Abstract Hematopoietic stem cell transplantation (HSCT) is a curative therapy for severe aplastic anemia (SAA); however, the optimal conditioning regimen for HSCT with an unrelated donor has not yet ...been defined. A previous study using a fludarabine (FLU), cyclophosphamide (Cy), and thymoglobulin conditioning regimen (Study A: 50 mg/kg of Cy once daily intravenously on days -9, -8, -7, and -6; 30 mg/m2 of FLU once daily intravenously on days -5, -4, -3, and -2; and 2.5 mg/kg of thymoglobulin once daily intravenously on days -3, -2, and -1) demonstrated successful engraftment (100%) but had a high treatment-related mortality rate (32.1%). Therefore, given that Cy is more toxic than FLU, we performed a new phase II prospective study with a reduced toxicity regimen (Study B: 60 mg/kg of Cy once daily intravenously on days -8 and -7; 40 mg/m2 of FLU once daily intravenously on days -6, -5, -4, -3, and -2; and 2.5 mg/kg of thymoglobulin once daily intravenously on 3 days). Fifty-seven patients were enrolled in Study A (n=28) and B (n=29), and donor type hematologic recovery was achieved in all patients in both studies. The overall survival (OS) and event free survival (EFS) rates of patients in Study B was markedly improved compared to those in Study A (OS: 96.7% vs. 67.9%, respectively, P =0.004; EFS: 93.3% vs. 64.3%, respectively, P =0.008). These data show that a reduced toxicity conditioning regimen with FLU, Cy, and thymoglobulin may be an optimal regimen for SAA patients receiving unrelated donor HSCT.
The effects of anti-allergic drugs on intestinal mastocytosis and the expulsion of Neodiplostomum seoulense were observed in Sprague-Dawley rats, after oral infection with 500 metacercariae. The ...drugs used were hydroxyzine (a histamine receptor H1 blocker), cimetidine (a H2 blocker), cyclosporin-A (a helper T-cell suppressant), and prednisolone (a T- and B-cell suppressant). Infected, but untreated controls, and uninfected controls, were prepared. Worm recovery rate and intestinal mastocytosis were measured on weeks 1, 2, 3, 5, and 7 post-infection. Compared with the infected controls, worm expulsion was significantly (P < 0.05) delayed in hydroxyzine- and cimetidine-treated rats, despite mastocytosis being equally marked in the duodenum of all three groups. In the cyclosporin-A- and prednisolone-treated groups, mastocytosis was suppressed, but worm expulsion was only slightly delayed, without statistical significance. Our results suggest that binding of histamine to its receptors on intestinal smooth muscles is more important in terms of the expulsion of N. seoulense from rats than the levels of histamine alone, or mastocytosis.
The purpose of this study was to identify correlations among the continence function, cognitive function, and activities of daily living(ADL) in elderly male patients with dementia in geriatric ...hospitals. The subjects were 64 patients aged 65 or above who were diagnosed with dementia among the hospitalized male patients in a geriatric hospital. For the subjects' cognitive function, a questionnaire developed for the Korean Mini Mental Status Examination(K-MMSE) was used. For the continence function and ADL, data were collected using a patient evaluation table. As a result, a lower level of cognitive function resulted in corresponding higher levels of dependence in all items of ADL except bathing(p<.05), and a lower level of cognitive function led to corresponding declines in the continence function(bowel control, bladder control)(p<.01). In addition, a higher level of dependence in ADL resulted in corresponding higher levels of difficulty in bowel and bladder control(p<.01). This study showed correlations among the cognitive function, ADL, and continence function of elderly men with dementia. The results of this study may be used as basic data for the management and treatment of hospitalized elderly male patients with dementia in geriatric hospitals.
Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more ...effective for preventing graft-versus-host disease (GVHD) and the rejection of organ transplants. After the promising results of our preliminary study, we conducted a phase II prospective multicenter clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and thymoglobulin conditioning regimen to allow good engraftment in patients who underwent unrelated transplantation for SAA. Twenty-eight patients underwent bone marrow (N = 15) or mobilized peripheral blood (N = 13) transplantation from HLA-matched unrelated donors with Cy (50 mg/kg once daily intravenously (i.v.) on days −9, −8, −7, and −6), Flu (30 mg/m2 once daily i.v. on days −5, −4, −3, and −2), and thymoglobulin (2.5 mg/kg once daily i.v. on days −3, −2, and −1). Donor-type hematologic recovery was achieved in all patients. The estimated survival rate (SR) was 67.9%, and all the events were treatment-related mortality (TRM), which included thrombotic microangiopathy (N = 2), pneumonia (N = 1), myocardiac infarction (N = 1), posttransplantation lymphoprolifarative disease (N = 3), and chronic GVHD-associated complications (N = 2). The SR of patients who received bone marrow (60.0%) was not different from that of patients who received mobilized peripheral blood (76.9%) ( P = .351), but the SR of patients who received more than 15 units of red blood cells before transplantation (45.5%) was significantly lower than that of the other patients (82.4%) ( P = .048). The Flu, Cy, and thymoglobulin conditioning regimen achieved promising results for successful engraftment, but the TRM was high. This study was registered at www.clinicaltrials.gov (NCT00737685), and now we are performing a new multicenter study (NCT00882323) to decrease the TRM by reducing the dose of Cy.
Plant homeodomain finger protein 2 （PHF2）, which contains a plant homeodomain and a Jumonji-C domain, is an epigenetic regulator that demethylates lysine 9 in histone 3 （H3K9me2）. On the other hand, ...runt-related tran-scription factor 2 （Runx2） plays essential roles in bone development and regeneration. Given previous reports that the PHF2 mutation can cause dwarfism in mice and that PHF2 expression is correlated with that of Runx2 in differ- entiating thymocytes, we investigated whether PHF2 regulates Runx2-mediated bone formation. Overexpression of PHF2 facilitated bone development in newborn mice, and viral shRNA-mediated knockdown of PHF2 delayed calvarial bone regeneration in adult rats. In primary osteohlasts and C2C12 precursor cells, PHF2 enhances osteoblast differentiation by demethylating Runx2, while suppressor of variegation 3-9 homolog 1 （SUV39H1） inhibits bone formation by methylating it. The PHF2-Runx2 interaction is mediated by the Jumonji-C and Runt domains of the two proteins, respectively. The interaction between Runx2 and osteocalcin promoter is regulated by the methylation status of Runx2, i.e., the interaction is augmented when Runx2 is demethylated. Our results suggest that SUV39H1 and PHF2 reciprocally regulate osteoblast differentiation by modulating Runx2-driven transcription at the post-translational level. This study may provide a theoretical basis for the development of new therapeutic modalities for patients with impaired bone development or delayed fracture healing.
ZAS3 is a large zinc finger transcription repressor that binds the κB-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated ...cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed NFκB-activated transcription by competing with NFκB for the κB-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of NFκB. Here, we present evidence that upon TNFα stimulation, ZAS3 inhibits NFκB-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on NFκB activity is mediated by neither direct association with NFκB nor disrupting nuclear localization of NFκB. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of NFκB, TRAF1 and TRAF2, thereby sensitizing cells to TNFα-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.
We present the MR findings of hepatic choriocarcinoma in a 2-week-old infant. Two masses of heterogeneous signal intensity were evident; one was an extensive mass on the left side of the liver and ...the other was a "daughter" nodule in the right lobe. Peripheral portions of the masses were hyperintense on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) suggesting subacute hemorrhage. Central portions of the masses were hypointense on T1WI and bright on T2WI. T1-weighted postgadolinium imaging showed peripheral enhancement of both tumor nodules. The infant's mother had normal serum beta-human chorionic gonadotropin levels and pelvic CT.
Effects on phase evolution caused by the addition of a new sintering agent, lithium borosilicate, Li2O B2O3 SiO2 (LBS) glass to 0.9MgTiO3-0.1CaTiO3 ceramic and resultant dielectric properties were ...investigated. The added LBS glass, a liquid phase sintering agent, significantly lowered the densification temperature from 1300 degrees to about 950 degrees C, while yielding decomposition of MgTiO3 into MgTi2O5 and Mg2TiO4. At the same time, the by-products of the decomposition reaction, MgO and TiO2, were dissolved into the glass network. Such phase evolution partly compensated the influence of deleterious glass addition so that the specimen demonstrated fairly good apparent dielectric properties.PUBLICATION ABSTRACT
A bacterium producing a fibrinolytic enzyme was isolated from Cheonggukjang. The bacterium was identified as a strain of Bacillus amyloliquefaciens by 16S rDNA analysis and designated as B. ...amyloliquefaciens HC188. The optimum culture medium appeared to be one containing 0.5% (w/v) maltose and 0.5% (w/v) soytone. Bacterial growth in the optimal medium at 37℃ reached the stationary phase after 27 h of incubation and the fibrinolytic enzyme showed optimum activity at 24 h. The enzyme was purified by 20-80% ammonium sulfate precipitation, CM Sepharose fast flow ion exchange chromatography, and Sephacryl S-200HR column chromatography. Its specific activity was 38359.3 units/mg protein and the yield was 5.5% of the total activity of the crude extracts. The molecular weight was 24.7 kDa and the amino acids of the N-terminal sequence were AQSVPYGVSQIKAPA. The fibrinolytic enzyme activity had an optimum temperature of 40℃ and an optimum pH of 8.0, and the enzyme was stable in the ranges 20-40℃ and pH 6.0-8.0. Enzyme activity was increased by Ca²⁺ and Co²⁺ but inhibited by Cu²⁺ EDTA, and PMSF. It is suggested that the purified enzyme is a metallo-serine protease.
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