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M Ikeda

Publications and source records attributed to M Ikeda.

At least 181 records · Page 10Linked to original sources
PubMed2001

Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with an increased number of infiltrating macrophages, which release a variety of proinflammatory cytokines. Interleukin (IL)-18 has been implicated in the modulation of mucosal CD4(+) T cells towards Th1 responses, which are implicated in the pathogenesis of CD. Here we assess the role of macrophages and of IL-18 in the murine model of intestinal inflammation that mimics the immunologic characteristics of human CD. METHODS: Colitis was induced in C57BL/6 mice immunized with 2,4,6-trinitrobenzene sulfonic acid (TNBS) followed by rectal administration of TNBS in ethanol. Mice were treated with either an antibody directed against macrophages conjugated to the ribosome-inactivating protein saporin (anti-Mac-1-saporin) or with a neutralizing antibody against IL-18. In addition, we assessed whether an identical TNBS immunization/challenge protocol could induce colitis in IL-18(-/-) mice. RESULTS: The colonic mucosa of TNBS-treated mice was marked by infiltration of Mac-1-positive macrophages and up-regulation of IL-18. The administration of the anti-Mac-1-saporin antibody or the neutralizing anti-IL-18 antibody resulted in a dramatic attenuation of mucosal inflammation in this model. In addition, TNBS was unable to induce significant colitis in the IL-18(-/-) mice. CONCLUSIONS: Our data underscore the pivotal role of macrophages, and the macrophage-derived IL-18, in the establishment of TNBS-induced colitis in mice. Our results highlight the potential use of therapy directed against IL-18 in the treatment of patients with CD.

Animals↗
PubMed2001

Pigmented intraosseous odontogenic carcinoma of the maxilla: a pediatric case report and differential diagnosis.

We report a pigmented intraosseous odontogenic carcinoma of the maxilla occurring in a 6-year-old Japanese boy. Grossly, the tumor showed solid, gray-yellow, and markedly pigmented appearance. Histology showed neoplastic growths of atypical epithelial cells that occasionally contained melanin pigments. Melanocytes with dendritic processes were often found in the tumor cell clusters, and solitary or aggregated melanophages were scattered within the dense fibrovascular stroma. The tumor cells were diffusely positive for cytokeratins and epithelial membrane antigen, and focally positive for vimentin, neuron specific enolase, neurofilament protein, carcinoembryonic antigen, and amelogenin. Ultrastructural studies showed well-developed intercellular junctions, mainly desmosomes, and glycogen particles. In addition, some tumor cells contained melanosomes and/or a few neurosecretory granules. We consider that the present tumor suggests a close association of ectoderm, mesenchyma, and neuroectoderm in embryogenesis of the tooth, and can raise a diagnostic confusion with melanotic neuroectodermal tumor.

Antigens, Neoplasm↗
PubMed2001

Cyst-like lesions of the lunate resembling Kienböck's disease: a case report.

A 33-year-old man presented with a cyst-like lesion of the lunate resembling Kienböck's disease. Radiographs showed collapse of the proximal portion of the lunate and a lucent lesion in the triquetrum. T1-weighted magnetic resonance images showed a low signal in the collapsed part of the lunate but not in the remaining area. During surgery the lesion of the triquetrum contained serous fluid and the lunate was partially collapsed. Histologically, the triquetrum consisted of fibrous connective tissue and the lunate consisted of a mixture of bone, cartilage, and fibrous tissue without necrosis. The lunate lesion was diagnosed as a collapsed cyst-like lesion, although radiographs resembled Kienböck's disease. The lesion was successfully treated surgically with curettage, bone grafting, and external skeletal fixation. The patient is asymptomatic 3.5 years after surgery with some recovery of the trabecular pattern of the lunate.

Adult↗
PubMed2001

Enhanced protein levels of protein thiol/disulphide oxidoreductases in placentae from pre-eclamptic subjects.

Recent studies have indicated that pre-eclampsia is closely associated with oxidative stress both in maternal circulation and in the placenta. Protein thiol/disulphide oxidoreductases, such as thioredoxin, glutaredoxin, and protein disulphide isomerase have recently been found to eliminate reactive oxygen species (ROS) and regenerate oxidatively damaged proteins. Protein thiol/disulphide oxidoreductases may also play a role in combating pre-eclampsia. In this study, we examined the accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins, which are markers of lipid peroxidation, in human placentae of normal and pre-eclamptic subjects. We also examined the protein levels of thioredoxin, glutaredoxin, and protein disulphide isomerase in placentae. Immunoblotting and immunohistochemistry showed that HNE-modified proteins accumulated to a greater extent in pre-eclamptic placentae than in normal placentae. In both normal and pre-eclamptic placentae, thioredoxin, glutaredoxin, and protein disulphide isomerase were detected in the trophoblasts of the floating villi. The levels of these proteins were increased approximately 2- to 3-fold in the pre-eclamptic placentae compared to the normal placentae. These results indicated that the pre-eclamptic placentae were exposed to oxidative stress and that the protein thiol/disulphide oxidoreductases were adaptively induced in pre-eclamptic placentae, suggesting possible roles for thioredoxin, glutaredoxin, and protein disulphide isomerase in protecting placental functions against oxidative stress caused by pre-eclampsia.

Adult↗
PubMed2001

Cyclic AMP regulates the calcium transients released from IP(3)-sensitive stores by activation of rat kappa-opioid receptors expressed in CHO cells.

We analyzed intracellular Ca(2+)and cAMP levels in Chinese hamster ovary cells expressing a cloned rat kappa opioid receptor (CHO-kappa cells). Although expression of kappa(kappa)-opioid receptors was confirmed with a fluorescent dynorphin analog in almost all CHO-kappa cells, the kappa-specific agonists, U50488H or U69593, induced a Ca(2+) transient only in 35% of the cells. The Ca(2+) response occurred in all-or-none fashion and the half-maximal dosage of U50488H (812.1nM) was higher than that (3.2nM) to inhibit forskolin-stimulated cAMP. The kappa-receptors coupled to G(i/o)proteins since pertussis toxin significantly reduced the U50488H actions on intracellular Ca(2+) and cAMP. The Ca(2+) transient originates from IP(3)-sensitive internal stores since the Ca(2+) response was blocked by a PLC inhibitor (U73122) or by thapsigargin depletion of internal stores while removal of extracellular Ca(2+) had no effect. Interestingly, application of dibutyryl cAMP (+ 56.2%) or 8-bromo-cAMP (+ 174.7%) significantly increased the occurrence of U50488H-induced Ca(2+) mobilization while protein kinase A (PKA) inhibitors, Rp-cAMP (-32.3%) or myr-psi PKA (-73.9%) significantly reduced the response. Therefore, it was concluded that cAMP and PKA activity can regulate the Ca(2+) mobilization. These results suggest that the kappa receptor-linked cAMP cascade regulates the occurrence of kappa-opioid-mediated Ca(2+) mobilization.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Inhibition of neuronal nitric oxide synthase ameliorates renal hyperfiltration in streptozotocin-induced diabetic rat.

Systemic inhibition of nitric oxide synthase (NOS) in streptozotocin-induced (STZ-induced) diabetic rats results in decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) and an increase in renal vascular resistance (RVR). However, the exact isoform of NOS involved in diabetic renal hyperfiltration has not been determined. This study was conducted to clarify whether NO derived from neuronal NOS is involved in diabetic renal hyperfiltration when using a selective inhibitor of neuronal NOS, 7-nitro indazole (7-NI). Continuous infusion of NG-nitro-L -arginine methyl ester (L-NAME) at 5 microg/kg/min ameliorated renal hyperfiltration, decreased RPF, and increased RVR in diabetic rats without affecting the mean arterial pressure (MAP). 7-NI administered intraperitoneally in diabetic rats significantly reduced GFR without affecting MAP, but the renal hyperfiltration was still observed after the administration of 7-NI. The combined administration of L-NAME after 7-NI caused a further decrease in GFR in diabetic rats and ultimately resulted in normalization of GFR. 7-NI did not change any parameters of renal hemodynamics in control rats. Urinary excretion of nitrite/nitrate and cyclic guanosine monophosphate was significantly increased in diabetic rats over values found in control rats. Our results suggested that a local inhibition of NO in the kidney was involved in the amelioration of diabetic renal hyperfiltration and that NO derived from neuronal NOS is involved, at least in part, in renal hyperfiltration in STZ-induced diabetic rats.

Animals↗
PubMed2001

Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene.

Diffuse mesangial sclerosis is a rare renal disease, occurring either in isolation or as part of Denys-Drash syndrome. Denys-Drash syndrome originates from mutations of the Wilms tumor suppressor gene (WT1 ). We describe the presence of WT1 mutations in 7 Japanese children with isolated diffuse mesangial sclerosis.

Female↗
PubMed2001

Interrater reliability of the Physical Self-Maintenance Scale and the Instrumental Activities of Daily Living Scale in a variety of health professional representatives.

This study was performed to assess interrater reliability of the Japanese version of the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living Scale (IADL), which are simple and efficient assessment instruments of functional abilities in elderly patients. The subjects were 25 consecutive patients with Alzheimer's disease who were outpatients of the Department of Neuropsychiatry in Ehime University School of Medicine and their principal caregivers. One neuropsychiatrist administered the PSMS and IADL, and all sessions were videotaped. Then one clinical psychologist, one public health nurse and one neurologist, and one occupational therapist from another institution, viewed the videotape and performed reassessments. All interrater reliabilities between the neuropsychiatrist and the neurologist, the public health nurse, the clinical psychologist and the occupational therapist were extremely good. Interrater reliability between the public health nurse and the clinical psychologist, between the clinical psychologist and the neurologist and between the public health nurse and the neurologist was also extremely good. The PSMS and IADL showed good interrater reliability between personnel from different disciplines. They are likely to be useful tests for everyday medical consultations and for field research.

Activities of Daily Living↗
PubMed2001

Retroperitoneoscopic unroofing of a renal cyst under epidural anesthesia.

Laparoscopic surgery has routinely been performed under general anesthesia. Our first case of a large renal cyst treated successfully with retroperitoneoscopic unroofing under epidural anesthesia is presented here. Epidural anesthesia can be used for retroperitoneoscopic surgery if necessary.

Anesthesia, Epidural↗
PubMed2001

Suppression of arthritis by forced expression of cyclin-dependent kinase inhibitor p21(Cip1) gene into the joints.

Rheumatoid synovial fibroblasts (RSF) express cyclin-dependent kinase (CDK) inhibitors p16(INK4a) and p21(Cip1) when they are growth-inhibited in vitro. The induction of p16(INK4a) is characteristic of RSF and intra-articular p16(INK4a) gene therapy has been shown to suppress adjuvant arthritis (AA) of rats. The other inducible CDK inhibitor, p21(Cip1), has multiple functions depending on the cell type. They include inhibition of CDK as well as promotion of active CDK complex formation and induction of apoptosis. This study is to discern the biological effects of p21(Cip1) gene transfer into RSF and its therapeutic effects on AA. A recombinant adenovirus containing a human p21(Cip1) gene and control adenoviruses were prepared. RSF infected with these viruses were examined for their cell growth. Apoptotic cell death was evaluated by nuclear staining and DNA fragmentation analysis. In vivo gene therapy of rat AA was carried out by intra-articular injection of the viruses. Severity of the arthritis was clinically scored. The treated joints were examined histologically and proliferating cell nuclear antigens (PCNA) were detected immunohistochemically. The adenoviral p21(Cip1) gene transfer inhibited growth of RSF without inducing apoptosis. p21(Cip1) gene therapy suppressed AA clinically and histologically. The effects were comparable to p16(INK4a) gene therapy. PCNA expression was reduced in the p21(Cip1)-treated joints. The adenoviral gene transfer of p21(Cip1) ameliorated rat AA. The effect was attributable to inhibition of proliferation. Because p21(Cip1) is induced more easily by many chemicals than p16(INK4a), it also appears to be a feasible target in developing anti-rheumatic drugs.

Adenoviridae↗
PubMed2001

Phase I trial of gemcitabine in patients with advanced pancreatic cancer.

BACKGROUND: Gemcitabine is the most promising new agent currently being tested in pancreatic cancer. The present study was conducted to confirm the tolerability of a weekly schedule of gemcitabine at a dose of 1000 mg/m2 in Japanese patients with advanced pancreatic cancer. METHODS: The primary end-point was to evaluate the frequency of dose-limiting toxicity. Gemcitabine 1000 mg/m2 was administered over 30 min weekly in two schedules: gemcitabine x3 every 4 weeks (Schedule 1) and gemcitabine x7 followed by a week of rest and then gemcitabine x3 every 4 weeks thereafter (Schedule 2). At least three patients entered each schedule and three additional patients were treated in the presence of dose-limiting toxicity. RESULTS: Eleven chemo-naive patients with a good Karnofsky performance status of > or =80 points and distant metastasis were entered into this trial. In Schedule 1, no dose-limiting toxicity was observed in the three patients. In Schedule 2, the evaluation of dose-limiting toxicity was complete in six of the eight enrolled patients and two patients showed dose-limiting toxicity in this Schedule; one patient experienced both grade 4 leukocytopenia and grade 4 neutropenia, and both grade 4 neutropenia and grade 3 GOT/GPT increased in another patient. Two patients (18%) showed a partial response and a clinical benefit response was also achieved in two (29%) of the seven evaluable patients. CONCLUSION: Gemcitabine 1000 mg/m2 weekly x7 followed by a week of rest and weekly x3 every 4 weeks thereafter may be tolerated in Japanese patients with advanced pancreatic cancer.

Adult↗
PubMed2001

Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma: a comparative study.

BACKGROUND: Radiofrequency ablation (RFA) is a novel thermal ablation technique to achieve coagulative necrosis of hepatocellular carcinoma. A study was conducted to compare the antitumor effect and adverse effect of RFA with those of percutaneous ethanol injection (PEI) in patients with solitary small hepatocellular carcinoma. METHODS: The study population consisted of 119 consecutive patients with solitary hepatocellular carcinoma smaller than 3 cm in diameter. Among these, 23 patients were treated with RFA and the remaining 96 patients were treated with PEI. The antitumor effects of both treatments were assessed by contrast-enhanced computed tomography 1 month after treatment. RESULTS: Complete tumor necrosis was achieved in 23 patients (100%) of the RFA group and 90 patients (94%) of the PEI group (p = 0.48) and local recurrence rates at 1 year were 15% in the RFA group and 14% in the PEI group (p = 0.80). RFA required an average of 1.5 sessions to achieve complete necrosis, whereas PEI required an average of 4.0 sessions. As a consequence, the hospital stay in the RFA group (median 10 days) was significantly shorter than that in the PEI group (median 17 days). There were no serious adverse effects or complications except for one case of cholangitis in the PEI group, although deterioration of serum transaminase after RFA was significantly more severe than that after PEI. CONCLUSION: RFA achieved complete tumor necrosis for small hepatocellular carcinoma with fewer treatment sessions compared with PEI. There were no serious complications.

Adult↗
PubMed2001

Spontaneous regression of hepatocellular carcinoma with multiple lung metastases: a case report.

Spontaneous regression of hepatocellular carcinoma is an extraordinarily unusual phenomenon. We present here a case of a 75-year-old man in whom multiple lung metastases of hepatocellular carcinoma regressed spontaneously. He underwent systemic chemotherapy for hepatocellular carcinoma with multiple lung metastases. However, the chemotherapy was not effective and he was therefore followed up without any anticancer treatments in an outpatient clinic. Four months later, multiple lung nodules regressed dramatically and the serum alpha-fetoprotein level decreased markedly. After an 8-month period of the regression, however, intrahepatic lesions gradually enlarged, although multiple lung metastatic lesions remained regressed. The mechanisms underlying this intriguing phenomenon remain unknown.

Aged↗
PubMed2001

Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice.

Green tea contains various antioxidative flavan-3ols (tea catechins), such as (-)-epigallocatechin gallate (EGCg, the major catechin), which exert potent inhibitory effects on LDL oxidation in vitro and ex vivo in humans. In this study, the antiatherogenic effects of tea catechins were examined in atherosclerosis-susceptible C57BL/6J, apoprotein (apo)E-deficient mice. Male apoE-deficient mice (10 wk old) were fed an atherogenic diet for 14 wk; during that time, one group (tea) was supplied drinking water supplemented with green tea extract (0.8 g/L), and another group (control) was offered the vehicle only. The tea extract consisted of the following (g/100 g): EGCg, 58.4; (-)-epigallocatechin (EGC), 11.7; (-)-epicatechin (EC), 6.6; (-)-gallocatechingallate (GCg), 1.6; (-)-epicatechin gallate (ECg), 0.5; and caffeine, 0.4. The estimated actual intake of tea catechin was 1.7 mg/(d. mouse). Tea ingestion did not influence plasma cholesterol or triglyceride concentrations. Plasma lipid peroxides were reduced in the tea group at wk 8, suggesting that the in vivo oxidative state is improved by tea ingestion. Atheromatous areas in the aorta from the arch to the femoral bifurcation and aortic weights were both significantly attenuated by 23% in the tea group compared with the control group. Aortic cholesterol and triglyceride contents were 27 and 50% lower, respectively, in the tea group than in the control group. These results suggest that chronic ingestion of tea extract prevents the development of atherosclerosis without changing the plasma lipid level in apoE-deficient mice, probably through the potent antioxidative activity of the tea.

Animals↗
PubMed2001

Lipophilic statins augment inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes.

Nitric oxide production by inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of cardiovascular dysfunction. We investigated the effects of statins on iNOS expression and subsequent nitric oxide synthesis in cardiac myocytes and the mechanism by which statins exert their effects. We measured the production of nitrite, a stable metabolite of nitric oxide, in cultured neonatal rat cardiac myocytes with the Griess reagent. iNOS mRNA and protein expression were assayed by reverse transcription polymerase chain reaction and Western blotting, respectively. The lipophilic statins fluvastatin and lovastatin significantly increased interleukin-1beta-induced nitrite production by cardiac myocytes, whereas hydrophilic pravastatin did not. Increased nitrite production by fluvastatin was accompanied by increased iNOS mRNA and protein accumulation. Exogenous mevalonate, but not squalene, significantly blocked the stimulatory effect of fluvastatin on nitrite production. Cotreatment with geranylgeranyl-pyrophosphate also reversed the effect of fluvastatin. Furthermore, both Rho inhibitor C3 exoenzyme and Rho kinase inhibitor Y-27632 significantly increased interleukin-1beta-induced nitrite accumulation in cardiac myocytes. These results demonstrated that lipophilic statins upregulate iNOS expression and subsequent nitric oxide formation in cardiac myocytes via inhibition of Rho.

Animals↗
PubMed2001

Further reduction of radiation dose in helical CT for lung cancer screening using small tube current and a newly designed filter.

A new aluminum filter, 5.8 mm thick at the center, was designed. The effective energy, exposure dose, absorbed dose, and noise were measured by using low-dose technique, very low-dose technique with a conventional filter, and very low-dose technique with a new filter on a chest phantom. Accuracy of very low-dose computed tomography (CT) with a new filter was compared against standard helical CT in 40 patients and against chest radiography in 35 patients. Effective energies were 42.6 keV and 51.6 keV at a conventional filter and the new filter, respectively. Compared against 20mA with a conventional filter, exposure dose was reduced by 17%, and absorbed dose was equivalent, at 30 mA with the new filter. Noise was improved by 9%. Compared with standard helical CT, the sensitivity, specificity, and accuracy of very-low-dose helical CT were 100%, 88%, and 95%, respectively. Very-low-dose helical CT was found to be significantly superior to chest radiography in the detection of lung cancers. Using a smaller tube current and an appropriate filter allows a further reduction in radiation dose in helical CT for lung cancer screening.

Adult↗
PubMed2001

A morphological study of age changes in adult human auricular cartilage with special emphasis on elastic fibers.

OBJECTIVE: It is well known that the size of the human auricle increases after it has finished development. The reason why the size of the human auricle continues to enlarge until advanced age after reaching adulthood was investigated by observation of the ultrastructure of elastic fibers in human auricular cartilage. METHODS: A total of 1958 subjects (966 males and 992 females) were classified into 18 age groups from 0 to 5 years up to 85 years and above by 5-year intervals. Ear length, ear width, and length of ear attachment were measured with calipers. Human auricular cartilage was obtained from 26 subjects (16 males and 10 females) aged 14 to 79 years, stained by orcein, and examined by light and electron microscopy. RESULTS: Each item of measurement of human auricular size increased significantly with age in both males and females. On morphological examination by light and electron microscopy after orcein staining, elastic fibers in the cartilage were almost homogeneous in diameter and surrounded the cartilage lacuna in bundle-like fashion in young persons, whereas those in elderly persons were heterogeneous in thickness and had many fragments surrounding the territorial matrix. In elderly persons, collagen-like fibers and small vesicles with heterogeneous electron density were frequently observed near elastic bundles around the territorial matrix. CONCLUSION: Structural changes of auricular cartilage associated with morphological age changes of elastic fibers may be one of the causes of expansion of the auricle after reaching adulthood.

Adolescent↗