Factors Influencing Health Behavior Compliance in Adult Moyamoya Patients

Purpose@#The purpose of this study was to identify factors influencing health behavior compliance in adult patients with moyamoya. @*Methods@#A descriptive correlation study was conducted to investigate the factors influencing health behavior compliance. Participants were 142 adult patients diagnosed with moyamoya disease who were hospitalized or visited an outpatient clinic in the Gyeonggi province. Data were collected from December 16, 2019 to April 14, 2020 using self-report questionnaires and analyzed using the IBM SPSS 26.0 Win software. @*Results@#The hierarchical multiple regression analysis demonstrated that self-efficacy (β = .60, p < .001), social support (β = .13, p = .032), and age (β = .21, p = .005) affected the health behavior of adults with moyamoya disease. These 3 variables explained 62.0% of the variance of health behavior compliance, and the most influential factor was self-efficacy. @*Conclusion@#Based on the results of this study, it concludes that nursing interventions should be focused on self-efficacy and social support to improve health behavior compliance with adult patients diagnosed with moyamoya disease. For that, various strategies to enhance self-efficacy and social support should be developed and actively applied in the clinical setting for adult moyamoya patients.

Nutrition Support and Transition to Oral Intake in Cancer Patients with Dysphagia / 대한연하장애학회지

Dysphagia in cancer patients are mainly caused by brain tumor, head and neck cancer and esophageal cancer. Also both paralytic and mechanical dysphagia may occur with a high rate of malnutrition that has been reported. In cases when oral ingestion is impossible for a long time due to cancer treatments including surgery, decision should be made on if it may be an indication of nutrition support or not. In the case of nutrition support having to be initiated, the route and method of nutrition support must be determined. During enteral nutrition supply, we should predict and monitor probable complications according to the feeding rate depending on the change of patient's conditions, and if required, medication assistances may be needed. Through VFSE (Video fluoroscopic swallowing exam), when the transition to oral intake is carried out, nutritional supply should be monitored to plan the tapering and discontinuation of nutrition support. Since the effort of international standardization regarding dysphagia stage has been sustained, it is necessary to make the viscosity- and texture-based dysphagia diet standardization on the ground of clinical evidence in Korea, too.

An Electrode Configuration for Recording Muscle Motor Evoked Potentials in the Upper Extremities during Intraoperative Neurophysiological Monitoring

OBJECTIVE: The main aim of the present study is to examine the electrode configurations used to record the muscle motor evoked potential (mMEP) in the upper extremities during surgery with the goal of producing a high and stable mMEP signal, in particular among the abductor pollicis brevis (APB), abductor digiti minimi (ADM), and across the APB-ADM muscles, which have been widely used for the mMEP in the upper extremities. METHODS: Thirty right-handed patients were recruited in this prospective study. No patients showed any adverse events in their mMEP signals of the upper extremities during surgery. The mMEPs were recorded independently from the signals for the APB and ADM and for those across the APB-ADM. RESULTS: The mMEP amplitude from across the APB-ADM was statistically higher than those recorded from the APB and ADM muscles. Moreover, the coefficient of variation of the mMEP amplitude from across the APB-ADM was smaller than those of mMEP amplitude recorded from the APB and ADM muscles. CONCLUSION: The mMEP from across the APB-ADM muscles showed a high yield with high stability compared to those in each case from the APB and ADM muscles. The configuration across the APB-ADM muscles would be best for mMEP recordings from the upper extremities for intraoperative neurophysiological monitoring purposes.

Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children / 대한혈액학회지

BACKGROUND: Immune reconstitution (IR) after hematopoietic stem cell transplantation (HSCT) reduces transplantation-related complications such as infection and improves HSCT outcomes. METHODS: We retrospectively analyzed IR of lymphocyte subpopulations in 38 pediatric patients for hematologic malignant diseases after allogeneic HSCT from April 2006 to July 2008. T-cell-, B-cell-, and natural killer (NK) cell-associated antigens were assayed in peripheral blood by flow cytometry analysis of 5 lymphocyte subsets, CD3+, CD3+/CD4+, CD4+/CD8+, CD16+/CD56+, and CD19+, before and 3 and 12 months after transplantation. RESULTS: Reconstitutions of CD16+/CD56+ and CD3+/CD8+ lymphocytes were achieved rapidly, whereas that of CD3+/CD19+ lymphocytes occurred later. Age was not related to reconstitution of any lymphocyte subset. Total body irradiation (TBI) and anti-thymocyte globulin (ATG) administration were related to delayed reconstitution of total lymphocytes and CD3+ lymphocytes, respectively. Reconstitutions of CD3+/CD4+ lymphocytes and CD3+/CD8+ lymphocytes were significantly delayed in patients who received umbilical cord blood stem cells. In patients with chronic graft-versus-host disease (cGVHD), recovery of the total lymphocyte count and CD19+ lymphocytes at 3 months post-transplant were significantly delayed. However, acute GVHD (aGVHD) and cytomegalovirus (CMV) reactivation did not influence the IR of any lymphocyte subset. Further, delayed reconstitution of lymphocyte subsets did not correspond to inferior survival outcomes in this study. CONCLUSION: We observed that some lymphocyte reconstitutions after HSCT were influenced by the stem cell source and preparative regimens. However, delayed CD19+ lymphocyte reconstitution may be associated with cGVHD.

The impact of HLA matching on unrelated donor hematopoietic stem cell transplantation in Korean children / 대한혈액학회지

BACKGROUND: The impact of HLA matching on outcomes of unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) varies in different racial or ethnic groups. Since little is known about the impact of such matching on URD HSCT in Korean children, we analyzed this issue. METHODS: We analyzed the outcomes of 142 patients who underwent URD HSCT at 4 Korean medical centers. All patient donor pairs were fully typed for HLA-A, -B, -C, and -DR alleles. RESULTS: At a median follow-up of 22 months, 3-year survival rates for patients with 8, 7, and < or =6 matched alleles were 88.4%, 70.7%, and 53.6%, respectively. A single mismatch (Mm) at HLA-B or -C was associated with lower survival compared with that associated with 8 matched alleles. No significant differences were observed between single-allele and single-antigen Mms with respect to survival rate or acute graft-versus-host disease (aGVHD) incidence rates. HLA disparity had a greater impact on the survival of patients with high-risk malignancy than of those with low-risk malignancy. Among pairs with a single Mm, only locus A showed a significant association and higher risk of grade III-IV aGVHD compared to those in patients with 8 matched alleles. CONCLUSION: Disparity in HLA class I, regardless of antigen or allele Mm, adversely affected both survival and grade III-IV aGVHD development. An increased number of HLA Mms was associated with a higher risk of post-transplantation complications. Further investigations using larger cohorts are required to confirm the effects of HLA mismatching on URD HSCT patient outcomes.

High Frequency of Male Microchimerism in Peripheral Blood Mononuclear Cells of Korean Women with Scleroderma, Resembling Skin Manifestations of Chronic Graft Versus Host Disease / 임상소아혈액종양

BACKGROUND: Bidirectional traffic of cells at the feto-maternal interface has been shown during pregnancy and fetal cells have been found to persist in maternal peripheral blood for decades after childbirth. Fetal-microchimerism has been reported in women with scleroderma, which shares a number of characteristics with chronic graft versus host disease (GVHD), although its contribution to the disease pathogenesis remains unclear. We performed this study to determine the frequency of male microchimerism in peripheral blood of patients with scleroderma or normal healthy women with son.METHODS: PCR targeting the Y chromosome specific DYZ1 sequence was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with scleroderma and 10 healthy women who had given birth to at least one son.RESULTS: Male DNA was detected in 16 of 26 (61.5%) women with scleroderma. Whereas male DNA was not detected in any healthy women who had given birth to son.CONCLUSION: Although fetal microchimerism in women with scleroderma was documented, additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune disease.

High Frequency of Male Microchimerism in Peripheral Blood Mononuclear Cells of Korean Women with Scleroderma, Resembling Skin Manifestations of Chronic Graft Versus Host Disease / 임상소아혈액종양

BACKGROUND: Bidirectional traffic of cells at the feto-maternal interface has been shown during pregnancy and fetal cells have been found to persist in maternal peripheral blood for decades after childbirth. Fetal-microchimerism has been reported in women with scleroderma, which shares a number of characteristics with chronic graft versus host disease (GVHD), although its contribution to the disease pathogenesis remains unclear. We performed this study to determine the frequency of male microchimerism in peripheral blood of patients with scleroderma or normal healthy women with son. METHODS: PCR targeting the Y chromosome specific DYZ1 sequence was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with scleroderma and 10 healthy women who had given birth to at least one son. RESULTS: Male DNA was detected in 16 of 26 (61.5%) women with scleroderma. Whereas male DNA was not detected in any healthy women who had given birth to son. CONCLUSION: Although fetal microchimerism in women with scleroderma was documented, additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune disease.

Clinical features of infantile hepatic hemangioendothelioma / 소아과

PURPOSE: Infantile hepatic hemangioendothelioma (IHHE) is the most common type of hepatic vascular tumor in infancy. We conducted this study to review our clinical experience of patients with IHHE and to suggest management strategies. METHODS: We retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13 females) treated at the Asan Medical Center between 1996 and 2009. RESULTS: Median age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%) were diagnosed with IHHE based on sonographically detected fetal liver masses, 5 (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging results, and were confirmed in three patients by histopathology analysis. Six patients were observed without receiving any treatment, whereas 12 received corticosteroids and/or interferon-alpha. One patient with congestive heart failure and a resectable unilobar tumor underwent surgical resection. Three patients with congestive heart failure and unresectable tumors were managed by hepatic artery embolization with/without medical treatment. At a median follow-up of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor disappearance or >50% decrease in tumor size. One patient died due to tumor-related causes. CONCLUSION: IHHE generally has a benign clinical course with low morbidity and mortality rates. Clinical course and treatment outcome did not differ significantly between medically treated and non-treated groups. Surgically unresectable patients with significant symptoms may be treated medically or with hepatic artery embolization.

Lineage Switch at Relapse of Childhood Acute Leukemia: A Report of Four Cases

Lineage switch in acute leukemia is an uncommon event at relapse, and therefore rarely reported in the literature. Here, we have described the clinical laboratory features of four cases in which the cell lineage switched from acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML). One patient was initially diagnosed with B-ALL, switched to T-ALL at the first relapse, and eventually, AML at the second relapse. A lineage switch represented either relapse of the original clone with heterogeneity at the morphologic level or emergence of a new leukemic clone. Further sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanisms of leukemic recurrence, with possible implications for treatment selection.

Early central nervous system complications after allogeneic hematopoietic stem cell transplantation in children / 대한혈액학회지

BACKGROUND: Central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (HSCT) have not been well characterized in the pediatric population. METHODS: We retrospectively analyzed data of 202 consecutive children who underwent allogeneic HSCT (60 from matched related donors, 9 from mismatched related donors, and 133 from unrelated donors) at Asan Medical Center between 1998 and 2009. RESULTS: Twenty-seven children (13.5%) developed CNS complications within 6 months after HSCT. Calcineurin inhibitor (CNI)-associated neurotoxicity was the most common CNS complication (n=16), followed by CNS infection (n=2), cerebrovascular events (n=2), thrombotic microangiopathy-associated events (n=2), metabolic encephalopathy (n=2), irradiation/chemotherapy injury (n=1), and encephalopathy/myelopathy of unknown causes (n=2). Univariate analysis showed that a transplant from an alternative donor and the occurrence of acute graft-versus-host disease (GVHD) (>grade 2) were associated with a significantly increased risk of CNS complications. In the multivariate analysis, acute GVHD >grade 2 was identified as an independent risk factor for early CNS complications. The 5-year overall survival rate was significantly lower in patients with CNS complications (52.1% vs. 64.9%, P=0.014), whereas CNI-associated neurotoxicity did not affect the survival outcome. CONCLUSION: CNS complications are frequent among children undergoing HSCT, contributing to early death after transplant. More attention should be paid to the development of CNS complications for recipients of alternative donor transplants and patients with severe acute GVHD who are at increased risk for CNS complications.

Effect of hyperglycemia on mortality rates in critically ill children / 소아과

PURPOSE: To verify the effect of hyperglycemia on mortality rates in critically ill children and to identify the blood glucose level that influences prognosis. METHODS: From July 2006 to June 2008, a total of 206 patients who were admitted to the pediatric intensive care unit (PICU) at Asan Medical Center and who survived for more than 7 days were retrospectively reviewed. We analyzed the maximum glucose value within 7 days in PICU, PRISM-III score and SOFA score within 24 hours, and mortality. We did not perform an adjustment analysis of drugs affecting glucose level. RESULTS: The maximum glucose level within 7 days in PICU was higher in the nonsurvival group than in the survival group. Using 4 cutoff values (125, 150, 175, and 200 mg/dL), the mortality of patients with hyperglycemia was found to be 13.0%, 14.4%, 19.8%, and 21.1%, respectively, and the cutoff values of 175 and 200 mg/dL revealed significant differences in mortalities between the hyperglycemic and normoglycemic groups. The PRISM-III score was not significantly different between the hyperglycemic and normoglycemic groups under a glucose cutoff value of 175 mg/dL, but the SOFA score was higher in the hyperglycemic group. Under a glucose cutoff value of 200 mg/dL, the PRISM-III score was higher in the hyperglycemic group, and the SOFA score did not differ between the 2 groups. CONCLUSION: Hyperglycemia with a maximal glucose value > or = 175 mg/dL during the first 7 days after PICU admission was associated with increased mortality in critically ill children.

Prognostic significance of minimal residual disease detected by a simplified flow cytometric assay during remission induction chemotherapy in children with acute lymphoblastic leukemia / 소아과

BACKGROUND: Our study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL). METHODS: A total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells. RESULTS: Thirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with > or =1% leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9% [18.7%] vs. 92.0% [5.4%], P=0.004). Stratification into 3 MRD groups (> or =1%, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, P=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance. CONCLUSION: An MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

Outcome and risk factors of pediatric hemato-oncology patients admitted in pediatric intensive care unit / 소아과

PURPOSE: To evaluate the risk factors for mortality and prognostic factors in pediatric hemato-oncology patients admitted to the pediatric intensive care unit (PICU). METHODS: We retrospectively reviewed the medical records of pediatric hemato-oncology patients admitted at the PICU of the Asan Medical Center between September 2005 and July 2008. Patients admitted at the PICU for perioperative or terminal care were excluded. RESULTS: Total 88 patients were analyzed. Overall ICU mortality rate was 34.1%. Mean age at PICU admission was 7.0+/-5.7 years and mean duration of PICU stay was 18.1+/-22.2 days. Hematologic diseases contributed to 77.3% of all the primary diagnoses, and the primary cause of admission was respiratory failure (39.8%). The factors related to increased mortality were C-reactive protein level (P<0.01), ventilation or dialysis requirement (P<0.01), and hematopoietic stem cell transplantation (P<0.05). In all, 3 scoring systems were investigated [Number of Organ System Failures (OSF number), the Pediatric Risk of Mortality III (PRISM III) score, and the Sequential Organ Failure Assessment (SOFA) score]; higher score correlated with worse outcome (P<0.01). The Oncological Pediatric Risk of Mortality (O-PRISM) scores of the 21 patients who had received hematopoietic stem cell transplantation were higher among the non-survivors, but not statistically significant (P=0.203). CONCLUSION: The PRISM III and SOFA scores obtained within 24 hours of PICU admission were found to be useful as early mortality predictors. The highest OSF number during the PICU stay was closely related to poor outcome.

Four Cases of Extracorporeal Membrane Oxygenation for Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) with severe pulmonary hypoplasia is associated with significant mortality. Recently, several new therapeutic methods have been suggested, such as high- frequency oscillatory ventilation and inhaled nitric oxide. For hypoxemic respiratory failure unresponsive to these advanced medical treatment options, extracorporeal membrane oxygenation (ECMO) serves as the last potentially effective treatment. An understanding of the pathophysiology of pulmonary hypertension associated with CDH led to a strategy involving preoperative stabilization and delayed surgical intervention with ECMO. We describe four cases of ECMO, including the first report of ECMO for neonatal CDH in Korea.

A Study on Nutrient Intake, Anthropometric Data and Serum Profiles among High School Students Residing in Seoul / 대한지역사회영양학회지

This study was performed to investigate the anthropometric data, serum profiles, and nutrient intakes of high school students who are living in Seoul. Anthropometric data showed that mean height and weight were 174.1 cm and 66.6 kg in 99 male and 161.4 cm and 54.0 kg in 116 female students. Mean BMI for male and female students were 21.9 and 22.3 kg/m2, and subjects with BMI > 25 kg/m2 were 14 and 7%, respectively. Total cholesterol, HDL- and LDL-cholesterol of subjects were 149.6 +/- 3.1, 46.4 +/- 1.3, 86.4 +/- 2.3 mg/dl for males and 169.2 +/- 3.1, 50.7 +/- 1.0, 100.9 +/- 2.7 mg/dl for females, respectively. Hemoglobin (Hb) and total iron binding capacity (TIBC) were 12.8 +/- 0.1 g/dl, 437.3 +/- 7.2 microgram/dl in male and 11.9 +/- 0.1 g/dl, 439.4 +/- 5.7 microgram/dl in female, respectively. Based on Hb classification, 45.6% of male and 45.0% of female students fell into anemic condition. Intakes of energy, Ca, Fe, Zn, riboflavin, and folate were below the Korean RDA. In particular Ca (male and female, respectively, 64.6 and 643% RDA) and Fe (male and female, respectively, 78.6 and 64.3%RDA) intakes were extremely low. Serum triglyceride was positively significantly correlated with weight (r = 0.22), BMI (r = 0.279), waist circumference (WC, r = 0.235), triceps skin-fold thickness (TSF, r = 0.197) and obesity index (OI, r = 0.279). Hb concentration was positively correlated with height (r + 0.387), weight (r = 0.349), BMI (r = 0.191) and waist/hip ratio (WHR, r = 0.380). As for the correlation between serum profiles and nutrient intakes, the Hb concentration was positively correlated with energy (r = 0.163), protein (r = 0.149), Na (r = 0.153), vitamin A (r = 0.165), thiamin (r = 0.201) and niacin (r = 0.192, p < 0.01). These result suggest that the prevalence of Ca and Fe deficiency of student is high and dietary guideline for prevent anemia in this age needs to contain the adequate intake of energy and its related vitamins.

Role of STAT3-Interacting Protein (STIP1) in delta12-Prostaglandin J2-Induced Cell Death

delta12-Prostaglandin J2 (delta12-PGJ2) is one of cyclopentenone prostaglandins. The delta12-PGJ2 is known to induce apoptosis of tumor cells, however, it's action mechanism is not clear. It has recently been reported that STAT3 is involved in tumorigenesis. In the present study, we investigated the role of STAT3-interacting protein (STIP1) in the cytotoxicity of delta12-PGJ2, since STIP1 was recently reported as a modulator of STAT3 activation by specifically binding to inactive (unphosphorylated) STAT3. The effect of delta12-PGJ2 was observed in stably overexpressing Neuro-2A cells transfected with full cDNA of STIP1, and cytotoxicity of delta12-PGJ2 in the transfected cells was increased, compared with the vector control cells. The cytotoxicity of delta12-PGJ2 treatment was significantly accentuated by pretreatment of the STIP1-transfected cells with protein kinase inhibitor, genistein, and less activation of STAT3 in STIP1-transfected cells was shown, compared with the vector control cells. Expression of bax was also increased in the STIP1-transfected cells. These data suggest that STIP1 inhibits cell growth via inhibition of STAT3 activation in delta12-PGJ2 treatment.

Cytochrome C-dependent Fas-independent apoptotic pathway in HeLa cells induced by delta12-prostaglandin J2

Cyclopentenone prostaglandins (PGs) have antiproliferative activity on various tumor cell growth in vitro. Particularly, 9-deoxy-(9,12)-13,14-dihydro PGD2( delta12-PGJ2) was reported for its antineoplastic and apoptotic effects on various cancer cells, but its mechanism inducing apoptosis is still not clear. In this study, we have characterized apoptosis induced by delta12-PGJ2in HeLa cells. Treatment of delta12-PGJ2induced apoptosis as indicated by DNA fragmentation, chromatin condensation, and formation of apoptotic body. We also observed release of cytochrome c from mitochondria and activation of caspase cascade including caspase-3, -8, and -9. And the pan-caspase inhibitor z-Val-Ala-Asp (OMe) fluoromethyl-ketone (z-VAD-fmk) and Q-Val-Asp (OMe)-CH2-OPH (Q-VD (OMe)-OPH) prevented cell death induced by delta12-PGJ2 showing participation of caspases in this process. However, protein expression level of Bcl-2 family was not altered by delta12-PGJ2, seems to have no effect on HeLa cell apoptosis. And ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase 8 indicating that Fas receptor-ligand interaction was not involved in this pathway. Treatment of delta12-PGJ2 also leads to suppression of nuclear factor kappaB (NF-kappaB) as indicated by nuclear translocation of p65/RelA and c-Rel and its DNA binding ability analyzed by EMSA. Taken together, our results suggest that delta12-PGJ2-induced apoptosis in HeLa cell utilized caspase cascade without Fas receptor-ligand interaction and accompanied with NF-kappaB inactivation.

Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A2 and 12-PGJ2

We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A2 and delta(12)-PGJ(12) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and Sox-4 transfection into the cells were able to induce apoptosis as observed by the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the induction of Sox-4 expression and blocked the formation of DNA fragmentation by PGA(2) and delta(12)-PGJ(12) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was accompanied with caspase-1 activation indicating that caspase cascade was involved in this apoptotic pathway. These results indicate that Sox-4 is involved in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.

Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction

3-Deazaadenosine (DZA), a cellular methylation blocker was reported to induce the caspase-3-like activities-dependent apoptosis in U-937 cells. In this study, we analyzed the activation pathway of the caspase cascade involved in the DZA-induced apoptosis using specific inhibitors of caspases. In the U-937 cells treated with DZA, cytochrome c release from mitochondria and subsequent activation of caspase-9, -8 and -3 were observed before the induction of apoptosis. zDEVD-Fmk, a specific inhibitor of caspase-3, and zLEHD-Fmk, a specific inhibitor of caspase-9, prevented the activation of caspase-8 but neither caspase-3 nor caspase-9, indicating that caspase-8 is downstream of both caspase-3 and caspase-9, which are activated by independent pathways. zVAD-Fmk, a universal inhibitor of caspases, kept the caspase-3 from being activated but not caspase-9. Moreover, ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase-8 and induction of apoptosis by DZA. In addition, zVAD-Fmk and mitochondrial permeability transition pore (MPTP) inhibitors such as cyclosporin A (CsA) and bongkrekic acid (BA) did not block the release of cytochrome c from mitochondria. Taken together, these results suggest that in the DZA-induced apoptosis, caspase-8 may serve as an executioner caspase and be activated downstream of both caspase-3 and caspase-9, independently of Fas receptor-ligand interaction. And caspase-3 seems to be activated by other caspses including IETDase-like enzyme and caspse-9 seems to be activated by cytochrome c released from mitochondria without the involvement of caspases and CsA- and BA- inhibitory MPTP.

Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction

3-Deazaadenosine (DZA), a cellular methylation blocker was reported to induce the caspase-3-like activities-dependent apoptosis in U-937 cells. In this study, we analyzed the activation pathway of the caspase cascade involved in the DZA-induced apoptosis using specific inhibitors of caspases. In the U-937 cells treated with DZA, cytochrome c release from mitochondria and subsequent activation of caspase-9, -8 and -3 were observed before the induction of apoptosis. zDEVD-Fmk, a specific inhibitor of caspase-3, and zLEHD-Fmk, a specific inhibitor of caspase-9, prevented the activation of caspase-8 but neither caspase-3 nor caspase-9, indicating that caspase-8 is downstream of both caspase-3 and caspase-9, which are activated by independent pathways. zVAD-Fmk, a universal inhibitor of caspases, kept the caspase-3 from being activated but not caspase-9. Moreover, ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase-8 and induction of apoptosis by DZA. In addition, zVAD-Fmk and mitochondrial permeability transition pore (MPTP) inhibitors such as cyclosporin A (CsA) and bongkrekic acid (BA) did not block the release of cytochrome c from mitochondria. Taken together, these results suggest that in the DZA-induced apoptosis, caspase-8 may serve as an executioner caspase and be activated downstream of both caspase-3 and caspase-9, independently of Fas receptor-ligand interaction. And caspase-3 seems to be activated by other caspses including IETDase-like enzyme and caspse-9 seems to be activated by cytochrome c released from mitochondria without the involvement of caspases and CsA- and BA- inhibitory MPTP.