Aantifungal agents were tested against 30 clinical isolates of Cryptococcus neoformans var. neoformans using the NCCLS method (M27-A2). Posaconazole, itraconazole and amphotericin B had lower MIC than the remaining four antifungal agents. The MIC result for posaconazole was over 220-fold lower active than fluconazole. Fluconazole MICs for most isolates fell within the dose-dependant range. The overall MIC ranges and MIC50s were amphotericin B (0.03-0.25; 0.25), fluconazole (0.5-64; 16), itraconazole (0.015-1; 0.125), terbinafine (0.06->2; 1), caspofungin (8-32; 32), voriconazole (0.015-0.5; 0.25), and posaconazole (0.015-0.25; 0.06 microg/ml), respectively. In conclusion, the MIC50s of these drugs did not exhibit any sign of an upward shift with the exception of fluconazole and tendency cross-resistance between the seven drugs was not observed. We conclude that in vitro resistance to antifungal agents has not significantly changed despite the recent wide-spread use of triazoles for long-term treatment of Cryptococcal meningitis.
Amphotericin B* ; Antifungal Agents ; Cryptococcus neoformans* ; Cryptococcus* ; Fluconazole* ; Itraconazole* ; Meningitis, Cryptococcal ; Triazoles

Purpose: Reliable landmarks of ankle syndesmosis change in various positions is important for managing ankle injury. The purpose of our study was to investigate and compare radiographic landmarks of normal ankle in various positions. Methods: The study involved both ankle radiographs of 30 subjects (15 males, 15 females) without clinical or radiographic abnormality. Tibiofibular clear space (TFCS) and tibiofibular overlap (TFO) were measured on anteroposterior (AP) and mortise radiographs in non-standing (NS) and standing (S) neutral and dorsiflexion 10° (DF10) and 20° (DF20). The radiographic measurements were used to calculate means, standard deviations, and intra- and interobserver reliabilities, and compare TFCS and TFO in various positions and genders. Results: On the AP view, the mean TFCS in NS, S, DF10, and DF20 positions were 4.00±0.97, 4.00±0.83, 4.35±0.95, and 4.45±0.89 mm and the mean TFO on the same positions were 6.58±2.27, 4.27±1.90, 3.44±1.96, and 2.38±1.91 mm. On the mortise view, the mean TFCS in NS, DF10, and DF20 positions were 3.62±0.88, 4.08±0.86, and 3.88±0.97 mm and the mean TFO on the same positions were 3.57±2.13, 2.31±1.77, and 3.57±2.14 mm. The reliabilities in all positions except TFCS on some positions were excellent. No measurement was significantly different between females and males except TFO in NS on mortise view (p=0.006) and DF10 on AP view (p=0.032). Conclusion Increase of TFCS and decrease of TFO on AP view reflects syndesmosis change from NS to DF20 on standing. Clinically, the effect of weight-bearing and reliability of TFO should be considered.

Ammonia excretion in the renal collecting duct is critical in the regulation of the acid-base homeostasis. A novel family of ammonium transporter protein, Rh B Glycoprotein (RhBG) was recently identified in the mouse and rat kidney collecting duct. The purpose of this was to examine the ultrastructural localization of RhBG in the collecting duct. Rat kidneys were processed for light and electron microscope immunocytochemistry using anti-RhBG rabbit polyclonal antibody. Strong RhBG immunolabeling was observed in the basolateral plasma membrane of type A intercalated cells in the collecting duct. In contrast, RhBG labeling was very weak or negative in type B intercalated cells and principal cells. Transmission electron microscopy confirmed that RhBG immunostaining was located mainly in the basolateral plasma membrane and infoldings of type A intercalated cells, but very weak in type B cells. RhBG labeling was not observed in the apical plasma membrane both in type A and B cells. These results demonstrate that RhBG is a basolateral transporter in acid-secreting type A cells and may mediate ammonia excretion in the collecting duct.
Ammonia ; Ammonium Compounds* ; Animals ; B-Lymphocytes ; Cell Membrane ; Glycoproteins ; Homeostasis ; Humans ; Immunohistochemistry ; Kidney Tubules, Collecting* ; Kidney* ; Mice ; Microscopy, Electron, Transmission ; Rats*

Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3beta has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3beta-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3beta. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3beta in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3beta-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation.
Adenine ; Alzheimer Disease ; Autophagy ; Glycogen ; Glycogen Synthase ; Glycogen Synthase Kinase 3 ; Glycogen Synthase Kinases ; Neurofibrillary Tangles ; Phosphorylation ; Trehalose

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured

Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.
Autopsy* ; Diagnosis ; Frontotemporal Dementia* ; Frontotemporal Lobar Degeneration ; Humans ; Korea ; Motor Neuron Disease* ; Motor Neurons* ; Neurites ; Pathology

Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.
Autopsy* ; Diagnosis ; Frontotemporal Dementia* ; Frontotemporal Lobar Degeneration ; Humans ; Korea ; Motor Neuron Disease* ; Motor Neurons* ; Neurites ; Pathology

BACKGROUND AND OBJECTIVES: Tympanic membrane perforation is an important clinical problem found in various populations of the world. In large number of cases, acute traumatic perforations heal spontaneously, and in the healing process, stem cells appear to play an important role. However, no studies have been reported regarding somatic stem cells in the tympanic membrane. Herein, we tried to show that guinea pig's tympanic membrane contains cells that display the characteristic features of stem cells. MATERIALS AND METHOD: The tympanic membrane was obtained from the guinea pig. The cells were cultured in a medium with epidermal growth factor (EGF) and fibroblast growth factor (FGF). Proliferating cells were checked with stem cell markers, bromodeoxyuridine (BrdU) and nestin. Differentiated cells from stem cells are checked with betaIII tubulin and S-100. RESULTS: We observed that some of the cultured cells from the tympanic membrane were stained with both stem cell markers, BrdU and nestin. And we observed that these cells differentiated into neuron and gilal cells, which expressed betaIII tubulin and S-100, respectively. CONCLUSION: These results suggest that the tympanic membrane of guinea pigs may have neural stem cells. Further study is needed for finding the origin of stem cells.
Adult ; Adult Stem Cells ; Animals ; Bromodeoxyuridine ; Cells, Cultured ; Epidermal Growth Factor ; Fibroblast Growth Factors ; Guinea ; Guinea Pigs ; Humans ; Intermediate Filament Proteins ; Nerve Tissue Proteins ; Neural Stem Cells ; Neurons ; Stem Cells ; Tubulin ; Tympanic Membrane ; Tympanic Membrane Perforation

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.