BACKGROUND: The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. METHODS: In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. RESULTS: Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. CONCLUSION: An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drug-susceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.
DNA ; Drug Therapy ; Glass ; Mass Screening ; Mycobacterium tuberculosis* ; Mycobacterium* ; Point Mutation* ; Rifabutin ; Rifampin ; Tuberculosis

Brucellosis is a zoonosis caused by several species of Brucella. Brucellosis is usually an acute or sub-acute febrile illness that histologically develops granulomatous inflammation. Brucella prostatitis is a very rare complication and is usually accompanied by epididymo-orchitis. We now report a case of histologically proven granulomatous prostatitis due to Brucella without clinical evidence of epididymo-orchitis. A 61-year-old farmer presented with myalgia, low back pain, and fever. A needle biopsy of the prostate was performed due to symptoms of urinary frequency and high prostate specific antigen levels (17.3 ng/mL). Histologically, the prostate showed granulomatous inflammation without caseous necrosis. Polymerase chain reaction (PCR) studies of blood and prostatic tissue for Brucella were positive, while a PCR study for Mycobacterium tuberculosis was negative. The patient was treated with doxycycline and rifampin. A possibility of Brucella prostatitis should be considered in the differential diagnosis of granulomatous prostatitis or prostatitis of unknown origin associated with or without epididymo-orchitis.
Biopsy, Needle ; Brucella ; Brucellosis ; Diagnosis, Differential ; Doxycycline ; Fever ; Granuloma ; Humans ; Inflammation ; Korea ; Low Back Pain ; Middle Aged ; Mycobacterium tuberculosis ; Necrosis ; Polymerase Chain Reaction ; Prostate ; Prostate-Specific Antigen ; Prostatitis ; Rifampin

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.
Biocompatible Materials ; Bioengineering ; Biological Therapy ; Cell- and Tissue-Based Therapy ; Embryonic Stem Cells ; Heart ; Humans ; Induced Pluripotent Stem Cells ; Models, Animal ; Myocytes, Cardiac ; Pluripotent Stem Cells ; Regeneration ; Regenerative Medicine ; Therapeutic Uses

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

Acute fatty liver of pregnancy (AFLP) is one of the sudden unexpected causes in pregnancy and maternal deaths. It has been considered as a potential fatal disease in pregnancy, but the postmortem findings of AFLP is not well known. Because an unexpected maternal death may lead to a legal dispute, forensic pathologists should be aware of clinical presentations and postmortem findings of AFLP. Therefore, we presented our case and reviewed with literatures.
Autopsy ; Dissent and Disputes ; Fatty Liver* ; Forensic Pathology ; Maternal Death* ; Pregnancy*

BACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes. METHODS: We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed. RESULTS: Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival. CONCLUSIONS: IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.
Carcinoma, Renal Cell* ; Humans ; Insulin-Like Growth Factor II ; Neoplasm Metastasis ; Nephrectomy ; Retrospective Studies ; Tumor Suppressor Protein p53

BACKGROUND: Recent reports have indicated that renal cell carcinoma (RCC) with rhabdoid features follows an aggressive clinical course. We investigated the prognostic significance and nature of the rhabdoid component. METHODS: We retrospectively analyzed the incidence and clinicopathologic characteristics of RCC with rhabdoid features in 174 radical nephrectomy cases. The specimens were examined histologically and immunohistochemically. RESULTS: Twelve of the 174 RCC cases (6.9%) showed rhabdoid features. Histologically, all the tumors with rhabdoid features were of the clear cell type. The presence of rhabdoid features was significantly associated with higher Fuhrman's nuclear grade and higher pathologic tumor stage at presentation. Among the 12 patients who showed the rhabdoid component, nine (75%) developed metastasis and seven (58.3%) died of disease-related causes. The presence of rhabdoid features was independently associated with metastasis and disease-related mortality. The rhabdoid cells were positive for vimentin; variably positive for pan-cytokeratin, epithelial membrane antigen, and CD10; and negative for cytokeratin 7, smooth muscle actin, desmin, E-cadherin, and c-Kit. No case showed loss of integrase interactor-1; one was p53 positive, and five were insulin-like growth factor mRNA binding protein 3 positive. The Ki-67 labeling index was 1-25% (mean, 5.5%). CONCLUSIONS: The rhabdoid component is an independent prognostic factor for metastasis of RCC; therefore, identification of this component is critical.
Actins ; Cadherins ; Carcinoma, Renal Cell ; Carrier Proteins ; Desmin ; Humans ; Incidence ; Integrases ; Keratin-7 ; Kidney ; Mucin-1 ; Muscle, Smooth ; Neoplasm Metastasis ; Nephrectomy ; Prognosis ; Retrospective Studies ; Rhabdoid Tumor ; RNA, Messenger

A ganglioneuroma is a very rare neoplasm in the gastrointestinal tract and consists of ganglion cells, nerve fibers, and supporting cells. A gastrointestinal ganglioneuroma is occasionally related to inherited diseases, like neurofibromatosis type I and multiple endocrine neoplasm type 2b. We have experienced a case of a solitary polypoid ganglioneuroma in the cecum of a patient with no history of inherited diseases. The patient was a 56-yr-old male who had suffered from dyspepsia for a year. On the colonoscopic examination, a sessile polyp, measuring 0.7 x 0.7 cm in greatest dimensions, was discovered and eliminated. The remaining large intestine was unremarkable. Microscopically, the polyp was composed of isolated or nested ganglion cells admixed with a proliferation of spindle cells in the mucosa and the submucosa. The background showed interspersed cystic glands in an expanded lamina propria. Immunohistochemically, the ganglion cells were positive for NSE and NeuN while the spindle cells demonstrated a positive response to S-100 protein. Since a ganglioneuroma has a benign nature, complete resection is the treatment of choice.
Cecum ; Dyspepsia ; Ganglion Cysts ; Ganglioneuroma ; Gastrointestinal Tract ; Humans ; Intestine, Large ; Male ; Mucous Membrane ; Neurofibromatosis 1 ; Neurons ; Polyps ; S100 Proteins

OBJECTIVE: Cerebral endothelial cells have unique biological features and are fascinating candidate cells for stroke therapy. METHODS: In order to understand the molecular mechanisms of human cerebral endothelial cell (hCMEC/D3) transplantation in a rat stroke model, we performed proteomic analysis using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein expression was confirmed by quantitative real-time PCR and Western blot. RESULTS: Several protein spots were identified by gel electrophoresis in the sham, cerebral ischemia (CI), and CI with hCMEC/D3 treatment cerebral ischemia with cell transplantation (CT) groups, and we identified 14 differentially expressed proteins in the CT group. Proteins involved in mitochondrial dysfunction (paraplegin matrix AAA peptidase subunit, SPG7), neuroinflammation (peroxiredoxin 6, PRDX6), and neuronal death (zinc finger protein 90, ZFP90) were markedly reduced in the CT group compared with the CI group. The expression of chloride intracellular channel 4 proteins involved in post-ischemic vasculogenesis was significantly decreased in the CI group but comparable to sham in the CT group. CONCLUSION: These results contribute to our understanding of the early phase processes that follow cerebral endothelial cell treatment in CI. Moreover, some of the identified proteins may present promising new targets for stroke therapy.
Animals ; Blotting, Western ; Brain ; Brain Ischemia ; Cell Transplantation ; Cell- and Tissue-Based Therapy ; Electrophoresis ; Endothelial Cells* ; Fingers ; Humans* ; Ischemia ; Mass Spectrometry ; Neurons ; Proteomics ; Rats* ; Real-Time Polymerase Chain Reaction ; Stroke ; Transplants

BACKGROUND: The long-term prognosis of BK virus-associated nephropathy (BKVAN) in kidney transplant recipients (KTRs) is uncertain. We evaluated the long-term prognosis in KTRs with BKVAN and the clinical significance of BKVAN on post-transplant clinical outcome. METHODS: We retrospectively analyzed the medical records of 582 patients who underwent kidney transplant (KT) between 2001 and 2014. We divided the patients into a BKVAN group (15 patients) diagnosed by allograft biopsy and a control group (356 patients). RESULTS: The incidence of BKVAN was 4.0%, and the mean follow-up duration was 93.1 ± 52.3 months. Median time from KT to BKVAN diagnosis was 5.9 months (interquartile range [IQR], 4.4–8.7). In the BKVAN group, 9 (60.0%) KTRs with combined acute rejection progressed to graft failure, and the median time from BKVAN diagnosis to graft failure was 36.2 months (IQR, 9.7–65.5). Death-censored graft survival rate and patient survival rate in the BKVAN group were significantly lower than those in the control group. BKVAN and rejection were independent risk factors for graft failure. In the subgroup analysis, death-censored graft survival rate of KTRs with BKVAN with acute rejection was significantly worst in comparison with similar patients without BKVAN regardless of acute rejection (P < 0.001). CONCLUSION: The long-term prognosis of BKVAN with acute rejection was very poor because of graft failure caused by inadequate treatment for acute rejection considering BKVAN. Therefore, we should carefully monitor the allograft status of KTRs through regular surveillance tests after treatment for BKVAN with acute rejection.
Allografts ; Biopsy ; BK Virus ; Diagnosis ; Follow-Up Studies ; Graft Survival ; Humans ; Incidence ; Kidney Transplantation ; Kidney* ; Medical Records ; Prognosis* ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplant Recipients* ; Transplants