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1.
Am J Transplant ; 17(3): 635-645, 2017 03.
Article in English | MEDLINE | ID: mdl-27598231

ABSTRACT

Belatacept is the first costimulatory blockade agent approved for maintenance immunosuppression in kidney transplant recipients. Clinical results have indicated that belatacept is associated with superior renal function and improved metabolic profile; however, higher incidence of acute rejection and posttransplant lymphoproliferative disorder are the shortcomings of this agent. In this study, ASP2409, a new cytotoxic T-lymphocyte associated protein 4-immunoglobulin possessing 14-fold higher in vitro CD86 binding affinity than belatacept, was tested for renal allograft survival in cynomolgus monkeys. ASP2409 monotherapy dose-dependently prolonged renal allograft survival. Low-dose ASP2409 in combination with a subtherapeutic dose of tacrolimus showed much longer median survival time than monotherapy. Similar allograft survival results were observed in regimens based on high-dose ASP2409, belatacept, and therapeutic-dose tacrolimus. The results of renal allograft histopathology with high-dose ASP2409-based regimens were not inferior to the belatacept-based regimen. Moreover, higher frequencies of FoxP3-positive regulatory T cells in renal allografts were observed in ASP2409- and belatacept-based regimens compared with tacrolimus-based regimens. No serious side effects related to ASP2409 administration were found during the study. These data suggest that ASP2409 is a promising candidate for calcineurin inhibitor-sparing or -avoidance regimens.


Subject(s)
Abatacept/pharmacology , Graft Rejection/drug therapy , Graft Survival/drug effects , Immunoconjugates/pharmacology , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Tacrolimus/pharmacology , Animals , B7-2 Antigen/immunology , Drug Therapy, Combination , Glomerular Filtration Rate , Graft Rejection/etiology , Immunosuppressive Agents/pharmacology , Kidney Function Tests , Macaca fascicularis , Male , T-Lymphocytes, Cytotoxic/immunology , Transplantation, Homologous
2.
Eur J Vasc Endovasc Surg ; 50(6): 738-43, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26427847

ABSTRACT

OBJECTIVE/BACKGROUND: Recently, the indications for thoracic endovascular aortic repair (TEVAR) have been expanding, and the applicability of TEVAR for acute type B aortic dissection (TBAD) is proposed with regard to the high mortality of open surgery for chronic TBAD. TEVAR in the acute phase may lead to remodeling of the false lumen (FL), but it is controversial whether it completely resolves the aortic expansion in the chronic phase. In this study, operative results and the relationship between FL status and the time before surgical intervention were retrospectively analyzed. METHODS: From January 2008 to September 2013, 234 patients underwent open surgery for chronic TBAD. Most patients were on left heart bypass. By considering Japanese aortic disease treatment guidelines and the smaller physique of Japanese patients, operative indications were aneurysm >50 mm in diameter or rapid aneurysm enlargement of >5 mm in a 6 month period. RESULTS: In 180 cases, the FL was patent. The mean interval between onset of TBAD and operation was 61 ± 54 months. There was no significant difference between patients in the patent FL group and those in the thrombosed FL group (p = .44). Mean ratio of FL diameter to maximum aortic diameter (FL/AD) was 0.64 ± 0.21. There was no correlation between FL and AD before the operation (r = .12). Descending thoracic aortic replacement (DTAR) was performed in 127 cases and thoracic ascending aortic replacement (TAAR) in 107 cases (Crawford type I, n = 9; Crawford type II, n = 65; Crawford type III and IV, n = 22, respectively; Safi type V, n = 11). The overall operative mortality was 6.8%: 3.9% (5/127) for DTAR and 10.3% (11/107) for TAAR. The three year survival was 86.7, and the freedom from re-intervention rate was 97.0%. CONCLUSION: Enlargement of uncomplicated TBAD in the chronic phase was poorly related to FL status and the results of open repair have improved. However, further prospective study is necessary.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation , Aged , Aortic Dissection/diagnosis , Aortic Dissection/mortality , Aortic Dissection/physiopathology , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/mortality , Aortic Aneurysm, Thoracic/physiopathology , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Chronic Disease , Disease-Free Survival , Female , Humans , Japan , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Risk Factors , Time Factors , Time-to-Treatment , Treatment Outcome , Vascular Patency
3.
J Fish Dis ; 38(6): 507-14, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24820532

ABSTRACT

A new cell line named CCF-K104 predominantly consisting of fibroblastic cells showed optimal growth at temperatures from 25 °C to 30 °C. Serial morphological changes in the cells induced by Cyprinid herpesvirus 3 (CyHV-3) included cytoplasmic vacuolar formation, cell rounding and detachment. Mature virions were purified from CyHV-3-infected CCF-K104 cells by sucrose gradient ultracentrifugation and had a typical herpesvirus structure on electron microscopy. Infectious CyHV-3 was produced stably in CCF-K104 cells over 30 viral passages. Our findings showed that CCF-K104 is a useful cell line for isolation and productive replication of CyHV-3. A temperature shift from 25 °C to 15 °C or 35 °C did not allow serial morphological changes as observed at 25 °C for 14 days. Under the same conditions, real-time PCR showed that CyHV-3 was present with low viral DNA loads, suggesting that CyHV-3 may establish latent infection in CCF-K104 cells. Amplification of the left and right terminal repeat sequences of the CyHV-3 genome arranged in a head-to-tail manner was detected by nested PCR following an upshift in temperature from 25 °C to 35 °C. The PCR results suggested that the circular genome may represent a latent form of CyHV-3.


Subject(s)
Cell Line , Fish Diseases/virology , Herpesviridae Infections/veterinary , Herpesviridae/physiology , Temperature , Virus Latency/physiology , Animals , Carps , Genome, Viral/genetics , Herpesviridae/genetics , Herpesviridae/growth & development , Herpesviridae/isolation & purification , Herpesviridae/ultrastructure , Herpesviridae Infections/virology , Molecular Sequence Data , Virus Latency/genetics , Virus Replication/physiology
4.
J Appl Microbiol ; 116(5): 1218-28, 2014 May.
Article in English | MEDLINE | ID: mdl-24450783

ABSTRACT

AIMS: The aims of this study were to evaluate the effectiveness of nisin A to control the growth of spore-forming bacteria, Bacillus and Paenibacillus, in chilled high-fat, milk pudding and to reduce heat treatment to improve aroma and flavour. METHODS AND RESULTS: Nisin A was added to milk pudding containing 5·0 and 7·5% fat to final concentrations of 40, 80, 120 and 240 IU ml(-1). Spores from Bacillus thuringiensis, Bacillus cereus and Paenibacillus jamilae were inoculated into samples at 10 spores ml(-1) prior to pasteurization at 130°C for 2 s. Milk pudding without inoculation was pasteurized using less heat condition (100, 110 and 120°C for 2 s) to measure the effect of adjusting the ingredients to prevent naturally occurring bacteria. The viable cells during storage at 15, 20 and 30°C showed nisin A inhibited spiked bacteria to varying degrees depending on species, sensitivities to nisin A concentration and fat content, and inhibited natural populations at 80 IU g(-1) nisin A in 5·0% fat and at 120 IU g(-1) in 7·5% fat milk pudding. An aroma compound analysis and organoleptic assessment showed processing at 110 and 120°C decreased the temperature-dependent unpleasant odours, for example, reduced dimethyl sulfide and dimethyl disulfide by 1·2-1·5 times and increased rankings in taste tests compared with 130°C treated pudding. CONCLUSIONS: Nisin A was found to be effective as a natural preservative to control spoilage bacteria in high-fat milk pudding and extend its shelf life, when using reduced heat treatments to improve the flavour and aroma without compromising food safety. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing nisin A is effective in reducing spoilage bacteria in high-fat, chilled dessert, milk pudding. Therefore, nisin A can be used to improve milk puddings to satisfy both industry and consumer demand for food quality and safety.


Subject(s)
Anti-Bacterial Agents/pharmacology , Dairy Products/microbiology , Food Preservatives/pharmacology , Nisin/pharmacology , Bacillus cereus/drug effects , Bacillus thuringiensis/drug effects , Food Storage , Hot Temperature , Paenibacillus/drug effects , Spores, Bacterial/drug effects
5.
Oper Dent ; 49(3): 336-344, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38807319

ABSTRACT

OBJECTIVE: Tooth color matching is challenging, and digital photocolorimetry using eLABor_aid (eLAB) provides objective evaluation through polarized photographs. However, its comparability with spectrophotometry remains unclear. METHODS AND MATERIALS: Bovine incisor root canals (n=30) were prepared to simulate an incomplete root apex. The teeth were randomly assigned to three groups based on intracanal medication: control (without medication); calcium hydroxide/propylene glycol; and triple-antibiotic paste (n=10 each). Tooth color was assessed using both eLAB and spectrophotometry. Measurements were taken at the crown medio-cervical region on five-time intervals (baseline, 1, 3, 7, and 14 days). Statistical analysis included two-way repeated-measures ANOVA, Sidak post hoc and Pearson's correlation test (α=0.05). RESULTS: No significant differences were observed between the two methods for either medication or follow-ups (p>0.05). Triple-antibiotic paste exhibited higher color variation (p<0.05). After 7 days, all groups presented significant color changes (p<0.05). Moderate to high correlations (R2 from 0.51 to 0.84, p<0.0001) were found between both methods for all groups at all intervals. CONCLUSION: The eLAB is a reliable method for detecting tooth color changes, and its results are comparable to spectrophotometry analysis.


Subject(s)
Colorimetry , Spectrophotometry , Cattle , Animals , Spectrophotometry/methods , Colorimetry/methods , Anti-Bacterial Agents , Color , In Vitro Techniques , Calcium Hydroxide , Incisor/anatomy & histology , Propylene Glycol , Tooth Discoloration , Root Canal Irrigants/therapeutic use , Metronidazole/therapeutic use , Ciprofloxacin/therapeutic use , Dental Pulp Cavity/anatomy & histology
6.
Oper Dent ; 48(5): 490-499, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37721111

ABSTRACT

OBJECTIVE: This study aimed to compare the tooth color matching of two dental colorimetric methods: the spectrophotometric analysis (SPM) and the standardized digital photocolorimetric analysis (DPC). METHODS: The color of 60 maxillary central incisors of 30 volunteers (22.5 ± 7.6 years) was analyzed. In the DPC method, tooth photographs were standardized with the eLABor_aid protocol, processed with Adobe Photoshop Lightroom software, and the values of L*, a*, and b* were obtained with a Digital Color Meter software. For the SPM, L*, a*, and b* were measured directly with a handheld spectrophotometer. Data were submitted to paired t-test and Pearson correlation test (α=0.05). Mean color difference between the two methods was calculated with CIELAB formula. RESULTS: All color coordinates revealed different values when comparing DPC to SPM in the same tooth (p<0.0001). Mean color difference (ΔEab) between SPM and DPC was 11.5 ±3.1. A positive correlation was observed for L* (R2=0.73,p<0.0001), a* (R2=0.31, p=0.017), and b* (R2=0.83, p<0.0001). CONCLUSIONS: Even though the color coordinate values were different in both methods, they were correlated, revealing that the DPC is a viable alternative to determine the tooth color matching.


Subject(s)
Colorimetry , Incisor , Humans , Spectrophotometry , Photography, Dental , Software
7.
J Intern Med ; 271(6): 598-607, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21988283

ABSTRACT

BACKGROUND: The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). METHODS: Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (<0.01 µg L(-1) , undetectable), detectable but still within the normal range (0.01-0.027 µg L(-1) ) and increased (≥0.028 µg L(-1) , ≥99th percentile). The final diagnosis was adjudicated by two independent cardiologists blinded to the s-cTnI levels. Median follow-up in patients with AHF was 371 days. RESULTS: Levels of s-cTnI were higher in patients with AHF (n = 377, 57%) compared to patients with noncardiac causes of acute dyspnoea (median 0.02 vs. <0.01 µg L(-1) , P < 0.001). In patients with AHF, in-hospital mortality increased with increasing s-cTnI in the three strata (2%, 5% and 14%, P < 0.001). One-year mortality also increased with increasing s-cTnI (21%, 33% and 47%, P < 0.001). s-cTnI remained an independent predictor of 1-year mortality [adjusted odds ratio 1.03 for each increase of 0.1 µg L(-1) , 95% confidence interval (CI) 1.02-1.05, P < 0.001] after adjustment for other risk factors including B-type natriuretic peptide. The net reclassification improvement was 68% (P < 0.001), and absolute integrated discrimination improvement was 0.18 (P < 0.001). The diagnostic accuracy of s-cTnI for the diagnosis of AHF as quantified by the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.75-0.82). CONCLUSIONS: Sensitive cardiac troponin I is a strong predictor of short- and long-term prognosis in AHF that helps to reclassify patients in terms of mortality risk. Detectable levels of s-cTnI, even within the normal range, are independently associated with mortality.


Subject(s)
Heart Failure/diagnosis , Troponin I/blood , Acute Disease , Aged , Aged, 80 and over , Algorithms , Biomarkers/blood , Confidence Intervals , Emergency Service, Hospital , Female , Follow-Up Studies , Heart Failure/blood , Heart Failure/mortality , Humans , Male , Odds Ratio , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis
8.
J Immunoassay Immunochem ; 33(1): 59-65, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22181821

ABSTRACT

A commercially available multi-antigen lateral flow assay (LFA) for detection of antibodies to Mycobacterium bovis was evaluated by testing dairy cattle in Baja California, México. Sera and tissue samples were obtained from 268 dairy cattle at a slaughterhouse and were tested by LFA, bacteriological culture, and polymerase chain reaction (PCR). Of 107 culture positive samples, 70 (65.4%) were positive by PCR and 49 (45.8%) were positive by LFA. The PCR and LFA gave positive results with an additional 59 (36.6%) and 77 (47.8%) of the 161 culture negative samples, respectively. The false negative rate for the PCR was 34.6% and 54.2% for the LFA. Due to the high false positive rate for both PCR and LFA observed in this study, the LFA cannot be a useful test, even in combination with PCR.


Subject(s)
Antibodies, Bacterial/analysis , Immunoassay/methods , Tuberculosis, Bovine/diagnosis , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Cattle , Dairying , Mycobacterium bovis/genetics , Mycobacterium bovis/immunology , Polymerase Chain Reaction , Tuberculosis, Bovine/blood , Tuberculosis, Bovine/immunology , Tuberculosis, Bovine/microbiology
9.
J Fish Biol ; 78(3): 848-59, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21366577

ABSTRACT

The distribution of mucous cells was examined in the skin on the ocular and blind sides of Japanese flounder Paralichthys olivaceus. Observations were performed on both body sides at the following regions: cheek, lower jaw (blind side), gill cover (ocular side), dorsal side, lateral line, belly and caudal peduncle. The mucous cells observed were elliptic and positively stained for periodic acid Schiff reaction and Mayer's mucicarmine and showed a higher density and larger size on the ocular side compared to the blind side. Low densities of mucous cells were observed on the lower jaw compared with other regions of the body. The depth of the crack located between scales was deeper on the ocular side than the blind side, which might reflect total epidermis area and total number of mucous cells. Bacterial infection elucidated some information on the effect on the density and size of mucous cells, where the density and size decreased slightly after infection. Only the lower jaw, however, showed an increased number of mucous cells. The results show that the potential of skin to secrete mucus is higher on the ocular than on the blind side and bacterial infection decreases mucous secretion.


Subject(s)
Mucus/cytology , Skin/cytology , Animals , Cell Count , Cell Size , Edwardsiella tarda/physiology , Enterobacteriaceae Infections/pathology , Enterobacteriaceae Infections/veterinary , Fish Diseases/pathology , Flounder
10.
J Int Med Res ; 37(2): 367-77, 2009.
Article in English | MEDLINE | ID: mdl-19383230

ABSTRACT

The predictive value of combined (123)iodine-labelled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid imaging ((123)I-BMIPP) and early technetium-99m ((99m)Tc)-tetrofosmin imaging was compared with combined (123)I-BMIPP and delayed (99m)Tc-tetrofosmin or (123)I-BMIPP and thallium-201 ((201)Tl) imaging for functional outcome of stunned myocardium after acute myocardial infarction (AMI) in 37 patients with AMI. All patients underwent successful percutaneous coronary intervention with/without stenting within 24 h of symptoms. Resting (201)Tl, (99m)Tc-tetrofosmin and (123)I-BMIPP imaging were performed within 10 days of hospital admission; (99m)Tc-tetrofosmin imaging was also performed 6 months later. Segments were mismatched when the (123)I-BMIPP score was greater than the (99m)Tc-tetrofosmin or (201)Tl scores, and were matched when all scores were the same. Left ventricular function was estimated using wall motion score. Sensitivity and regional wall motion were significantly better in mismatching (99m)Tc-tetrofosmin-early/(123)I-BMIPP segments than mismatching (201)Tl/(123)I-BMIPP or (99m)Tc-tetrofosmin-delayed/(123)I-BMIPP segments. It is concluded that mismatching of (123)I-BMIPP and early (99m)Tc-tetrofosmin uptake can predict improvement in wall motion of stunned myocardium better than the other two imaging combinations.


Subject(s)
Diagnostic Imaging , Fatty Acids , Iodobenzenes , Myocardial Stunning/diagnostic imaging , Myocardial Stunning/etiology , Organophosphorus Compounds , Organotechnetium Compounds , Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography , Coronary Angiography , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Thoracic Wall , Treatment Outcome
11.
Endoscopy ; 40(11): 936-8, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18819060

ABSTRACT

Double-balloon endoscopy (DBE) is a new technique that allows diagnosis and treatment throughout the entire small intestine. We have recently developed a method that allows a single operator to perform DBE, by employing "grip and pinch" and "hold (or 'keep') and slide" techniques. This one-person method obviates the need for two operators who must cooperate closely.


Subject(s)
Endoscopy/methods , Intestine, Small/surgery , Female , Humans , Middle Aged , Pilot Projects
12.
Clin Nephrol ; 70(4): 348-53, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18826862

ABSTRACT

AIM: To contribute to understanding the pathogenesis of hyperkalemia that often occurs in patients with diabetes. MATERIALS AND METHODS: We describe 3 familial cases of mitochondrial diabetes mellitus. The mitochondrial A3243G point mutation was confirmed in a mother and her 2 children. We examined their clinical features and pathological findings, and assessed heteroplasmy of mutant mitochondria DNA (mtDNA) by molecular analysis. RESULTS: The second son had spontaneous hyperkalemia and hyporeninemic hypoaldosteronism. Histopathological examination revealed severe tubulointerstitial and vascular changes around the juxtaglomerular apparatus. The mother only showed intermittent hyperkalemia concurrently with the aggravation of heart failure, and the pathological changes in her kidneys were mild. Heteroplasmy was more severe in the second son than in the mother. CONCLUSION: Heteroplasmy of mitochondrial cytopathy combined with diabetes mellitus led to abnormalities resembling those seen in Type IV renal tubular acidosis.


Subject(s)
Hyperkalemia/genetics , Mitochondrial Myopathies/genetics , Adult , Aged , Cardiomyopathies/genetics , Deafness/genetics , Diabetes Mellitus/genetics , Female , Humans , Hypoaldosteronism/genetics , Male
13.
Circulation ; 101(6): 640-6, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10673256

ABSTRACT

BACKGROUND: There has been debate regarding whether technically demanding right internal thoracic artery (RITA) grafting via the transverse sinus can be extensively applied to patients in high-risk groups, such as patients with a small body size, elderly patients, and woman with relatively smaller coronary artery and internal thoracic artery (ITA) diameters. METHODS AND RESULTS: Of the 1456 patients who underwent isolated coronary artery bypass grafting between January 1989 and December 1998 at Kumamoto Central Hospital, 393 patients (mean age, 62.4+/-9.0 years) with the RITA anastomosed to the major branches of the circumflex artery were studied. Left ITA grafting was performed in 384 patients, and in 369, the in situ left ITA was anastomosed to the left anterior descending coronary artery using standard methods. Early postoperative angiography was performed in 381 patients. The RITA was occluded in 4 patients, and string-like artery and significant stenosis were present in 11 and 7 patients, respectively; RITA graft patency was thus 94.1%. Of the preoperative variables and angiographic data, simple and multiple logistic regression analyses identified decreased severity of native stenosis, diffuse sclerosis of native vessels, and residual side branches of the ITA as independent predictors of nonfunctional grafts. The method of ITA grafting did not influence the patency of the graft. CONCLUSIONS: The excellent patency rate demonstrated by this study, the largest angiographic study to date of RITA grafting via the transverse sinus, indicates that this technique can provide reliable revascularization of the left ventricle and that it has the potential to be applied to a wide variety of patients with diseased circumflex arteries.


Subject(s)
Coronary Artery Bypass , Graft Rejection/diagnostic imaging , Mammary Arteries/diagnostic imaging , Mammary Arteries/surgery , Adolescent , Adult , Aged , Angiography , Female , Humans , Male , Mammary Arteries/physiopathology , Middle Aged , Predictive Value of Tests , Risk Factors
14.
J Am Coll Cardiol ; 14(1): 150-4, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2525582

ABSTRACT

Plasma fibrinopeptide A levels, beta-thromboglobulin levels and platelet factor 4 levels were estimated by enzyme-linked immunosorbent assay before and after hyperventilation in 12 patients with coronary vasospastic angina and in 12 control subjects matched for age and gender. In all 12 study patients, anginal attacks accompanied by electrocardiographic (ECG) changes (ST elevation in 11 patients and ST depression in 1 patient) were induced by hyperventilation. Coronary angiography was performed on 11 of the 12 patients, and coronary artery spasm with the same ECG changes was induced by intracoronary injection of acetylcholine in all 11. The plasma fibrinopeptide A levels increased significantly from 2.0 +/- 0.4 to 10.0 +/- 2.4 ng/ml during the attack (p less than 0.001) in the study patients, but remained unchanged before and after hyperventilation in the control subjects. The plasma levels of beta-thromboglobulin and platelet factor 4 remained unchanged after hyperventilation in both groups. Our data indicate that coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery.


Subject(s)
Coronary Vasospasm/complications , Fibrinogen/metabolism , Fibrinopeptide A/metabolism , Heart Diseases/etiology , Hyperventilation/physiopathology , Thrombosis/etiology , Aged , Coronary Angiography , Coronary Vasospasm/blood , Coronary Vasospasm/diagnostic imaging , Coronary Vasospasm/physiopathology , Electrocardiography , Female , Heart Diseases/blood , Humans , Male , Middle Aged , Thrombosis/blood , beta-Thromboglobulin/metabolism
15.
Curr Drug Targets Inflamm Allergy ; 4(4): 489-95, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16101527

ABSTRACT

The history of studies in biology regarding reactive oxygen species (ROS) is approximately 40 years. During the initial 30 years, it appeared that these studies were mainly focused on the toxicity or microbicidal-related agents of ROS. However, recent studies have identified another action regarding oxidative signaling, other than toxicity of ROS. Basically, it is suggested that ROS are reactive, and degenerate to biomacromolecules such as DNA and proteins, leading to deterioration of cellular functions as an oxidative stress. On the other hand, recent studies have shown that ROS act as oxidative signaling in cells, resulting in various gene expressions. For example, NADPH oxidase, a major source of superoxide radicals (O(2)(-)), expresses in various tissues such as leukocytes and cardiovascular systems, and ROS derived from the enzyme play important roles in cell proliferation, differentiation, and cell death. In this review, we have focused on and described the basic properties, toxicity, and roles of ROS.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/metabolism , Reactive Oxygen Species/metabolism , Animals , Antioxidants/metabolism , Humans , Oxygen/chemistry , Signal Transduction/physiology
16.
Clin Cancer Res ; 4(6): 1527-32, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9626473

ABSTRACT

We investigated the presence of K-ras gene mutation in plasma DNA and assessed its clinical value in patients with pancreatic adenocarcinoma. Mutations in codon 12 of the K-ras gene were examined by mutant allele-specific amplification method using DNA extracted from surgical specimens and plasma samples of 21 patients with pancreatic adenocarcinoma. K-ras gene mutation was detected in 15 of 21 (71%) primary tumors. In 9 of 15 (60%) patients with K-ras gene mutation-positive tumors, an identical mutation was detected in the plasma DNA. None of four patients with chronic pancreatitis or five healthy subjects had such mutations in plasma DNA. Tumors positive for K-ras gene mutation in plasma DNA were significantly larger (P = 0.04) and less likely to result in a curative cure after surgical resection (P = 0.09) than those negative for the mutation. Other clinicopathological features, including age, sex, histological type, mode of invasion, and metastasis, did not correlate with K-ras gene mutations in plasma DNA. Treatment resulted in disappearance of K-ras gene mutations in plasma DNA in six of nine (67%) patients. Three patients with a persistently positive K-ras gene mutation in pre- and post-treatment plasma samples were likely to show early recurrence or have a progressive disease. Our findings suggest that K-ras gene mutation can be detected in plasma DNA of patients with pancreatic adenocarcinoma. Detection of K-ras mutations in plasma may be clinically useful for evaluating tumor burden and efficacy of treatment.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , DNA/blood , Genes, ras , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Point Mutation , Adenocarcinoma/blood , Adenocarcinoma/surgery , Adult , Aged , Base Sequence , Chronic Disease , Codon , DNA Primers , Female , Humans , Male , Middle Aged , Neoplasm Staging , Palliative Care , Pancreatectomy , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/surgery , Pancreatitis/blood , Pancreatitis/genetics , Pancreatitis/pathology , Polymerase Chain Reaction , Reference Values
17.
Clin Cancer Res ; 5(8): 2018-24, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10473081

ABSTRACT

The level of cyclooxygenase (COX)-2 has been investigated recently in various human carcinomas. In the present study, we examined the distribution and extent of COX-2 protein in human pancreatic tumors using immunohistochemistry. A strong expression of COX-2 protein was present in 23 of 52 (44%) pancreatic carcinomas, a moderate expression was present in 24 of 52 (46%) pancreatic carcinomas, and a weak expression was present in 5 of 52 (10%) pancreatic carcinomas. In contrast, benign tumors showed weak expression or no expression of COX-2, and only islet cells displayed COX-2 expression in normal pancreatic tissues. Overexpression of COX-2 in carcinoma tissues was also confirmed by Western blot analysis. Furthermore, consistent with the results at protein levels, reverse transcription-PCR analyses indicated that COX-2 mRNA was overexpressed in 7 of 13 (54%) carcinomas, but in none of 3 benign tumors. Our findings suggest that COX-2 inhibitors might be potentially effective against pancreatic carcinomas and that COX-2 may be involved in certain biological processes in pancreatic islets.


Subject(s)
Adenocarcinoma/enzymology , Carcinoma, Adenosquamous/enzymology , Isoenzymes/biosynthesis , Pancreatic Neoplasms/enzymology , Prostaglandin-Endoperoxide Synthases/biosynthesis , Blotting, Western , Cyclooxygenase 2 , Humans , Immunohistochemistry , Isoenzymes/metabolism , Membrane Proteins , Prostaglandin-Endoperoxide Synthases/metabolism , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
18.
Transplant Proc ; 37(4): 1764-6, 2005 May.
Article in English | MEDLINE | ID: mdl-15919458

ABSTRACT

Tacrolimus was approved in Japan in April 1996 for the prevention of allograft rejection in patients receiving kidney transplants. There has been a concern that immunosuppressive therapy may be associated with cardiovascular and metabolic complications, including hyperlipidemia, hypertension, and posttransplant diabetes mellitus. A multicenter (59 institutions) study was conducted in Japan in patients who underwent renal transplantation and received tacrolimus immunosuppression. Patients were followed for >5 years, from April 1996 to December 2002. Of the 1569 patients enrolled, 1542 were evaluated. In this analysis, graft survival rate and medication usage patterns of antihyperlipidemics, antihypertensives, insulin, and oral hypoglycemics were observed for >5 years in patients receiving tacrolimus immunosuppression. The graft survival rates of patients requiring antihyperlipidemic therapy and experiencing acute rejection were significantly lower compared with all other patients (P < .05). The risk of graft rejection was significantly greater in patients with cardiovascular complications requiring antihyperlipidemics or antihypertensives. Graft survival was significantly lower in patients with acute rejection and antihyperlipidemic therapy than in other patients.


Subject(s)
Kidney Transplantation/physiology , Tacrolimus/therapeutic use , Follow-Up Studies , Graft Survival/drug effects , Humans , Hypolipidemic Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Japan , Kidney Transplantation/immunology , Postoperative Complications/epidemiology , Retrospective Studies , Safety , Time Factors
19.
Transplant Proc ; 37(4): 1769-70, 2005 May.
Article in English | MEDLINE | ID: mdl-15919460

ABSTRACT

The safety and efficacy of tacrolimus (Tac)-based immunosuppressive treatments were studied in 115 pediatric renal transplant recipients (mean follow-up period, approximately 20 months). The acute rejection rate was 22.7% 6 months after transplantation and the steroid-resistant acute rejection rate was 6.4%. The 5-year patient and graft survival rates were 98.6% and 95.9%, respectively. Major adverse effects included infection, ie, cytomegalovirus (CMV) antigenemia (41.7%), renal dysfunction (29.6%), and impaired glucose tolerance (20.9%). The incidences of these adverse events were significantly decreased among patients who had undergone transplantation after March 2000 (n = 43), namely, 30.2%, 18.6%, and 11.6%, respectively.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Tacrolimus/therapeutic use , Adult , Cadaver , Female , Follow-Up Studies , Glucose Intolerance/epidemiology , Graft Rejection/epidemiology , Humans , Infections/epidemiology , Japan , Kidney Transplantation/mortality , Living Donors , Male , Nervous System Diseases/epidemiology , Postoperative Complications/classification , Postoperative Complications/epidemiology , Retrospective Studies , Survival Analysis , Time Factors , Tissue Donors
20.
Transplant Proc ; 37(4): 1771-3, 2005 May.
Article in English | MEDLINE | ID: mdl-15919461

ABSTRACT

INTRODUCTION: To date, no reports have concurrently investigated the quality of life (QOL) of both pediatric renal transplant recipients and their caregivers. We conducted a survey at nine institutions in Japan with regard to changes in QOL before and after renal transplantation. METHODS: We chose 68 pediatric renal transplant recipients whose surgery was followed by tacrolimus-based immunosuppressive therapy. Both patients and their caregivers were asked to complete self-rating questionnaires. For the patients' surveys, we used 29 questions relevant to pediatric patients, which were excerpted from Kidney Disease Quality of Life (Japanese version). The SF-36 (Japanese version) was taken by their caregivers. RESULTS: Fifty-six patients (82.4%) responded to the questionnaires. The mean age at renal transplantation and at the time of the survey was 11.1 and 15.3 years old, respectively. The general questions of the patients' survey indicated a significant QOL improvement in each of the subscales (such as physical functioning and vitality) after transplantation as compared to prior. In the questions pertaining to kidney diseases, significant QOL improvement was observed in many subscales, such as symptoms/problems and effects of kidney disease. Of the 54 caregivers (79.4%) who answered SF-36 questionnaires, 47 (87.0%) were living donors. After renal transplantation surgery for the children, a significant improvement of QOL was seen in the subscales for caregivers' mental well-being. However, a significant decrease was observed for QOL in regard to physical health.


Subject(s)
Caregivers , Kidney Transplantation/psychology , Living Donors/psychology , Quality of Life , Tacrolimus/therapeutic use , Adolescent , Child , Emotions , Humans , Immunosuppressive Agents/therapeutic use , Surveys and Questionnaires
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