Autophagic failure promotes the exocytosis and intercellular transfer of alpha-synuclein

The accumulation of abnormal protein aggregates is a major characteristic of many neurodegenerative disorders, including Parkinson's disease (PD). The intracytoplasmic deposition of alpha-synuclein aggregates and Lewy bodies, often found in PD and other alpha-synucleinopathies, is thought to be linked to inefficient cellular clearance mechanisms, such as the proteasome and autophagy/lysosome pathways. The accumulation of alpha-synuclein aggregates in neuronal cytoplasm causes numerous autonomous changes in neurons. However, it can also affect the neighboring cells through transcellular transmission of the aggregates. Indeed, a progressive spreading of Lewy pathology among brain regions has been hypothesized from autopsy studies. We tested whether inhibition of the autophagy/lysosome pathway in alpha-synuclein-expressing cells would increase the secretion of alpha-synuclein, subsequently affecting the alpha-synuclein deposition in and viability of neighboring cells. Our results demonstrated that autophagic inhibition, via both pharmacological and genetic methods, led to increased exocytosis of alpha-synuclein. In a mixed culture of alpha-synuclein-expressing donor cells with recipient cells, autophagic inhibition resulted in elevated transcellular alpha-synuclein transmission. This increase in protein transmission coincided with elevated apoptotic cell death in the recipient cells. These results suggest that the inefficient clearance of alpha-synuclein aggregates, which can be caused by reduced autophagic activity, leads to elevated alpha-synuclein exocytosis, thereby promoting alpha-synuclein deposition and cell death in neighboring neurons. This finding provides a potential link between autophagic dysfunction and the progressive spread of Lewy pathology.

Development of Brugada Syndrome Following Photodynamic Therapy in a Patient with Cholangiocarcinoma

Brugada syndrome can be unmasked by several conditions including a febrile state, marked leukocytosis, and electrolyte disturbances. Herein, we describe a 62-year-old man with cholangiocarcinoma in the first reported case of Brugada syndrome onset following photodynamic therapy.

Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers

Parkinson's disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of alpha-synuclein. Previous studies have suggested that DA can interact with alpha-synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and alpha-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human alpha-synuclein produces non-fibrillar, SDS-resistant oligomers, while beta-sheet-rich fibril formation is inhibited. Pharmacologic elevation of the cytoplasmic DA level increased the formation of SDS-resistant oligomers in DA-producing neuronal cells. DA promoted alpha-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of alpha-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of alpha-synuclein oligomers may contribute to the progressive loss of the dopaminergic neuronal population and the pronounced neuroinflammation observed in the SNpc in patients with PD.

Comparison of (18F)FDG PET/CT and CT/MRI for the Diagnosis of Recurrent or Metastatic Disease after Treatment: In Head and Neck Cancer Patients

PURPOSE: We evaluated the accuracy of 18FFDG PET/CT for the detection of recurrence or metastasis after treatment in patients with primary head and neck cancer, and compared the results with those of CT/MRI. MATERIALS AND METHODS: We studied 34 patients with the diagnosis of head and neck cancer, who underwent treatment and follow up with 18FFDG PET/CT and CT/MRI. The patients were divided into two subgroups based on the difference in follow-up time interval and the type of treatment. Accuracy was evaluated by follow-up information and histopathology findings. The results of the 18FFDG PET/CT and CT/MRI were compared by statistical analysis. RESULTS: For the 18FFDG PET/CT results, 19 FDG uptake lesions were detected in 17 patients. Among these lesions, 18 were confirmed as recurrent or metastatic lesions and one as an inflammatory reaction from radiation therapy. Four lesions that had high FDG uptake were not detected by the CT/MRI. The sensitivity and specificity were 100% and 94.4% for the 18FFDG PET/CT and 77.8% and 94.4% for the CT/MRI (p<0.05). For the subgroup that received radiation therapy, 18FFDG PET/CT was more sensitive than CT/MRI (sensitivity = 100% vs. 63.6%, p<0.05). CONCLUSION: The results of this study showed that 18FFDG PET/CT was a useful screening modality for detecting recurrent or metastatic disease after treatment of patients with head and neck cancer, especially post-radiation.

Occult Papillary Thyroid Carcinoma Analysis: 214 Cases

PURPOSE: Occult papillary thyroid carcinomas (OPC) are defined as tumors measuring 0.5 cm in size. Therefore, we prefer near-total or total thyroidectomy with central lymph node dissection. Early detection and treatment of OPC might be warranted by the routine use of thyroid USG and USG-guided FNA.

Usefulness of MR Cholangiopancreatography after Intravenous Morphine Administration

PURPOSE: We wanted to assess the usefulness of MRCP after intravenous morphine administration in the evaluation of the hepatopancreatic pancreatico-biliary ductal system. MATERIALS AND METHODS: We studied 15 patients who were suspected of having disease of hepatopancreatic ductal system and they did not have any obstructive lesion on ultrasonography and/or CT. MRCP was acquired before and after morphine administration (0.04 mg/kg, intravenously). Three radiologists scored the quality of the images of the anatomic structures in the hepatopancreatic ductal system. We directly compared the quality of the images obtained with using the two methods and the improvement of the artifacts by pulsatile vascular compression. RESULTS: The MRCP images obtained after intravenous morphine administration were better than those obtained before morphine administration for visualizing the hepatopancreatic ductal system. On direct comparison, the MRCP images obtained after morphine administration were better in 12 cases, equivocal in two cases, and the images before morphine administration were better in only one case. In three patients, MRCP before morphine injection showed signal loss at the duct across the pulsatile hepatic artery. In two of three patients, MRCP after morphine injection showed no signal loss in this ductal area. CONCLUSION: MRCP after intravenous morphine administration enables physicians to see the hepatopancreatic ductal system significantly better and the artifacts caused by pulsation of the hepatic artery can be avoided.

Treatment of Malignant Gastroduodenal Obstruction with Using a Newly Designed Complex Expandable Nitinol Stent: Initial Experiences

PURPOSE: We wanted to evaluate the usefulness of a new type of a complex expandable nitinol stent that was designed to reduce the stent's propensity to migration during the treatment of malignant gastroduodenal obstructions. MATERIALS AND METHODS: Two types of expandable nitinol stent were constructed by weaving a single thread of 0.2 mm nitinol wire in a tubular configuration: an uncovered stent 18mm in diameter and a covered stent 16mm in diameter. Both ends of the covered stent were fabricated by coaxially inserting the covered stent into the tubular uncovered stent and then attaching the two stents together with using nylon monofilament. Under fluoroscopic guidance, the stent was placed in 29 consecutive patients (20 men and 9 women, mean age: 65 years) who were suffering with malignant gastric outlet obstruction (n=20), duodenal obstruction (n=6) or combined obstruction (n=3). Clinical improvement was assessed by comparing the food intake capacity before and after the procedure. The complications were investigated during the follow up period. RESULTS: Stent placement was successful in all the patients. After stent placement, the symptoms improved in all but one patient. During the follow up, stent migration occurred in one patient (3%) at 34 days after the procedure. Despite the stent migration, the patient was able to resume a soft diet. Six patients developed recurrent symptoms of obstruction with tumor overgrowth at a mean of 145 days after the procedure; all the patients underwent coaxial placement of an additional stent with good results. One patient showed recurrence of obstruction due to tumor in-growth, and this was treated by placement of a second stent. Two patients with stent placement in the duodenum suffered from jaundice 26 days and 65 days, respectively, after their procedures. CONCLUSION: Placement of the newly designed complex expandable nitinol stent seems to be effective for the palliative treatment of malignant gastroduodenal obstructions. The new stent also seems to help overcome the disadvantage of the increased migration observed for the covered stent.

CT Findings of Gastrointestinal Stromal Tumor versus Lymphoma of the Small Intestine

PURPOSE: To compare CT features of gastrointestinal stromal tumors (GIST) with those of lymphomas in the small intestine. MATERIALS AND METHODS: CT findings of 11 pathologically confirmed GIST patients and 10 lymphoma patients were retrospectively reviewed. CT findings were analyzed with regard to location, size, margin, growth patterns, internal character, enhancement, invasion, vascular encasement, lymphadenopathy, intestinal obstruction and ascites. RESULTS:An extraluminal mass was present in 82% (9/11) of the GIST patients versus 30% (3/10) of the lymphoma patients. Circumferential wall thickening was observed in 80% (8/10) of the lymphoma patients (p.05). CONCLUSION: Features revealed by CT scans are highly useful in differentiating GIST from lymphoma of the small intestine. Extraluminal growth and internal necrosis or gas are more common in patients with GIST compared with lymphoma. CT features of circumferential wall thickening and associated lymphadenopathy are more common in patients with lymphoma.

Percutaneous Radiofrequency Ablation of Inoperable Primary Lung Cancer

PURPOSE: To present the initial experience of percutaneous radiofrequency ablation (RFA) of inoperable primary lung cancer, and to assess the technical feasibility and potential complications. MATERIALS AND METHODS: Twenty patients with inoperable lung cancer underwent percutaneous RFA. Nineteen of 20 patients had stage III or IV non-small cell lung cancer, and the remaining one had stage I lung cancer with pulmonary dysfunction. The mean tumor size was 4.6+/-0.4 cm (range, 1.8-8.4 cm). RFA was performed with a single (n=18) or cluster (n=2) cool-tip RF electrode and a generator under CT guidance using local anesthesia and conscious sedation. Twenty tumors were treated in 28 sessions. Patients were assessed by contrast-enhanced CT in all cases at 1 week, 1 month, and 3 months. Eleven patients received chemotherapy (n=10) or radiotherapy (n=1) after RFA. RESULTS: RFA was technically successful and well tolerated in all patients. Complete necrosis was attained in 7 lesions (35%), near complete (90-99%) necrosis in 10 lesions (50%), and partial (50-89%) necrosis in 3 lesions (15%). During the mean follow up of 202 days (21 to 481 days), tumor size was decreased in 13 patients, unchanged in 3, and increased in 4. In the latter four, additional RFA was performed. One patient underwent surgery three months after RFA and the histopathologic findings showed a large cavity with thin fibrotic wall suggestive of complete necrosis. During or after the procedure, pneumothorax (n=10), moderate pain (n=4), blood tinged sputum (n=2), and pneumonia (n=2) were developed. Chest tube drainage was required in only 1 patient due to severe pneumothorax. Other patients were managed conservatively. Seven patients died at 61 to 398 days (mean, 230 days) after RFA. The remaining 13 patients were alive 21 to 481 days (mean, 187 days) after RFA. CONCLUSION: RFA appears to be a technically feasible and relatively safe procedure for the cytoreductive treatment of inoperable, non-small cell lung cancer and warrants further investigation as a complementary treatment to chemotherapy or radiation therapy.

Cardiovascular Responses to Endotracheal Intubation in Patients Receiving Desflurane Anesthesia for Anesthetic Induction / 대한마취과학회지

BACKGROUND: Desflurane is known to augment central and systemic sympathetic nervous activity. The present study was aimed at examining the effects of desflurane on cardiovascular responses to intubation. METHODS: Seventy-five ASA physical status I patients (aged 35-60 yr) were assigned randomly to receive one of three treatment regimens (n = 25 each): 1 minimum alveolar concentration (MAC) of sevoflurane, 1 MAC of desflurane or 2 MAC of desflurane. Anesthesia was induced with IV thiopental (5 mg/kg), while patients were ventilated with 100% oxygen. Tracheal intubation was facilitated with IV vecuronium (0.12 mg/kg). After intubation, patients received each anesthetic gas in oxygen via a semiclosed anesthesia circuit. Systolic arterial blood pressure (SAP), heart rate (HR) and rhythm, and plasma catecholamine concentrations were measured. RESULTS: The intubation resulted in immediate increases of SAP and HR in all groups; peak effects occurred within 1 min of the intubation. In addition, 2 MAC desflurane elicited a secondary hemodynamic effect at 3 to 5 min after the intubation. The plasma concentrations of norepinephrine increased significantly when measured at 1 min after intubation in all groups, and returned to preintubation values at 5 min in the 1 MAC desflurane groups, but showed further increases at 5 min in the 2 MAC group. CONCLUSIONS: These results show that 2 MAC desflurane elicits a biphasic hemodynamic response along with an augmented norepinephrine release, where the first appears within 1 min and the second at 3 to 5 min after intubation.

Transarticular Invasion of the Sacroiliac Joints by Malignant Pelvic Bone Tumors

PURPOSE: To describe modes of transarticular invasion, with reference to the size and location of a tumor, the anatomic characteristics of invaded cartilage, and the existence of ankylosis in SI joint. MATERIALS AND METHODS: Eleven histologically confirmed malignant pelvic bone tumors involving transarticular invasion of sacroiliac joints, were retrospectively analysed. Transarticular invasion of a joint was defined as involvement of its opposing bones. The anatomic site and size of the tumors were analysed, and invaded sacroiliac joint was divided into upper, middle and lower parts on the basis of the anatomic characteristics of the intervening cartilage: synovial hyaline or fibrous ligamentous. The existence of ankylosis was determined, and transarticular invasion directly across a joint was classified as direct invasion. Extension of tumors around a joint from its periphery to the opposing bone were considered as indirect invasion. RESULTS: All tumors were located near the sacroiliac joint, eight at the ilium and three at the sacrum. Six invasions were indirect and five were direct. Average tumor area was larger in indirect cases than in direct: 191.8 cm2 vs. 69.6 cm2. In all indirect invasions, a huge soft tissue mass abutted onto the peripheral portion of the sacroiliac joint. In five of six cases of indirect transarticular invasion, the upper part of the joint posteriorly located fibrous ligamentous cartilage. In the other, the lower part was invaded, and this involved a detour around the joint space, avoiding the invasion of intervening cartilage. Ankylosis occurred in one of the indirect cases. Among the five cases of direct invasion, there was invasion of the posteriorly located ligamentous fibrous cartilage in three without ankylosis. In the other two cases, involving ankylosis, the synovial hyaline cartilage was invaded directly at the lower part of the joint. CONCLUSION: Transarticular invasions of sacroiliac joint via fibrous cartilage are most common. Ankylosis of the sacroiliac joint facilitates hyaline cartilage invasion. We consider that in transarticular invasion of malignant pelvic bone tumors, indirect invasion is more common than direct.

Malignant Duodenal Obstructions: Palliative Treatment with Covered Expandable Nitinol Stent

PURPOSE: To evaluate the feasibility and clinical effectiveness of using a polyurethane-covered expandable nitinol stent in the palliative treatment of malignant duodenal obstruction. MSTERIALS AND METHODS: Under fluoroscopic guidance, a polyurethane-covered expandable nitinol stent was placed in 12 consecutive patients with malignant duodenal obstructions. All presented with severe nausea and recurrent vomiting. The underlying causes of obstruction were duodenal carcinoma (n=4), pancreatic carcinoma (n=4), gall bladder carcinoma (n=2), distal CBD carcinoma (n=1), and uterine cervical carcinoma (n=1). The sites of obstruction were part I (n=1), part II (n=8), and part III (n=3). Due to pre-existing jaundice, eight patients with part II obstructions underwent biliary decompression prior to stent placement. An introducer sheath with a 6-mm outer diameter and stents 16 mm in diameter were employed, and to place the stent, an after-loading technique was used. RESULTS: Stent placement was technically successful in ten patients, and no procedural complications occurred. In one of two patients in whom there was technical failure, and in whom the obstructions were located in part III, the stent was placed transgastrically. Stent migration occurred in one patient four days after the procedure, and treatment involved the placement of a second, uncovered, nitinol stent. After stent placement, symptoms improved in all patients. During follow-up, obstructive symptoms [due to stent stenosis (n=1), colonic obstruction (n=1), and multiple small bowel obstructions (n=1)] recurred in three patients. Two of these were treated by placing additional stents in the duodenum and colon, respectively. One of the eight patients in whom a stent was placed in the second portion of the duodenum developed jaundice. The patients died at mean 14 (median, 9) weeks after stent placement. CONCLUSION: The placement of a polyurethane-covered expandable nitinol stent seems to be technically feasible, safe and effective for the palliative treatment of malignant duodenal obstructions.

Intraosseous Neurilemmoma of the Sternum: A Case Report

Intraosseous neurilemmoma is a rare benign neoplasm that accounts for less than 1% of all primary bone tumors. The most frequent site of involvement is the mandible. We report a case of intraosseous neurilemmoma of the sternum which was discovered incidentally.

Rapidly Growing Mature Teratoma in the Anterior Mediastinum: Case Report

Mature teratoma is a benign tumor composed of a number of different types of well-differentiated tissues. Mature teratomas of the mediastinum usually grow slowly and are commonly asymptomatic. We report a case of mediastinal mature teratoma with rapid growth resulting in rupture

The Analysis of Radiation Exposure of Hospital Radiation Workers / 대한방사선종양학회지

PURPOSE: This investigation was performed in order to improve the health care of radiation workers, to predict a risk, to minimize the radiation exposure hazard to them and for them to realize radiation exposure danger when they work in radiation area in hospital. METHODS AND MATERIALS: The documentations checked regularly for personal radiation exposure in four university hospitals in Pusan city in Korea between January 1, 1993 and December 31, 1997 were analyzed. There were 458 persons in this documented but 111 persons who worked less then one year were excluded and only 347 persons were included in this study. RESULTS: The average of yearly radiation exposure of 347 persons was 1.52+/-1.35 mSv. Though it was less than 50mSv, the limitaion of radiation in law but 125 (36%) people received higher radiation exposure than non-radiation workers. Radiation workers under 30 year old have received radiation exposure of mean 1.87+/-1.01 mSv/year, mean 1.22+/-0.69 mSv between 31 and 40 year old and mean 0.97+/-0.43 mSv/year over 41year old ( p<0.001). Men received mean 1.67+/-1.54 mSv/year were higher than women who received mean 1.13+/-0.61 mSv/year ( p<0.01). Radiation exposure in the department of nuclear medicine department in spite of low energy sources is higher than other departments that use radiations in hospital ( p<0.05). And the workers who received mean 3.69+/-1.81 mSv/year in parts of management of radiation sources and injection of sources to patient receive high radiation exposure in nuclear medicine department ( p<0.01). In department of diagnostic radiology high radiation exposure is in barium enema rooms where workers received mean 3.74+/-1.74 mSv/year and other parts where they all use fluoroscopy such as angiography room of mean 1.17+/-0.35 mSv/year and upper gastrointestinal room of mean 1.74+/-1.34 mSv/year represented higher radiation exposure than average radiation exposure in diagnostic radiology ( p<0.01). Doctors and radiation technologists received higher radiation exposure of each mean 1.75+/-1.17 mSv/year and mean 1.60+/-1.39 mSv/year than other people who work in radiation area in hospital ( p<0.05). Especially young doctors and technologists have the high opportunity to receive higher radiation exposure. CONCLUSION: The training and education of radiation workers for radiation exposure risks are important and it is necessary to rotate worker in short period in high risk area. The hospital management has to concern health of radiation workers more and to put an effort to reduce radiation exposure as low as possible in radiation areas in hospital.

Color Doppler Ultrasound of Hepatocellular Carcinoma: Evaluation of Recurrence after Transcatheter Arterial Chemoembolization

PURPOSE: To evaluate the efficacy of color and pulsed Doppler ultrasound (US) for the detection of arterial revascularization of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: One hundred and four histologically proven HCCs (0.7-12.5 cm, mean 4.14 cm) of 87 consecutive patients who had undergone TACE using a Lipiodol-chemoagent suspension were examined using color Doppler equipment. The criteria for diagnosing arterial revascularization of HCC were detection of inward blood vessels within HCC and demonstration by spectral Doppler US of pulsatile arterial flow within the vessel. Color Doppler US was prospectively performed using a multi-Hertz probe (2.5-5 Hz), and was followed by digital subtraction angiography (DSA). RESULTS: In 37 of 104 HCCs in 87 patients treated with TACE, color and spectral Doppler US demonstrated intratumoral arterial flows, with peak systolic velocity of 4.2-220 (mean, 59) cm/sec. DSA revealed neovascularity or tumor stains in 38 HCCs (3.4-12.5 cm, mean 5.9 cm in size) including 37 which on Doppler US showed arterial flow. The remaining 66 of 104 HCCs (0.7-6.3 cm, mean 3.2 cm) did not stain during DSA. Doppler US showed a false negative result in only one HCC (4.6 cm, located at segment VII of the Couinaud classification), which stained faintly during DSA. The sensitivity, specificity, and accuracy of color and spectral Doppler US used for the detection of recurrent HCC were 97.4%, 100%, and 99%, respectively. CONCLUSIONS: Color and spectral Doppler US is an effective method for the evaluation of arterial revascularization of HCC after TACE.

A Case of AML Atypical M2 with Granulocytic Sarcoma in the Meninges Induced Remission by All-Trans Retinoic Acid and Combined Chemotherapy / 대한혈액학회지

We repoarted a rare case of AML atypical M2 who developed granulocytic granulocyte sarcoma in the meninges which was induced complete remission with all-trans retinoic acid (ATRA), daunorubicin and cytosine arabinoside (Ara-C). Morphological and immunophenotypic study of leukemic cells in this patient suggested acute promyelocytic leukemia. However, leukemic clees lacked both t (15;17) and PML-RARalpha gene rearragement, rather showed t (8;21). The patient was diagnosed as AML atypical M2.

Six Cases of Congenital Absence of the Vagina Managed by McIndoe Operation / 대한산부인과학회잡지

Mullerian agenesis or dysgenesis, rare developmental anomaly presenting as primary amenorrhea, is characterized by absence of vagina and absence or rudimentary development of the uterus. Anatomic anomalies of the axial skeleton and kindney often accompany this psychologically devatating condition. There are various methods of surgical treatment for congenital absence of the vagina. The six cases reviewed in this paper were all treated with McIndoe technique. All of 6 women experienced satisfactory sexual activity and were satisfied with vaginal depth following vaginal creation using a split thickness skin graft technique. Despite the existence of several alternative methods, the McIndoe technique is a relatively simple and highly successful procedure and hence is still prefered by many surgeons.

Clinical Trial of Endoscopic Botulinum Toxin Injection for the Treatment of Primary Achalasia / 대한소화기내시경학회지

Primary achalasia is a disorder of swallowing in which the lower esophageal sphincter fails to relax. Traditional treatment methods are balloon dilatation and myotomy, but these methods have critical complications and even fatal including esophageal perforation, gastroesophageal reflux, and continuing dysphagia. Botulinum toxin, which has been used for dystonias of skeletal muscles, is presented as a new alternative treatment method for achalasia, aimed to lowering of LES pressure by Pasricha et al. They also reported that endoscopic botulinum toxin injection into LES was effective, safe, and simple method without any significant complication. We report 7 cases of primary achalasia treated with endoscopic botulinum toxin injection, who showed clinical improvement without any complication. We compared results of pre-treatment with those of post-treatment using botulinum toxin in the aspects of clinical, radiological, manometrical recording in these cases. Symptomatic improvement was shown in 4 cases(57.1%), symptom score was decreased from 7.43+/-0.53 to 4.43+/-2.51(p=0.03), The luminal diameter at esophagogastric junction increased from a mean of 3.21+/-0,99 mm to 5.14+/-0.90 mm (p=0.015), and luminal diameter at esophageal body decreased from a mean of 40.29+/-19.37 mm to 32.71+/-15.45 mm (p=0.015). In follow up manometric recording, peristaltic waves at the body were recovered in 2 cases(28.6%), gastroesophageal pressure gradient(AP) was non-significantly decreased from 6.30+/-4.0 mmHg to 3.12+/-4.47 mmHg (p=0.45). One patient complained of transient chest pain within one hour after the botulinum toxin injection, but she did not need any medication. We concluded that botulinum injection was a simple, safe, and effective therapeutic method for primary achalasia, even though further evaluatian should be performed in the much more cases and the results of long term follow-up, and cost-effectiveness of this method.

Ultrastructural and immunohistochemical studies of ameloblastoma

No abstract available.