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Biomedical subjects

S Ito

Publications and source records attributed to S Ito.

At least 37 records · Page 2Linked to original sources

Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients.

Prediction of peritoneal relapse is extremely important for gastric cancer patients after curative surgery. The present study prospectively validates the prognostic ability of quantifying carcinoembryonic antigen (CEA) mRNA in peritoneal washes by real-time reverse transcriptase-polymerase chain reaction. Based on a retrospective study of 197 curatively resected gastric cancer patients (training set), we determined a cutoff value of CEA mRNA using receiver-operating characteristic curve. We used this cutoff value to validate the risk of peritoneal recurrence in a new cohort of 86 gastric cancer patients (validation set) between July 2000 and December 2002 in a prospective study. During the median 30 months of postoperative surveillance, 20 of the 86 patients died, and 13 of the 20 developed peritoneal metastases. Peritoneal recurrence-free survival as well as overall survival was significantly worse in patients with positive CEA mRNA (P<0.0001). Multivariate analysis with the Cox proportional hazards model showed that positive CEA mRNA was a significant independent risk factor with both survival (P=0.0130) and peritoneal recurrence-free survival (P=0.0006) as end points. These results indicate that quantitation of CEA mRNA in peritoneal washes is a reliable prognostic indicator of peritoneal recurrence in the clinical setting.

Adenocarcinoma↗

Inhibitory effects of aloe carboxypeptidase fraction on streptozotocin-induced enhancement of vascular permeability in the pancreatic islets.

The protective actions of components isolated from Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japanese) on streptozotocin (Sz)-induced necrosis of B cells in the pancreatic islets of the mouse were investigated to clarify its action mechanism involved in anti-diabetic effects. In this experiment, phenol low molecular weight components of aloin and aloin A that were anti-oxidants and derived from the leaf skin or pulp extract, an aloe carboxypeptidase fraction that is a inhibitor of enhanced vascular permeability and a glycoprotein component that decreases blood glucose were tested with mice precedently administered with Sz which is known as a cytotoxin specific to B cells. The results showed that the treatment group receiving Sz followed by the aloe carboxypeptidase fraction increased the inhibition of dye leakage by 75.8% (p<0.001) in the extract of whole pancreas in comparison to the control group and the aloe carboxypeptidase fraction group also increased the inhibition effect by 68.4% (p<0.001) in the extract of pancreatic islets as compared to the control group. The carboxypeptidase is an aloe-derived protease known to inhibit the acetic acid-related enhancement of intraperitoneal vascular permeability in mice. Further, the elevation of blood glucose in Sz-induced diabetic mice intraperitoneally given the aloe carboxypeptitase fraction was significantly (p<0.01-0.001) restrained at 3, 7 and 14 days after the injection as compared to the control group given solvent only. The results of this experiment suggested that the inhibitory effect on the enhancement of vascular permeability related to the vascular acute inflammatory response at Sz-induced lesions of pancreatic islets was involved in the action mechanism of this enzyme.

Aloe↗

Unilateral agenesis and hypoplasia of the internal carotid artery: a report of three cases.

We report one patient with agenesis and two with hypoplasia of the internal carotid artery (ICA) from an angiographic series of 1275 consecutive patients. In all three patients, MRI and MR angiography were used to establish the anatomical situation; however, they may not clearly distinguish between hypoplasia and agenesis or acquired stenosis or occlusion of the ICA. In such cases, CT of the skull base may be obtained to clarify matters. In all patients, retrograde flow via a large posterior communicating artery was demonstrated. Single-photon emission computed tomography confirmed both the adequacy of cerebral perfusion and the preservation of vasomotor reactivity.

Aged↗

Spontaneous lymphocyt ic thyroiditis in interferon regulatory factor-1 deficient non-obese diabetic mice.

Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in interferon-mediated immune reaction, CD8+ T cell differentiation and development of T helper 1 immune reaction. We have recently demonstrated that IRF-1 is pivotal in iodine-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice. However, it remains unclear whether the mechanism involved in spontaneous LT is identical with iodine-induced LT in NOD mice. To determine the role of IRF-1 in spontaneous LT, we used IRF-1 deficient NOD mice as well as IRF-1 +/+ and +/- mice which were free from treatments for LT induction, and LT was evaluated at 24 weeks of age. IRF-1 +/+, +/- and -/- mice developed LT spontaneously, and there were no differences among the 3 IRF-1 genotypes in the incidence and severity of LT. Whereas both CD4+ and CD8+ T cells were present in the diseased thyroid of IRF-1 +/+ mice, CD8+ T cells were absent in the thyroid of IRF-1 -/- mice. MHC class II antigen expression was induced in the inflamed thyroid of IRF-1 -/- mice comparable to IRF-1 +/+ mice. There was a selective reduction in the number of CD8+ T cells in the spleen of IRF-1 -/- mice. IFNgamma production, but not IL-10, by concanavalin A-stimulated splenocytes was significantly reduced in IRF-1 deficient mice. These results suggest that IRF-1 plays only a minor role in spontaneous LT in NOD mice and, furthermore, the mechanism involved in spontaneous LT is different from that of iodine-induced LT in NOD mice.

Animals↗

Oedema formation in experimental photo-irradiation therapy of brain tumours using 5-ALA.

BACKGROUND: Five-aminolevulinic acid (5-ALA) induces the specific accumulation of photosensitising porphyrins in malignant gliomas and has been explored for photo-irradiation therapy of these tumours. However, information is unavailable on whether and to what extent this treatment modality may induce the formation of brain oedema, and how potential oedema might be treated. METHODS: Rats were implanted with C6 gliomas. Eight days later magnetic resonance images (MRI) were obtained. On day 9 rats received 100 mg 5-ALA/kg b.w. and were craniotomized for photo-irradiation of tumours 6 hours later (100 J/cm2, 635 nm argon-dye laser). Part of the animals was treated with daily dexamethasone injections (0.3 mg/kg), beginning 6 hours before phototherapy. 72 hours later, brains were removed and dissected according to tumour dimensions on pre-therapy MRI into "tumour", "brain around tumour" (BAT), residual cortex and basal ganglia, for measurements of water contents. Measurements were also performed in untreated animals with tumours, with or without steroid treatment and in control animals. An additional group of animals lacking tumours, with or without steroid treatment, underwent 5-ALA-phototherapy to determine effects on normal brain. RESULTS: C6 gliomas induced brain oedema, which responded to steroid treatment. 5-ALA-phototherapy resulted in additional oedema, which responded partly to steroids. 5-ALA-phototherapy of normal brain increased water content moderately in irradiated cortex. This oedema was also partly counteracted by steroids. CONCLUSIONS: Photo-irradiation therapy with 5-ALA induces oedema which is partly counteracted by steroid therapy. The possibility of steroid resistant oedema formation should be considered when planning human trials with this treatment modality.

Aminolevulinic Acid↗

Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS).

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major in vivo substrate for protein kinase C in the brain and has been implicated in cellular processes associated with cytoskeletal restructuring such as synaptic trafficking and neurotransmitter release. A phosphorylation-site specific antibody against Ser159-phospho-MARCKS (pS159-Mar-Ab) revealed that MARCKS is phosphorylated at Ser159 by Rho-kinase and that its phosphorylation is inhibited by the Rho-kinase specific inhibitor H-1152. Since the function of MARCKS is regulated by phosphorylation at multiple sites, here we examined the involvement of Rho-kinase in relation to phosphorylation of MARCKS at Ser159 in inflammatory and neuropathic pain by H-1152. When intrathecally administered 10 min before s.c. injection of formalin, H-1152 at 10 and 100 ng attenuated the second-phase, but not the first-phase, pain-like behaviors in the formalin test. Neuropathic pain induced by selective L5 spinal nerve transection was also relieved by intrathecal injection of H-1152. Nitric oxide synthase activity visualized by NADPH diaphorase histochemistry increased in the superficial layer of the spinal cord 30 min after formalin injection and 7 days after nerve transection, which were blocked by H-1152. Phosphorylation of MARCKS at Ser159 was detected in the spinal cord by pS159-Mar-Ab and the level of phosphorylation increased in the superficial layer after nerve transection. In contrast, immunoreactivities of neuronal nitric oxide synthase and MARCKS did not change significantly in the spinal cord before and after nerve transection. Taken together, the present study demonstrates that Rho-kinase is involved in inflammatory pain and the maintenance of neuropathic pain through phosphorylation of MARCKS at Ser159.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

A novel diagnostic method for evaluation of vascular lesions in the digestive tract using infrared fluorescence endoscopy.

BACKGROUND AND STUDY AIMS: We have developed an infrared fluorescence endoscope to evaluate gastrointestinal vascular lesions. Infrared endoscopy (IRE) after intravenous administration of indocyanine green (ICG) is used at present to examine vascular lesions such as esophageal varices. However, no previous study has compared the sensitivity of infrared fluorescence endoscopy (IRFE) with that of IRE. In this study, we compared the usefulness of IRFE and IRE. PATIENTS AND METHODS: For IRFE we used an infrared endoscope equipped with excitation and barrier filters and an intensified charge-coupled device camera. In preliminary experiments, the observable tissue depth was assessed by wrapping increasing numbers of layers of commercially available pork around a syringe containing a uniform concentration of ICG or by changing the concentration of ICG in a syringe covered by a piece of pork of uniform thickness. In the clinical part of the study, ICG was administered intravenously at different concentrations to patients with esophageal varices and the resulting infrared fluorescent images were evaluated. RESULTS: The preliminary experiments revealed that the depth of tissue that could be visualized was significantly greater in IRFE than it was in IRE (11.2 mm in IRFE vs. approximately 3.2 mm in IRE). Clear infrared fluorescence was obtained by IRFE at lower concentrations of ICG than the concentrations required to obtain clear images using IRE. In the clinical part of the study, clear infrared fluorescence was observed in a region where esophageal varices had been detected by conventional endoscopy when ICG was administered in doses of 0.005 mg/kg to 0.01 mg/kg, which was lower than the doses used in IRE. CONCLUSIONS: Compared with conventional IRE, IRFE facilitated the observation of deeper layers, and esophageal varices were observed by IRFE following the intravenous administration of a markedly reduced dose of ICG. IRFE, in combining the characteristics of reflected infrared light and fluorescence, may be a useful novel procedure in the diagnosis of vascular lesions in the gastrointestinal tract.

Aged↗

High salt diet enhances cardiovascular responses from the nucleus tractus solitarius and ventrolateral medulla of Sprague-Dawley rats.

High salt intake has been shown to augment the sensitivity of rostral ventrolateral medulla (RVLM) sympathoexcitatory neurons. We examined the effects of 4 weeks of high dietary salt (8%) on the sensitivity of nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM) in controlling RVLM. In chloralose-anesthetized Sprague-Dawley rats, high salt intake did not elevate baseline arterial pressure or heart rate (HR). In high-salt group, NTS, CVLM, and RVLM responses to glutamate were greater. NTS responses to acetylcholine or serotonin, which is independent of baroreflex, also were greater. Phenylephrine or nitroprusside (i.v.) elicited similar changes in arterial pressure and heart rate, the baroreflex sensitivity also was similar in both groups of rats. These results suggest that high salt intake augments the sensitivity of NTS and CVLM sending inhibitory input to RVLM. This presumably may inhibit the RVLM, thereby inhibiting the elevation of arterial pressure.

Acetylcholine↗

Radiation protection system at the RIKEN RI beam factory.

The RIKEN RI (radioactive isotope) Beam Factory is scheduled to commence operations in 2006, and its maximum energy will be 400 MeV u(-1) for ions lighter than Ar and 350 MeV u(-1) for uranium. The beam intensity will be 1 pmicroA (6 x 10(12) particles s(-1)) for any element at the goal. For the hands-on-maintenance and the rational shield thickness of the building, the beam loss must be controlled with several kinds of monitors. Three types of radiation monitors will be installed. The first one consists of a neutron dose equivalent monitor and an ionisation chamber, which are commercially available area monitors. The second one is a conventional hand-held dose equivalent monitor wherein the logarithmic signal is read by a programmable logic controller based on the radiation safety interlock system (HIS). The third one is a simple plastic scintillator called a beam loss monitor. All the monitors have threshold levels for alarm and beam stop, and HIS reads all these signals.

Equipment Design↗

Mapping of plumage colour and blood protein loci on the microsatellite linkage map of the Japanese quail.

The objective of this work was to map classical markers (plumage colours and blood proteins) on the microsatellite linkage map of the Japanese quail (Coturnix japonica). The segregation data on two plumage colours and three blood proteins were obtained from 25 three-generation families (193 F2 birds). Linkage analysis was carried out for these five classical markers and 80 microsatellite markers. A total of 15 linkage groups that included the five classical loci and 69 of the 80 microsatellite markers were constructed. Using the BLAST homology search against the chicken genome sequence, three quail linkage groups, QL8, QL10 and QL13, were suggested to be homologous to chicken chromosomes GGA9, GGA20 and GGA24, respectively. Two plumage colour loci, black at hatch (Bh) and yellow (Y), and the three blood protein loci, transferrin (Tf), haemoglobin (Hb-1) and prealbumin-1 (Pa-1), were assigned to CJA01, QL10, QL8, CJA14 and QL13, respectively.

Animals↗

Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan.

BACKGROUND: The tumour necrosis factor (TNF) gene family, which includes TNF, LTA, and LTB, is located consecutively on human chromosome 6p21 region, which has been linked to asthma by several genome-wide screens. (LTA, lymphotoxin-alpha; LTB, lymphotoxin-beta). OBJECTIVE: The aim of the present study was to determine whether genes on 6q21 are related to development of atopic asthma. Methods We screened for mutations in the coding and promoter regions of genes in the TNF-LTA region, including BAT1, NFKBIL1, LTA, TNF, LTB, AIF, and BAT2, and conducted a transmission disequilibrium test of 41 polymorphisms in 137 families identified through pro-bands with childhood-onset atopic asthma. (BAT1, HLA-B-associated transcript 1; NFKBIL1, nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor-like 1; AIF, allograft inflammatory factor 1). RESULTS: Haplotypes of the LTA/TNF linkage disequilibrium block were associated significantly with asthma (global P=0.0097). Transmission patterns of the common haplotypes to asthmatic offspring were predicted by a single-nucleotide polymorphism in the LTA promoter region. The G allele of the LTA-753G/A polymorphism was transmitted preferentially to asthma-affected individuals (P=0.001). Luciferase reporter assays with constructs containing the 5' and 3' flanking regions of the LTA gene showed 30-50% lower transcriptional activity when the -753A allele was present than that of other haplotypes. CONCLUSION: Our results suggest that LTA is one of the genes that contributes to susceptibility to atopic asthma, and that the association of the TNF/LTA haplotypes to asthma may be defined by the polymorphism in the LTA promoter region in the Japanese population.

Adolescent↗

Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells.

BACKGROUND: Oxidative stress, including the generation of reactive oxygen species (ROS), is involved in hepatofibrogenesis. The authors' previous studies have shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates the activation of cultured rat hepatic stellate cells (HSCs), which possess oestrogen receptor subtype beta and are also activated by ROS. AIMS: To define the mechanisms by which female sex hormones play an antifibrogenic role in activated HSCs, the effects of oestradiol and progesterone on ROS generation processes and intracellular pathways, leading to the activation of HSCs undergoing oxidative stress, was examined. METHODS: HSCs, isolated from rats, were cultured for 7 days with oestradiol or progesterone for 24 hours as pretreatment, and oxidative stress was then induced by exposure to low doses of hydrogen peroxide for another 24 hours. RESULTS: Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced transforming growth factor-beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the activation of mitogen activated protein kinase (MAPK) pathways and transcription factors. Progesterone exerted a stimulatory effect through the progesterone receptor on the induction of ROS generation processes and intracellular pathways, resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were inhibited by oestradiol. CONCLUSION: These findings show for the first time that oestradiol inhibits the activation of transcription factors by suppressing ROS generation processes and the MAPK pathways, and inactivates the downstream transcription processes involved in TGF-beta1 expression and HSC activation, whereas progesterone acts in opposition to the favourable effects of oestradiol and its effects are blocked by oestradiol.

Animals↗

HyperIgEaemia in patients with juvenile muscular atrophy of the distal upper extremity (Hirayama disease).

BACKGROUND: Juvenile muscular atrophy of the distal upper extremity (Hirayama disease) is characterised by anterior horn cell loss in the lower cervical cord, presumably caused by anterior displacement of the dural sac during neck flexion. A recent report suggests that atopy and IgE may contribute to anterior horn damage. OBJECTIVE: To investigate whether IgE is a contributing factor in Hirayama disease. METHODS: Serum total IgE and allergen specific IgE were examined in 20 consecutive patients, and their correlations with clinical profiles investigated. RESULTS: Past or present history of allergy/atopy was found in only four patients (20%), but serum IgE was raised in 14 (70%). Patients with hyperIgEaemia had more severe clinical disabilities than those without (p = 0.01). In patients whose history of Hirayama disease was less than five years, serum total IgE was higher than in those with the disease for five years or more (p = 0.05). CONCLUSIONS: The results suggest that hyperIgEaemia is often associated with Hirayama disease and can facilitate its pathophysiology, particularly in the early phases of the disease. HyperIgEaemia does not appear to involve the anterior horn cells primarily.

Adolescent↗

Effects of positive pressure in odontogenic keratocysts.

Intracystic fluid pressure is thought to be involved in odontogenic cyst growth. In this study, we investigated the effects of positive pressure on the expression of interleukin-1alpha (IL-1alpha), matrix metalloproteinases (MMPs), and prostaglandin E2 (PGE2) in odontogenic keratocysts to determine whether this pressure stimulates inflammatory cytokine production and signaling of osteoclastogenic events. Positive pressure enhanced the expression of IL-1alpha mRNA and protein in odontogenic keratocyst epithelial cells, and increased the secretion of MMP-1, MMP-2, MMP-3, and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and the epithelial cells. The pressure-induced secretions were inhibited by an interleukin-1 receptor antagonist. Recombinant human interleukin-1alpha (rhIL-1alpha) increased the secretion of MMP-1, MMP-2, MMP-3, and PGE2 in the fibroblasts. Furthermore, in the fibroblasts, rhIL-1alpha enhanced the expression of macrophage colony-stimulating factor (M-CSF) mRNA, and rhIL-1alpha-induced PGE2 increased the expression of nuclear factor kappaB ligand (RANKL) mRNA. Thus, positive pressure may play a crucial role in odontogenic keratocyst growth via stimulating the expression of IL-1alpha in epithelial cells.

Carrier Proteins↗

[Pulmonary pleomorphic carcinoma; report of a case].

We report a case of a 64-year-old man with pleomorphic carcinoma of the lung and thymic cyst. He was admitted to our hospital because of an abnormal shadow observed on chest X-ray. Computed tomography (CT) showed a mass lesion located in the right upper lobe and a non-invasive anterior mediastinal tumor adjacent to the left brachiocepharic vein. On enhanced CT, the lung mass showed central low-attenuation areas with a substantial enhancement in the periphery. Preoperative transbronchial blushing cytology of the mass revealed adenocarcinoma. With a diagnosis of primary lung cancer (cT3N0M0) and mediastinal tumor, an operation was performed through a median sternotomy. The mediastinal tumor was excised and a right upper lobectomy and were also accomplished, because the lung tumor did not show adhesion or pleural invasion. Histopathologic examination of the resected specimen revealed that the lung tumor composed of a mixture of spindle and giant cell features and contained a component of adenocarcinoma and squamous cell carcinoma. This finding yielded a pathological diagnosis of pleomorphic carcinoma (pT2N0M0). The mediastinal tumor was diagnosed as thymic cyst. The postoperative course was uneventful, and he is currently well 6 months after surgery.

Adenocarcinoma↗