OBJECTIVE: To explore the association between two single nucleotide polymorphisms (SNPs), namely, rs4691383 and rs7667857, in the platelet-derived growth factor-C (PDGF-C) gene, the genotypes, environmental exposure factors, and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Western Chinese population. METHODS: A total of 268 case-parent trios were selected, and two SNPs (rs4691383 andrs7667857) were genotyped by using polymerase chain reaction and restriction enzyme fragment length polymorphic method and direct sequencing method. Hardy-Weinberg equilibrium, linkage disequilibrium test, transmission disequilibrium test, and haplotype analysis were conducted to analyze the data. Meanwhile, the questionnaires on the epidemiology of cleft lip and palate filled by the included samples were collected, and the interaction between the genotypes of the two SNPs and environmental exposure factors was assessed by conditional logistic regression. RESULTS: The A allele at rs4691383 and the G allele at rs7667857 of PDGF-C gene were over-transmitted for NSCL/P (P<0.05). No interaction effect was observed between the three environmental exposure factors (history of smoking/passive smoking, folic acid supplementation, and long-term inhalation of harmful environmental gases) and the PDGF-C genotypes among NSCL/P (P>0.05). CONCLUSIONS The rs4691383 and rs7667857 at PDGF-C gene are closely related to the occurrence of NSCL/P in Western Chinese population. However, the interaction between environmental exposure factors and PDGF-C genotypes is not obvious in the occurrence of NSCL/P.
Case-Control Studies ; Cleft Lip ; Cleft Palate ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphokines ; Platelet-Derived Growth Factor ; Polymorphism, Single Nucleotide

PURPOSE: Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1alpha (HIF-1alpha) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1alpha-induced invasive characteristics. MATERIALS AND METHODS: Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on HIF-1alpha, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1alpha and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1alpha, tissue analysis was done. RESULTS: Hypoxia induces HIF-1alpha expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1alpha via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1alpha with RNA interference suppressed hypoxia-induced HIF-1alpha and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1alpha. These were confirmed in the orthotopic FTC model. CONCLUSION: Hypoxia induced HIF-1alpha, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.
Adenocarcinoma, Follicular/*genetics/metabolism ; Animals ; Anoxia/*genetics ; Cadherins/genetics ; Epithelial-Mesenchymal Transition/*genetics ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism ; Lymphokines ; Mice ; Neoplasm Invasiveness ; Phenotype ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Thyroid Neoplasms/*genetics/metabolism ; Transcriptional Activation ; Twist Transcription Factor/*genetics/metabolism ; Vimentin/metabolism

A secondary aortoenteric fistula (AEF) is a direct communication between the gastrointestinal tract and the aorta in a patient who has undergone major surgery on the aorta, often an aorta graft operation. We experienced a patient who had undergone graft interposition for abdominal aortic aneurysm and was admitted due to three episodes of hematemesis and following hamatochezia. Gastroscopy, colonoscopy, and radioactive iodine scan failed to identify the bleeding site in the patient. He was diagnosed with AEF by double balloon enteroscopy and recovered after surgical intervention.
Aorta ; Aortic Aneurysm, Abdominal ; Colonoscopy ; Double-Balloon Enteroscopy ; Fistula ; Gastrointestinal Tract ; Gastroscopy ; Hematemesis ; Hemorrhage ; Humans ; Iodine ; Lymphokines ; Transplants

PURPOSE: To determine the quantitative parameters of breast MRI that predict tumor invasion in biopsy-proven DCIS. MATERIALS AND METHODS: From January 2009 to March 2010, 42 MRI examinations of 41 patients with biopsy-proven DCIS were included. The quantitative parameters, which include the initial percentage enhancement (E1), peak percentage enhancement (E(peak)), time to peak enhancement (TTP), signal enhancement ratio (SER), arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC) value, long diameter and the volume of the lesion, were calculated as parameters that might predict invasion. Univariate and multivariate analyses were used to identify the parameters associated with invasion. RESULTS: Out of 42 lesions, 23 lesions were confirmed to be invasive ductal carcinoma (IDC) and 19 lesions were confirmed to be pure DCIS. Tumor size (p = 0.003; 6.5 +/- 3.2 cm vs. 3.6 +/- 2.6 cm, respectively) and SER (p = 0.036; 1.1 +/- 0.3 vs. 0.9 +/- 0.3, respectively) showed statistically significant high in IDC. In contrast, E1, Epeak, TTP, ADC, AEF and volume of the lesion were not statistically significant. Tumor size and SER had statistically significant associations with invasion, with an odds ratio of 1.04 and 22.93, respectively. CONCLUSION: Of quantitative parameters analyzed, SER and the long diameter of the lesion could be specific parameter for predicting invasion in the biopsy-proven DCIS.
Breast ; Carcinoma in Situ ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Diffusion ; Humans ; Lymphokines ; Magnetic Resonance Imaging ; Multivariate Analysis ; Odds Ratio ; Thymine Nucleotides

The incidence of peri-stent graft infection (PGI) following thoracic endovascular aortic repair (TEVAR) is low, but the associated mortality rates are extremely high. The diagnosis of this complication can be difficult due to nonspecific symptoms. Here, we report a case of PGI combined with an aorto-esophageal fistula (AEF) diagnosed by computed tomography (CT) and positron emission tomography (PET) imaging after TEVAR. A 50-year-old woman with a history of diabetes mellitus and chronic hemodialysis had received a stent graft for a contained rupture of a pseudoaneurysm of the descending thoracic aorta. Three months after stent-grafting, she experienced back pain. CT and PET imaging suggested a PGI. The patient underwent surgical treatment for PGI with AEF.
Aneurysm, False ; Aorta, Thoracic ; Back Pain ; Diabetes Mellitus ; Esophageal Fistula ; Female ; Fistula ; Humans ; Incidence ; Lymphokines ; Middle Aged ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Renal Dialysis ; Rupture ; Stents ; Transplants

OBJECTIVETo identify the IgE-binding epitopes in the allergen Der p 1 of main house dust mites, which can be recognized by the specific IgE in the sera from allergic individuals, and obtain a hypoallergen derived from the T-B epitope fused peptide for potential use in specific immunotherapy (SIT).

METHODSThirty-one peptides containing 15 amino acids each, which covered the full 222 amino acids of Der p 1 protein sequence, were synthesized on the cellulous membrane by solid-phase peptide (SPOTs) synthesis, with 8 overlapping amino acids between every two neighboring peptides. The membrane bearing the spots of the synthesized peptides were incubated with the allergic serum pools consisting of the sera from 5 allergic individuals. The membrane was then probed with HRP-conjugated anti-human IgE, followed by enhanced chemiluminescence (ECL) for visualization and gray scale analysis of the positive peptide spots.

RESULTSThree strong IgE-binding epitopes were identified in the amino acid sequence of Der p 1 molecule, namely Ep1 (amino acids 85-99), Ep2 (amino acids 106-120) and Ep3 (amino acids 190-204).

CONCLUSIONThe 3 IgE-binding epitopes (B cell epitopes) identified in Der p 1 confirm the presence of linear epitopes in Der p 1, suggesting the possibility of constructing T/B epitope-fused hypoallergens.

Amino Acid Sequence ; Animals ; Antigens, Dermatophagoides ; immunology ; Arthropod Proteins ; immunology ; Binding Sites, Antibody ; Cysteine Endopeptidases ; immunology ; Epitopes ; immunology ; Immunoglobulin E ; immunology ; Lymphokines ; immunology ; Mites ; immunology ; Molecular Sequence Data

Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naive or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naive and pre-activated T cells in which IL-10 and IDO play important roles.
Animals ; Cell Proliferation ; Cells, Cultured ; Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors/metabolism ; Interleukin-10/*biosynthesis ; *Lymphocyte Activation ; Lymphokines/pharmacology ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, Interleukin-10/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Tryptophan/analogs & derivatives/pharmacology

Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naive or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naive and pre-activated T cells in which IL-10 and IDO play important roles.
Animals ; Cell Proliferation ; Cells, Cultured ; Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors/metabolism ; Interleukin-10/*biosynthesis ; *Lymphocyte Activation ; Lymphokines/pharmacology ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, Interleukin-10/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Tryptophan/analogs & derivatives/pharmacology

The nomenclature "embryonic lymphoid tissue inducer (LTi) cell" reflects the fundamental role of the cell in secondary lymphoid tissue organization. In addition, it is equally important in primary lymphoid tissue development as it regulates central tolerance to self-antigens in the thymus. An adult LTi cell constitutively expresses two sets of tumor necrosis factor (TNF) family members, whereas its embryonic counterpart expresses only one. The first set is lymphotoxin (LT)alpha, LTbeta, and TNFalpha, which are essential for the secondary lymphoid organogenesis during embryogenesis and for maintaining an organized secondary lymphoid structure during adulthood. The second set is OX40- and CD30-ligands, which are critical for memory T cell generation. Adult LTi cells regulate adaptive immune responses by providing LTbetaR signals to stromal cells to maintain secondary lymphoid tissue structure, and determine adaptive immune responses by providing OX40 and CD30 survival signals to activated T cells in memory T cell generation. Along with the consideration of the roles of embryonic LTi cells in primary and secondary lymphoid tissues, this review highlights the roles of adult LTi cells in secondary lymphoid tissue function.
Adult ; Animals ; Humans ; Lymphoid Tissue/cytology/embryology/*immunology ; Lymphokines/immunology/metabolism ; T-Lymphocytes, Helper-Inducer/cytology/*immunology/metabolism ; Thymus Gland/cytology/embryology/*immunology

Animals ; Fatty Liver ; metabolism ; pathology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Lymphokines ; metabolism ; Male ; Platelet-Derived Growth Factor ; metabolism ; Rats ; Rats, Sprague-Dawley