Heat shock response is an adoptive response to proteotoxic stress, and a major heat shock transcription factor 1 (HSF1) has been believed to protect cells from cell death by inducing heat shock proteins (Hsps) that assist protein folding and prevent protein denaturation. We found a proapoptotic Tdag51 (T-cell death associated gene 51) gene as a direct target gene of HSF1 and that heat shock response and other stresses induced different levels of Hsps and Tdag51, which depend on cell types. Hsps bound directly to the N-terminal pleckstrin-homology like (PHL) domain of Tdag51, and suppressed the death activity. Tdag51, but not major Hsps, were induced in male germ cells exposed to high temperatures, in addition, analysis of Tdag51-null testes showed that Tdag51 played substantial roles in promoting heat shock-induced cell death in vivo. Therefore, it was suggested that cell fate on proteotoxic condition is determined at least by balance between Hsp and Tdag51 levels, which are differently regulated by HSF1.

View full abstract

We encountered four cases of thrombotic thrombocytopenic purpura (TTP) with poor prognsosis despite early diagnosis in a short period. The first case developed cerebral infarction and thrombocytopenia after administration of clopidogrel. The activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospodin type1 motif13) was moderately decreased. The thrombocytopenia improved substantially after plasma infusion (PI) and plasma exchange (PE), however, the patient died of sepsis after a month. The second patient had anemia, thrombocytopenia, hepatic and renal dysfunctions, and restlessness. ADAMTS13 activity was moderately decreased. The patient was treated with PI and PE. The thrombocytopenia improved initially. However, it worsened despite repeated PI and PE, and the patient died of worsening of general condition after a month. The third patient was intitially diagnosed as Evans syndrome by the presence of hemolytic anemia and thrombocytopenia. These were exacerbated acutely, and later diagnosed as TTP by the marked fragmentation of red cells, markedly decreased ADAMTS13 activity and increased titer of inhibitor. The patient died on the day of admission of respiratory failure. The fourth patient had weakness of the lower extremities and thrombocytopenia. TTP was diagnosed by the markedly decreased ADAMTS13 activity and increased titer of inhibitor. PE was repeatedly performed, however without effect. The patient died of worsening of general condition after 3 months. These results suggested that our cases include typical and atypical cases of TTP which are varied in the pathogenesis, clinical manifestations, activities of ADAMTS13, inhibitors and their concentrations, and the therapeutic effects of PE and PI. Early diagnosis and appropriate treatment are necessary for the treatment of TTP with poor prognosis.

View full abstract

A 56-year-old woman was admitted to our hospital because of a palpable right breast mass. After diagnosis of breast cancer, modified radical mastectomy was performed on the 7th of month 2003. The patient then developed a drug-induced pneumonia, requiring the discontinuation of treatment on the 10th of month 2003. CA19-9 was increasing from 11th 2004 and CT revealed multiple lung metastases. For chemotherapy, triweekly EC was followed by weekly paclitaxel treatmemts for approximately 6 months. The patient experienced a near-complete response to the chemotherapy. The patient, however, began to complaint of dullness of both arms and gait disturbances beginning on the 5th of month 2006; brain CT demonstrated multiple brain metastases. Whole brain radiotherapy with a total dose of 40 Gy in 2. 5 to 3 Gy daily fractions was administered. After the radiation treatment, CT indicated a reduction of mass of brain metastases concomitant with improvement in clinical symptoms. The patient has remained well without any aggravation of clinical symptoms on the 2th of month 2007.

View full abstract