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1.
Neuropathol Appl Neurobiol ; 46(2): 125-141, 2020 02.
Article in English | MEDLINE | ID: mdl-31179553

ABSTRACT

AIMS: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. METHODS: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. RESULTS: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of ß-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. CONCLUSIONS: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.


Subject(s)
Forkhead Box Protein M1/metabolism , Gene Expression Regulation, Neoplastic , Meningioma/metabolism , Animals , Brain/metabolism , Cell Line, Tumor , Cell Proliferation , Disease Progression , Humans , Mice, Inbred BALB C , Mice, Nude , Neovascularization, Pathologic/metabolism , Progression-Free Survival
2.
Acta Anaesthesiol Scand ; 61(8): 935-941, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28707325

ABSTRACT

BACKGROUND: Pain is considered as being one cause of post-operative emergence agitation (EA) from sevoflurane anaesthesia. The purpose of this study was to investigate the pure effect of post-operative pain on EA after sevoflurane anaesthesia in preschool children undergoing excision of scalp nevi. METHODS: Forty-four children, 1-7 years old, undergoing scalp nevus excision were enrolled. Patients were randomly assigned to two groups: the remifentanil group received single intravenous injection of short-acting synthetic opioid, remifentanil 1 µg/kg just before the scalp incision, and the block group received scalp nerve block with 0.25% ropivacaine after intubation. The end-tidal sevoflurane concentration was maintained around 1.5 vol% unless the mean arterial pressure is out of ±20% range of preoperative values during surgery in both groups. Watcha behaviour scale for EA and face, legs, activity, cry, consolability (FLACC) scale scores for pain were recorded post-operatively. RESULTS: There was no difference in end-tidal sevoflurane concentration between the two groups during surgery and the emergence period. Agitation incidence and scores were not different between the two groups during the recovery period. FLACC scale was significantly lower in the block group than in the remifentanil group at post-anaesthesia care unit (PACU) arrival, at 10 and 20 min after PACU arrival, respectively. CONCLUSION: The scalp nerve block decreased the early post-operative pain after paediatric nevus excision, but it did not decrease the incidence of EA with sevoflurane anaesthesia.


Subject(s)
Nerve Block , Nevus/surgery , Pain, Postoperative/prevention & control , Psychomotor Agitation/prevention & control , Scalp/innervation , Scalp/surgery , Amides , Anesthetics, Inhalation , Anesthetics, Intravenous , Anesthetics, Local , Child , Child Behavior , Child, Preschool , Emergence Delirium , Female , Humans , Infant , Male , Methyl Ethers , Pain, Postoperative/epidemiology , Pain, Postoperative/psychology , Piperidines , Prospective Studies , Psychomotor Agitation/epidemiology , Psychomotor Agitation/psychology , Remifentanil , Ropivacaine , Sevoflurane , Single-Blind Method
3.
Genet Mol Res ; 16(2)2017 May 25.
Article in English | MEDLINE | ID: mdl-28549200

ABSTRACT

Cell death-inducing DFF45-like effector (CIDE) B is a member of the CIDE family of apoptosis-inducing factors. In the present study, we detected a single nucleotide polymorphism (SNP), c.414G>A, which corresponds to the synonymous SNP 414Arg, in CIDE-B in the Berkshire pigs. We also analyzed the relationships between the CIDE-B SNP and various meat quality traits. The SNP was significantly associated with post-mortem pH24h, water-holding capacity (WHC), fat content, protein content, drip loss, post-mortem temperature at 12 h (T12) and 24 h (T24) in a co-dominant model (P < 0.05). A significant association was detected between the SNP and post-mortem pH24h, fat content, protein content, drip loss, shear force, and T24 in gilts; and color parameter b*, WHC, and T24 in barrows (P < 0.05). The SNP was significantly correlated with the fat content, and CIDE-B mRNA expression was significantly upregulated during the early stage of adipogenesis, suggesting that CIDE-B may contribute towards initiation of adipogenesis (P < 0.05). Furthermore, CIDE-B mRNA was strongly expressed in the liver, kidney, large intestine, and small intestine, and weakly expressed in the stomach, lung, spleen, and white adipose tissue. These results indicate that the CIDE-B SNP is closely associated with meat quality traits and may be a useful DNA marker for improving pork quality.


Subject(s)
Apoptosis Regulatory Proteins/genetics , Meat/standards , Quantitative Trait, Heritable , Swine/genetics , Animals , Apoptosis Regulatory Proteins/metabolism , Polymorphism, Single Nucleotide , RNA, Messenger/genetics , RNA, Messenger/metabolism
4.
Mol Plant Microbe Interact ; 29(12): 938-949, 2016 12.
Article in English | MEDLINE | ID: mdl-28001093

ABSTRACT

The nonprotein amino acid γ-aminobutyric acid (GABA) is the most abundant amino acid in the tomato (Solanum lycopersicum) leaf apoplast and is synthesized by Arabidopsis thaliana in response to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (hereafter called DC3000). High levels of exogenous GABA have previously been shown to repress the expression of the type III secretion system (T3SS) in DC3000, resulting in reduced elicitation of the hypersensitive response (HR) in the nonhost plant tobacco (Nicotiana tabacum). This study demonstrates that the GABA permease GabP provides the primary mechanism for GABA uptake by DC3000 and that the gabP deletion mutant ΔgabP is insensitive to GABA-mediated repression of T3SS expression. ΔgabP displayed an enhanced ability to elicit the HR in young tobacco leaves and in tobacco plants engineered to produce increased levels of GABA, which supports the hypothesis that GABA uptake via GabP acts to regulate T3SS expression in planta. The observation that P. syringae can be rendered insensitive to GABA through loss of gabP but that gabP is retained by this bacterium suggests that GabP is important for DC3000 in a natural setting, either for nutrition or as a mechanism for regulating gene expression. [Formula: see text] Copyright © 2016 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .


Subject(s)
Amino Acid Transport Systems/metabolism , Plant Diseases/immunology , Pseudomonas syringae/drug effects , Solanum lycopersicum/immunology , Type III Secretion Systems/drug effects , gamma-Aminobutyric Acid/pharmacology , Amino Acid Transport Systems/genetics , Arabidopsis/immunology , Arabidopsis/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Solanum lycopersicum/microbiology , Plant Diseases/microbiology , Plant Leaves/immunology , Plant Leaves/microbiology , Pseudomonas syringae/metabolism , Pseudomonas syringae/pathogenicity , Sequence Deletion , Nicotiana/immunology , Nicotiana/microbiology , Virulence
5.
Genet Mol Res ; 15(4)2016 Nov 03.
Article in English | MEDLINE | ID: mdl-27819726

ABSTRACT

Single nucleotide polymorphisms (SNPs) are useful genetic markers that allow correlation of genetic sequences with phenotypic traits. It is shown here that HSD17B4, a bifunctional enzyme mediating dehydrogenation and anhydration during ß-oxidation of long-chain fatty acids, contains a non-synonymous SNP (nsSNP) of chr2:128,825,976A>G, c.2137A>G, I690V, within the sterol carrier protein-2 domain of the HSD17B4 gene, by RNA-Seq of liver RNA. The HSD17B4 mRNA was highly expressed in the kidney and liver among various other tissues in four pig breeds, namely, Berkshire, Duroc, Landrace, and Yorkshire. The nsSNP was significantly associated with carcass weight, backfat thickness, and drip loss (P < 0.05). Furthermore, HSD17B4 may play a crucial role during the early stages of myogenesis when expression of its mRNA was significantly high. In conclusion, HSD17B4 may serve as a possible regulator of muscle development, and its identification should help to select for improved economic traits of Berkshire pigs such as carcass weight, backfat thickness, and drip loss.


Subject(s)
17-Hydroxysteroid Dehydrogenases/genetics , Genetic Association Studies , Meat/standards , Polymorphism, Single Nucleotide/genetics , Quantitative Trait, Heritable , Sus scrofa/genetics , Animals , Female , Gene Expression Regulation, Enzymologic , Liver/enzymology , Male , Mice , Real-Time Polymerase Chain Reaction
6.
Gene Ther ; 22(4): 325-32, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25588739

ABSTRACT

Gene therapy using RNA interference can be directed against tumors through various strategies, but has been hindered owing to the inefficiency of non-viral delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2 (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the polyethylenimine (PEI) and an ultrasound gene delivery method, human breast carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL-2Rγ(null)) mice. The results showed greater tumor regression (*P<0.05) as well as an increased survival rate in the group receiving ANT2 shRNA+two types of enhancer relative to the groups receiving ANT2 shRNA without enhancer. These findings demonstrate that the introduction of PEI and ultrasound with SonoVue exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI and ultrasound provided the best results with respect to tumor regression, the antitumor effects from the individual enhancers were approximately equivalent. In addition, we confirmed that there was no toxicity on aspartate aminotransferase and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen or creatine kinase levels in the kidney following the various gene delivery methods.


Subject(s)
Adenine Nucleotide Translocator 2/metabolism , Antineoplastic Agents/metabolism , Polyethyleneimine/pharmacology , RNA, Small Interfering/metabolism , Animals , Cell Line, Tumor/drug effects , Gene Transfer Techniques , Heterografts , Kidney/drug effects , Liver/drug effects , Mice , Microbubbles , Neoplasm Transplantation , RNA, Small Interfering/toxicity , Ultrasonic Therapy
7.
Opt Express ; 23(7): 9464-76, 2015 Apr 06.
Article in English | MEDLINE | ID: mdl-25968775

ABSTRACT

We report in-plane slotted patch antenna-coupled electro-optic phase modulators with a carrier-to-sideband ratio (CSR) of 22 dB under an RF power density of 120 W/m(2) and a figure of merit of 2.0 W(-1/2) at the millimeter wave frequencies of 36-37 GHz based on guest-host type of second-order nonlinear polymer SEO125. CSR was improved more than 20 dB by using a SiO(2) protection layer. We demonstrate detection of 3 GHz modulation of the RF carrier. We also derive closed-form expressions for the modulated phase of optical wave and carrier-to-sideband ratio. Design, simulation, fabrication, and experimental results are discussed.

8.
Appl Opt ; 53(1): 51-63, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-24513989

ABSTRACT

Using a simple optical setup to detect and characterize transmission gratings in the far field, we demonstrate that going beyond the diffraction limit is not possible using linear interaction of nonclassical illumination with the target grating. We also confirm that nonlinear optical interactions with the target grating, or with the optical medium around it, do allow improvement in resolution.

9.
Int J Tuberc Lung Dis ; 28(8): 367-373, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39049169

ABSTRACT

BACKGROUNDLittle is known about the level of physical activity (PA) among patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), the relationship between PA levels and NTM-PD, and the relationship between handgrip strength and NTM-PD.METHODSWe conducted a case-control study comparing the PA levels and handgrip strength of patients with NTM-PD and controls. Patients with NTM-PD were prospectively enrolled at Severance Hospital, Seoul, whereas controls were selected at a 1:2 propensity score matching from the Korea National Health and Nutrition Examination Survey conducted between 2014 and 2019. Multivariate logistic regression analysis was conducted to evaluate these relationships.RESULTSThe total PA level in the NTM-PD group was lower than that in the control group (120.0 vs. 560.0 MET-min/week, P < 0.001). Physical inactivity was significantly associated with both NTM-PD (aOR 2.87, 95% CI 1.73-4.75) and severity of NTM-PD (aOR 3.82, 95% CI 1.61-9.05; cavity ≥1). Low handgrip strength was found to be associated with NTM-PD (aOR 2.14, 95% CI 1.14-4.02), but no significant association was observed with the severity of NTM-PD.CONCLUSIONSPhysical inactivity was associated with both NTM-PD and NTM-PD severity, whereas low handgrip strength was associated with NTM-PD..


Subject(s)
Hand Strength , Mycobacterium Infections, Nontuberculous , Humans , Male , Female , Middle Aged , Case-Control Studies , Mycobacterium Infections, Nontuberculous/epidemiology , Republic of Korea/epidemiology , Aged , Prospective Studies , Sedentary Behavior , Lung Diseases/physiopathology , Lung Diseases/microbiology , Exercise/physiology , Adult
10.
Endoscopy ; 45(2): 106-13, 2013.
Article in English | MEDLINE | ID: mdl-23212727

ABSTRACT

BACKGROUND AND STUDY AIMS: Endoscopic bilateral drainage for inoperable malignant hilar biliary strictures (HBS) using metal stents is considered to be technically difficult. Furthermore, endoscopic revision of bilateral stenting after occlusion can be challenging. This study was performed to evaluate the long-term efficacy of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents in high-grade malignant HBS and planned endoscopic bilateral revision. PATIENTS AND METHODS: A total of 84 patients with inoperable high-grade malignant HBS were enrolled from three academic tertiary referral centers. Two cross-wired metal stents were inserted using a bilateral stent-in-stent placement method. Bilateral endoscopic revision was also performed during follow-up using either identical metal stents or plastic stents. The main outcome measurements were technical and functional success, complications, stent patency, and endoscopic revision efficacy. RESULTS: The technical and clinical success rates of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents were 95.2% (80/84) and 92.9% (78/84), respectively. Median patency (range) and survival were 238 days (10-429) and 256 days (10-1130), respectively. Obstruction of primary bilateral stents occurred in 30.8% (24/78) of patients with functionally successful stent placement. The technical and clinical success rates of planned bilateral endoscopic revision for occluded stents were 83.3% (20/24) and 79.2% (19/24), respectively. For revision, bilateral metallic stents were placed in 11 patients (55.0%); the remaining patients received plastic stents. CONCLUSIONS: Palliative endoscopic bilateral stent-in-stent placement of cross-wired metallic stents was effective in patients with inoperable HBS. Revision endoscopic bilateral stenting may be feasible and successful in cases where the primary deployed metal stents are occluded.


Subject(s)
Bile Duct Neoplasms/complications , Bile Ducts, Intrahepatic , Cholangiocarcinoma/complications , Cholestasis, Intrahepatic/therapy , Drainage/methods , Gallbladder Neoplasms/complications , Prosthesis Implantation/methods , Stents , Aged , Aged, 80 and over , Cholestasis, Intrahepatic/etiology , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Metals , Middle Aged , Prospective Studies , Prosthesis Design , Prosthesis Failure , Prosthesis Implantation/adverse effects , Reoperation , Stents/adverse effects , Time Factors
11.
Endoscopy ; 44(1): 60-5, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22127960

ABSTRACT

INTRODUCTION: Selective cannulation fails in approximately 3 % of endoscopic retrograde cholangiography (ERC) procedures. An endoscopic ultrasound-guided rendezvous technique (EUS - RV) may salvage failed cannulation. The aims of the current study were to determine the safety and efficacy of EUS - RV. METHODS: A total of 40 patients underwent salvage EUS - RV. EUS - RV was attempted immediately after failed biliary cannulation. A dilated intra- or extra-hepatic biliary duct (IHBD or EHBD) was punctured from the stomach or the small intestine under EUS guidance followed by cholangiography and antegrade manipulation of the guide wire into the small intestine. Finally, the echoendoscope was exchanged for an appropriate endoscope and biliary cannulation was achieved over or adjacent to the guide wire. RESULT: EUS-RV appears safe and effective and may be considered as a primary salvage technique after failed cannulation. Antegrade manipulation of the guide wire into the small intestine was achieved in 29 of 40 patients (73 %; EHBD 25 /31 and IHBD 4/9). The reasons for failure were inability to advance the guide wire through an obstruction or a native ampulla. Re-attempt at ERC immediately after failed EUS - RV was made in seven of the 11 patients, and was successful in four. The remaining seven patients underwent percutaneous drainage within 3 days. Complications occurred in five patients (13 %), including pancreatitis, abdominal pain, pneumoperitoneum, and sepsis/death, which was unlikely to be related to the procedure. CONCLUSION: EUS - RV is safe and effective and should be considered as a primary salvage technique after failed cannulation. Immediate re-attempt at ERC after failed EUS - RV is warranted, as EUS-guided cholangiogram can facilitate biliary cannulation in some cases. Finally, prompt alternative biliary drainage should be available.


Subject(s)
Bile Duct Diseases/surgery , Cholangiography/methods , Endoscopy, Digestive System/methods , Salvage Therapy/methods , Ultrasonography, Interventional , Abdominal Pain/etiology , Adult , Aged , Aged, 80 and over , Bile Duct Diseases/diagnostic imaging , Bile Ducts/diagnostic imaging , Catheterization/methods , Cholangiography/adverse effects , Drainage/methods , Endoscopy, Digestive System/adverse effects , Female , Humans , Male , Middle Aged , Pancreatitis/etiology , Pneumoperitoneum/etiology , Retrospective Studies , Salvage Therapy/adverse effects
12.
Colorectal Dis ; 14(5): 611-5, 2012 May.
Article in English | MEDLINE | ID: mdl-21752174

ABSTRACT

AIM: Various techniques have been described for performing a pudendal nerve block (PNB) and have associated problems such as multiple needle injections, the need for special equipment and consumption of time. This study aimed to describe a nerve-stimulator-guided PNB using a pararectal approach and to evaluate the safety and the efficacy of that procedure. METHOD: We conducted a prospective study of 53 patients who underwent a PNB from December 2009 to July 2010. With the index finger of the left hand inserted into anus, we guided the nerve stimulator needle along the second finger tip on the ischial spine to the site where the maximal contraction of the external anal sphincter could be felt. Once the position of the needle tip had been confirmed, the desired drug was injected. Of the 53 patients, a cohort of eight underwent manometry before and after the pudendal block. RESULTS: A total of 53 patients underwent the nerve-stimulator-guided procedure: 13 patients for pudendal neuralgia and the other 40 patients for anorectal disease. The mean maximal resting and squeezing pressures before the block were 55 and 161 mmHg, respectively, compared with 35 and 67 mmHg after the block. The PNB took just minutes to perform, was well tolerated by the patients, and resulted in neither severe complications nor repeated attempts. CONCLUSION: Nerve-stimulator-guided PNB using a pararectal approach proved to be easy and safe, with acceptable patient tolerance. In addition, it can be used for a variety of anorectal procedures where relaxation of anal tone is required.


Subject(s)
Anal Canal/surgery , Autonomic Nerve Block/methods , Electric Stimulation , Pudendal Nerve , Adult , Aged , Aged, 80 and over , Anal Canal/physiology , Autonomic Nerve Block/adverse effects , Bupivacaine , Electromyography , Female , Humans , Male , Manometry , Middle Aged , Prospective Studies , Pudendal Neuralgia/therapy , Triamcinolone , Young Adult
13.
Endoscopy ; 43(8): 702-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21425042

ABSTRACT

BACKGROUND AND STUDY AIMS: Endoscopic transpapillary gallbladder drainage for symptomatic gallbladder disease is a safe and effective bridge therapy in patients at high risk for surgery or who have terminal liver disease and are awaiting transplantation. However, there are few reports on long-term results in terms of stent patency and clinical course. Our study was designed to investigate the long-term patency and clinical course after endoscopic transpapillary gallbladder stenting (ETGS) in patients with symptomatic gallbladder disease. PATIENTS AND METHODS: A total of 29 patients who were unsuitable for cholecystectomy underwent ETGS from June 2006 to March 2010 using a 7-Fr double-pigtail stent between the gallbladder and the duodenum. Their clinical progress, adverse events, and stent patency after ETGS were recorded prospectively in two tertiary referral centers. RESULTS: Technically, ETGS was successful in 23 (79.3%) of the 29 patients. The mean procedure time was 22.4 ± 11.5 min. Postprocedure adverse events were mild pancreatitis (8.7%) and cholestasis (8.7%), all of which resolved with conservative management. During the follow-up period (median 586 days, range 11-1403 days), 20 patients were analyzed as per protocol, and scheduled follow-up was performed. Late adverse events developed in four patients (20%), including distal migration (n = 2), cholangitis (n = 1), and recurrent biliary pain (n = 1). The remaining 16 patients were followed for more than 12 months (nine patients were followed for more than 24 months). Median stent patency was 760 days, as determined by the Kaplan-Meier method. CONCLUSIONS: As a primary therapy, ETGS is technically feasible and effective in patients who are unsuitable for cholecystectomy. ETGS may also provide long-term stent patency without the need for scheduled stent exchanges.


Subject(s)
Drainage/methods , Endoscopy, Digestive System/methods , Gallbladder Diseases/surgery , Stents , Adult , Aged , Aged, 80 and over , Cholestasis/etiology , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pancreatitis/etiology , Prospective Studies , Prosthesis Failure , Stents/adverse effects , Treatment Outcome
14.
Gut ; 58(12): 1680-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19240063

ABSTRACT

Autoimmune pancreatitis (AIP) is distinct from calcifying and obstructive forms of chronic pancreatitis. Clinically and histologically it has two distinct subsets: (i) lymphoplasmacytic sclerosing pancreatitis or type 1 AIP which appears to be a systemic disease characterised by abundant infiltration of affected organs with immunoglobulin G4 (IgG4)-positive plasma cells and (2) duct-centric or type 2 AIP characterised by granulocyte epithelial lesions in the pancreas without systemic involvement. In AIP a marked lymphoplasmacytic infiltrate that responds dramatically to steroid therapy suggests an autoimmune aetiology. However, the target autoantigen(s) and the effector cells in AIP remain speculative. Despite the consistent elevation in serum IgG4 levels and tissue infiltration with IgG4-positive plasma cells in type 1 AIP, the role of IgG4 in its pathogenesis remains unknown. Recent development of animal models of AIP will help improve our understanding of the pathogenesis of these newly described forms of chronic pancreatitis.


Subject(s)
Autoimmune Diseases/diagnosis , Pancreatitis, Chronic/diagnosis , Aged , Animals , Autoantibodies/analysis , Autoimmune Diseases/drug therapy , Autoimmune Diseases/etiology , Disease Models, Animal , Female , Genetic Predisposition to Disease , Glucocorticoids/therapeutic use , Humans , Immunity, Cellular , Male , Middle Aged , Pancreatitis, Chronic/drug therapy , Pancreatitis, Chronic/etiology
15.
Br J Cancer ; 101(10): 1658-63, 2009 Nov 17.
Article in English | MEDLINE | ID: mdl-19826418

ABSTRACT

BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m(-2); days 1 and 3), leucovorin (400 mg m(-2); day 1), and 5-FU (2000 mg m(-2); days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m(-2); day 1), leucovorin (400 mg m(-2); day 1), and 5-FU (2000 mg m(-2); days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n=31) or mFOLFOX (n=30) regimen. The six-month survival rates were 27% (95% confidence interval (CI)=13-46%) and 30% (95% CI=15-49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI=10-42%) and 17% patients (95% CI=6-35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Deoxycytidine/administration & dosage , Deoxycytidine/therapeutic use , Disease-Free Survival , Drug Resistance, Neoplasm , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Survival Rate , Treatment Outcome , Gemcitabine
16.
Science ; 219(4589): 1233-5, 1983 Mar 11.
Article in English | MEDLINE | ID: mdl-6131537

ABSTRACT

Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry. The majority of these neurons localized to area X of Rexed contact ependyma. Thus, spinal AADC neurons have the enzymatic capacity to catalyze directly the conversion of the amino acids tyrosine, tryptophan, or phenylalanine to their respective amines tyramine, tryptamine, or phenylethylamine. These amines normally present in the central nervous system may be of potential clinical significance as endogenous psychotomimetics.


Subject(s)
Aromatic-L-Amino-Acid Decarboxylases/metabolism , Biogenic Amines/metabolism , Brain/metabolism , Spinal Cord/metabolism , Animals , Neurons/enzymology , Neurotransmitter Agents/biosynthesis , Rats
17.
Science ; 285(5433): 1579-82, 1999 Sep 03.
Article in English | MEDLINE | ID: mdl-10477524

ABSTRACT

Photoperiodic responses in plants include flowering that is day-length-dependent. Mutations in the Arabidopsis thaliana GIGANTEA (GI) gene cause photoperiod-insensitive flowering and alteration of circadian rhythms. The GI gene encodes a protein containing six putative transmembrane domains. Circadian expression patterns of the GI gene and the clock-associated genes, LHY and CCA1, are altered in gi mutants, showing that GI is required for maintaining circadian amplitude and appropriate period length of these genes. The gi-1 mutation also affects light signaling to the clock, which suggests that GI participates in a feedback loop of the plant circadian system.


Subject(s)
Arabidopsis Proteins , Arabidopsis/genetics , Arabidopsis/physiology , Circadian Rhythm , Genes, Plant , Plant Proteins/genetics , Cloning, Molecular , Crosses, Genetic , DNA-Binding Proteins/genetics , Darkness , Feedback , Gene Expression Regulation, Plant , Light , Molecular Sequence Data , Mutation , Photoperiod , Plant Leaves/physiology , Plant Proteins/chemistry , Plant Proteins/physiology , Plant Structures/physiology , Sequence Deletion , Transcription Factors/genetics
18.
Endoscopy ; 41(10): 842-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19798610

ABSTRACT

BACKGROUND AND STUDY AIMS: Although endoscopic ultrasound (EUS)-guided transmural drainage (EUD) is preferred over conventional transmural drainage (CTD) of pancreatic pseudocysts by endoscopy in many centers, its superiority with respect to technical success and clinical outcome has not yet been demonstrated in a prospective randomized trial. We conducted this prospective randomized trial to compare the technical success and clinical outcomes of EUD and CTD in treating pancreatic pseudocysts. PATIENTS AND METHODS: A total of 60 consecutive patients with pancreatic pseudocysts were randomly divided into two groups to undergo either EUD (n = 31) or CTD (n = 29) of pancreatic pseudocysts. The technical success rate, complications, and short-term and long-term results were prospectively evaluated. RESULTS: The rate of technical success of the drainage was higher for EUD (94 %, 29/31) than for CTD (72 %, 21/29; P = 0.039) in intention-to-treat analysis. In cases where CTD failed (n = 8), because the pseudocysts were nonbulging, a crossover was made to EUD, which was successfully performed in all these patients. Complications occurred in 7 % of the EUD and 10 % of the CTD group ( P = 0.67). During short-term follow-up, pseudocyst resolution was achieved in 97 % (28/29) in the EUD group and in 91 % (19/21) in the CTD group ( P = 0.565). Long-term results analyzed on a per-protocol basis showed no significant difference in clinical outcomes between EUD (89 %, 33/37) and CTD (86 %, 18/21, P = 0.696). CONCLUSIONS: We found that EUD and CTD can both be considered first-line methods of endoscopic transmural drainage of bulging pseudocysts, whereas EUD should be preferred for nonbulging pseudocysts.


Subject(s)
Drainage/methods , Endosonography , Pancreatic Pseudocyst/diagnostic imaging , Pancreatic Pseudocyst/surgery , Aged , Cholangiopancreatography, Endoscopic Retrograde , Female , Humans , Male , Middle Aged , Treatment Outcome
19.
Gut ; 57(12): 1704-12, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18583399

ABSTRACT

BACKGROUND: Autoimmune pancreatitis (AIP) is a peculiar type of chronic pancreatitis that responds dramatically to steroid therapy. To date, there are no worldwide consensus criteria for AIP. Different criteria with institutional preference (HISORt, revised Kim and the revised Japanese criteria) are being used to diagnose AIP, and there is controversy regarding the inclusion of steroid responsiveness in the diagnostic criteria. In contrast to the HISORt and revised Kim criteria, the revised Japanese criteria do not include steroid responsiveness as a diagnostic component. AIMS: This study was performed to evaluate whether "a 2-week steroid trial and subsequent assessment of its response" is a useful diagnostic tool for the differentiation of AIP from pancreatic cancer. A further aim was to discover the surgical and clinical outcome for a patient who followed the treatment algorithm based on the steroid responsiveness. PATIENTS AND METHODS: From January 2004 to June 2007, in the setting of clinically suspected AIP, 22 consecutive patients with atypical imaging for AIP, while not meeting the classic imaging criteria for pancreatic cancer, were challenged to undergo 2 weeks of steroid therapy (0.5 mg/kg of oral prednisolone per day). After the 2-week steroid trial, steroid responsiveness was assessed based on a marked improvement of narrowing of the main pancreatic duct and a reduction of the pancreatic mass. The steroid trial was continued in the case of positive steroid responsiveness, whereas surgical exploration was conducted in the case of negative steroid responsiveness. The final diagnosis was made by surgical exploration or long-term clinical and radiological follow-up. RESULTS: All patients (n = 15) who responded to steroids were diagnosed as having AIP, whereas all patients (n = 7) who did not show a response to steroids were confirmed as having pancreatic cancer. Complete resection was possible in all (6/6; 100%), except one individual who refused surgery. CONCLUSION: In the clinical setting of suspected AIP with the continued need for differentiation from pancreatic cancer due to atypical imaging for AIP, "a 2-week steroid trial and subsequent assessment of its response" may be helpful in confirming the diagnosis of AIP without negative consequences for resectable pancreatic cancer. However, a steroid trial should be performed carefully only by specialists in pancreatology.


Subject(s)
Autoimmune Diseases/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Pancreatitis/diagnostic imaging , Steroids , Adult , Aged , Autoimmune Diseases/drug therapy , Diagnosis, Differential , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/drug therapy , Pancreatitis/drug therapy , Prospective Studies , Reproducibility of Results , Steroids/administration & dosage , Tomography, X-Ray Computed , Treatment Outcome
20.
Hand Surg Rehabil ; 38(1): 59-66, 2019 02.
Article in English | MEDLINE | ID: mdl-30401613

ABSTRACT

Hand osteoarthritis reduces a person's ability to perform work activities and return to their occupation. We investigated the effects of a finger exercise program on hand grip strength, pain, physical function, and stiffness in automobile manufacturing workers with hand osteoarthritis. This randomized controlled trial was conducted on 29 subjects. Fifteen experimental subjects received a finger exercise program with paraffin baths, while 14 control subjects received only paraffin baths. Hand grip strength, pain, physical function, and stiffness were assessed at baseline and 8 weeks later. In the experimental group, hand grip strength (P < 0.001) and Australian/Canadian osteoarthritis hand index (AUSCAN) scores (pain, P < 0.001; stiffness, P < 0.001; physical function, P < 0.001) were significantly improved by 3.52 ± 2.03, 21.6 ± 8.3 (pain), 16.8 ± 10.21 (stiffness), and 13.86 ± 4.54 (physical function) compared with preintervention values. In the control group, hand grip strength (P = 0.004) and AUSCAN scores (pain, P < 0.001; stiffness, P = 0.019; physical function, P < 0.001) were significantly improved by 0.57 ± 0.62, 7.85 ± 5.46 (pain) 11.42 ± 7.18 (stiffness), and 10.28 ± 14.41 (physical function) compared with preintervention values. Significant differences between groups were found for postintervention hand grip strength (P = 0.015) and AUSCAN index subscale scores (pain, P < 0.001; physical function, P = 0.020). A combined finger exercise and paraffin bath program is effective in reducing pain, improving physical function, and increasing hand grip strength in workers with hand osteoarthritis.


Subject(s)
Exercise Therapy , Hand/physiopathology , Osteoarthritis/rehabilitation , Automobiles , Baths , Combined Modality Therapy , Disability Evaluation , Hand Strength , Humans , Middle Aged , Occupations , Osteoarthritis/physiopathology , Pain Measurement , Paraffin , Range of Motion, Articular
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