The activation of neurotrophic signaling pathways following the upregulation of glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β family, has a potential neuroprotective effect in the adult brain. Herein, we report that hippocampal transduction of adeno-associated virus serotype 1 (AAV1) with a constitutively active form of ras homolog enriched in brain [Rheb(S16H)], which can stimulate the production of brain-derived neurotrophic factor (BDNF) in hippocampal neurons, induces the increases in expression of GDNF and GDNF family receptor α-1 (GFRα-1), in neurons and astrocytes in the hippocampus of rat brain in vivo . Moreover, upregulation of GDNF and GFRα-1 contributes to neuroprotection against thrombin-induced neurotoxicity in the hippocampus. These results suggest that AAV1-Rheb(S16H) transduction of hippocampal neurons, resulting in neurotrophic interactions between neurons and astrocytes, may be useful for neuroprotection in the adult hippocampus.

Quetiapine is an atypical antipsychotic drug that can cause sinus tachycardia, hypotension, coma, etc. with overdose, and rarely convulsions, rhabdomyolysis and neuroleptic malignant syndrome. Posterior reversible encephalopathy syndrome usually occurs in association with hypertension, but can occur rarely in rhabdomyolysis accompanied by acute kidney injury and arginine vasopressin axis hyperstimulation. We report the experience of a patient hospitalized with a quetiapine overdose who developed drug-induced rhabdomyolysis and reversible encephalopathy without hypertension after acute renal injury.

INTRODUCTION: Diffuse interstitial lung diseases (DILD) comprise of a large group of lung diseases with diverse etiologies. They are classified into four categories based on the etiology and pathological findings. In Korea, epidemiological data on DILD has never been reported in a prospective manner. METHOD: From May 2002 to April 2004, total 487 patients with DILD were prospectively registered at Samsung Medical Center. The prospective observational analysis of the etiologies, its classification based on 2002 ATS/ERS (American Thoracic Society/European Respiratory Society) guidelines, as well as diagnostic tests and the retrospective analysis of the treatment modalities were carried out. Any infectious and malignant causes were excluded. RESULTS: 1) The patients were classified into idiopathic interstitial pneumonia (IIP) in 269 patients (55.2%), known causes of DILD in 168 patients (34.5%), sarcoidosis in 27 patients (5.5%), other forms of DILD in 14 patients (2.9%), and undetermined DILD in 9 patients (1.9%). 2) The diagnostic test showed that most patients had undergone chest high resolution computed tomography (HRCT) and pulmonary function test (PFT) (97%, 89%). Transbronchial lung biopsy (TBLB) and surgical lung biopsy (SLB) were performed in limited patients (38%, 29%). 3) Among 269 patients with IIP, 220 (82%) had idiopathic pulmonary fibrosis (IPF) while 23 (9%) had nonspecific interstitial pneumonia. SLB was carried out in 36% of patients with IIP. 4) Symptomatic supportive care was given to 67% of IPF, but specific medical treatment including corticosteroids was administered to 89% of non-IPF patients. CONCLUSION: A nationwide registry of DILD patients is required to determine the annual incidence, etiology, and practice pattern of diagnosis and treatment in Korea.
Adrenal Cortex Hormones ; Biopsy ; Classification ; Diagnosis ; Diagnostic Tests, Routine* ; Humans ; Idiopathic Interstitial Pneumonias ; Idiopathic Pulmonary Fibrosis ; Incidence ; Korea ; Lung ; Lung Diseases ; Lung Diseases, Interstitial ; Respiratory Function Tests ; Retrospective Studies ; Sarcoidosis ; Thorax

PURPOSE: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor, and express the KIT protein. Previous studies have reported KIT phosphorylation to be the principal biological event in the tumoriogenesis of GIST, which is generally evoked by the conformational mutation of KIT receptors. The aim of this study was to evaluate the frequency and category of c-kit mutations and their prognostic relevance. METHODS: The frequency and category of the c-kit mutations and the correlation between clinical outcome and the c-kit mutations were analyzed and the significance of the c-kit mutations examined as independent prognostic factors in 84 cases of GIST. The c-kit mutations were measured by polymerase chain reaction and DNA sequencing, using an ABI 3700 sequencer. RESULTS: c-kit mutations were noted in 14 of the 84 cases (16.7%) of GIST. Mutations in exon 11 were found in 11 cases (78.6%), exon 9 in 2 (14.3%) and exon 13 in 1 (7.1%), but no mutation was noted in exon 17. Of the mutations in exon 11, missense mutations were observed in 9 cases and frameshift mutations in 2. Among the 14 cases with c-kit mutations, 1 (7.1%) was found in a very low risk patient, 4 (28.6%) in intermediate risk patients and 9 (64.3%) in high risk patients. The c-kit mutations were observed more frequently in high risk patients (P=0.0366). However, there was no significant difference between the c-kit mutations and the survival rate. CONCLUSION: These results suggest that kit mutations might have a pathogenetic role in GIST, 550~560 in exon 11 of c-kit gene is the conserving area of mutation and c-kit mutations are uncertain as prognostic factors in GIST. However, further study will be required.
Exons ; Frameshift Mutation ; Gastrointestinal Stromal Tumors* ; Humans ; Mutation, Missense ; Phosphorylation ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Survival Rate

PURPOSE: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor, and express the KIT protein. Previous studies have reported KIT phosphorylation to be the principal biological event in the tumoriogenesis of GIST, which is generally evoked by the conformational mutation of KIT receptors. The aim of this study was to evaluate the frequency and category of c-kit mutations and their prognostic relevance. METHODS: The frequency and category of the c-kit mutations and the correlation between clinical outcome and the c-kit mutations were analyzed and the significance of the c-kit mutations examined as independent prognostic factors in 84 cases of GIST. The c-kit mutations were measured by polymerase chain reaction and DNA sequencing, using an ABI 3700 sequencer. RESULTS: c-kit mutations were noted in 14 of the 84 cases (16.7%) of GIST. Mutations in exon 11 were found in 11 cases (78.6%), exon 9 in 2 (14.3%) and exon 13 in 1 (7.1%), but no mutation was noted in exon 17. Of the mutations in exon 11, missense mutations were observed in 9 cases and frameshift mutations in 2. Among the 14 cases with c-kit mutations, 1 (7.1%) was found in a very low risk patient, 4 (28.6%) in intermediate risk patients and 9 (64.3%) in high risk patients. The c-kit mutations were observed more frequently in high risk patients (P=0.0366). However, there was no significant difference between the c-kit mutations and the survival rate. CONCLUSION: These results suggest that kit mutations might have a pathogenetic role in GIST, 550~560 in exon 11 of c-kit gene is the conserving area of mutation and c-kit mutations are uncertain as prognostic factors in GIST. However, further study will be required.
Exons ; Frameshift Mutation ; Gastrointestinal Stromal Tumors* ; Humans ; Mutation, Missense ; Phosphorylation ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Survival Rate

PURPOSE: Paraffin-embedded tissue samples from the gastrointestinal tract, which had been diagnosed as tumors of a mesenchymal origin, were reviewed by an immunohistochemical staining method. The prognostic significances of the immunohistochemical subtypes and anatomical locations were also investigated. GIST, as a new grading system, was compared with the pre-existing system for its useful prognostic significance. METHODS: 122 cases were evaluated and classified by immunohistochemical staining for KIT, CD34, actin, desmin, vimentin, S-100 protein and NSE. RESULTS: Positivity for both KIT and CD34 of 92.6 and 73.8%, respectively, indicated that KIT was more effective for the diagnosis of GISTs. The stomach (62.3%) and small bowel (23.7%) were most common organs of GIST. There was no difference in the prognosis between these two organs. Immunophenotypically, the uncommitted, myoid, combined and neural types were 37.7, 23.7, 20.2 and 7%, respectively. There was no significant difference in the prognosis between these types. The old grading system showed no difference between the borderline and malignant groups (P=0.14), whereas, the new grading system showed a significant difference between the intermediate and high risk groups (P=0.01). CONCLUSION: KIT is more useful for the diagnosis of GOSTs. The immunophenotypical classification and anatomical location showed no prognostic significance in GISTs. Therefore, the new grading system might be more useful than older system.
Actins ; Classification ; Desmin ; Diagnosis* ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Immunohistochemistry* ; Prognosis ; S100 Proteins ; Stomach ; Vimentin