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1.  Detection of Chikungunya Virus Antigen by a Novel Rapid Immunochromatographic Test 
Journal of Clinical Microbiology  2014;53(2):382-388.
Chikungunya fever is a mosquito-borne disease of key public health importance in tropical and subtropical countries. Although severe joint pain is the most distinguishing feature of chikungunya fever, diagnosis remains difficult because the symptoms of chikungunya fever are shared by many pathogens, including dengue fever. The present study aimed to develop a new immunochromatographic diagnosis test for the detection of chikungunya virus antigen in serum. Mice were immunized with isolates from patients with Thai chikungunya fever, East/Central/South African genotype, to produce mouse monoclonal antibodies against chikungunya virus. Using these monoclonal antibodies, a new diagnostic test was developed and evaluated for the detection of chikungunya virus. The newly developed diagnostic test reacted with not only the East/Central/South African genotype but also with the Asian and West African genotypes of chikungunya virus. Testing of sera from patients suspected to have chikungunya fever in Thailand (n = 50), Laos (n = 54), Indonesia (n = 2), and Senegal (n = 6) revealed sensitivity, specificity, and real-time PCR (RT-PCR) agreement values of 89.4%, 94.4%, and 91.1%, respectively. In our study using serial samples, a new diagnostic test showed high agreement with the RT-PCR within the first 5 days after onset. A rapid diagnostic test was developed using mouse monoclonal antibodies that react with chikungunya virus envelope proteins. The diagnostic accuracy of our test is clinically acceptable for chikungunya fever in the acute phase.
doi:10.1128/JCM.02033-14
PMCID: PMC4298496  PMID: 25411170
2.  A Unique Case Involving a Female Patient with Upshaw-Schulman Syndrome: Low Titers of Antibodies against ADAMTS13 prior to Pregnancy Disappeared after Successful Delivery 
Summary
Background
Upshaw-Schulman syndrome (USS) is usually suspected based on severe deficiency of ADAMTS13 activity without ADAMTS13 antibody, but the definitive diagnosis is made by ADAMTS13 gene analysis. We present a unique case of USS with low titers of ADAMTS13 antibodies before pregnancy. Interestingly, titers of ADAMTS13 antibodies decreased to almost undetectable levels after delivery.
Case Report
In patient LL4, the diagnosis of USS was confirmed at age 27 by ADAMTS13 gene analysis. She became pregnant at age 30. During the pregnancy, she received regular fresh frozen plasma (FFP) infusion. Plasma von Willebrand factor levels increase as pregnancy progresses. To prevent platelet thrombi, much more ADAMTS13 supplementation is necessary during late gestation in patients with USS. Therefore, we shortened the interval between and increased the volume of FFP infusions as pregnancy progressed. At 39 weeks, she delivered a healthy baby girl. Before pregnancy, she had low titers of both neutralizing and binding anti-ADAMTS13 antibodies. Despite frequent FFP infusions, titers of the antibodies did not increase, but rather decreased to almost undetectable levels during pregnancy.
Conclusion
Both the neutralizing and binding antibodies against ADAMTS13 decreased to almost undetectable levels after delivery in this patient, which can be caused by an immunological reset.
doi:10.1159/000370225
PMCID: PMC4404895  PMID: 25960717
Upshaw-Schulman syndrome; Pregnancy; ADAMTS13 antibody; ADAMTS13 gene mutation; Fresh frozen plasma
3.  Extension of lifespan and protection against oxidative stress by an antioxidant herb mixture complex (KPG-7) in Caenorhabditis elegans 
Excessive generation of reactive oxygen species within cells results in oxidative stress. Furthermore, accumulation of reactive oxygen species has been shown to reduce cell longevity. Many dietary supplements are believed to have anti-aging effects. The herb mixture KPG-7 contains several components with antioxidant activity. We aim to clarify the mechanisms responsible for the antioxidant activity of KPG-7 and to establish whether KPG-7 has an anti-aging effect. We examined whether dietary supplementation with KPG-7 could provide protection against oxidative stress, extend lifespan, and delay aging in Caenorhabditis elegans (C. elegans). We found that KPG-7 extended lifespan and delayed aging in adult C. elegans. The expression of oxidation resistance 1 protein was induced by juglone and this effect was significantly suppressed in KPG-7-treated. In addition, the amount of oxidized protein was significantly lower in KPG-7-treated worms than untreated worms. Furthermore, locomotive activity was increased in C. elegans at 3 days of age following the treatment with KPG-7. On the other hand, the level of cellular ATP was lower at 3 days of age in worms treated with KPG-7 than in untreated worms. KPG-7 increases lifespan and delays aging in C. elegans, well corresponding to its activity to protect against oxidative stress.
doi:10.3164/jcbn.13-11
PMCID: PMC3774924  PMID: 24062604
oxidative stress; C. elegans; aging; herb mixture; antioxidant
4.  Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura 
Objectives
We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP).
Background
The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA).
Methods
Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals.
Results
Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without.
Conclusions
Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival.
doi:10.1016/j.jacc.2007.04.093
PMCID: PMC3167088  PMID: 17868804

Results 1-4 (4)