Subject(s)
Creutzfeldt-Jakob Syndrome/genetics , PrPSc Proteins/metabolism , Prions/genetics , Aged , Base Sequence , Blotting, Western , Brain/metabolism , Brain/pathology , Creutzfeldt-Jakob Syndrome/pathology , Creutzfeldt-Jakob Syndrome/physiopathology , Fatal Outcome , Female , Humans , Molecular Sequence Data , Mutation , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , PrPSc Proteins/genetics , Prion ProteinsABSTRACT
Doppel protein (Dpl) is a paralog of the cellular form of prion protein (PrP(C)). Its ectopic expression in the CNS elicits significant cerebellar Purkinje cell degeneration in some lines of PrP knockout mice. However, little is known about the Dpl-mediated neurodegenerative mechanism. To understand the molecular and intracellular pathways underlying Purkinje cell degeneration, here, we investigated the regulation of calcium-release channel protein, type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) gene in Ngsk mice. These knockout mice express high levels of Dpl and eventually develop cerebellar degeneration. We observed that the expression level of IP(3)R1 gene is reduced in the cerebella of Ngsk mice as early as 3 months of age compared with age-matched controls along with the reduction in DNA binding activity of nuclear factor of activated-T cells (NFAT) which is transcription factor of IP(3)R1. Notably, expression of PrP restored the reduced DNA binding activity of NFATc4 by Dpl. Reduced expressions of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptor subtype 2 or B (GluR2), which are regulated by NFATc4, were also restored by PrP expression. In light of these findings, we suggest a mechanism for Dpl-mediated Purkinje cell degeneration linked to reduced gene expression of proteins related to neuronal activity. Decrease in IP(3)R1 gene expression may lead to functional deficits and ultimately death of Purkinje cells in Ngsk mice.
Subject(s)
Cerebellar Diseases/metabolism , Inositol 1,4,5-Trisphosphate Receptors/genetics , Nerve Degeneration/metabolism , Prions/metabolism , Purkinje Cells/metabolism , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cerebellar Diseases/genetics , Cerebellar Diseases/physiopathology , Disease Models, Animal , Down-Regulation/genetics , GPI-Linked Proteins , Gene Expression Regulation/genetics , Mice , Mice, Knockout , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Nerve Degeneration/genetics , Nerve Degeneration/physiopathology , PrPC Proteins/genetics , PrPC Proteins/metabolism , Prions/genetics , Purkinje Cells/pathology , Receptors, AMPA/genetics , Receptors, AMPA/metabolismABSTRACT
Fluorescent probe techniques were used to evaluate the effect of bupivacaine.HCl on the physical properties (transbilayer asymmetric lateral and rotational mobilities, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. An experimental procedure was used based on selective quenching of both 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer (RET) from the tryptophans of membrane proteins to Py-3-Py. Bupivacaine.HCl increased the bulk lateral and rotational mobilities, and annular lipid fluidity in SPMVs lipid bilayers, and had a greater fluidizing effect on the inner monolayer than that of the outer monolayer. The magnitude of increasing effect on annular lipid fluidity in SPMVs lipid bilayer induced by bupivacaine.HCl was significantly far greater than magnitude of increasing effect of the drug on the lateral and rotational mobilities of bulk SPMVs lipid bilayer. It also caused membrane proteins to cluster. These effects of bupivacaine.HCl on neuronal membranes may be responsible for some, though not all, of the local anesthetic actions of bupivacaine.HCl.
Subject(s)
Anesthetics, Local/pharmacology , Bupivacaine/pharmacology , Cell Membrane/drug effects , Membrane Fluidity , Neurons/drug effects , Synaptosomes/drug effects , Animals , Cattle , Cell Membrane/physiology , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Cytoplasmic Vesicles/drug effects , Cytoplasmic Vesicles/physiology , Fluorescent Dyes , Neurons/physiology , Synaptosomes/physiologyABSTRACT
BACKGROUND: Previous studies on colorectal cancer risk suggest that obesity, serum lipids and glucose might be related to colorectal carcinogenesis. This case-control study was conducted to investigate the association between obesity, serum lipids and glucose, and the risk of advanced colorectal adenoma and cancer. METHODS: Patients with histologically confirmed colorectal cancers (n=105), same number of patients with advanced colorectal adenomas matched by age and sex, and the same number of controls matched by age and sex were selected in Hanyang University Guri Hospital between January 2002 and June 2004. RESULTS: Adenoma and cancer group showed significantly higher levels of mean body mass index and serum glucose. Cancer group also showed significantly lower mean serum lipids levels than controls. We used an unordered polytomous logistic model to calculate multivariate odds ratios for advanced adenoma and cancer relative to controls. Higher serum glucose level was more strongly associated with increased risk of cancer relative to controls (odds ratio, 3.0; 95% confidence interval, 0.9-9.8) than with increased risk of advanced adenoma (odds ratio, 2.1; 95% confidence interval, 0.9-5.4). Higher body mass index was strongly associated with increased risk of advanced adenoma (odds ratio, 10.8; 95% confidence interval, 4.6-25.3), but associated with attenuated risk of cancer (odds ratio, 2.3; 95% confidence interval, 0.9-5.8). Serum triglycerides and cholesterol levels were strongly associated with reduced risk of cancer (odds ratio, 0.3; 95% confidence interval, 0.1-0.8 and odds ratio, 0.2; 95% confidence interval, 0.1-0.6, respectively). CONCLUSIONS: Obesity and hyperglycaemia are positively related to advanced colorectal adenoma formation. Furthermore, hyperglycaemia plays an important role in progression to cancer. Findings on an inverse relationship between serum triglyceride and cholesterol levels and the risk of colorectal cancer may be the secondary results from metabolic or nutritional changes in advanced colorectal cancer patients and should be clarified in further studies.
Subject(s)
Adenomatous Polyps/blood , Adenomatous Polyps/complications , Blood Glucose/analysis , Colorectal Neoplasms/blood , Colorectal Neoplasms/complications , Lipids/blood , Obesity/complications , Body Mass Index , Case-Control Studies , Female , Humans , Hyperglycemia/blood , Korea , Male , Middle Aged , Multivariate Analysis , Risk FactorsABSTRACT
A diospyrobezoar is a type of phytobezoar that is considered to be harder than any other types of phytobezoars. Here, we describe a new treatment modality, which effectively and easily disrupted huge gastric diospyrobezoars. A 41-year-old man with a history of diabetes mellitus was admitted with lower abdominal pain and vomiting. Upper gastrointestinal endoscopy revealed three huge, round diospyrobezoars in the stomach. He was made to drink two cans of Coca-Cola every 6 h. At endoscopy the next day, the bezoars were partially dissolved and turned to be softened. We performed direct endoscopic injection of Coca-Cola into each bezoar. At repeated endoscopy the next day, the bezoars were completely dissolved.
Subject(s)
Bezoars/pathology , Bezoars/therapy , Carbonated Beverages , Diospyros/adverse effects , Stomach Diseases/pathology , Stomach Diseases/therapy , Administration, Oral , Adult , Bezoars/diet therapy , Bezoars/etiology , Endoscopy , Humans , Male , Stomach Diseases/diet therapyABSTRACT
Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.
Subject(s)
Autoantibodies/immunology , Cholangitis/immunology , Liver Cirrhosis, Biliary/immunology , Mitochondria/immunology , Cholangitis/pathology , Female , Humans , Liver Cirrhosis, Biliary/pathology , Middle AgedABSTRACT
This study was designed to test the activity and feasibility of 5'-deoxy-5-fluorouridine (5'-DFUR) and cisplatin combination therapy in the treatment of advanced gastric cancer. Nineteen patients with inoperable and/or metastatic gastric cancer, which was histologically proven, were orally administered 5'-DFUR 1,200 mg/m2 on days 1 to 4 and days 15-18 combined with 70 mg/m2 of cisplatin being repeated every 4 weeks. Five partial responses (PRs) were achieved. Seven patients had stable disease and 6 progressed on therapy. The overall response rate was 27.7% (95% confidence interval: 9.69% to 53.5%). The median survival duration of all 18 patients was 25 weeks (9-64). The majority of patients had WHO grade I/II toxicity, but there was no treatment-related death. These data support that the combinations of oral 5'-DFUR and cisplatin are well tolerable and have a moderate activity with low toxicity in the treatment of advanced gastric cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Drug Administration Schedule , Female , Floxuridine/administration & dosage , Humans , Infusions, Intravenous , Male , Middle AgedABSTRACT
A flat depressed early colon cancer (FDEC) is characterized by non-polypoid growth pattern, no association of adenomatous tissues and a tendency of even small lesions toward submucosal invasion and lymph node metastasis. It supports de novo carcinogenesis of colorectal cancer, although most colorectal cancers arise in pre-existing adenoma (adenoma-carcinoma sequence). There have been few reports of small depressed cancers because of the difficulty in colonoscopic detection and the rapid development to ulcerating advanced cancers. We report a case of flat depressed early colon cancer confined to mucosa detected by indigo carmine contrast colonoscopy.