TEL/AML1 Fusion Gene in Childhood Acute Lymphoblastic Leukemia in Southern Taiwan

Chromosomal abnormalities are found in 80–90% of childhood cases of acute lymphoblastic leukemia (ALL). Leukemia-specific chromosome aberrations not only have prognostic value, but also provide important clues for further investigation into leukogenesis, leukemic cell transformation, and proliferation. This study used reverse transcriptase–polymerase chain reaction techniques to detect transcripts of the leukemia-specific chromosome fusion gene, TEL/AML1, and to monitor the expression levels of the TEL-AML1 fusion transcript in ALL patients at sequential intervals during their treatment course. Twenty-five ALL patients were enrolled, including 20 who were newly diagnosed and five in relapse. The incidence of the TEL/AML1 fusion gene in this study was 32%. The clinical features of our eight TEL/AML1-positive ALL cases were similar to those in other studies. Blotting analysis of the levels of the TEL-AML1 fusion transcript was used to detect minimal residual disease. Reduced levels of TEL/AML1 expression were found in four of the six patients whose bone marrow or peripheral blood samples were obtained after treatment. Further investigation with a larger sample size is warranted

THE EFFECTS Of VOLLEYBALL ATTACKING ON SCORE POINTS: A CASE STUDY OF 2014 TVL IN TAIWAN

Volleyball is a sport in which team tactical and players' attacking skills determine to score points. Therefore, an effective team tactical is achieved by main spikers' and middle blockers' skills. To name but a few, delayed spike, open spike and back-row spike are main spikers' skills, yet quick spike, and individual time difference attack are associated with middle blockers'. Under this aspect, a case study of male teams of Taiwan Top Volleyball League (TVL) was yield out, which aimed at exploring the effects of team tactical and players attacking skills on score points. The results indicated that the attacking point ratio of main spikers and middle blockers in the champion team was higher than others. This was because the middle blockers gave cover to main spikers as attacking. By doing so, it promoted point ratio to main spikers. Furthermore, it found that to strengthen main spikers and middle blockers' skills would increase team's attacking point ratio

5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy

Novel variant Pro143Ala in HTRA2 contributes to Parkinson’s disease by inducing hyperphosphorylation of HTRA2 protein in mitochondria

Mutations in the gene encoding the mitochondrial protein high temperature requirement A2 (HTRA2) are inconsistently associated with a risk of Parkinson’s disease (PD). We assessed the presence of HTRA2 mutations among patients with PD and performed functional assay of identified mutations or variants. Among the total 1,373 subjects, the entire HTRA2 coding region was sequenced in 113 early-onset PD (EOPD), 20 familial PD patients and 150 control subjects. An additional 390 sporadic late-onset PD patients and 700 controls were subsequently screened to validate possible mutations found in the first set. We identified two novel heterozygous variants, c.427C > G (Pro143Ala) and c.906 +3 G > A, in 2 (1.5%) EOPD patients. The missense variant, Pro143Ala, was also observed in one late-onset PD patient but was absent in total 850 control subjects (relative risk 2.3, 95% CI 1.5–2.8, P = 0.04). Expressing Pro143Ala variant of HTRA2 in primary dopaminergic neurons causes neurite degeneration. Following exposure to rotenone, the ultra-structural mitochondrial abnormality, the percentage of mitochondrial dysfunction and apoptosis in cells carrying the HTRA2 Pro143Ala variant was significantly higher than wild-type cells. Mechanistically, protein level of phosphorylated HTRA2 was increased in cells carrying the Pro143Ala variant, suggesting Pro143Ala variant promotes HTRA2 phosphorylation with resultant mitochondrial dysfunction. Our results support a biologically relevant role of HTRA2 in PD susceptibility in Taiwanese. Further large-scale association studies are warranted to confirm the role of HTRA2 Pro143Ala variant in the risk of PD

Empiric antibiotic choices for community-acquired biliary tract infections

SummaryBackgroundThe study was conducted to reveal the most appropriate empiric antibiotics for the treatment of community-acquired biliary tract infections (CA-BTI) at a regional hospital in Taiwan.MethodsThe study was performed between October 1, 2010 and October 31, 2012. All positive bile culture results of presumptive community-acquired origins were collected. The associated etiologic microorganisms and their antimicrobial susceptibilities were analyzed. The appropriateness of empiric therapy (defined as the effectiveness of the antibiotics against the etiologic agents) and the subsequent treatment response were examined through the review of medical records.ResultsA total of 115 patients (cholecystitis, 83 cases, 72.2%; cholangitis, 32 cases, 27.8%) and 189 isolates (136 Gram-negative bacilli, 37 Gram-positive cocci, and 16 anaerobes) were analyzed. The most frequent pathogens were Escherichia coli (n = 69, 36.5%), Klebsiella spp. (n = 37, 19.6%), enterococci (n = 29, 15.3%), and Bacteroides spp. (n = 11, 5.8%). Penicillin resistance (5.4%) was low in Gram-positive cocci, whereas higher resistance (>20%) to cefazolin, cefuroxime, and ampicillin–sulbactam was found in Gram-negative bacilli. Anaerobes also demonstrated high resistance to clindamycin (37.5%) but less to metronidazole (12.5%). Appropriate empiric therapy was found in 92 (80%) cases, and among them, 83 (90.2%) were treated successfully. The treatment success rate (69.6%) was significantly lower among the remaining 23 cases with inappropriate empiric therapy (16 of 23 vs. 83 of 92, p < 0.05). A high treatment success rate (97.2%) was observed among cases empirically treated with ceftriaxone plus metronidazole.ConclusionThe combination of ceftriaxone plus metronidazole appears to be the most appropriate empiric antibiotics for the treatment of CA-BTI at this hospital. Because different hospitals may encounter microorganisms of different antimicrobial susceptibilities, similar approaches may be followed by other hospitals where appropriate empiric therapy has not yet been established for the treatment of CA-BTI

Overexpression of Nuclear Protein Kinase CK2 α Catalytic Subunit (CK2α) as a Poor Prognosticator in Human Colorectal Cancer

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. Thus, novel therapeutic approaches are badly needed. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 α subunit (CK2α) in tumor progression, and in the prognosis of human CRC. METHODOLOGY/PRINCIPAL FINDINGS: Expression levels of nuclear CK2α were analyzed in 245 colorectal tissues from patients with CRC by immunohistochemistry, quantitative real-time PCR and Western blot. We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients. Overexpression of nuclear CK2α was significantly correlated with depth of invasion, nodal status, American Joint Committee on Cancer (AJCC) staging, degree of differentiation, and perineural invasion. Patients with high expression levels of nuclear CK2α had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2α. In multi-variate Cox regression analysis, overexpression of nuclear CK2α was proven to be an independent prognostic marker for CRC. In addition, DLD-1 human colon cancer cells were employed as a cellular model to study the role of CK2α on cell growth, and the expression of CK2α in DLD-1 cells was inhibited by using siRNA technology. The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition. CONCLUSIONS/SIGNIFICANCE: Taken together, overexpression of nuclear CK2α can be a useful marker for predicting the outcome of patients with CRC

Epinephrine administration via a laryngeal mask airway: what is the optimal dose?

Background. The aim of this animal study was to clarify the effects of laryngeal mask airway (LMA)-administrated epinephrine and to assess the optimal dose. Methods. Thirty pigs were anesthetized and intubated with a cuffed tracheal tube (TT) and an LMA. Then they were assigned to one of five groups. The control group received distilled water 10 mL via the TT; the TT group received epinephrine 50 μg/kg via the TT; and the other three groups received two, four or six times the TT dose of epinephrine via the LMA. Heart rate (HR) and arterial pressure were monitored before and after drug administration for 15 minutes. Results. After epinephrine administration, the LMA-6 and TT groups had elevated systolic, diastolic and mean arterial pressures at 1 min and there was no significant difference between the two groups. In the TT group, these parameters peaked at 2 min then declined rapidly. In the LMA-6 group, they increased more slowly, and then maintained a plateau. The control, LMA-2 and LMA-4 groups failed to display significant persistent (>2 min) hemodynamic changes. Conclusions. We could not identify an optimal LMA-administrated epinephrine dose. The TT route is suitable when a high peak drug effect is required and the LMA route may be preferable if a persistent plateau effect is desired. Effective LMA administration of drugs may require larger doses than those given via TT