BACKGROUND: Few studies have evaluated the performance of the recently introduced MicroScan Synergies plus Positive Combo 3 Panels (SIPC3) (Dade Behring Inc., USA). We evaluated the clinical efficacy of the panels in identification (ID) and antimicrobial susceptibility testing (AST) of Staphylococcusaureus and enterococci. METHODS: To evaluate the panels' accuracy of identification, the results obtained using the test panels were compared with those obtained by using conventional biochemical tests in conjunction with VITEK 2 system (bio-Merieux, USA). In addition, the AST results obtained using the panels were compared with those obtained by performing CLSI broth microdilution. RESULTS: The overall agreement between the approaches for the ID of S. aureus and enterococci was 100% and 96%, respectively. The categorical and essential agreements (CA and EA) for S. aureus were 98%, each. Very major errors (VME), major errors (ME), and minor error (mE) for S. aureus were 0.45%, 0.3%, and 4.2%, respectively. The majority of VMEs were for oxacillin (8.6%), penicillin (2.0%), erythromycin (7.9%), clindamycin (3.8%), and tetracycline (4.1%). For enterococci, the CA, EA, VME, ME, and mE were 88.8%, 93.7%, 4.4%, 0%, and 2.8%, respectively. The 80.5% (29/36) of Enterococcus faecium had concordant ID with the reference. Most of the categorical errors (3 VMEs and 14 mEs) were observed for quinupristin/dalfopristin (Synercid; Catalytica Pharmaceuticals Inc., USA). CONCLUSIONS: The panels compared favorably with conventional methods for the ID and AST of S. aureus. However, we expected a better performance for ID of E. faecium and AST using Synercid.
Anti-Bacterial Agents/*pharmacology ; Clindamycin/pharmacology ; Drug Resistance, Bacterial ; Enterococcus/*drug effects/isolation & purification ; Erythromycin/pharmacology ; Microbial Sensitivity Tests/instrumentation/*methods ; Oxacillin/pharmacology ; Penicillins/pharmacology ; Reagent Kits, Diagnostic ; Staphylococcus aureus/*drug effects/isolation & purification ; Tetracycline/pharmacology

BACKGROUND: Immature platelet fraction (IPF, %) is a measure of reticulated platelets (RPs), which represents the state of thrombopoiesis. The IPF is obtained from an automated hematology analyzer as one of the platelet parameters. This study was performed to establish reference intervals of IPF and its cut-off values for the differential diagnosis of thrombocytopenia. METHODS: Blood samples from 2,039 healthy individuals (1,161 males, 878 females) were obtained to establish reference intervals. The patient group included patients with idiopathic thrombocytopenic purpura (ITP) (N=150) and aplastic anemia (AA) (N=51) with platelet counts of less than 100x10(9)/L. We evaluated the reliability of the IPF measurements, the reference intervals, and cut-off value for the diagnosis of ITP. RESULTS: The reference intervals of IPF were 0.5-3.2% in males and 0.4-3.0% in females (95% confidence interval). The median IPF% of ITP and AA were 7.7% (range, 1.0-33.8%) and 3.5% (range, 0.6-12.9%), respectively. Statistical analysis revealed a significant difference between the IPF% of ITP and AA (P<0.0001). The cut-off value of IPF for differentiating ITP from AA was 7.3% with a sensitivity and specificity of 54.0% and 92.2%, respectively. CONCLUSIONS: A rapid and inexpensive automated measurement of IPF can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. This study determined the reference intervals of IPF from a large population of healthy individuals, including children. Further studies are needed to establish the clinical utility of IPF.

Heat shock protein (HSP) 90 is expressed in most living organisms, and several client proteins of HSP90 are necessary for cancer cell survival and growth. Previously, we found that HSP90 was cleaved by histone deacetylase (HDAC) inhibitors and proteasome inhibitors, and the cleavage of HSP90 contributes to their cytotoxicity in K562 leukemia cells. In this study, we first established mouse xenograft models with K562 cells expressing the wild-type or cleavage-resistant mutant HSP90β and found that the suppression of tumor growth by the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was interrupted by the mutation inhibiting the HSP90 cleavage in vivo. Next, we investigated the possible function of thioredoxin interacting protein (TXNIP) in the HSP90 cleavage induced by SAHA. TXNIP is a negative regulator for thioredoxin, an antioxidant protein. SAHA transcriptionally induced the expression of TXNIP in K562 cells. HSP90 cleavage was induced by SAHA also in the thymocytes of normal mice and suppressed by an anti-oxidant and pan-caspase inhibitor. When the thymocytes from the TXNIP knockout mice and their wild-type littermate control mice were treated with SAHA, the HSP90 cleavage was detected in the thymocytes of the littermate controls but suppressed in those of the TXNIP knockout mice suggesting the requirement of TXNIP for HSP90 cleavage. We additionally found that HSP90 cleavage was induced by actinomycin D, β-mercaptoethanol, and p38 MAPK inhibitor PD169316 suggesting its prevalence. Taken together, we suggest that HSP90 cleavage occurs also in vivo and contributes to the anti-cancer activity of various drugs in a TXNIP-dependent manner.

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.

Purpose: This study aimed to investigate and analyze the current fertility-related practices for breast cancer patients; the results are intended to help improve the quality of life of young patients and survivors. Methods: This study collected voluntary responses to a questionnaire that was used to survey Korean breast cancer specialists. The questionnaire consisted of five categories: knowledge, practice behaviors regarding fertility preservation, barriers to discussing fertility preservation, attitude toward fertility issues, and demographics and medical background. Results: A total of 120 copies of the questionnaire were distributed; the response rate was 89%. The section of the questionnaire regarding knowledge indicated that most respondents had adequate fertility preservation knowledge for cancer patients. However, 13.1% of the respondents indicated that they thought pregnancy increased the cancer recurrence risk. Respondents’ knowledge and attitudes about fertility preservation were not correlated with actual practice. The absence of patient’s expressions (24.30%), high recurrence risk (27.10%), insufficient time in the clinic (21.50%), and hospital conditions such as no reproductive specialists or infertility clinic (16.82%), were considered major barriers to discussing fertility issues. Conclusion Although more than 50% of the respondents thought that cancer treatment is more important than fertility preservation and it is complex and difficult, the Korean breast surgical oncologists were generally encouraging when discussing fertility issues with young breast cancer patients. Hence, breast clinicians should share with young patients the updated evidence regarding the feasibility and safety of pregnancy after cancer treatment and the available options so that the best decisions can be made.

Blood chimerism in twins is known to occur through the transfer of hematopoietic stem cells between the fetuses via a common placenta. We present a case of blood chimerism in a dizygotic dichorionic twin pregnancy. The female twin was delivered at 34 weeks of gestation, and the male twin was stillborn. Pathologic examination confirmed dichorionic diamniotic placentas. The karyotype of the female child was obtained using peripheral blood sample, and it revealed a mixture of 46,XX and 46,XY cells (chi 46,XY[13]/46,XX[7]). FISH analysis performed on the buccal cells by using CEP X/Y probe (Abbott Molecular Inc., USA) revealed 100% XX signals (nuc ish Xcen(DXZ1x2)[500]). Gross examination of the external genitalia and abdominal ultrasonography revealed no definitive abnormal findings in relation to sex differentiation. When XX/XY chimerism is present in blood lymphocytes, careful examination of external genitalia and reproductive organs and further studies are required to detect chimerism in non-hematopoetic tissues. This is a rare case of blood chimerism in dichorionic placentas, in contrast to those in monochorionic placentas.
Adult ; Blood Group Incompatibility/*genetics/ultrasonography ; Chimerism/*embryology ; Diseases in Twins/*genetics/ultrasonography ; Female ; Fertilization in Vitro ; Gestational Age ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Karyotyping ; Male ; Pregnancy ; Twins, Dizygotic/*genetics ; Ultrasonography, Prenatal

BACKGROUND: Cystic fibrosis (CF) is one of the most common hereditary disorders among Caucasians. The most common mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been well established among Caucasian populations. In Koreans, however, there are very few cases of genetically confirmed CF thus far, and the spectrum of mutations seems quite different from that observed in Caucasians. METHODS: In the present study, we describe the cases of 2 Korean CF patients, present sequencing results identifying mutations in their CFTR gene, and summarize the results of CFTR mutational spectrum from previously reported Korean CF patients. The mutations described were identified by performing direct sequencing analysis of the complete coding regions and flanking intronic sequences of the CFTR gene, followed by multiplex ligation-dependent probe amplification (MLPA) analysis in order to detect gene deletions or duplications that could not be identified by a direct sequencing method. RESULTS: Three CFTR mutations were identified in the 2 patients, including p.Q98R, c.2052delA, and c.579+5G>A. In an analysis of 9 Korean CF patients that included the 2 patients presented in this study, p.Q98R mutation was the only recurrently observed mutation with a frequency of 18.8% (3/16 alleles). Furthermore, only one of the mutations (c.3272-26A>G) was found among the 32 common mutations in the screening panel for Caucasians from the Cystic Fibrosis Mutation Database. CONCLUSIONS: Sequencing of the entire CFTR gene followed by MLPA analysis, rather than using the targeted sequencing-based screening panel for mutations commonly found in Caucasian populations, is recommended for genetic analysis of Korean CF patients.
Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Cystic Fibrosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Republic of Korea ; Sequence Analysis, DNA ; Young Adult