates, while the AMPs derived from H2A have not to our knowledge been reported in mollusca. In the present study, gene cloning, mRNA expression of H2A from scallop Chlamys farreri, and the recombinant expression of its N-terminus were conducted to investigate whether a similar mechanism exists in mollusca. The full-length DNA of H2A was identified by the techniques of homology cloning and genomic DNA walking. The full-length DNA of the scallop H2A was 696bp long, including a 5'-terminal untranslated region (UTR) of 90bp, a 3'-terminal UTR of 228bp with a stem-loop structure and a canonical polyadenylation signal sequence AATAAA, and an open reading frame of 375bp encoding a polypeptide of 125 amino acids. The mRNA expression of H2A in the hemocytes of scallop challenged by microbe was measured by semi-quantitative RT-PCR. The expression of H2A was not upregulated after stimulation, suggesting that H2A did not participate in immunity response directly. The DNA fragment of 117bp encoding 39 amino acids corresponding to the N-terminus of scallop H2A, which was homologous to buforin I in vertebrates, was cloned into Pichia pastoris GS115. The transformants (His(+) Mut(+)) containing multi-copy gene insertion were selected with increasing concentration of antibiotic G418. The peptide of 39 amino acids was expressed by induction of 0.5% methanol. The recombinant product exerted antibacterial activity against both Gram-positive (G(+)) and Gram-negative (G(-)) bacteria. The antibacterial activity toward G(+) bacteria was 2.5 times more than that against G(-) bacteria. The results elucidated that N-terminus of H2A was a potential AMP and provided a promising candidate for a new antibiotic screening. However, whether H2A is really involved in scallop immune response mechanisms needs to be further investigated.

Amino Acid Sequence↗

PubMed2006

Preparation and characterization of recombinant protein ScFv(CD11c)-TRP2 for tumor therapy from inclusion bodies in Escherichia coli.

Dendritic cells (DCs)-based immunotherapy represents an approach to the prevention and treatment of cancers. Targeting antigens to receptors on DCs can be expected to enhance immune response. We have constructed an expression vector pET32a(+)-ScFv(CD11c)-TRP2 based on a single-chain antibody fragment (ScFv) that targets the high affinity receptor CD11c which is expressed on murine DCs. The 3'-terminal end of the ScFv was ligated to the gene for MHC class I molecule-recognized peptide from mouse tyrosine-related protein 2 (TRP2). Using this vector, we have expressed and purified ScFv(CD11c)-TRP2, a fusion protein that could target TRP2 peptide to CD11c on DCs in vivo to elicit anti-tumor responses. This fusion protein was expressed in inclusion bodies in Escherichia coli BL21(DE3) and was refolded and purified on-column effectively by immobilized metal affinity chromatography using His-tag. Flow cytometry assays showed the specific binding ability of ScFv(CD11c)-TRP2 to DCs, which could be blocked by a hamster anti-mouse CD11c produced by N418 hybridoma. Further studies demonstrated that ScFv(CD11c)-targeted TRP2 peptide processed by DCs was capable of stimulating T cells proliferation. Thus, this fusion protein provides a basis for further research in cancer therapy in vivo.

Animals↗

PubMed2006

Axon guidance by diffusible chemoattractants: a gradient of netrin protein in the developing spinal cord.

Gradients of diffusible long-range attractant and repellent proteins have been proposed to guide growing axons during nervous system development, but such gradients have never been visualized directly. In the embryonic spinal cord, commissural axons pioneer a circumferential trajectory to the floor plate at the ventral midline directed by secreted proteins of the netrin family. In the embryonic chick spinal cord netrin-1 mRNA is expressed by floor plate cells and netrin-2 mRNA by neural epithelial cells. Antibodies to the two netrins reveal a gradient of netrin protein directly in the path of commissural axons. The netrin-1 gradient itself extends many cell diameters dorsal to the floor plate, the site of netrin-1 expression. A similar distribution of netrin-1 protein has been detected in embryonic rat and mouse spinal cord. The detection of a gradient of netrin-1 protein supports the operation of long-range chemotropic mechanisms in the developing nervous system.

Animals↗

PubMed2006

Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) are of great therapeutic potential after myocardial ischemic injury. However, little is known about the biological characteristics of MSCs in patients with coronary artery disease and their effects on infracted myocardium. The present study evaluated the biological characteristics of MSCs from patients with coronary artery disease and their effects after being transplanted into infarcted myocardium using a rat model. METHODS: Sternal bone marrow aspirates were taken at the time of coronary artery bypass graft surgery. Mononuclear cells isolated from bone marrow were cultured based on plastic adherence. The morphology and growth characteristics of MSCs were observed in primary and successive passages. A myocardial infarction model was created in 27 adult rats. Two weeks later, animals were randomized into two groups: culture medium (group I, n=13) or MSCs (2x10(6)) from early passages labeled with BrdU (group II, n=14) were injected into the infarcted myocardium. Echocardiography, histological examination, and reverse transcription-polymerase chain reaction (RT-PCR) were performed four weeks after cell transplantation. RESULTS: Flow cytometry analyses demonstrated that adherent spindle cells from bone marrow are mesenchymal stem cells (positive for CD29 and CD44, but negative for CD34 and CD45). Growth curves showed that MSCs have great proliferative capability especially at early passages. MSCs implantation in the infarcted border zone improved left ventricular function significantly in group II compared with group I. However, despite improved left ventricular function, we did not observe significant regeneration of cardiac myocytes. Immunohistochemistry revealed only the expression of desmin in the engrafted MSCs, a marker of premature myocyte. Moreover, the improved left ventricular function in this study seemed to be secondary to the beneficial reverse remodeling induced by the increase of collagen in infarcted zone, the decrease in the adjacent myocardium, and the increase of neovascularization (capillary density: 192+/-7.8/mm2 in group II vs. 165+/-5.9/mm2 in group I, P<0.05). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the expression levels of collagen I, collagen III, SDF-1 (stromal cell-derived factor-1), and VEGF (vascular endothelia growth factor) in the infarcted border zone were significantly higher in the MSCs treated group. CONCLUSIONS: The MSCs from patients with coronary artery disease have a typical phenotype with highly proliferative potential and the engrafted MSCs may regulate extracellular collagens and cytokines to prevent the ventricular scar from pathologic thinning and attenuate the contractile dysfunction of the infarcted heart.

Animals↗

PubMed2006

Atopic diseases, immunoglobulin E and risk of cancer of the prostate, breast, lung and colorectum.

There is increasing epidemiological evidence for a role of allergic/atopic disorders in cancer development. However, findings have been inconsistent, which may be partly due to differences in defining allergy and the associated atopic disorders. The use of a biological marker for atopy may enhance the exploration of the association with cancer risks. To examine the association of atopy with common malignancies, we compared the prevalence of atopy in 318 patients with prostate cancer, 381 patients with breast cancer, 196 patients with lung cancer, 477 patients with colorectal cancer and 4,271 controls in a case-control analysis of participants of 2 prospective studies conducted in Saarland, Germany. Data on physician-diagnosed atopy-related diseases (asthma, hay fever and atopic dermatitis) were obtained by self-administered questionnaire. Allergen-specific immunoglobulin E (IgE) was assessed among cases and controls to define atopy. We observed a significantly increased risk of prostate cancer (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.00-1.83) and a tentatively, statistically not significant increased risk of breast cancer (OR 1.20, 95% CI 0.87-1.66) and lung cancer (OR 1.29, 95% CI 0.87-1.92) with specific IgE positivity. No consistent associations were found with atopy-related diseases. Our findings are consistent with other epidemiological evidence suggesting an increased risk of prostate cancer with atopy and indicate a complex association between atopy/atopy-related diseases and cancer risk that varies by type of atopy-related disorders and the particular type of cancer under consideration. The effect on cancer risk by atopy, defined by IgE reactivity, may differ from the effect by atopy-related clinically defined diseases such as asthma, hay fever and atopic dermatitis.

Aged↗

PubMed2006

Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol-induced impairment of long-term potentiation in rat hippocampal slices.

Enhancing inhibition via gamma-aminobutyric acid type A (GABA(A)) receptors contributes to anesthetic-induced impairment of long-term potentiation (LTP) of excitatory synaptic transmission, which may account for general anesthesia-associated memory impairment (amnesia). The neuron-specific K+ -Cl- cotransporter 2 (KCC2) is necessary for fast synaptic inhibition via maintaining the low intracellular chloride concentration required for the hyperpolarizing actions of GABA via GABA(A) receptors. To explore a possible role of KCC2-dependent inhibition in anesthetic-induced impairment of LTP, we used field excitatory postsynaptic potentials (fEPSP) recording and immunoblotting to study the effect of propofol on LTP maintenance and KCC2 expression in CA1 region of rat hippocampal slices. We found that propofol (30 microM) not only impaired LTP expression but also prevented LTP-accompanied downregulation of KCC2 without affecting the basal transmission of glutamatergic synapses. Moreover, the recurrent inhibition in hippocampal slices was enhanced by propofol. These propofol-induced effects were completely abolished by picrotoxin, a specific GABA(A) receptor-chloride channel blocker. Thus, enhancement of GABAergic inhibition and suppression of neuronal excitability may account for the sustained expression of KCC2 and the impairment of LTP by propofol. Together, this study supports a novel role for KCC2 in LTP expression and gives hints to a molecular mechanism, by which anesthetics might cause impairment of LTP.

Analysis of Variance↗

PubMed2006

Differential binding of plasminogen, plasmin, and angiostatin4.5 to cell surface beta-actin: implications for cancer-mediated angiogenesis.

Angiostatin4.5 (AS4.5) is the product of plasmin autoproteolysis and consists of kringles 1 to 4 and approximately 85% of kringle 5. In culture, cancer cell surface globular beta-actin mediates plasmin autoproteolysis to AS4.5. We now show that plasminogen binds to prostate cancer cells and that the binding colocalizes with surface beta-actin, but AS4.5 does not bind to the cell surface. Plasminogen and plasmin bind to immobilized beta-actin similarly, with a Kd of approximately 140 nmol/L. The binding is inhibited by epsilon-aminocaproic acid (epsilonACA), indicating the requirement for a lysine-kringle domain interaction. Using a series of peptides derived from beta-actin in competitive binding studies, we show that the domain necessary for plasminogen binding is within amino acids 55 to 69 (GDEAQSKRGILTLKY). Substitution of Lys61 or Lys68 with arginine results in the loss of the ability of the peptide to block plasminogen binding, indicating that Lys61 and Lys68 are essential for plasminogen binding. Other actin peptides, including peptides with lysine, did not inhibit the plasminogen-actin interaction. AS4.5 did not bind actin at concentrations up to 40 micromol/L. Plasminogen, plasmin, and AS4.5 all contain kringles 1 to 4; however, kringle 5 is truncated in AS4.5. Isolated kringle 5 binds to actin, suggesting intact kringle 5 is necessary for plasminogen and plasmin to bind to cell surface beta-actin, and the truncated kringle 5 in AS4.5 results in its release from beta-actin. These data may explain the mechanism by which AS4.5 is formed locally on cancer cell surfaces and yet acts on distant sites.

Actins↗

PubMed2006

[Effect of epidermal growth factor signal pathway on integrin alpha5 beta1 in prostate cancer cell line DU145].

OBJECTIVE: To investigate the molecular mechanism of epidermal growth factor (EGF) signal pathway on the expression of integrin alpha5 beta1 in prostate cancer cell line DU145. METHODS: Using flow-cytometry, the effects of EGF and the mitogen-activated protein kinase (MAPK) signal pathway inhibitor PD98059 on the expression of integrin alpha5 and beta1 subunits on DU145 cell surface were analyzed. RT-PCR and Western blot methods were used to examined the expression of mRNA and cell total protein of integrin alpha5 and beta1 subunits. And the metastatic phenotypes in DU145 cell were investigated. RESULTS: The expression levels of integrin alpha5 beta1, which was the receptor for fibronectin, were changed. EGF up-regulated the protein and mRNA expression of beta1 subunit on DU145 cell surface, 231% and 248% (P < 0.01) compared to the control respectively, and it could significantly promote the ability of DU145 cell adhesion to fibronectin and migration. However PD98058, which was the inhibitor of MAPK signal pathway, down-regulated the protein and mRNA expression of beta1 subunit, 60% and 63% (P < 0.01) compared to the control respectively, and it had the contrary function on the adhesion and migration ability of DU145 cell. But both had no effect the expression of alpha5 subunit. CONCLUSIONS: EGF might promote the metastatic ability mainly by up-regulating the expression of beta1 subunit by activating MAPK signal pathway in DU145 cells. Their regulation effects are on the mRNA transcriptional level.

Cell Adhesion↗

PubMed2006

Thymosinalpha1 stimulates cell proliferation by activating ERK1/2, JNK, and increasing cytokine secretion in human pancreatic cancer cells.

In this study, we investigated the expression and function of thymosinalpha1 (Thyalpha1) in human pancreatic cancer. We found that human pancreatic cancer cell lines Panc-1, Panc03.27, ASPC-1, and PL45 cells significantly over-expressed the mRNA of Thyalpha1 as compared to the normal human pancreatic ductal epithelium (HPDE) cells.. Thyalpha1 mRNA and protein levels were also over-expressed in clinical pancreatic adenocarcinoma specimens. In addition, synthetic Thyalpha1 significantly promoted Panc-1 cell proliferation and increased phosphorylation of ERK1/2 and JNK. Furthermore, Thyalpha1 increased the secretion of multiple cytokines including IL-10, IL-13, and IL-17 in Panc-1 cells. Thus, Thyalpha1 may have a new role in pancreatic cancer pathogenesis.

Cell Line, Tumor↗

PubMed2006

In utero exposure to alcohol alters cell fate decisions by hematopoietic progenitors in the bone marrow of offspring mice during neonatal development.

Fetal alcohol syndrome and alcohol related birth defects represent a spectrum of disorders that can result from the consumption of alcohol during pregnancy. Previous studies from this laboratory have shown that alcohol exposure in utero adversely affects hematopoietic progenitors in the bone marrow. Neonatal mice that were exposed in utero to alcohol showed a marked delay in B lymphocyte development. Recent studies have focused on an oligopotential progenitor cell, with the phenotype of HSA(lo)CD43(lo)Lin(-), which yields both B cells and myeloid lineage cells at a high frequency when cultured in vitro with stromal cells and the appropriate cytokines. However, these progenitor cells isolated from neonatal offspring of alcohol fed dams showed a significant decrease in the frequency of B cell formation following in vitro culture. In order to understand the mechanism underlying this defect we examined the expression of key transcription factors (early B cell factor, EBF, and Pax5) in this progenitor pool. Here, we report that >95% of HSA(lo)CD43(lo)Lin(-) cells express EBF and 5% express Pax5. Following liquid culture in the presence of IL-7, these progenitor cells respond by up-regulating Pax5 and the surface expression of CD19 indicating that the cells have committed to the B lineage. By contrast 75% of HSA(lo)CD43(lo)Lin(-) cells isolated from the bone marrow of neonatal animals exposed in utero to alcohol expressed EBF but at a level that was less than 25% the level of cells isolated from control animals. Furthermore, these alcohol-exposed progenitor cells failed to up-regulate Pax5 in response to IL-7 indicating a greatly reduced capacity to expand and differentiate to B lineage cells in liquid cultures. However, the HSA(lo)CD43(lo)Lin(-) cells isolated from the alcohol exposed animals retained the capacity to differentiate to myeloid lineage cells. These results suggest that the interference with the sequential expression of transcription factors in early progenitor cells by in utero alcohol exposure is a potential mechanism for the observed decrease in B lymphocytes in neonatal mice.

Animals↗