Byung Kee Kim

Prevalence of metallo-β-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii in a Korean University hospital and comparison of screening methods for detecting metallo-β-lactamase

To identify the metallo-β-lactamases (MBLs) prevalent in Korea, a total of 130 clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii (99 P. aeruginosa and 31 A. baumannii) with a reduced susceptibility to imipenem (IPM) and/or ceftazidime (CAZ) was subjected to PCR analyses with primers specific to blaIMP-1, blaVIM-1, and blaVIM-2. In addition, inhibitor-potentiated disk diffusion methods (IPD) using two kinds of substrate–inhibitor combinations (ceftazidime–2-mercaptopropionic acid (2MPA) and imipenem–EDTA) were investigated. Thirty-three isolates (29 P. aeruginosa and 4 A. baumannii) carried blaVIM-2 and two P. aeruginosa isolates harbored blaIMP-1. The enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) pattern revealed that many of the VIM-2-producing P. aeruginosa isolates were clonally related, whereas the A. baumannii isolates were diverse. The inhibitor-potentiated disk diffusion test using imipenem–EDTA was highly sensitive and specific for detecting the VIM-2 producer. These results suggest that VIM-2 is an important MBL in P. aeruginosa and A. baumannii in the Korean hospital of this study and that the IMP-1-producing P. aeruginosa has also emerged. Screening for MBLs and strict infection control for these isolates will contribute to prevent further spread of resistance.

CT and MRI findings of cystadenofibromas of the ovary

Abstract.The aim of this study was to assess imaging findings on CT or MR images of histologically proven ovarian cystadenofibromas. In the period 1995–2001, 32 histologically proven ovarian cystadenofibromas were identified in 28 women. Of the 32 ovarian cystadenofibromas, 16 tumors were purely cystic and the remaining 16 were complex cystic on CT or MR images. Solid components of 16 complex cystic tumors were seen as nodular (n=8) or trabecular (n=9) solid areas. One tumor had both nodular and trabecular solid components. Among 16 complex cystic tumors, 14 had thick or irregular septa; thus, half of ovarian cystadenofibromas had morphological imaging features of malignancy on CT or MR images. On histology, solid components in the cystic tumors were correlated with fibrous stromas that occasionally made a false-positive result for malignancy on imaging.

Loss of heterozygosity of chromosome 8p and 11p in the dysplastic nodule and hepatocellular carcinoma

Background and Aim: In hepatocarcinogenesis, both de novo and multistep pathways have been suggested, and in the latter a dysplastic nodule is the proposed precancerous lesion. But genetic changes involved in the dysplastic nodule are not well understood. In this study, we tried to determine whether allelic loss of the chromosome 8p and/or 11p could be involved in the development of the dysplastic nodule and/or hepatocellular carcinoma. Platelet‐derived growth factor‐receptor beta‐like tumor suppressor gene (PRLTS) and deletion in liver cancer‐1 tumor suppressor gene are located at 8p21.3‐p22. The hepatitis B virus integration site and WT1 tumor suppressor gene are located at 11p13.

Expression of Functional Markers in Acute Nonlymphoblastic Leukemia

Multidrug resistance parameters, tissue infiltration parameters, receptors for colony-stimulating factors (CSFr) and cell cycle parameters were analyzed using flow cytometry in 145, 109 initial and 36 relapsed or refractory, acute nonlymphoblastic leukemia (ANLL) patients to find out clinically more reliable functional parameters. Lung resistance-associated protein (LRP) was most frequently expressed in ANLL (44.1%) followed by P-glycoprotein (PGP) (35.9%) and multidrug resistance-associated protein (MRP) (8.3%). LRP and PGP were expressed more frequently in relapsed or refractory ANLL than initial ANLL cases. Complete remission rate after standard chemotherapy falls in PGP-positive cases (p = 0.001). CD44-positive ANLL cases relapsed more frequently. The organ tropism is different depending on the infiltration parameters, vascular cell adhesion molecule to splenomegaly, matrix metalloprotease-2 to hepatomegaly and to extramedullary infiltration other than spleen, liver or lymph node. The percentage of the granulocyte-macrophage-CSFr expression was high in M4 and M5, and granulocyte-CSFr-positive ANLL showed less extramedullary infiltration (p = 0.007) and more PGP expression. Ki-67 was expressed significantly less in refractory ANLL than initial ANLL and DNA topisomerase IIα was expressed significantly more in the surviving patients group. In conclusion, analysis of these new functional parameters could help to predict and overcome the clinical behavior of each ANLL at the time of diagnosis.

Epstein-Barr virus infection, drug resistance and prognosis in Korean T- and NK-cell lymphomas.

T‐cell lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. We tried to understand the effect of Epstein–Barr virus (EBV) on lymphogenesis, prognostic factors and drug resistance of T‐cell lymphomas, and to establish their relationship with international prognostic factors. Formalin‐fixed paraffin‐embedded tissue sections from 35 patients (12 women and 23 men) with T‐cell lymphomas were examined to detect the presence of EBV using RNA in situ hybridization for EBV‐encoded small nuclear RNA (EBER) 1/2 and immunohistochemical stain for latent membrane protein (LMP)‐1. We also tried to establish the expression of p53 and P‐glycoprotein (P‐gp) using immunohistochemistry. The distribution according to the subgroup was: two T‐lymphoblastic lymphomas, 13 NK/T‐cell lymphomas, one angioimmunoblastic T‐cell lymphoma, 17 peripheral T‐cell lymphomas, unspecified, and two anaplastic large cell lymphomas. The EBER was detected in 15 of 35 T‐cell lymphomas (42.9%) and among these it was detected in five of 17 nodal lymphomas (29.4%) and 10 of 18 extranodal lymphomas (55.6%). There was close correlation between EBER positivity and NK/T‐cell lymphoma (P= 0.032). Expression of LMP was found in a proportion of tumor cells in seven of the 15 EBER‐positive cases (46.7%). There was no correlation between EBER expression and complete response (CR rate), but coexpression of EBER and p53 was associated with treatment failure (P= 0.047). The 18 patients (51.4%) with p53 expression had significantly poorer outcomes compared with the 17 patients without p53 expression (CR rate, P< 0.0005; overall survival, P= 0.0102). Twenty of 35 patients (57.1%) were positive for P‐gp expression. P‐gp expression was significantly associated with treatment failure (P= 0.001) and overall survival (P= 0.0089). Seventeen of 35 patients (48.6%) treated with systemic chemotherapy or radiation therapy achieved a CR after initial treatment. When the prognostic factors were grouped using the international prognostic index, the CR rate was 58.8% for the low risk group, 50.0% for the low–intermediate risk group, 14.3% for the high–intermediate risk group, and 0% for the high risk group. In conclusion, high incidence of EBV was detected among Korean patients with T‐cell lymphomas. Our study supports the prediction that patients who express p53 and P‐gp have a poorer prognosis than those who do not and this should be considered when treatment strategies for individual patients are selected.

Immunotactoid glomerulopathy associated with idiopathic hypereosinophilic syndrome.

A case of immunotactoid glomerulopathy in an 18-year-old man with an idiopathic hypereosinophilic syndrome is presented. The patient showed cervical lymphadenopathy, asymptomatic proteinuria of nephrotic range, and hematuria without any defined immunologic disease. Marked and prolonged hypereosinophilia was found in peripheral blood (eosinophil count; 6,248/mm3) and bone marrow (eosinophil series; 32%). Diffuse and/or nodular eosinophilic infiltration was identified in multiple organs such as kidney, stomach, liver, lymph node, and skin. Renal biopsy revealed endocapillary proliferative features of typical immunotactoid glomerulopathy with IgG and C3 deposition and microtubular structures of variable size, 20–80 nm in diameter, mainly in the subendothelium. This study suggests that immunotactoid glomerulopathy may be a secondary immunologic manifestation of the tissue damage by eosinophils in the idiopathic hypereosinophilic syndrome.

Immunological alterations associated with Plasmodium vivax malaria in South Korea.

Various haematological and immunological studies on patients infected with Plasmodium vivax were undertaken, at diagnosis (day 0), after treatment with chloroquine but during primaquine treatment (day 10) and after all treatment (day 59), in South Korea (where there has been a recent and abrupt increase in the incidence of such infection). The main aims were to gain an understanding of the haemato-immunological alterations of this malarial infection, both before and after treatment, and to identify at least one useful marker for the diagnosis and post-treatment monitoring of P. vivax malaria. Thirty-eight patients with P. vivax malaria were compared with 20, apparently healthy controls. At diagnosis, the patients had lymphopenia, marked eosinopenia (the eosinophil count being correlated with the platelet count) and thrombopenia. Cells of most of the lymphocyte subsets investigated [i.e. CD3+, CD8+, CD19+, CD56+, CD3−/CD56+ and CD8+/CD56+ but not CD4+, CD3+/CD56+ or CD25+] were significantly less common among the lymphocytes of patients at diagnosis than among those of the controls. After initiating treatment, the numbers of CD19+ lymphocytes gradually increased (to normal values by day 59), whereas those of CD3+/56+ lymphocytes remained abnormally low throughout the follow-up period. The proportions of lymphocytes identified as CD4+ appeared to be unaffected by treatment. Although serum concentrations of IgE (and, to a lesser extent, IgM) were elevated in the patients at diagnosis, they were subnormal on day 10 post-treatment and normal at the day-59 follow-up. Serum concentrations of IgG and IgA in the patients were always found to be similar to those in the controls. At diagnosis the serum concentrations of complements C3 and C4 were significantly elevated in the patients. C3 remained at the same high concentration during follow-up but the concentration of C4, like that of IgE, was found to be subnormal on day 10 and normal 7 weeks later. The level of parasitaemia (%) was only found to be significantly correlated with haemoglobin concentration. The observation of eosinopenia with elevated IgE and C4 could be a useful indicator of P. vivax malaria, and treatment response could be followed by serial monitoring of serum concentrations of IgE and C4.

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I β2-µglobulin (β2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers

In an effort to understand whether HLA class I and II plays any role in the process of tumorigenesis and metastasis, we have immunohistochemically examined expression of HLA class I and II antigen by using the monoclonal antibodies (mAb) L368 (for β2m of HLA class I), HC-10 (for HLA-B, C heavy chains), and LGII-612.14 (for HLA class II heavy chain) in 5 borderline serous malignancy (BSM), 20 serous adenocarcinomas (SA), 15 borderline mucinous malignancy (BMM), and 10 mucinous adenocarcinomas (MA) of human ovary tumor case tissues. In BSM, the distribution and intensity of HLA expressions failed to reach statistical significance. In SA, HLA class I β2-µglobulin (β2m), HLA-B, C heavy chains and HLA class II heavy chain antigen expressions were down-regulated. Although expressions of HLA-B, C heavy chains and class II heavy chain were down-regulated in metastatic SA, there were no differences in HLA expression levels between primary and metastatic lesions. In BMM, class II heavy chain expressions were down-regulated. In MA, β2m, HLA-B, C heavy chains and class II heavy chain expressions were also down-regulated. Thus, we could distinguish the reduction or absence of HLA molecule expression was related to malignant potential. Loss of HLA class I and II molecules in invasive ovarian cancers raises the possibility that this could be a factor for tumor cells to retain invasiveness.

Eosinophilic cholangitis: US, CT, and cholangiography findings.

We report a case of eosinophilic cholangitis, with US, CT, and cholangiographic findings. The lesion showed marked wall thickening of cystic and common bile ducts on US and CT together with mild diffuse narrowing of the common duct on cholangiography.