Gait Ignition Failure in JNPL3 Human Tau-mutant Mice

Cognitive impairments and motor dysfunction are commonly observed behavioral phenotypes in genetic animal models of neurodegenerative diseases. JNPL3 transgenic mice expressing human P301L-mutant tau display motor disturbances with age- and gene dose-dependent development of neurofibrillary tangles, suggesting that tau pathology causes neurodegeneration associated with motor behavioral abnormalities. Although gait ignition failure (GIF), a syndrome marked by difficulty in initiating locomotion, has been described in patients with certain forms of tauopathies, transgenic mouse models mirroring human GIF syndrome have yet to be reported. Using the open field and balance beam tests, here we discovered that JNPL3 homozygous mice exhibit a marked delay of movement initiation. The elevated plus maze excluded the possibility that hesitation to start in JNPL3 mice was caused by enhanced levels of anxiety. Considering the normal gait ignition in rTg4510 mice expressing the same mutant tau in the forebrain, GIF in JNPL3 mice seems to arise from abnormal tau deposition in the hindbrain areas involved in locomotor initiation. Accordingly, immunohistochemistry revealed highly phosphorylated paired helical filament tau in JNPL3 brainstem areas associated with gait initiation. Together, these findings demonstrate a novel behavioral phenotype of impaired gait initiation in JNPL3 mice and underscore the value of this mouse line as a tool to study the neural mechanisms and potential treatments for human GIF syndrome.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Evaluation of the Feasibility of Applying Metabolic Target Volume in 4D RT Using PET/CT Image / 의학물리

In this study, we evaluated feasibility of applying MTV (Metabolic Target Volume) to respiratory gated radiotherapy for more accurate treatment using various SUV (Standard Uptake Value) from PET images. We compared VOI (Volume of Interest) images from 50%, 30% and 5% SUV (standard uptake volume) from PET scan of an artificial target with GTV (Gross Tumor Volume) images defined by percentage of respiratory phase from 4D-CT scan for respiratory gated radiotherapy. It is found that the difference of VOI of 30% SUV is reduced noticeably comparing with that of 50% SUV in longitudinal direction with respect to total GTV of 4D-CT image. Difference of VOI of 30% SUV from 4D-PET image defined by respiratory phase from 25% inhalation to 25% exhalation, and GTV from 4D-CT with the same phase is shown below 0.6 cm in maximum. Thus, it is better to use 4D-PET images than conventional PET images for applying MTV to gated RT. From the result that VOI of 5% SUV from 4D-PET agrees well with reference image of 4D-CT in all direction, and the recommendation from department of nuclear medicine that 30% SUV be advised for defining tumor range, it is found that using less than 30% SUV will be more accurate and practical to apply MTV for respiratory gated radiotherapy.

The Effects of TWEAK, Fn14, and TGF-beta1 on Degeneration of Human Intervertebral Disc

OBJECTIVE: The purpose of this study is to explain the effect and reciprocal action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-beta1 (TGF-beta1) on degeneration of human intervertebral disc (IVD). METHODS: Human intervertebral disc tissues and cells were cultured with Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in 37degrees C, 5% CO2 incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an antagonistic receptor for TWEAK and TGF-beta1, the level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic acid (mRNA) levels were estimated by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: When human IVD tissue was cultured for nine days, the sGAG content was elevated in proportion to culture duration. The sGAG was decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9 mRNA levels decreased with TWEAK in IVD tissue TGF-beta1 20 ng/mL elevated the sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK was increased with Fn14 or TGF-beta1 but the result was insignificant statistically. TGF-beta1 increased the Sox9 mRNA expression to 180% compared to control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK were increased with TGF-beta1 in primary cultured IVD cells, however, Fn14 did not show increasing effect on Sox9 and versican. CONCLUSION: This study suggests that TWEAK would act a role in intervertebral disc degeneration through decreasing sGAG and the mRNA level of versican and Sox9.

A Complicated Case of Endovascular Stent Assisted Coil Embolization of an Aneurysm / 대한뇌혈관외과학회지

Endovascular coiling is one of the recent methods for treating cerebral aneurysm and this method is considered to be an alternative method for treating aneurysms. Yet there are several disadvantages of endovascular coiling. As is well known, a wide-necked aneurysm is not completely treated with endovascular coiling. Infarction of the parent artery due to coil compaction, recanalization and embolization is a significant problem of endovascular coiling for a wide-necked aneurysm. Wide-necked aneurysms have been recently treated with stent assisted coil embolization. Stent-assisted coil embolization results in a higher rate of complication. In this case report, we present a case with complication after stent-assisted endovascular coiling. We concluded that precise, cautious procedures are needed when performing complicated stent assisted endovascular coiling to prevent thromboembolic complications.

A Case of Haemophilus parainfluenzae Endocarditis / 대한임상미생물학회지

The HACEK group of bacteria (Haemophilus parainfluenzae, H. aphrophilus, H. paraphrophilus, Actinobacilus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corodens, and Kingella kingae) are the normal flora of the upper respiratory tract and oropharynx. The organisms infect abnormal cardiac valves, causing subacute native endocarditis or prosthetic valve endocarditis more than one year after valve surgery. Haemophilus species are responsible for only 0.5~1% of all infective endocarditis cases. Embolization occurs in 60% and the mortality rate ranges from 16~45% of cases of infective endocarditis caused by H. parainfluenzae. We experienced a case of infective endocarditis due to H. parainfluenzae in a 37-year-old male admitted with high fever, chills, nausea & vomiting, chest discomfort, and blurred vision. The organism was isolated from a blood culture and was identified as H. parainfluenzae by factor V requirement, negativity at urea, positivity at ornithine decarboxylase, and acid production from glucose and maltose. The patient was treated with antibiotics and symptoms and signs were improved

Modified FOLFOX-6 Chemotherapy for Recurrent or Inoperable Gastric Cancer Patients

PURPOSE: We wanted to evaluate the efficacy and toxicity of modified FOLFOX-6 chemotherapy for treating recurrent or inoperable gastric cancer patients. MATERIALS AND METHODS: From April 2006 to August 2007, 35 patients with recurrent gastric cancer after curative resection and 43 patients with inoperable gastric cancer underwent chemotherapy, and the results were retrospectively investigated. RESULTS: 78 patients were assessable for response and toxicity, and they underwent an average of 7.1 cycles of chemotherapy. The response was evaluated according to the RECIST criteria. 11 partial responses (14.1%), 35 cases of stable disease (44.9%), and 32 cases of progressive disease (41%) were observed. The median time to progression was 6 months, and the average overall survival was 13 months. CTCAE grade 1 or 2 anemia (52.6%) was the most prevalent toxicity. Other common toxicities included thrombocytopenia (17.9%) and peripheral neuropathy (30.8%). There were 13 changes in the chemotherapy regimen to S1-cisplatin due to disease progression, but only an average of 1.76 cycles of S1-cisplatin were delivered due to severe toxicities and poor compliance. CONCLUSION: Acceptable efficacy and toxicity were seen as 59% of the patients showed non-progression, and no grade 3 or 4 toxicities were observed. In conclusion, the modified FOLFOX-6 chemotherapy is considered to be the proper 1st-line choice as a palliative treatment for recurrent or inoperable gastric cancer patients.

Stomach Cancer Secondary to Hematologic Diseases

PURPOSE: Patients with hematologic diseases such as chronic myeloid leukemia (CML) or chronic lymphoid leukemia (CLL) are known to have an increased chance of acquiring a secondary neoplasm. Stomach cancer is one of the most common malignant diseases in Korea, and we investigated whether the incidence of secondary stomach cancer in patients with a hematologic disease increases, in order to determine if a more intensive screening program for detecting secondary gastric cancer was required. We also investigated the safety of performing a gastrectomy in hematologic disease patients. MATERIALS AND METHODS: From 1992 to 2006, the medical records of 8376 patients diagnosed with one of the six common hematologic diseases were reviewed. RESULTS: Nine secondary stomach cancers were found among the 8376 patients during the 15-year observation period. No surgical-related complications occurred, and there was no recurrence of stomach cancer if detected early. CONCLUSION: It seems that a more intensive screening program for detecting secondary gastric cancer in hematologic disease patients is not required, and surgery is not risky in these patients.

Evaluation of the DG Gel System using the Microtube Column Agglutination Technique for Antibody Screening and Identification / 대한수혈학회지

BACKGROUND: For the antibody screening test, the classical LISS tube indirect antiglobulin test has been replaced by the microtube column agglutination system in Korea. This system was first created in 1990 by Lapierre and it is distributed through DiaMed (DiaMed Ag, Cresssier, Morat, Switzerland) around the world. Similar systems, such as Ortho BioVue, have been developed and competed after that. We evaluated a newly developed microtube column agglutination system, DG Gel (Diagnostic Grifols, Barcelona, Spain), and we compare it with the other established systems. METHODS: In a comparative study, a total of 126 samples, including 76 antibody screening positive samples and 50 negative samples, were tested in parallel by the LISS/Coombs card (DiaMed Ag, Cresssier, Morat, Switzerland) and the DG Gel microtube column agglutination system. The positive samples that were proved by the LISS/Coombs card and the DG Gel system were identified by the ID-Dia panel (DiaMed Ag, Cresssier, Morat, Switzerland) and Identisera Diana (Diagnostic Grifols, Barcelona, Spain). Discrepant samples were rechecked with I, II and III cells that were supplied by the panel of the Korea Red Cross Blood Center. RESULTS: Among the 126 samples, the DG Gel antibody screening system showed 98.7% (75/76) sensitivity and 100% (50/50) specificity. We obtained concordant results in 75 samples (98.7%) and discrepant results in one sample (1.32%) between the DG Gel and DiaMed-ID for antibody identification. CONCLUSION: Both the microtube column agglutination systems work well and showed high estimated sensitivity and specificity with high concordance. Therefore, the DG gel microtube column agglutination system can be used with good results.

Evidence for Cyclooxygenase-2 Association with Caveolin-3 in Primary Cultured Rat Chondrocytes

The purpose of this study was to demonstrate the cellular localization of cyclooxygenase-2 (COX-2) and caveolin-3 (Cav-3) in primarily cultured rat chondrocytes. In normal rat chondrocytes, we observed relatively high levels of Cav-3 and a very low level of COX-2 mRNA and protein. Upon treating the chondrocytes with 5 microM of CdCl2 (Cd) for 6 hr, the expressions of COX-2 mRNA and protein were increased with the decreased Cav-3 mRNA and protein expressions. The detergent insoluble caveolae-rich membranous fractions that were isolated from the rat chondrocytes and treated with Cd contained the both proteins of both COX-2 and Cav-3 in a same fraction. The immuno-precipitation experiments showed complex formation between the COX-2 and Cav-3 in the rat chondrocytes. Purified COX-2 with glutathione S-transferase-fused COX-2 also showed complex formation with Cav-3. Confocal and electron microscopy also demonstrated the co-localization of COX-2 and Cav-3 in the plasma membrane. The results from our current study show that COX-2 and Cav-3 are co-localized in the caveolae of the plasma membrane, and they form a protein-protein complex. The co-localization of COX-2 with Cav-3 in the caveolae suggests that the caveolins might play an important role for regulating the function of COX-2.

Epidemiology of Respiratory Viral Infection in 2004-2006 / 대한진단검사의학회지

BACKGROUND: The information on the incidence, seasonal variation and clinical pattern of respiratory virus infections is very important for clinicians in managing their patients. This study was aimed to define the epidemiology of respiratory viral pathogens in Seoul and the neighboring areas from March 2004 to February 2006. METHODS: A total of 6,533 specimens were cultured for respiratory viruses during the study period. Madin-Darby canine kidney (MDCK), LLC-MK2, and HEp-2 cells, or R-mix cells (Diagnostic Hybrids Inc., Athens, Ohio, USA) were used for culture. Influenza virus types A & B (Inf A & B), parainfluenza virus (PIV), respiratory syncytial virus (RSV), and adenovirus (ADV) were identified by indirect immuno-fluorescent staining. Medical records of the patients with positive virus cultures were reviewed retrospectively. RESULTS: One or more viral agents were isolated from 1682 specimens (25.7%). The pathogens identified were RSV 37.2%, ADV 19.9%, Inf A 18.9%, PIV 17.5% and Inf B 6.4%. The most frequent pathogen of pneumonia and acute bronchiolitis was RSV and that of croup was PIV. Upper respiratory tract infections were more prevalent in adults and the most frequently caused by influenza virus. Influenza virus itself was more frequently isolated in children less than six years old, which was different from previous reports. Influenza virus was mostly isolated in the winter and spring, while RSV was usually isolated from early fall with a peak incidence in the winter. Inf A and RSV showed a dampening effect on the occurrence of other viruses during their major epidemic. PIV was mostly detected in the spring and summer. ADV was isolated throughout the whole year. CONCLUSIONS: The epidemiological characteristics of respiratory virus infections in Seoul and the neighboring areas in 2004-2006, were similar to the findings of previous reports except for some minor changes. These findings could be useful to clinicians in managing their patients.

Clinical characteristics of rapidly progressive glomerulonephritis / 대한내과학회지

BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is microscopically characterized by formation of crescents in more than 50% of glomeruli observed. The patients usually move on rapidly to renal failure and the prognosis is not favorable. But there was only a few study because of the rarity in incidence. METHODS: We reviewed and analyzed the records of 15 patients diagnosed as crescentic glomerulonephritis (CrGN) by renal biopsy from March 1990 to December 2003. RESULTS: Fifteen out of 1055 biopsy cases were CrGN including 6 (40%) of pauci-immune glomerulonephritis (PIGN) and 9 (60%) of immune complex glomerulonephritis (ICGN). Underlying diseases of PIGN were: unknown 2, Wegener's granulomatosis 2, focal segmental glomerulosclerosis 1, and rectal cancer 1. For ICGN were: IgA nephropathy 3, lupus nephritis class IV 3, Henoch-Schonlein purpura 2, and HBV-associtated membranoproliferative glomerulonephritis type I. The incidence of major manifestation in PIGN vs. ICGN was respectively: hypertension 50% vs. 22.2%, nephrotic syndrome 50% vs. 88.9%, percents of crescents 73.9% vs. 57.3%. The levels of BUN (mg/dL) and serum creatinine (mg/dL) were higher in PIGN as 76.8 +/- 14.3 and 6.6 +/- 1.2 vs. 26.9 +/- 8.9 and 1.6 +/- 0.3 in ICGN. With methylprednisolone pulse, 5 out of 7 patients showed some improvement in their renal function. A case of Wegener's granulomatosis taken oral prednisolone and another case of lupus nephritis given cyclophosphamide pulse also had relatively favorable course. At the end of follow-up, the more crescents they had the higher creatinine level (r=0.711, p<0.01). CONCLUSION: RPGN manifested nephrotic syndrome commonly and many of them progressed to the chronic kidney disease or even developed end stage renal disease. But appropriate immunosuppre- ssive treatment could help to preserve renal function. When considering the proportion of crescentic glomeruli, it was related to the worse prognosis. It is necessary to make an effort to diagnose early and treat vigorously.

Clinical courses of the adult patients with idiopathic membranous nephropathy / 대한내과학회지

BACKGROUND: Idiopathic membranous nephropathy (IMN) causes variable clinical courses, such as from asymptomatic urinary abnormalities, nephrotic syndrome to end-stage renal failure. We evaluated clinical findings and effects of steroid and steroid with chlorambucil in patients with IMN. METHODS: We reviewed 37 cases of biopsy-proven patents of IMN whose follow-up duration was at least 2 years, retrospectively. The mean follow-up duration of the cases was 74 +/- 49 months. In the cases of steroid therpy, prednisolone 40, 50 or 60 mg/day was given for maximal 16 weeks. Steroid-chlorambucil treatment was done for the cases of no response or relapse after steroid therapy, severe nephrotic syndrome or elevated serum creatinine more than 1.2 mg/dL. We did 3 cycles of treatment. Every cycle was consisted of intravenous 1 gram of methylprednisolone for 3 days followed by prednisolone 0.5 mg/kg/day orally for 27 days then chlorambucil 0.2 mg/kg/day for 28 days. Therapeutic results were evaluated. RESULTS: The mean age was 41 +/- 15 years and 5-6th decade was 48.6%. Male to female ratio was 1.3 : 1. Nephrotic syndrome was in 86.5% in the cases. The results of prednisolone therapy was done in 25 cases were 20% of complete remission (CR), 28% of patial remission (PR) and 52% of no respone (NR). There was no difference between the response rate and dosage of prednisolone. Steroid-chlorambucil therapy was done in 18 cases totally, 5 cases in the first treatment and 13 cases of no response or relapsed cases after prednisolone treatment. The results were 22.2% of CR, 50% of PR and 27.8% of NR. This results were no difference between steroid and chlorambucil combined therapy. Spontaneous remission was observed 35.1% of the total cases, 21.6% of spontaneous CR and 13.5% of spontaneous PR after the final observations. The final results were 16.2% of CR and 10.8% of PR after prednisolone or chlorambucil combined therapy. Progressive renal disease were developed in 6 cases (16.2%) and the mean renal surval time measured by projected reciprocal creatinine from diagnosis to the point of 0.1 was 129 +/- 79 months. CONCLUSION: Nephrotic syndrome was presented in 86.5% of cases and with high remission rates such as 37.8% of complete and 24.3% of partial remission in IMN. Progressive renal failure was occurred in 16.2% of cases and most of the cases progressed very slowly. There was no different results between steroid alone and chlorambucil combined therapy.

Frequency Due to Bladder Amyloidosis in Patients with Rheumatoid Arthritis: Two Cases Reports / 대한류마티스학회지

Secondary amyloidosis is characterized by accumulation of an amorphous proteinous material in the various tissue and organs with infectious disease or inflammatory disease. Symptoms of the amyloidosis are variable according to the involved organs. Reactive amyloidosis of bladder in rheumatoid arthritis (RA) is a rare condition with hematuria in the most cases. However, we report two cases of patients with RA, who have frequency due to secondary amyloidosis of bladder without hematuria. Therefore secondary amyloidosis of urinary bladder should be considered as a possible cause of frequency in patients with long-term RA.

Esophageal Cancer Metastasis to the Kidney

We report a case of 54-year-old man who presented with a right renal tumor secondary to an esophageal cancer, which was detected during a periodic follow-up computerized tomographic examination. In December 2000, the patient underwent a transhiatal esophagectomy with a cervical esophagogastrostomy and a histological examination showed an infiltrative squamous carcinoma (T3N1M0, stage III). The patient was treated with 6 cycles of adjuvant chemotherapy with 5-FU (500 mg/m2) and cisplatinum (40 mg/m2). Subsequently, a follow-up study revealed no evidence of recurrence until December 2001. In June 2002, he attended a follow-up examination and complained of general weakness and a 3 kg weight loss over a month. CT scan detected a hypodense space occupying lesion in the inferior pole of the right kidney and enlarged aortocaval lymph nodes below the right renal vein. Intravenous pyelography showed a phantom calyx in the inferior pole after a contrast infusion. The cystoscopic examination was negative. He underwent a right nephrectomy and a periaortic lymph node dissection under the impression of a metachronous transitional cell carcinoma. However, a histological examination revealed that the tumor was a metastatic squamous carcinoma with lymph nodes involvement from the previous esophageal squamous carcinoma.