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Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 19 recordsLinked to original sources

Group IVA phospholipase A2-mediated production of fibronectin by oxidized LDL in mesangial cells.

The deposition of atherogenic lipoproteins such as oxidized low-density lipoprotein (oxLDL) within the mesangium is involved in the overproduction of extracellular matrix proteins, a key event in the progression of glomerular diseases including glomerulosclerosis. To clarify the mechanisms underlying the oxLDL-induced production of extracellular matrix proteins, we examined the possible involvement of group IVA phospholipase A(2) (PLA(2)) using human mesangial cells and group IVA PLA(2)-deficient mouse mesangial cells. oxLDL accelerated the production of fibronectin and collagen (type IV), components of extracellular matrix proteins, with the preceding release of arachidonic acid. Methyl arachidonyl fluorophosphonate (MAFP), known as an inhibitor of group IVA PLA(2), markedly suppressed the oxLDL-induced production of fibronectin as well as the release of arachidonic acid, whereas it did not inhibit the production of collagen. The inhibitory effect of MAFP on the production of fibronectin was reversed by adding arachidonic acid and 12-hydroxyeicosatetraenoic acid. Furthermore, we found that in group IVA PLA(2)-deficient mouse mesangial cells, the production of fibronectin in response to oxLDL was weak as compared with that in wild-type cells. However, the production by oxLDL of collagen was not suppressed in the group IVA PLA(2)-deficient cells. These findings suggest that group IVA PLA(2) is involved in the production of fibronectin in oxLDL-stimulated mesangial cells.

Arachidonic Acid↗

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer.

To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0-2), age<or=75 years, and adequate organ function. The patients' characteristics were: male/female=56/5; PS 0/1/2=19/38/4; median age (range)=68 years(51-75 years); limited disease (LD)/extensive disease (ED)=27/34. The patients received irinotecan (50 mg m-2) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were evaluated. In all, 31 patients were treated with four or more courses of chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a partial response (PR), nine had stable disease (SD), and one had progressive disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72-91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17-41%; LD 37%, ED 21%). The median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%), respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia, and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In conclusion, the combination of irinotecan and carboplatin is an active and well-tolerated regimen in cases of SCLC.

Aged↗

Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse.

AIMS: Although interleukin 8 (IL-8) is not produced in the normal cornea, it has been detected there in several pathological conditions. In this study, the direct effects of IL-8 overexpression on the cornea was examined. METHODS: The corneal surface of severe combined immunodeficiency mice was infected by the adenovirus vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were observed at various time points. RESULTS: Clinically, marked angiogenesis and ulcer formation in the cornea were observed by 12 hours and 24 hours, respectively. Histologically, prominent angiogenesis was observed in the corneal stroma at 12 hours. Cleft formation between the corneal epithelium and stroma, and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24 hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the cornea. In contrast, infection with the control adenovirus carrying the beta galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5 resulted in the production of IL-8 by corneal and conjunctival stromal cells. CONCLUSION: Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.

Adenoviridae↗

Enhancement of chemosensitivity toward peplomycin by calpastatin-stabilized NF-kappaB p65 in esophageal carcinoma cells: possible involvement of Fas/Fas-L synergism.

Chemosensitivity to anticancer drugs was compared between two human esophageal carcinoma cell lines, T.Tn and YES-6 cells. T.Tn cells were more resistant than YES-6 cells to peplomycin (PEP) but not to the other anticancer drugs such as camptothecin, mitomycin C and cytosine arabinoside. Western blot analysis showed higher expression levels of m-calpain and activated mu-calpain in T.Tn cells than in YES-6 cells. On the other hand, YES-6 cells showed a high expression level of calpastatin, which is a calpain-specific endogenous inhibitor. To investigate whether calpain activity was involved in the chemosensitivity, T.Tn cells were transfected with calpastatin cDNA in an inducible expression vector. The induction of calpastatin was accompanied by increased chemosensitivity to PEP. The increases in calpastatin levels were followed by serial increases in the expression levels of NF-kappaB p65 and Fas. Since purified m- or mu-calpain degraded NF-kappaB p65 in vitro, it is possible that calpastatin suppressed calpain-mediated degradation of NF-kappaB p65. Fas ligand (Fas-L) protein levels increased after treatment of the parental T.Tn and calpastatin-transfected cells with PEP, suggesting the synergism between calpastatin-induced Fas and PEP-induced Fas-L. These results suggest that calpain/calpastatin expression levels are effective markers for predicting the sensitivity of human esophageal carcinoma cells to PEP.

Antibiotics, Antineoplastic↗

Endoscopic submucosal dissection for rectal epithelial neoplasia.

BACKGROUND AND STUDY AIMS: The technique of endoscopic submucosal dissection (ESD) has recently been developed for en-bloc resection of gastric tumors. For oncological reasons and in order to improve the patients' quality of life, it may be desirable to use the same technique for rectal neoplasia. PATIENTS AND METHODS: Thirty-five consecutive patients with rectal neoplasia who had a preoperative diagnosis of large intraepithelial neoplasias with submucosal fibrosis or located on the rectal folds were enrolled. ESD was carried out with the same technique previously described for the stomach, with some modifications. The efficacy, complications, and follow-up results of the treatment were assessed. RESULTS: The rates of en-bloc resection and en-bloc plus R0 resection were 88.6 % (31 of 35) and 62.9 % (22 of 35), respectively. Hemoglobin levels did not drop by more than 2 g/dl in any of the patients after ESD. None of the patients had to receive blood transfusions or undergo emergency colonoscopy due to bleeding during ESD or hematochezia after ESD. Perforation during ESD occurred in two patients (5.7 %), who were managed with conservative medical treatment after endoscopic closure of the perforation. Excluding three patients in whom additional surgery was carried out, all but one of 32 patients were free of recurrence during a mean follow-up period of 36 months (range 12 - 60 months). The exception was a patient in whom a multiple-piece resection was required; the recurrent (residual) tumor, found 2 months after ESD, was a small adenoma that was again treated endoscopically. CONCLUSIONS: ESD is applicable in the rectum with promising results, but the technique is still at a developmental stage and patients should be informed of the potential risks.

Chi-Square Distribution↗

Successful nonsurgical management of perforation complicating endoscopic submucosal dissection of gastrointestinal epithelial neoplasms.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. PATIENTS AND METHODS: We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. RESULTS: Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 degrees C, the mean white blood cell count was 9733/mm3, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). CONCLUSION: Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Aged↗

Suppression of TNFalpha production in LPS induced liver failure in mice after intravenous injection of cationic liposomes/NFkappaB decoy complex.

NFkappaB decoy, double stranded oligonucleotides containing NFkappaB binding sequences, inhibits NFkappaB-mediated production of inflammatory cytokines, and therefore NFkappaB decoy has been applied to several diseases. However, naked NFkappaB decoy, which is quickly cleared from the circulation in mice after intravenous injection, is readily absorbed into the systemic circulation. In order to deliver enough NFkappaB decoy for a therapeutic effect, it is necessary to develop a carrier, which enables much more NFkappaKB decoy to transfer to the target cells. In this study, using N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride (DOTMA)/cholesterol (1 :1) liposomes, the therapeutic effect of NFkappaB decoy was investigated in an LPS induced acute hepatitis model mice. The mean diameter of the cationic liposomes/NFkappaB decoy complex was about 70.9 nm and the zeta potential of complex was about 37.4 mV. Tissue distribution was determined by measuring the radioactivity of a cationic liposomes/ [32P] NFkappaB decoy complex after intravenous injection. The cationic liposomes/[32P] NFkappaB decoy complex was rapidly accumulated in the lung and gradually moved to the liver. The therapeutic effect was determined by the serum concentration of TNFalpha in LPS treated mice. The production of TNFalpha was significantly inhibited by cationic liposomes/NFkappaB decoy complex but not by cationic liposomes/random decoy complex or naked NFkappaB decoy. These results suggested that NFkappaB decoy therapy could be achieved using cationic liposomes. This information is of great value for the design of NFkappaB decoy carrier systems.

Animals↗

Isolated posterior cerebral artery dissection: report of three cases.

Isolated dissection of the posterior cerebral artery (PCA) is a rare but important cause of stroke in younger patients, particularly women. We present 3 cases of dissection of the P2 segment of the PCA. In 2 patients, an association with minor axial head trauma was documented, suggesting shearing injury of the PCA as it crosses over the free edge of the tentorium. The clinical and imaging findings are discussed, and the therapeutic management is reviewed.

Aortic Dissection↗

Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer.

The correlation between serum pepsinogen (PG) levels and the gross types was investigated in 128 consecutive patients with early gastric cancer. Although there was no significant difference in age, gender, cancer location, or cancer depth among gross appearances, the distribution of histological type was significantly different between polypoid and depressed cancers: all polypoid cancers except one were intestinal type, whereas nearly a third of depressed cancers were diffuse type. All the patients in whom Helicobacter pylori status was investigated had Helicobacterpylori infection. Combination of gross appearances and histology (polypoid cancer with intestinal type, depressed cancer with intestinal type and depressed cancer with diffuse type) showed a clear difference in distribution of serum PG levels and a ratio between levels of PG I and PG II (I/II ratio). In polypoid cancer with intestinal type, a PG I level and a I/II ratio were significantly lower than those of the others. In depressed cancer with diffuse type, PG I and PG II levels were significantly higher. These findings revealed that backgrounds such as intragastric acidity and extent of gastric atrophy might differ among early gastric cancers with different morphology and histology.

Adult↗

Mediastinoscope-assisted transhiatal esophagectomy for esophageal cancer.

BACKGROUND: Transthoracic esophagectomy (TTE) is a radical strategy for treatment of esophageal cancer, and the morbidity and mortality are high. Transhiatal esophagectomy (THE) is advantageous because it avoids thoracotomy and has a shorter surgical time, but risk of intraoperative morbidity stresses the surgeon and lymph node sampling is not possible. METHODS: Mediastinoscope-assisted transhiatal esophagectomy (MATHE) was performed in 42 patients with esophageal cancer. Patients with superficial esophageal cancer and medical risk were included. Feasibility and efficacy of this procedure are discussed by examining short- and long-term morbidity, mortality, and survival. RESULTS: With the mediastinoscope, esophagectomy was performed safely under direct vision. There was only a small amount of bleeding, and surgical time was short. Little morbidity and no deaths were recorded. CONCLUSION: MATHE is a safe and minimally invasive technique that allows direct visualization of mediastinal structures Lymph node sampling was feasible because of clear visualization of the mediastinum.

Adenocarcinoma↗

Presynaptic dopaminergic properties of differentiated mouse embryonic stem cells.

This study characterized the presynaptic dopaminergic properties of neuronally differentiated mouse embryonic stem (ES) cells. Approximately 30% of the ES cells expressed tyrosine hydroxylase (TH) immunoreactivity when co-cultured with PA6 cells. These cultures expressed high affinity, sodium-dependent dopamine uptake as well as depolarization-induced and calcium-dependent dopamine release of this transmitter. These and other important dopaminergic genes found expressed in these cultures by RT-PCR included Nurr1, vesicular monoamine transporter 2 (VMAT2), TH, dopamine transporter (DAT), and glial cell line-derived neurotrophic factor (GDNF) receptors c-Ret and GFRalpha1. These results demonstrate that differentiated ES cells have the presynaptic functions for maintaining dopaminergic homeostasis, which may be essential for their long-term use in restoring CNS levels of this transmitter.

Animals↗

Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: One of the major complications of endoscopic mucosal resection (EMR) for gastrointestinal tumors is perforation, and the most effective way of preventing perforation is to elevate the lesion sufficiently by endoscopic injection of fluid into the submucosa. MATERIALS AND METHODS: In order to compare the lesion-lifting properties of several different solutions, 1 ml of each of the following solutions was injected into the submucosa of the resected porcine stomach: normal saline, 3.75 % NaCl, 20 % dextrose water, 10 % glycerin with 0.9 % NaCl plus 5 % fructose, and two sodium hyaluronate (SH) solutions. RESULTS: Significantly higher initial elevation was produced by both SH solutions, and it remained higher than that achieved by the other solutions at all times. Hypertonic solutions, especially 10 % glycerin with 0.9 % NaCl plus 5 % fructose, tended to produce and maintain greater mucosal elevation than normal saline, but the difference was not significant. CONCLUSIONS: SH solutions were the most suitable ones for producing and maintaining long-term mucosal elevation, while the superiority of hypertonic solutions over normal saline was not clearly demonstrated.

Animals↗

Different mixtures of sodium hyaluronate and their ability to create submucosal fluid cushions for endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Sodium hyaluronate (SH) is a promising submucosal injection solution during endoscopic mucosal resection, but its high cost is an obstacle to more widespread use. The aim of this study was to identify an appropriate low-cost SH solution by varying the molecular weight of SH and mixing various solutions with it. MATERIALS AND METHODS: The viscoelasticity of various SH solutions was first measured. The concentrations of two 1 % SH preparations with different molecular weights (800 kDa and 1900 kDa) were adjusted to 0.5 %, 0.25 %, and 0.125 %, using 0.9 %/3.75 % normal saline (NS), 5 %/20 % dextrose water (DW), and a glycerin solution (Glyceol): 10 % glycerin with 0.9 % normal saline plus 5 % fructose. The ability of these SH solutions to create submucosal fluid cushions (SFCs) was then investigated in the stomachs of two live minipigs. RESULTS: The 0.25 % 1900 kDa SH/NS solution and the 0.125 % 1900 kDa SH/20 % DW solution created a similar viscoelasticity to that of the 0.5 % 800 kDa SH/NS solution. The ability of these solutions to create SFCs was also similar. In addition, the 0.125 % 1900 kDa SH/Glyceol solution created similar SFCs, with a synergistic effect of increased viscoelasticity and the hypertonic nature of glycerin. CONCLUSIONS: A mixture of higher molecular weight sodium hyaluronate with a sugar solution (particularly 20 % dextrose), with or without glycerin, should be regarded as a cost-effective option for creating SFCs instead of the conventional SH solution made with the same amount of a 1 % 800 kDa SH preparation and normal saline.

Animals↗

Thermoinduction of genes encoding the enzymes of gibberellin biosynthesis and a putative negative regulator of gibberellin signal transduction in Eustoma grandiflorum.

Eustoma grandiflorum Shinn requires vernalization for the induction of stem elongation and flowering. To investigate the role of gibberellins (GAs) in vernalization, the expression levels of genes encoding enzymes of GA biosynthesis, copalyl diphosphate synthetase, GA 20-oxidase and GA 3 beta-hydroxylase, were examined using two culitvars that show different responses to vernalization. The three genes were induced in a vernalization- and a cultivar-dependent manner. EgSPY, a putative negative regulator of GA signal transduction, was also induced during the vernalization period. The results suggest that the expression of the genes encoding GAs biosynthesis is regulated by vernalization. We postulate that EgSPY functions as a negative regulator of GA signal transduction during vernalization, inhibiting adventitious shoot elongation during vernalization.

Alkyl and Aryl Transferases↗