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ABSTRACT CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.
RESUMO CONTEXTO: A síndrome de microangiopatia trombótica, ou púrpura trombocitopênica trombótica-síndrome hemolítico urêmica (PTT-SHU), descreve doenças diversas com clínica e achados patológicos comuns: anemia hemolítica microangiopática e trombocitopenia, na ausência de outra causa aparente. RELATO DO CASO: Primigesta de 18 anos no segundo trimestre apresenta-se com quadro de 15 dias de fraqueza intensa seguida por diarreia há seis dias. Relata ter plaquetas baixas desde a infância e nega sangramentos e anormalidades menstruais. Investigação laboratorial identificou anemia com esquizócitos, plaquetopenia e hipo-haptoglobulinemia. Foi realizada transfusão de plaquetas e concentrado de hemácias. A hipótese de PTT ou SHU foi aventada e realizou-se pesquisa da atividade da enzima ADAMTS13. A paciente evoluiu com elevação das plaquetas, mesmo sem tratamento específico, tendo alta. Retornou após um mês da alta com queixa de fraqueza há um dia e inchaço de face e pernas. A atividade da ADAMTS13 foi menor que 5%, sem autoanticorpos. Nas duas internações anteriores (aos 9 e 16 anos), com quadros similares, houve remissão espontânea na primeira internação e, na segunda, o diagnóstico de PTT foi suspeitado e foi realizada plasmaférese, porém sem a pesquisa da atividade da ADAMTS13. CONCLUSÃO: Até esta data, este é único relato de TTP congênita com duas remissões espontâneas na literatura. Este relato revela a importância da suspeição desta patologia na presença de anemia hemolítica microangiopática e trombocitopenia sem outra causa aparente.
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Humans , Female , Pregnancy , Pregnancy Complications, Hematologic , Purpura, Thrombotic Thrombocytopenic/congenital , Abortion, Spontaneous/etiology , Pregnancy Trimester, Second , Purpura, Thrombotic Thrombocytopenic/complications , Recurrence , Remission, Spontaneous , Biomarkers/analysis , ADAMTS13 Protein/analysisABSTRACT
Objective To explore correlation of Xinjiang Kazakh population who suffered from COPD with polymor?phisms of F+1,S2,T1,ST+5 locus of ADAM33 gene. Methods Blood samples (n=193) from healthy controls (Control group, n=193) and COPD patients (Case group, n=197) were detected by SNP SNaP shot. Results Comparing case group with the control group, gene frequency and allele frequency of F+1 locus were of significant differences (P0.05). The gene frequencies and allele frequency of S2、T1 and ST+5 locus were not significantly differ?ent between case group and control group (P>0.05). F+1 and S2 locus were analyzed by haplotype analysis which showed that there was significant differences in Hap1 (CC) haplotype between case group and control group (P1 revealed that its haplotype may increase the risk of COPD . The distri?bution of Hap2 (TG) and Hap4 (CG) were not significantly different (P>0.05) between the 2 groups. T1 and ST+5 locus were analyzed by haplotype analysis which showed significant differences in haplotypes between case group and control group (P<0.05). Conclusion The occurrence of COPD may be related to the polymorphism of ADAM33 gene in F+1 locus in Xinjiang Kazakh.
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Objective To investigate the association between polymorphism of S1, S2 locus allele in ADAM 33 gene and chronic obstructive pulmonary disease (COPD) and lung function in Xinjiang Uygur population. Methods Blood sam?ples from 217 COPD patients and 218 healthy controls were collected. Samples of DNA was extracted, and S1, S2 single nu?cleotide polymorphism (ADAM 33) was detected by ABI SNaPshot SNP genotyping. Results There were no significant dif?ferences in the frequencies of S1 locus CC, CT, TT genotypes and C, T alleles between patient group and control group (P>0.05). There were no significant differences in the frequencies of S1 locus CC, CG, GG genotypes and C, G alleles between patient group and control group (P>0.05). In patient group, there were no significant differences in S1, S2 locus genotype and clinical indicators of lung function display, and in the FEV1%predicted and FEV1/FVC (P>0.05). Haplotype analysis showed that there were no significant differences in three kinds of haplotypes between patient group and control group ( P>0.05). Conclusion There is no significant difference in the polymorphism of S1, S2 locus allele in ADAM 33 gene and the susceptibility to COPD in Xinjiang Uygur population.
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Objective This study is aimed at determining whether anti-von Willebrand factor (VWF) autoantibodies are present in the plasma of idiopathic thrombotic thrombocytopenic purpura (TTP) patients with normal ADAMTS13 activity and undetectable anti-ADAMTS13 antibodies,and at examining whether murine monoclonal antibodies (mAbs) against human VWF decrease the susceptibility of VWF to ADAMTS13 in vitro.Methods Anti-VWF autoantibodies and ultralarge VWF (UL-VWF) multimers were measured in plasma samples of 53 adult patients with idiopathic TTP by enzyme-linked immunosorbent assay and sodium dodecylsulphate-agarose gel electrophoresis,respectively.Moreover,the effects of eight murine mAbs to different human VWF domains on VWF cleavage by ADAMTS13 were evaluated under fluid shear stress and static/denaturing conditions,respectively.Results Anti-VWF antibodies and UL-VWF multimers were detected in two TTP patients with normal ADAMTS13 activity and undetectable anti-ADAMTS13antibodies.The SZ34,an anti-VWF mAb,inhibited VWF proteolysis mediated by ADAMTS13 under flow,but not static conditions.Conclusion Anti-VWF antibody may be one of the causes of idiopathic TTP with normal ADAMTS13 activity and undetectable anti-ADAMTS13 antibodies.
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ObjectiveTo investigate the relationship between the polymorphisms of the promoter of a disintegrin and metalloproteinase 10(ADAM10) gene and sporadic Alzheimer's disease (SAD).Methods The promoter of ADAM10 gene in 10 controls and 10 SAD patients was sequenced.Three variations were found,then these variations in 298 SAD patients (SAD group) and 315 healthy controls (control group)were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThree polymorphisms were found in the promoter of ADAM10 gene: -279G/A (rs653765),- 630G/T( rs514049 ) and - 921GAGA/- ( rs33926666 ).For - 921GAGA/-,there were significant differences in genotype ( GAGA/GAGA:138 (46.3％ ),GAGA/-:155(52.0％),-/-:5(1.7％))and allele frequencies (GAGA:431 (73.6％),-:165 (27.7％) ) between SAD and control (genotype:x2 =34.130,P =0.000; allele:x2 =25.972,P =0.000). For - 279G/A,there were significant differences in genotype and allele frequencies between SAD and control in the subjects without ApoEε4 allele (genotype:x2 =8.734,P=0.013; allele:x2 =5.129,P=0.024). -279G and -921GAGA were relatively protective allele types for SAD,and they were not in linkage disequilibrium.ConclusionThe polymorphisms - 279G/A and - 921GAGA/- of ADAM10 are associated with SAD.Allele G or genotype G/G of -279G/A and the GAGA/GAGA genotype or the GAGA allele of -921GAGA/- might have a protective effect on SAD.
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The ADAMs(a disintegrin and metalloproteinase) are a family of transmembrane or secreted proteins with important roles in cell fusion,adhesion,degradation of extracellular matrix,proteolysis,and signaling.The most important domains of ADAMs includes metalloprotease domain and disintegrin domain.Some ADAMs have been observed in gastric and colorectai cancer,and produced a marked effects during the tumor development and metastasis.The further research of ADAMs may provide more choices for tumor target therapy.
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Objective To investigate the learning and memory functions,expression changes of disintegrin and metalloprotease 10 (ADAM10) mRNA in hippocampus in the aged rats with chronic cerebral hypoperfusion as well as the effect of atorvastatin on them.Methods A total of 72 rats were randomly divided into sham operation,cerebral hypoperfusion and atorvastatin treatment groups.A permanent bilateral common carotid artery occlusion (2VO)model was induced.Atorvastatin 10 mg/(kg · d) was administered orally after procedure in the atorvastatin treatment group.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of ADAM10 mRNA in bilateral hippoocampus at 1,2,4,and 16 weeks after modeling,Results Two weeks after modeling,the learning and memory functions were decreased significantly in the cerebral hypoperfusion group compared to the sham operation group (P ＜ 0.05).At 4 and 16 weeks after modeling,they were further decreased (P ＜0.01); there were no significant differences in the learning and memory functions at 1,2,and 3 weeks after modeling between the atorvastatin treatment group and the cerebral hypoperfusion group,however,they were improved significantly at 16 weeks compared to the cerebral hypoperfusion group (P＜0.01).The expression of ADAM10 mRNA in hippocampus at different time points after modeling in the cerebral hypoperfusion group was down-regulated by 22％,43％,35％,and 50％,respectively compared to the sham operation group (all P ＜0.05).The expression of ADAM 10 mRNA in hippocampus at 2 weeks in the atorvastatin treatment group was higher than 22％ in the cerebral hypoperfusion group (P＜0.05).There were not significant differences at other time points.Conelusions Chronic cerebral hypoperfusion results in the down-regulation of the expression of ADAM10 mRNA in hippocampus in the aged rats,and atorvastatin may inhibit down-regulation of the expression of ADAM10 mRNA at early stage.
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05). Conclusion The maternal serum level of ADAM 12 in the first-trimester is a potential marker for aneupolyhaploid screening and early fetal loss prediction, and is suggested to be tested at 9-12 gestational weeks as part of prenatal screening.