This study was purposed to investigate the changes of von Willebrand factor cleaving protease (ADAMTS13) activity and vWF antigen level in patients with acute myelogenous leukemia (AML) before and after treatment and evaluate their clinical significance. Seventy-three AML patients were enrolled in this study, the sodium citrate anticoagulated plasma was collected before and after their induction chemotherapy. Fluorescence resonance energy transfer substrate vWF73 (FRETS-vWF73) assay was established to detect the plasma ADAMTS13 activity while vWF antigen level was measured by ELISA. The results showed that the ADAMTS13 activity in newly diagnosed patients with AML before induction therapy was obviously lower than that in normal controls (63.3 ± 25.5)% vs (105.1 ± 37.7)(P < 0.01), while the vWF antigen level was higher than that in normal controls (226.6 ± 127.0)% vs (111.4 ± 39.7)% (P < 0.01). After standard induction chemotherapy, the ADAMTS13 activity of AML patients in complete remission period was higher than that in AML patients before therapy (P < 0.01), and was not significant difference with that in normal controls; the vWF antigen was significantly lower than that in AML patients before therapy (P < 0.01), but it still was higher than that in controls (P < 0.05). The ADAMTS13 activity in newly diagnosed AML patients complicated with infection before therapy was obviously lower than that in AML patients without infection (52.2 ± 20.6)% vs (73.9 ± 24.7)% (P < 0.01), while the vWF antigen level was significantly higher than that in AML patients without infection (262.2 ± 135.7)% vs (193.8 ± 110.2)% (P < 0.05). The ADAMTS13 activity in AML patients with disseminated intravascular coagulation (DIC) was significantly lower than that in AML patients without DIC (42.0 ± 14.5)% vs (73.4 ± 22.7)% (P < 0.01), while the vWF antigen level was obviously higher that in AML patients without DIC (274.2 ± 140.0)% vs (204.7 ± 115.5)% (P < 0.01). It is concluded that the ADAMTS13 activity in newly diagnosed AML patients befor induction therapy has been confiremed to be lower and the vWF antigen level to be higher, especially in AML patients with infection or DIC. The ADAMTS13 and vWF antigen may play a role in the pathogenesis of AML and the formation of infection and DIC.
ADAM Proteins ; blood ; ADAMTS13 Protein ; Disseminated Intravascular Coagulation ; Humans ; Leukemia, Myeloid, Acute ; blood ; von Willebrand Factor ; analysis

BACKGROUNDA disintegrin and metalloprotease 9 (ADAM9) is a membrane-anchored enzyme which is considered to be involved in some diseases including tumor. However, the role of ADAM9 in castration resistant prostate cancer (CRPC) is not clear. This study aimed to explore the different expressions on protein and messenger RNA (mRNA) level of ADAM9 between hormonal sensitive prostate cancer (HSPC) and CRPC tissue, and find the correlation with prognosis.

METHODSClinicopathologic characteristics of 106 HSPC and 76 CRPC cases were collected. The ADAM9 expressions were analyzed using immunohistochemistry. ADAM9 mRNA of 32 additional cases (16 HSPC and 16 CRPC patients) were analyzed via quantitative real-time polymerase chain reaction (RT-PCR). The prediction values of variables for overall survival (OS) of CRPC patients were analyzed using Cox regression.

RESULTSADAM9 protein expression was significantly downregulated in CRPC compared with HSPC tissue (31.6% vs. 81.1%, P < 0.001). The relativity transcription level of ADAM9 mRNA was 0.45 for CRPC tissue and 1.0 for HSPC tissue (P = 0.002). In the CRPC group, patients with low ADAM9 protein expression were significantly associated with shorter OS than patients with high expression (38.6 months vs. 57.8 months, hazard rate (HR) = 2.638, P = 0.023).

CONCLUSIONADAM9 expression was low in CRPC, correlated with poor prognosis and might be involved in the succession from HSPC to CRPC by various functions.

ADAM Proteins ; analysis ; genetics ; Aged ; Humans ; Male ; Membrane Proteins ; analysis ; genetics ; Middle Aged ; Orchiectomy ; Prognosis ; Proportional Hazards Models ; Prostatic Neoplasms ; chemistry ; mortality

Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL, respectively. From the area under the curve, sensitivity and specificity, the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC. Thus, analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity. Specifically, increases in cathepsin V, kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.
ADAM Proteins ; Biomarkers, Tumor ; analysis ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; analysis ; Membrane Proteins ; Mouth Neoplasms ; diagnosis ; metabolism ; Saliva ; chemistry

OBJECTIVETo investigate the association between the polymorphism of T(1) locus allele in ADAM33 gene and bronchial asthma in South China Han population.

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to determine the polymorphism of T(1) locus allele in ADAM33 gene in 160 unrelated patients with asthma and 95 unrelated healthy controls from South China Han population.

RESULTSNo significant difference was found in T(1) locus allele distribution frequency in populations of UK, US, Germany, Korea, and South China (Chi(2)=9.085, P=0.109). The frequencies of the genotypes (TT, TC, CC) were 80.6% (n=129), 16.9% (n=27) and 2.5% (n=4) in the 160 asthmatic patients and 94.7% (n=90), 3.2% (n=3) and 2.1% (n= 2) in the 95 controls, respectively, showing a significant difference in the distribution of the genotypes (TT, TC, CC ) between asthmatic patients and healthy controls (Chi(2)=10.955, P<0.05). The frequencies of the alleles (T, C) were 0.891 and 0.109 in the asthmatic patients and 0.963 and 0.037 in the controls, respectively, showing also a significant difference in the allele frequency between them (Chi square =8.299, P<0.05). The presence of C allele of ADAM33 gene T1 locus was found to be a greater risk factor in asthmatic patients than in the healthy controls. The odds ratio (OR) of TC and TC+CC were 6.279 (1.849-21.328) and 4.326 (1.620-11.550), respectively, with P value of 0.001 and 0.002, respectively, in comparison with TT genotype.

CONCLUSIONThe polymorphism of T(1) locus allele in ADAM33 gene is associated with the susceptibility to asthma in South China Han population.

ADAM Proteins ; genetics ; Asian Continental Ancestry Group ; genetics ; Asthma ; genetics ; China ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Restriction Fragment Length ; Sequence Analysis, DNA

BACKGROUNDvon Willebrand factor (vWF) mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arterial stenosis. On release from endothelial cells, vWF is rapidly cleaved by ADAMTS13/vWF-cleaving protease (vWF-CP). We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.

METHODSPlasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay (ELISA) and residual collagen binding assay respectively in patients with lupus nephritis (n = 31), primary nephritic syndrome (n = 25), diabetic nephropathy (n = 45), chronic glomerulonephritis (n = 38) and 40 normal controls. The relation of their levels with pathological and renal status was analyzed.

RESULTSIn all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls (both P < 0.01). vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity. vWF-CP activity was not changed two weeks after renal transplantation. Renal biopsy demonstrated that the vWF level in stage IV was higher than in stages II and III while vWF-CP activity was lower in patients with lupus nephritis. After eight-week treatment, the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema, disease activity index < 9, but not with index = 9. Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease, mesangial proliferative glomerulonephritis or IgA glomerulonephritis, the vWF level was not significantly different.

CONCLUSIONSThe alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies. Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF level and lower vWF-CP activity in chronic renal disease and thus a mechanism for worsening of chronic renal disease and thrombosis.

ADAM Proteins ; blood ; ADAMTS13 Protein ; Adolescent ; Adult ; Aged ; Chronic Disease ; Female ; Humans ; Kidney Diseases ; blood ; Kidney Transplantation ; Lupus Nephritis ; blood ; Male ; Middle Aged ; von Willebrand Factor ; analysis

BACKGROUND: We intended to find the mutations of von Willebrand factor (VWF) gene as the most important contributing factor of von Willebrand disease (VWD) in Korean patients. METHODS: In 40 known vWD patients mutations of vWF gene were sought by direct sequencing of PCR products targeting exons 18, 19, 20, 26, 28 and 52 frequently implicated as the locations of mutation. For factors other than VWF gene contributing to VWD phenotype, we tested ABO blood group and measured ADAMTS13 activity in VWD patients. RESULTS: Twenty-seven cases (67.5%) were type 1 vWD, 3 cases (7.5%) type 3, and 5 cases (12.5%) type 2A. Three cases were type 2A or 2B (7.5%) and 2 cases were suspected to be type 2N (5.0%). Among them six candidate missense mutations were found: V1279I, R1306W, R1308C, and V1316M were previously reported in type 2B and type 1 vWD, and C858W and T1477I were novel findings. All patients were heterozygotes. Blood group O was overly represented in VWD patients, while ADAMTS13 activity of the patients was not significantly different from that of normal control. CONCLUSIONS: Mutation of VWF gene detected by genetic studies can significantly improve the diagnostic accuracy, especially in subtype assignment of VWD. Two novel mutations, C858W and T1477I associated with VWD were found and expected to contribute to the elucidation of its pathophysiology.
ABO Blood-Group System ; ADAM Proteins/analysis ; Heterozygote ; Humans ; Korea ; *Mutation, Missense ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Analysis, DNA ; von Willebrand Disease/classification/diagnosis/*genetics ; von Willebrand Factor/analysis/*genetics

BACKGROUNDChronic obstructive pulmonary disease (COPD) is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha (TNF-alpha) is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-alpha converting enzyme (TACE) is involved in the activation of both TNF-alpha and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-alpha and ErbB3 and to explore the correlations among TACE, TNF-alpha and ErbB3 respectively.

METHODSThirty Wistar male rats were randomly divided into COPD group (group C, n = 10), saline solution parallel group (group P, n = 8), and normal control group (group N, n = 8). Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-alpha and ErbB3 in lungs of all rats were determined histochemically.

RESULTSThe expressions of TACE, TNF-alpha and ErbB3 were significantly higher in group C than in group N (P < 0.01). The contents of TNF-alpha in serum (P < 0.01) and bronchoalveolar lavage fluid (BALF) (P < 0.01) were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-alpha (r = 0.784, P < 0.01) and between TACE and ErbB3 (r = 0.526, P < 0.01) respectively.

CONCLUSIONSTNF-alpha and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-alpha and ErbB3.

ADAM Proteins ; analysis ; physiology ; ADAM17 Protein ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Immunohistochemistry ; Lung ; physiopathology ; Male ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Rats ; Rats, Wistar ; Receptor, ErbB-3 ; analysis ; physiology ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo study the effect of Panax notoginseng saponins (PNS) on expression of alpha-aecretase mRNA in the brains of senescence-accelerated SAMP8 mice.

METHODSAMP8 mice were randomly divided into the control group, the PNS high-dosage group (200 mg x kg(-1)), the PNS low-dosage group (100 mg x kg(-1)) and the huperzine A group (0.3 mg x kg(-1)), with eight mice in each group. The control group and each administration group were orally administered with the same volume of double distilled water once for consecutively two months. The expression of alpha-secretase (ADAM 9, ADAM10, ADAM17) mRNA was assayed by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR).

RESULTThe expression of ADAM9 mRNA in PNS high-dosage group and huperzine A group were significantly higher than that of the control group (P < 0.05). The expression of ADAM10 in the PNS high-dosage group, the PNS low-dosage group and the huperzine A group showed no significant difference from the control group.

CONCLUSIONPNS can up-regulate expressions of ADAM9 mRNA and down-regulate expressions of ADAM10 mRNA in the brains of SAMP8 mice.

ADAM Proteins ; genetics ; ADAM10 Protein ; Alzheimer Disease ; drug therapy ; metabolism ; Amyloid Precursor Protein Secretases ; genetics ; Animals ; Disease Models, Animal ; Gene Expression Regulation, Enzymologic ; drug effects ; Membrane Proteins ; genetics ; Mice ; Panax notoginseng ; RNA, Messenger ; analysis ; Saponins ; pharmacology

ADAM Proteins ; genetics ; ADAM17 Protein ; Adrenergic beta-Antagonists ; therapeutic use ; Animals ; Male ; Metoprolol ; therapeutic use ; Myocardial Infarction ; drug therapy ; physiopathology ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; genetics ; Ventricular Function, Left ; drug effects ; Ventricular Remodeling ; drug effects

OBJECTIVETo assess the association of a disintegrin and metallo-proteinase with thrombospondin type 1 motifs (ADAMTS-1) gene polymorphism and ischemic stroke caused by large artery atherosclerosis (LAA).

METHODSIn total 767 patients and 506 controls were recruited. Single nucleotide polymorphisms (SNPs) rs416905 (T/C) and rs402007 (G/C) of the ADAMTS-1 gene were genotyped by polymerase chain reaction and DNA sequencing.

RESULTSFrequencies of the rs402007 GC+CC genotype and the C allele were significantly different between the two groups (68.84% vs. 60.67%, χ2=9.012, P=0.003, OR=1.432; 45.24% vs. 38.54%, χ2=11.208, P=0.001, OR=1.318). Binary logistic regression has confirmed that the above difference was significant (P=0.001, OR=1.521, 95%CI: 1.183-1.955). The frequencies of TC+CC and GC+CC genotypes were similar between the two groups, and so was it with the C allele. The two SNPs had been in complete linkage disequilibrium (D'=1.0, r2=1.0).

CONCLUSIONThe rs416905 and rs402007 polymorphisms of the ADAMTS-1 gene may be associated with ischemic stroke caused by LAA. The C allele of the rs402007 locus may be a susceptibility factor for this subtype of stroke.

ADAM Proteins ; genetics ; ADAMTS1 Protein ; Aged ; Alleles ; Atherosclerosis ; complications ; Base Sequence ; Blood Glucose ; metabolism ; Brain Ischemia ; complications ; Fasting ; blood ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Risk Factors ; Sequence Analysis, DNA ; Smoking ; Stroke ; blood ; etiology ; genetics