ABSTRACT
OBJECTIVE@#To investigate the gene mutations types and the clinical characteristics in 3 patients with hereditary coagulation factor Ⅶ deficiency.@*METHODS@#The phenotype diagnosis was validated by detecting the coagulation parameters including prothrombin time (PT)，activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅦ activity (FⅦ: C) and specific antigens (FⅦ: Ag) of proband and its family members. All exons, exon-intron boundaries, 5＇ untranslated regions and 3＇ untranslated regions of F7 gene were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand.@*RESULTS@#A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency and family members, including 4 misssense mutations and 1 splice site mutation. Out of 3 cases of hereditary coagulation factor Ⅶ deficiency 2 had double heterozygous mutation, I had homozygous mutations. Patient 1 had p.His408Gln with p.Arg413Gln double heterozygous mutations, her sister had p.His408Gln with p.Arg413Gln double heterozygous mutations, another one had p.His408Gln mono-heterozygous mutation, their correspo FⅦ: C were 5%, 3%, 75%. Patient 2 had p.Arg364Gln with p.His408Gln double heterozygous mutations, her brother had p.Arg364Gln with IVS6-1G＞A double heterozygous mutations, their corresponding FⅦ: C were 2.0%, 2.0%. Patient 3 had p.Arg337Cys homozygous mutation, FⅦ: C was 3.0%.@*CONCLUSION@#A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency, the p.His408Gln is a common mutation, the FⅦ: C and FⅦ: Ag have no correlation with clinical phenotypes.
Subject(s)
Female , Humans , Male , Factor VII , Factor VII Deficiency , Heterozygote , Homozygote , Mutation , Pedigree , PhenotypeABSTRACT
Purpose To investigate the expression of lipocalin-2 (LCN2) and plateled derived growth factor-BB (PDGF-BB) in serum,carcinoma and bone metastases of lung cancer patients. Methods Protein chip were used to screen the differential expression of cytokines in serum of 19 lung cancer patients (9 patients with bone metastasis and 10 patients freedistant metastasis) . Immunohistochemistry was performed to assess the differential expression of LCN2 and PDGF-BB cytokines in 12 cases of primary lung cancer without distant metastasis and 12 cases of primary lung cancer with only bone metastasis. Results Serum level of lipid transport factor (LCN2) and PDGFBB in non-small cell lung cancer patients with bone metastasis were significantly higher than that without distant metastasis(P< 0. 05) . There was no difference cytokines between small cell lung cancer patients with bone metastasis and without metastasis group (P > 0. 05) . The results of immunohistochemistry showed that high expression of LCN2 and PDGF-BB in bone metastasis tissues was significantly higher than that in primary lung cancer tissues. Conclusions High expression of LCN2 and PDGF-BB in serum and bone metastasis tissue of patients with non-small cell lung cancer might be involved in the occurrence,development of bone metastasis of lung cancer in the bone marrow,may be an important biomarker and potential therapeutic target for bone metastasis of lung cancer.
ABSTRACT
The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.
ABSTRACT
The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.
Subject(s)
Adolescent , Adult , Female , Humans , Pregnancy , Abortion, Spontaneous , Metabolism , Pathology , Chorionic Villi , Metabolism , Pathology , Galectins , Hepatitis A Virus Cellular Receptor 2 , Interleukin-12 , Blood , Interleukin-4 , Blood , Membrane Proteins , Pregnancy Proteins , Up-RegulationABSTRACT
Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to characterize the antipyretic and anti-inflammatory effects in rats of Rhein, a major component in rhubarb. Twenty-four healthy male Sprague-Dawley (SD) rats were randomly into four groups, of 6 each. The rats in first group were injected intravenously with lipopolysaccharide (LPS, 100 microg x kg(-1)). The second group rats were given rhubarb decoction (RD, 1.54 g x kg(-1)) by oral administration alone. The rats belonging to third group were administered orally RD 30 min after LPS injection. The rest rats were given normal saline only as control group. Orbital sinus blood sampling was collected at different time points. The Rhein and NO concentration in plasma and body temperature (BT) were measured. Relevant data of PK-PD modeling were performed with Kinetica 5. 0. 11. RD could suppress the rise in BT and plasma NO concentration. The antipyretic and anti-inflammatory responses were best described by a Sigmod-E(max) model. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. The results showed that some parameters such as t1/2, C(max) and AUC were significantly increased in rats treated with LPS, compared to those in rats treated with normal saline. The EC50 for antipyretic effect and decrease of plasma NO concentration was respectively equal to 114.1, 90.80 microg x L(-1). The E(max) for antipyretic effect was about 111% of that for increase in BT after LPS injection. The E(max) for anti-inflammatory action was close to 8.399% of that for elevated NO level after modeling. Meanwhile, there was a difference in pharmacokinetic process of Rhein between the impact of normal saline and LPS. So, it can be concluded that the targets of regulating NO production and BT after RD administration may be at the same location. Not only do that, the antipyretic effect induced by RD maybe completely manifest through reducing the plasma concentration of NO.