Acute Monoblastic Leukemia with t(11;17)(q23;q21): Fusion of the KMT2A(MLL) and MLLT6(AF17) Genes

The KMT2A (formerly MLL) gene is associated with at least 10% of all cases of acute leukemia. More than 80 translocation partner genes of KMT2A have been discovered to date, six of which have been identified on the long arm of chromosome 17. Among these, the MLLT6 (formerly AF17) gene is located at 17q12 and fuses with the KMT2A gene in rare cases of acute leukemia. We report here a case of AML with a KMT2A/MLLT6 fusion that was confirmed using molecular genetic methods. According to a literature review, this is the first reported case of AML with a KMT2A/MLLT6 fusion in Korea.

The First Case of Otitis in Korea Caused by Brevibacterium otitidis

Brevibacterium spp. are gram-positive rods that are considered to be strictly nonpathogenic, and a very few cases of their infection in humans have been reported. In this study, we report a case of otitis caused by Brevibacterium otitidis. A 53-year-old woman, who visited the hospital, complained of symptoms, such as otorrhea from both ears, ear fullness, tinnitus, and hearing impairment, for several months. Ear discharge was cultured on blood agar for pathogen identification. Bacteria from the isolated colony were initially identified as Actinomyces odontolyticus by VITEK 2 (bioMerieux, France), whereas VITEK® MS (bioMerieux, France) identified them as Brevibacterium luteolum. Subsequently, bacteria from the isolated colony were confirmed as B. otitidis by 16S rRNA sequencing. Antimicrobial susceptibility testing confirmed their sensitivity to vancomycin and linezolid and resistance to clindamycin and penicillin. To our knowledge, this is the first reported case of otitis caused by B. otitidis in Korea.

Risk Factors for Adverse Events of Therapeutic Plasma Exchange Assessed in a Single Center Study / 대한수혈학회지

BACKGROUND: Therapeutic plasma exchange (TPE) is used to remove pathologic substances involved in various disease etiologies. The use of TPE is increasing steadily in a variety of disease. This study analyzed the incidence, type and severity of adverse events (AE) according to the initial TPE of each patient in a single center. The risk factors for AE of TPE were also elucidated. METHODS: The medical and laboratory records of patients, who received TPE from January 2014 to December 2018, were reviewed retrospectively. The signs or symptoms during and after TPE were analyzed. RESULTS: TPE sessions were performed on 95 patients. The mean age was 53.3 years and men comprised 63.2%. The most common indication for TPE was desensitization for ABO-incompatible liver transplantation (ABO-i LT) (N=56, 58.9%). A total of 27 patients (28.4%) experienced AE during the initial TPE. The types of AE were allergic reactions (N=14, 14.7%), anaphylactic reaction (N=3, 11.1%), hypotension (N=5, 5.3%), hypocalcemic reaction (N=4, 4.2%), and febrile nonhemolytic reaction (N=1, 1.1%). The severities of AE were evaluated as mild in eight procedures (8.4 %), moderate in seventeen (17.9 %), and severe in two (2.1 %). Multivariable logistic regression analysis showed that the desensitization for ABO-i LT (odds ratio (OR), 2.08; 95% CI, 1.03~4.22) and the amount of FFP (OR, 1.07; 95% CI, 1.01~1.09) were associated with a higher incidence of AE. CONCLUSION: TPE can be performed under careful patient monitoring to provide prompt intervention, particularly in patients with desensitization of ABO-i LT using FFP.

Evaluation of CD3+CD4-CD8- (Double-negative) T Cells in Bronchoalveolar Lavage Fluid: an Effective Tool for Pulmonary Disease Diagnosis

BACKGROUND: Cellular analysis of bronchoalveolar lavage fluid (BALF) is a useful diagnostic tool for interstitial lung diseases (ILDs). The lymphocytes in BALF consist of CD3+CD4+ T cells (T4), CD3+CD8+ T cells (T8), and a few B cells. However, sometimes, an increased number of CD3+CD4-CD8- T cells (double-negative T cells, DNTs) are noted in BALF. It is known that DNTs in the blood are associated with immunoregulation and autoimmune diseases. However, there are only few studies on DNTs in BALF. We evaluated the DNTs in BALF in patients with pulmonary diseases. METHODS: Immunophenotyping results of the BALF obtained from 122 pulmonary disease patients over an 8-yr period were reviewed. T-lymphocyte subsets (T4, T8, and DNT) and inflammatory markers were analyzed for each group of clinical diagnosis. T-lymphocyte percentage of more than 15% of the total cells was defined as BALF lymphocytosis, and DNT percentage of more than 5% of T lymphocytes was defined as high DNT. RESULTS: The most frequent diseases found in the patients were pneumonia (31.6%), autoimmune-related ILDs (18.0%), hypersensitivity pneumonitis (10.7%), and organizing pneumonia (10.7%). However, the occurrence of autoimmune-related ILDs was significantly high (40%) in patients with lymphocytosis and high DNT (P=0.002). All lung cancer patients showed lymphocytosis with high DNT. In addition, CD3-signal intensities of DNTs were significantly higher than those of other T-lymphocyte subtypes (P=0.003). CONCLUSION: The number of DNTs in BALF was increased in patients with autoimmune-related ILDs and lung cancer. High DNTs in BALF are useful as supportive diagnostic tools for autoimmune-related ILDs.

The Relationship between ABO Blood Group Phenotypes and Seroprevalence of Infectious Disease in Korea / 대한수혈학회지

BACKGROUND: The distribution of ABO and Rhesus D (RhD) blood group antigens differs according to race and region. Previous studies have reported that blood group type was associated with not only transfusion-related diseases but also various diseases, such as malignancy and infectious disease. However, true relationship of blood groups and many diseases remained controversial. The aim of this study was to determine whether ABO and RhD blood groups are correlated with several infectious diseases. METHODS: From January 2003 to December 2012, we retrospectively reviewed results for HBsAg, HCV Ab, HIV Ab, VDRL, HAV IgM, CMV IgM, EBV VCA IgM, and Clostridium difficile toxin A and B (CD toxin). We also reviewed ABO and RhD results of these patients. Data were analyzed using chi-square test and binary logistic regression test. Odds ratio and 95% confidence intervals were determined. RESULTS: A total of 109,898 medical records of ABO and HBsAg results were reviewed. Blood group type-A was more prone to have positive results with HBsAg, while blood group type-O was less affected (odds ratio 1.086, P=0.003, odds ratio 0.935, P=0.029, respectively). With 3,171 records of CD toxin, blood group type-O was more affected (odds ratio 1.247, P=0.027). The relationship of the other serologic results and blood groups was not statistically significant. CONCLUSION: Seroprevalence of HBsAg and CD toxin showed an association with blood group type. Blood group type-A had higher HBsAg seroprevalence than the other group. Blood group type-O was more prone to have CD toxin.

Prevalence and Clinical Characteristics of Mupirocin-Resistant Staphylococcus aureus / 대한임상미생물학회지

BACKGROUND: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a known risk factor for nosocomialtransmission and infection. In an effort to mitigate this problem, topical mupirocin has been widely used for clearing nasal carriage of MRSA. However, mupirocin resistance has become a worldwide concern due to increased use of the antibiotic. The aims of this study were to evaluate the clinical characteristics and prevalence of mupirocin resistance among clinical isolates of staphylococci and to investigate antimicrobial susceptibility. METHODS: A total of 175 S. aureus specimens recovered over a 4-month period from various body sites were tested for resistance to mupirocin and other antibiotics using the Vitek2 automated system. The presence of the mupA gene was assessed in isolates exhibiting resistance to mupirocin and in other selected organisms. The clinical characteristics of the isolates were also reviewed. RESULTS: Of the 175 S. aureus isolates, 9.1% (16/175) were resistant to mupirocin, with 1.7% (3/175) having high-level resistance (HR) and 7.4% (13/175) having low-level resistance (LR). Patients with HR-mupirocin-resistant S. aureus had a longer duration of hospitalization (P=0.026). Of the 13 LR-mupirocin-resistant S. aureus strains, 11 had identical antibiogram patterns. The mupA gene was detected only among HR isolates. CONCLUSION: The rate of mupirocin resistance in the S. aureus isolates was high. The spread of mupirocin-resistant S. aureus may be due to nosocomial infection.

Comparison of Analytical Performance between the Sysmex UF-100 flow cytometer and the Iris iQ200 Urine Microscopy System / 임상검사와정도관리

BACKGROUND: The UF-100 flow cytometer (Sysmex Co., Japan) and the Iris iQ200 (Iris Diagnostics, USA) are widely used for routine urinalysis in Korea. We compared the diagnostic accuracy of these two automated systems based on the microscopic finding, and evaluated the clinical performance of the automated systems. METHODS: A total of 323 fresh urine samples were selected and analyzed by conventional microscopy and the automation systems, the UF-100 and the iQ200. Quantification for RBCs, WBCs, and bacteria were also evaluated using both automated systems. RESULTS: For 158 of urine sample classified as normal urines, the agreement rate for the UF-100 and the iQ200 was 84.8% (N=134) and 89.9% (N=142), respectively. For 165 of urine samples classified as abnormal urines, the agreement rate for the UF-100 and the iQ200 was 90.9% (N=150) and 81.8% (N=135), respectively. The UF-100 showed a good linearity in the quantitative measurements of RBCs and WBCs. For both systems, false-negative value for WBCs and bacteria were about 30% in abnormal urines. Both systems showed inaccurate results for pathologic casts and bacteria. CONCLUSIONS: We compared the microscopic finding and the primary results of automated systems without user reclassification, and the agreement rate was about 85%. The agreement rate will be improved by deliberating "Review" comments of the instruments.

A Case of Natural Killer Cell Leukemia Misdiagnosed as Tuberculous Lymphadenopathy / 대한진단검사의학회지

Natural killer (NK) cell neoplasms are a group of rare but highly malignant tumors. We report here one case of NK cell leukemia. A 54-yr-old woman presented with a 2-month history of progressive left neck mass. Based on the positive result of tissue PCR for Mycobacterium tuberculosis, she was at first diagnosed with tuberculous lymphadenopathy. After two weeks, she developed generalized lymphadenopathy, hepatosplenomegaly, fever and anemia. Subsequent evaluation was performed including bone marrow aspiration and biopsy. Peripheral blood smear showed leukoerythroblastic features with 31% blasts. Bone marrow was packed with agranular blastoid cells, which were periodic acid-Schiff (PAS) positive and myeloperoxidase (MPO) negative. Immunophenotyping showed that these cells were positive for CD45 and HLA-DR, whereas negative for CD3, CD5, CD7, CD10, CD13, CD14, CD19, CD20, CD22, CD33, CD34, and CD61. Because of the absence of the markers of T-cell, B-cell, and myeloid lineage-specific antigens, we added CD16/56 for the immunophenotyping and the blasts were positive (94%). The tumor cells of biopsied lymph node were only positive for CD56, consistent with NK cell lymphoma. Epstein-Barr virus (EBV) was not detected by RNA in situ hybridization. Culture for M. tuberculosis was negative. Thus this patient was diagnosed with blastic NK cell lymphoma/leukemia involving bone marrow and lymph node.

Effect of Combination of Anticancer Agents and Nitroimidazoles on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions

PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.

Effect of antitumor agents on the survival of human hepatocellular carcinoma cells under hypoxic conditions / 대한내과학회지

BACKGROUND: In a previous study, we have shown that quinolones, antibiotics inhibiting topoisomerases, improve survival of tumor cells under hypoxic conditions. In this study, we tested whether antitumor agents such as doxorubicin that inhibit topoisomerases can also improve survival of tumor cells under hypoxic conditions. METHODS: Human hepatocellular carcinoma cells (HepG2) were grown in 4 mL of the culture medium at 2.5x10(5) cells/60 mm culture dish under normoxic conditions for 2 days before being transferred to fresh culture medium with different concentrations of doxorubicin or other antitumor agents under normoxic or hypoxic (1% oxygen concentration in air) conditions. Cell viability and the concentration of glucose and lactic acid in the medium were measured during cell culture. At the same time, the cells in the 60 mm dishes were lysed, and chromosomal DNA was isolated and loaded onto a 1.5% agarose gel for the DNA fragmentation assay. RESULTS: Doxorubicin inhibited cell growth under normoxic condition in a concentration-dependent manner for the 0~100 microgram/mL concentration range. However, doxorubicin improved cell viability under hypoxic conditions for a 0.1~10 microgram/mL concentration range by inhibiting apoptosis. Similar phenomena were observed for other antitumor agents that inhibit topoisomerases. CONCLUSIONS: Solid tumors usually have hypoxic regions in the tumor, under which conditions antitumor agents that inhibit topoisomerases may function to delay tumor cell death. This can reduce the efficacy of the antitumor agents.

Effect of Antibiotics on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions

PURPOSE: Antibiotics that kill or suppress the growth of bacteria also affect tumors directly or indirectly. The authors aimed to show whether some antibiotics can improve cancer cell survival under hypoxic conditions, and how the antibiotics improve the cells under hypoxic conditions. METHODS: Human hepatocellular carcinoma cells (HepG2) were grown at 1% oxygen concentration. Cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured at different incubation times, in the absence or presence of aminoglycosides, tetracyclines, quinolones, penicillins, cephalosporins, sulfonamides, or chloramphenicols. DNA fragmentation assay was performed to study the mechanism how some antibiotics improve the cell survival under hypoxic conditions. RESULTS: Of the antibiotics tested, only aminoglycosides, tetracyclines, quinolones and the chloramphenicol improved cell survival under hypoxic conditions. Geneticin (G418), an aminoglycoside chosen as an example, improved cell survival even if glucose in the medium was completely consumed. At the same time, the appearance of DNA ladder was delayed in the presence of geneticin, which was also the same for the other antibiotics that improved cell survival under hypoxic conditions. CONCLUSION: Some antibiotics improved hepatocellular carcinoma cells under ischemic conditions by inhibiting apoptosis. The results implies that the antibiotics might adversely affect solid tumors, by improving cancer cell growth where hypoxic or ischemic conditions occur in the core region. Therefore, we might be cautious in choosing antibiotics for cancer patients with solid tumors, especially when the patients should be treated with antibiotics for a long time.

Expression of Cell Surface Marker on Human Bone Marrow Derived Stromal Cells during Chondrogenic Differentiation / 대한류마티스학회지

OBJECTIVE: Multipotent bone marrow stromal cells have the ability to differentiate toward a variety of connective tissue lineages including cartilage. The future use of adult mesenchymal stem cells (MSCs) for human therapies depends on the establishment of preclinical studies. Therefore, in this preclinical study we demonstrated the expression of MSC surface markers CD29, CD105, and CD44 on human bone marrow derived stromal cells during chondrogenic differentiation. METHODS: Adult human bone marrow was collected from the iliac crest of 7 donors following informed consent. Mononuclear cells were isolated, incubated in monolayers, and embedded in alginate beads for three-dimensional cultures. Cellualr viability was assessed by MTT assay. Flow cytometry of alginate bead cultures was performed on days 0, 7, 14, 21, and 28 using monoclonal antibody against surface molecules, CD105, CD29, CD44, CD34 and CD45. Total contents of collagen and glycosaminoglycan (GAG) of the alginate beads was measured. SPSS 11.0 was used for data analysis. RESULTS: After 7 days of culture, 89% of the cells expressed the human integrin beta 1 antibody, CD29. The CD29-positive cells remained elevated at 83% on days 28. However, while only 18% expressed the type II TGF-beta receptor endoglin, CD105 on day 7, the CD105-positive cells increased abruptly 65% on day 14 remaining elevated up to day 28. The expression of CD44 was maximal in the first passage cell (63%). High concentration of TGF-beta 3 (10 ng/mL) was more favorable for sustaining cell viability than a low concentration (0.5 ng/mL)(n=4, p= 0.002, day 21). The total contents of collagen and GAG in the MSC-alginate beads increased during the three-dimensional culture (n=4, p=0.02, p=0.006) suggesting its differentiation into a chondrogenic lineage. CONCLUSION: CD29 was expressed earlier than CD105 during chondrogenic differentiation of human bone marrow MSC. CD44 expression was highest in the first passage cells and gradually decreased afterwards.

Moleculoepidemiological Characteristics of Extended-Spectrum beta-Lactamase Producing Escherichia coli and Klebsiella pneumoniae Strains in Daegu / 대한진단검사의학회지

BACKGROUND: The importance of extended-spectrum beta-lactamases (ESBL) produced in gramnegative bacilli is now well recognized, but most clinical laboratories have problems in detecting and interpreting ESBL and implicating the findings in nosocomial infections caused by ESBL producing gram-negative bacilli. The present study aims primarily to evaluate the distributions of these enzymes among Escherichia coli and Klebsiella pneumoniae, the most frequent isolates of Enterobacteriaceae producing ESBL, to differentiate the types of enzymes in theses isolates and finally to relate the clonality of specific types within a part of Daegu city. METHODS: The clinical isolates of 1, 242 E. coli and 859 K. pneumoniae were screened for ESBL production by the disk diffusion method of the National Committee of Clinical Laboratory Standard, and it was confirmed by the double-disk synergy test (DDS). Antimicrobial susceptibility test was performed by the agar dilution method. The presence of -lactamase was tested by polymerase chain reaction (PCR) and plasmid analysis. Isoelectric focusing and nucleotide sequence analysis were performed to evaluate ESBL types. Pulsed-field gel electrophoresis (PFGE) of XbaI-digested DNA fragments was carried out to determine the extend of clonality within the hospital. RESULTS: Of 34 isolates of E. coli and 31 isolates of K. pneumoniae ramdomly selected from those isolates screened for ESBL production were further tested by DDS to confirm its production: 30 (88.2%) E. coli and 29 (93.5%) K. pneumoniae were positive. TEM-52 and SHV-12 were present both in E. coli and K. pneumoniae, but SHV-2a was distributed only in K. pneumoniae. The resistance was transferable in 66.7% of E. coli and 68.9% of K. pneumoniae. Six and 5 PFGE patterns were shown by E. coli and K. pneumoniae, respectively. Among the 5 patterns of K. pneumoniae, type B was dominant, suggesting a clonal outbreak in the hospital. CONCLUSIONS: The ESBL specific enzyme types were TEM-52, SHV-2a and SHV-12. Despite many different PFGE patterns of the ESBL producing isolates, a few outbreak and edemic clones appear to be prevalent in Dongsan Medical Center.

Epidemiologic Trends of Rotavirus Infection in the Republic of Korea, July 1999 through June 2002 / 대한진단검사의학회지

BACKGROUND: Rotavirus is the most common cause of childhood diarrhea worldwide. Although rotavirus is also the leading cause of infant and childhood diarrhea in Korea, much remains unknown about the trends of rotavirus infection by month and geographic region in Korea. To monitor epidemiologic trends of rotavirus infection, a laboratory-based rotavirus surveillance network was established in 2002. This is the first nationwide, multicenter evaluation of rotavirus epidemiology in Korea. METHODS: The rotavirus test results were collected retrospectively from eight network laboratories, from July 1999 to June 2002. Four laboratories used latex agglutination, three used immunochromatography, and one used enzyme-linked fluorescent assay for the detection of rotavirus antigen. RESULTS: Of 10, 441 stool specimens, 2, 496 (23.9%) were positive for rotavirus. During the 3-year period, the rotavirus season began in December-January, and ended in April-May. The rotaviruspositive percentage of summer, autumn, winter, and spring was 11.5%, 10.0%, 32.8%, and 30.0%, respectively. A few hospitals revealed summer epidemics. The rotavirus positive rate in each hospital varied from 15.3% to 44.2%. A common feature of the three hospitals showing the lowest rotavirus-positive percentage (i.e. 800 beds). The secondary care hospitals showed a higher positive proportion (27.5%) compared with tertiary care hospitals (21.1%). CONCLUSIONS: Overall, the rotavirus-positive percentage among all diarrheal specimens was similar to that of other developed countries. The results of this study showed that the autumn epidemic of the rotavirus has declined or disappeared and the peak season for rotavirus has shifted to late winter/early spring in Korea.

Development of a Method for Testing Resistance of Anti-Rheumatic Drugs Using MDR1 Gene / 대한류마티스학회지

OBJECTIVE: A number of disease-modifying anti-rheumatic drugs (DMARDs) have been shown to be more effective than placebo in the management of rheumatoid arthritis (RA). However, most course of DMARDs, except methotrexate, are discontinued after 2 or 3 years, because of toxicity, lack of efficacy or escape from control. The multi-drug resistance (MDR) is a phenomenon in which cells develop cross-resistance to many agents such as anthracyclin, vinca alkaloids and colchicine. In our hypothesis, MDR phenomenon could be implicated in acquired resistance to DMARDs in RA. We have established a mdr1 cell line and tested whether DMARDs are substrate for P-glycoprotein (P-gp). METHODS: The mdr1-cDNA was cloned into retroviral vector, and the recombinant retroviral vector was transfected into PA317 cells. The target cells, NIH3T3, were infected with recombinant retroviruses. A colony most resistant to vinblastin was selected for the following experiments; expression of mdr1 gene in NIH3T3 cells was confirmed by RT-PCR, and biological function of mdr1 gene product, P-gp, was tested using Rhodamine-123 (Rh123) efflux assay. Resistance of the target cells expression P-gp which can survive against hydroxychloroquine (HCQ) and methotrxate (MTX) were measured by MTT assay. RESULTS: RT-PCR for mdr1 gene showed successful transfer of the gene into the NIH3T3 cells. Rh123 assay revealed expression of P-gp on the selected cells as follows; Rh123 efflux activity of uninfected NIH3T3 cells was 6%, that of PLXSN was 0.2%, and that of selected cells was 44%. The 50% proliferation inhibitory capacity of the selected cells were twice for HCQ but there was no difference of that for MTX. CONCLUSION: We established a mdr1 cell line and using the cell line, HCQ was a substrate of MDR, but MTX was not related to MDR.

Diagnostic Value of the Antiperinuclear Factor by Indirect Immunofluorescence Method / 대한진단검사의학회지

BACKGROUND: The antiperinuclear factor (APF) has been reported both as a diagnostic tool and as a prognostic marker for rheumatoid arthritis (RA). Our purpose is to study the diagnostic value of the APF, and to compare the detection method of the indirect immunofluorescence method (IIF) and the citrullinated cyclic peptides enzyme-linked immunosorbent assay (CCP-ELISA). METHODS: A total of 131 patients were included in this study. The APF were measured with both the IIF and ELISA. The IIF and ELISA procedures were carried out following the kit's instructions. The medical records such as C-reactive protein (CRP), erythroid sedimentation rate (ESR), the Ritchie index and diagnosis were reviewed retrospectively. SPSS (version 10.0, SPSS inc., USA) was used for statistical analysis. RESULTS: The patients were 94 with RA, 26 with osteoarthritis, 7 with fibromyalgia syndrome, and 3 with palindromic rheumatism, 2 with gout, 2 with systemic lupus erythematosus, 1 with Behcet's disease, and 7 with non specific rheumatic diseases. The sensitivity and the specificity of the APF test in patients with RA were 93%, and 81%, while those with the rheumatoid factor (RF) were 91% and 63% , suggesting the APF has a higher specificity than RF. The area under the curve of APF was 0.87 (95% confidence interval, 0.79 - 0.95), but RF was 0.77 (95% confidence interval, 0.67- 0.87). The kappa statistics between the two detection methods IIF and ELISA was 0.667 (P=0.000), indicating disagreement between these two methods. The detection sensitivety and specificity of APF-IIF were 89% and 73%, while those of ELISA were 80% and 73%. The area under the curve of APF-IIF was 0.82 (95% confidence interval, 0.72- 0.90), but CCP-ELISA was 0.77 (95% confidence interval, 0.67- 0.86). There was a statistically significant correlation between the APF grade and the clinical parameters such as RF (r=0.503, P=0.000), CRP (r=0.333, P=0.000) and ESR (r=0.261, P=0.003). CONCLUSIONS: Taken together, the APF could play a role in diagnosing RA in addition to RF. APF-IIF showed a higher sensitivity than ELISA.

The Effect of Doxycycline on the Survival of the Cells under Hypoxic Condition / 신경정신의학

OBJECTIVES: Cerebrovascular diseases seriously effect patient's quality of life, and the treatment has, its limitation to bring functional recovery unless a patient is brought to a hospital within several hours from the onset. In this study, we tried to find a way to prolong the survival cells under hypoxic conditions using cell culture. METHODS: Cultured rat glioma cells grew in normal and high glucose medium under hypoxic conditions, with or without doxycycline. Cell viability, glucose and lactic acid concentration were measured. RESULTS: The cells died after 1 day of culture under hypoxic conditions in normal glucose medium without doxycycline due to the total consumption of glucose. On the contrary, the cells still survived even after 3 days of culture under the same hypoxic conditions in normal glucose medium with doxycycline despite the total consumption of all glucose. For both cases, the cause of death was not, at least, due to the decrease of pH as the pH was kept neutral during the whole period of culture. In this case, doxycycline was the cell survival factor by suppressing apoptosis, which was proved by DNA fragmentation assay. On the other hand, the cells died after 60 hours of culture under hypoxic conditions in high glucose medium without doxycycline due to the decrease of pH. The cells still survived even after 70 hours of culture under the same hypoxic conditions in high glucose medium with doxycycline due to the inhibition of decreased pH. For both cases, the cause of death was not, at least, due to the consumption of total glucose because some glucose remained in the medium at the end culture. CONCLUSION: Doxycycline increased cell viability both in normal glucose and high glucose medium under hypoxic conditions, which might have an application for the treatment of patients with ischemic stroke.

Study of Serum S-100 Protein in Leprosy Patients / 나학회지

Leprosy is a granulomatous disease primarily affecting the peripheral nerves. The pathogenesis would be related to the cell-mediated response to mycobacterial antigens, metabolic and biochemical change of Schwann cell, circulating demyelinating factors and other autoimmune process. A specific nerve tissue protein, S-100 protein, has been demonstrated in normal nerves and nerve complexes. The stains of S-100 protein in dermal nerves of leprosy patients have been suggested in assessing the presence of nerve damage. We have estimated the concentration of S-100 protein in the sera of 64 leprosy patients(38 lepromatous leprosy, 26 tuberculoid leprosy) and that of 20 normal controls without neurologic disorders by ELISA. The results obtained were as follows: 1. The mean S-100 protein concentration was 0.0042ng/ml in a total of 64 leprosy patients, with 0.0062ng/ml in lepromatous type and 0.018ng/ml in tuberculoid type. The controls showed 0.0017ng/ml. 2. The analysis of age and serum S-100 protein concentration in both types showed lower value in the fifties of tuberculoid type(p0.05). 3. The analysis of duration of illness and serum S-100 protein concentration in both types showed higher value in the forties and fifties in lepromatous type(p0.05). 4. The mean S-100 protein concentration of patients with neurologic symptoms was 0.0577ng/ml, in contrast with 0.0016ng/ml in patients without neurologic symptoms (p<0.05). In conclusion, the measurement of serum S-100 protein would play a potential role of a useful marker of assessing nerve damage in leprosy patients, esp, with neurologic symptoms.

Quantitative Measurement of Eotaxin and RANTES mRNA in the Nasal Polyps / 대한임상병리학회지

BACKGROUND: Nasal polyps were developed from eosinophil infiltrations and activation by chronic inflammatory reactions. Eotaxin and RANTES have been postulated to be involved in the recruitment and activation of eosinophils to the inflamed tissues. The aim of this study is to estimate the mRNA expression of eotaxin and RNATES in the nasal polyps and it's effect on tissue eosinophils. METHODS: At first, we evaluated the linearity and precision of GeneAmp 5700R(PE Applied Biosystems, Foster, U.S.A) with M. tuberculosis DNA. We collected 17 allergic, 30 non-allergic nasal polyps and 15 normal inferior turbinates from the patients visiting Catholic University Hospital of Taegu Hyosung. We performed the quantitative polymerase chain reaction(PCR) for the eotaxin and RNATES, and the tissue immunohistochemical stain for the major basic protein. RESULTS: GeneAmp 5700R disclosed good linearity and precision. Compared with the normal inferior turbinates, eotaxin mRNA levels were increased in the allergic and non-allergic polyps, and showed significant correlation with eosinophils infiltration and activation. But the RANTES didn't revealed any significant differences among these groups, and no correlation with tissue eosinophils. The patients with allergic polyps showed increased eosinophils infiltration and activation in the tissue, while those with non allergic polyps disclosed increased eosinophils activation. CONCLUSIONS: Since eotaxin expression were increased in the tissue of the patients with nasal polyps and showed good correlation with eosinophils infiltration and activation in the tissue, it had been considered that eotaxin played an important role in the pathogenesis of allergic polyps and tissue eosinophilia.

Study of Anti-Galactocerebroside and Anti-Sulfatide Antibodies in Leprosy / 나학회지

Peripheral nerve damage in leprosy would be related to the local cell-mediated immune response to mycobacterial antigens and, presumedly, metabolic and biochemical changes of Schwann cell or circulating demyelinating factors and otherwise, autoimmune process would be involved. The neuralipid composing of cholesterol, ethanolamine glycerophosphatide, sphingomyelin, galactocerebroside(GalC), ethanolamine plasmalogen, serine and choline glycerophophatide, sulfatide are abundant in the myelin and have immunogenicity. Especially, GalC and sulfatide are known to play an important role in myelin function and its stability. The study was undertaken to detect the titers of anti-GalC and anti-sulfatide antibodies for the neural destruction mechanism of leprosy. Subjects tested were 53 leprosy patients with polar type consisting of 25 in tuberculoid leprosy(TT) and 28 in lepromatous leprosy(LL). The titeration of the antibody was done in the sera of patients and controls by enzyme-linked immunosorbent assay(ELISA). The results obtained were as follows ; 1. The detection rate of anti-GalC antibody was in 13(24.5%) of the 53 leprosy patients compared with 3(13.0%) of the 23 normal controls. Among the leprosy patients, there was 8(32.0%) in TT and 5(17.9%) in LL. 2. The detection rate of anti-sulfatide antibody was in 24(45.3%) of leprosy patients compared with 7(26.1%) of normal controls. Both types showed almost same rate of 46.4% and 44.0%, respectively. 3. Mean titer of anti-GalC antibody was 18.9+/-17.0EU/ml in leprosy patients and 12.8+/-8.8EU/ml in normal controls, with statistically insignificant level(p>0.05, one-way ANOVA). Among the leprosy patients, mean titer was 24.7+/-20.9EU/ml in TT and 13.8+/-10.5EU/ml in LL, with significance in TT(p0.05). Among the leprosy patients, mean titer was 26.0+/-15.4EU/ml in TT and 24.7+/-14.0EU/ml in LL, which was nearly same quantities in both types. 5. Examinations using Pearson correlation analysis revealed that the association between anti-GalC and anti-sulfatide antibodies was non-specific in LL(r=0.09) and TT(r=0.04). The analysis between duration of illness and anti-GalC antibody was decreasing correlation(r=-0.89, p0.05). In comparison with anti-sulfatide antibody and duration, LL was higher in 41-50 years, while being higher in 31-40 years in TT, but correlation in both types could not be found(r=0.08, -0.06) In conclusion, the anti-GalC and anti-sulfatide antibodies seemed to be related with nerve damage. Hereafter we think that more study for other neural lipid should be investigated