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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 217 records · Page 12Linked to original sources

Ubiquinone systems in fungi. V. Distribution and taxonomic implications of ubiquinones in Eurotiales, Onygenales and the related plectomycete genera, except for Aspergillus, Paecilomyces, Penicillium, and their related teleomorphs.

The ubiquinone (coenzyme Q) systems were determined for 176 teleomorphic isolates, 14 anamorphic isolates, and three samples of fruit-bodies of Dendrosphaera eberhardtii, which belonged to Eurotiales, Onygenales, and related taxa. In Eurotiales, Ascosphaera had Q-9, whereas Bettsia had Q-10. All isolates of Monascaceae had the Q-10 system, whereas those of four genera of Pseudeurotiaceae had the Q-10(H2) system. The Q-10(H2) system was found in genera of Trichocomaceae, except for Aspergillus, Penicillium, Paecilomyces, and their related taxa. However, Thermoascus had the Q-9 system. In Onygenales, members of Arthrodermataceae had Q-9, and those of Gymnoascaceae had Q-10(H2). Isolates of Myxotrichaceae were characterized by Q-10(H2) with few exceptions, which had Q-10. The quinones of Onygenaceae belonged to complex systems, i.e., Q-9, 0-10 and 0-10(H2), and a combination of two systems. Families Onygenaceae and Trichocomaceae are likely a phylogenetic heterogeneity. Ubiquinone analysis provides a very useful criterion of great promise for classifying eurotialean taxa and also for identifying their isolates.

Ascomycota↗

Prevention of death of axotomized hypoglossal neurones and promotion of regeneration by chitin grafting.

1. Chitin is known to promote skin wound healing. In this study, chitin, prepared from Zuwai crab shell, was used as a bridge between the proximal and distal stumps of cut hypoglossal nerves in shrews. We compared the effects of chitin on the regeneration of transected right hypoglossal nerve axons, with those of porcine dermis, bovine dermal aterocollagen, and autologous nerve bundles. 2. To assess the survival of neurones, the size of neuronal cell body, and number of motoneurones were determined in the absence of any bridged material and in the presence of porcine dermis, bovine dermal aterocollagen, chitin, or autologous nerve bundles as a bridge. 3. Our results revealed a significantly better outcome in chitin and autologous nerve bridged groups; the size of neuronal cell body and number of hypoglossal neurones were higher than in the other groups. Chitin also enhanced the regeneration of neurones; the number of horseradish peroxide positive neurones indicative of repaired axonal processes was significantly higher in chitin and autologous nerve-bridged groups than in other groups. 4. Our results demonstrated that the use of chitin sheet or autograft successfully prevented the death of severed neurones and promoted the regeneration of the lesioned nerve. Although the mechanisms underlying the effects of chitin are still unknown, chitin seems to be a potentially useful biocompatible material for nerve repair and regeneration.

Animals↗

Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo.

Protein kinase C (PKC) has been known to play an important role in ischemic preconditioning (IP). This study was designed to examine whether the translocation of PKC is associated with the cardioprotective effects of IP in vivo on infarct size and ventricular arrhythmias in a rat model. Using anesthetized rats, heart rate, systolic blood pressure, infarct size and ventricular arrhythmias during 45 min of coronary occlusion were measured. PKC activity was assayed in both the cytosolic and cell membrane fraction. Brief 3-min periods ofischemia followed by 10 min ofreperfusion were used to precondition the myocardium. Calphostin C was used to inhibit PKC. Infarct size was significantly reduced by IP (68.1 (2.5)%, mean (S.E.) vs. 45.2 (3.4)%, p < 0.01). The reduction in infarct size by IP was abolished by pretreatment with calphostin C. The total number of ventricular premature complex (VPC) during 45 min of coronary occlusion was reduced by IP (1474 (169) beats/45 min vs. 256 (82) beats/45 min, p < 0.05). The reduction the total number of VPC induced by IP was abolished by the administration of calphostin C before the episode of brief ischemia. The same tendency was observed in the duration of ventricular tachycardia and the incidence of ventricular fibrillation. PKC activity in the cell membrane fraction transiently increased immediately after IP (100 vs. 142%, p < 0.01) and returned to baseline 15 min after IP. Pretreatment with calphostin C prevented the translocation of PKC. The translocation of PKC plays an important role in the cardioprotective effect of IP on infarct size and ventricular arrhythmias in anesthetized rats.

Animals↗

Adaptive automation, trust, and self-confidence in fault management of time-critical tasks.

An experiment on adaptive automation is described. Reliability of automated fault diagnosis, mode of fault management (manual vs. automated), and fault dynamics affect variables including root mean square error, avoidance of accidents and false shutdowns, subjective trust in the system, and operator self-confidence. Results are discussed in relation to levels of automation, models of trust and self-confidence, and theories of human-machine function allocation. Trust in automation but not self-confidence was strongly affected by automation reliability. Operators controlled a continuous process with difficulty only while performing fault management but could prevent unnecessary shutdowns. Final authority for decisions and action must be allocated to automation in time-critical situations.

Adult↗

Functional neuroimaging of cognition impaired by a classical antihistamine, d-chlorpheniramine.

Antihistamine induced cognitive decline was evaluated using positron emission tomography (PET) measurement of histamine H1 receptor (H1R) occupancy and regional cerebral blood flow (rCBF). Cognitive performance in attention-demanding task deteriorated dose-dependently and the effects were statistically significant after the treatment of 2 mg of d-chlorpheniramine. There was no significant change in subjective sleepiness in the same dose. The regional blockade of H1R was observed mainly in the frontal, temporal and anterior cingulate cortices, and the intravenous administration of d-chlorpheniramine as a therapeutic dose (2 mg) blocked over 60% of H1R in the frontal cortices. The results from activation study using visual discrimination tasks demonstrated that enhanced activity in the right prefrontal and anterior cingulate cortices as well as a decreased activity in the left temporal and frontal cortices and midbrain after the treatment of d-chlorpheniramine. There were no changes in global CBF for the subjects treated with 2 mg d-chlorpheniramine (pre; 44.8+/-3.3 ml dl(-1) min(-1) vs post; 44.4+/-4.7 ml dl(-1) min(-1)). The results indicated that the attention system of human brain could be altered by therapeutic doses of H1R antagonists. These findings provide the information as to the potential risk of antihistamines in our daily activities. British Journal of Pharmacology (2000) 129, 115 - 123

Adult↗

Fulminant hepatitis B following bone marrow transplantation in an HBsAg-negative, HBsAb-positive recipient; reactivation of dormant virus during the immunosuppressive period.

It is widely accepted that seroconversion of HBsAg to HBsAb indicates clearance of hepatitis B virus. We describe a 50-year-old man with chronic myelocytic leukemia who developed lethal hepatitis B 22 months after allo-BMT. He had been negative for HBsAg and positive for HBsAb before BMT. Hepatitis B virus latently existing in the liver cells before BMT proliferated during the immunosuppressed period causing fatal hepatitis. Recipients with positive HBsAb should be considered to have the potential for active hepatitis B to emerge after BMT. Bone Marrow Transplantation (2000) 25, 105-108.

Bone Marrow Transplantation↗

Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat.

Phthalate esters, now regarded as endocrine disruptors, are widely used in the plastics industry. In particular, di-(2-ethylhexyl) phthalate (DEHP) is produced in large quantities, and is used in blood storage bags, catheters and haemodialysis instruments. Previous studies have demonstrated that treatment of rats with DEHP induces testicular atrophy with liver enlargement, although the precise nature and mechanism of the action of DEHP on these organs remains unclear. In the present study, we produced an experimental model of DEHP-induced spermatogenic disturbance in rats by feeding them a DEHP-containing diet. Liver enlargement occurred in rats fed either a 1 or 2% DEHP-containing diet. However, testicular atrophy accompanied by aspermatogenesis was induced by feeding with the 2% but not with the 1% DEHP-containing diet. This suggests that the critical DEHP dose for gonadotoxicity is higher than that for hepatotoxicity. Using the 2% DEHP-dose, the effect of simultaneous administration of antioxidant vitamins (= vitamins C and E) was next examined. It was found that the vitamin supplementation significantly prevented the testicular injury. The results suggest that antioxidant vitamins can protect the testes from DEHP-toxicity.

Animals↗

Immunohistochemical analysis of brainstem lesions in infantile spasms.

Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox-Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine-enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH-immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti-PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients.

Adolescent↗

Enhancement of rat hypoglossal nerve regeneration by chitin sheet plus gangliosides.

The effects of chitin sheet interposition with and without brain gangliosides on the regeneration of hypoglossal nerve fibres was studied in the rat following resection of a 5mm length of the nerve. At 10 weeks after operation, the number of horseradish peroxidase (HRP)-labelled motor neurones, indicative of the axonal repair process, on the side treated with chitin and gangliosides was higher than on the control side (where 5mm of the nerve was simply resected). The ratios of HRP-positive neurones in the right hypoglossal nucleus (treated side)/left hypoglossal nucleus (intact side) was 0 in the 5mm-resected group, 53% in the chitin-grafted group, 88% in the ganglioside (0.2 microg)-injected group, 90% in the ganglioside (2 microg)-injected group, 91% in the chitin with ganglioside (0.2mg)-injected group, 91% in the chitin with ganglioside (2 microg)-injected group and 85% in the autograft group, respectively. There were significant differences between the 5 mm-resected group and chitin-grafted group, ganglioside-injected group, chitin with ganglioside group and autograft group, and between the chitin-grafted group and ganglioside-injected, chitin with ganglioside and autograft groups (P< 0.005, respectively). Our results indicated that the use of chitin and gangliosides stimulated the regeneration of severed motor nerve fibres. These findings suggest that chitin and gangliosides might be therapeutically useful for treatment of neuronal degeneration.

Animals↗

What are the appropriate indications for endoscopic mucosal resection for early gastric cancer? Analysis of 256 endoscopically resected lesions.

BACKGROUND AND STUDY AIMS: Although endoscopic mucosal resection (EMR) for early gastric cancer (EGC) without ulceration or scarring has been very popular in Japan and thought to be beneficial, curability by EMR is still lower than that for surgical resection. We investigated patients whose EGCs were resected endoscopically in order to identify the factors affecting curability by EMR. PATIENTS AND METHODS: We investigated retrospectively 256 EGC lesions (251 patients) which were subjected to EMR between 1989 and 1998 with respect to patient profile, macroscopic type, location, maximum diameter of tumors, resection method and histological typing. The prognoses of the patients were also investigated as far as possible. RESULTS: The curative total resection rate for EMR of EGC was 74.2 %. Concerning the factors affecting curability, the size of the lesion (over 15 mm), the method of resection (divisional resection), and histological typing (poorly differentiated) had a statistically significant effect on the complete resection rate. Multivariate analysis of the factors confirmed these results. Submucosal invasion was suspected in 16 patients after EMR, but submucosal cancer was found in only one patient after further surgery. Where there was recurrence, the longest recurrence-free period after EMR of EGC was 48 months, whereas the mean recurrence-free period was 195.4 days. CONCLUSIONS: The appropriate indication for EMR for EGC is thought to be an intramucosal differentiated-type adenocarcinoma without ulceration or scarring, and no more than 15 mm in size regardless of macroscopic type. Periodic follow-up for at least 5 years is necessary.

Adenocarcinoma↗

Importance of gap junction in gastric mucosal restitution from acid-induced injury.

Evidence is accumulating that gap junctional intercellular communication (GJIC) plays an important role in the gastric mucosal defense system. This study was conducted to determine whether GJIC mediates a restitution process in gastric mucosa. Male Sprague-Dawley rats were fasted and anesthetized. Gastric injury was induced by luminal perfusion with 0.2N HCl for 10 minutes. Mucosal integrity was continuously monitored by measuring the clearance of chromium 51-labeled ethylenediaminetetraacetic acid, which was used for analysis of recovery from the injury. Perfusion with 0.25% octanol (OCT; inhibitor of GJIC) was started after acid injury to assess its effect on restitution. The effect of irsogladine (IG; activator of GJIC) was also tested. Gastric mucosal GJIC was immunohistochemically evaluated with monoclonal antibody gap junction protein (connexin 32). Recovery from acid-induced mucosal injury occurred rapidly when acid perfusion was discontinued (within about 60 minutes). OCT, which didn't cause any injury to normal gastric mucosa, significantly inhibited the restitution. IG reversed this inhibition in a dose-dependent manner. In an immunohistochemical study, OCT-induced damage of gap junction was demonstrated, but not after IG pre-treatment. These findings suggest that GJIC may play a critical role in restitution in rat gastric mucosa and that gap junction function may be one of the important factors for the mucosal defense system.

Animals↗

Early clearance of circulating hepatitis C virus enhanced by induction therapy with twice-a-day intravenous injection of IFN-beta.

To improve the long-term efficacy of interferon (IFN) for treatment of chronic hepatitis C virus (HCV) infection, we proposed induction therapy with twice-a-day IFN-beta injection. This study was intended to clarify the antiviral mechanism. Thirty patients were randomly assigned to two groups: group A (twice-a-day therapy) received 3 MU IFN-beta intravenously (i.v.) twice a day for 2 weeks; group B (once-a-day therapy) received 6 MU of IFN-beta daily. HCV RNA, IFN-beta, alanine aminotransferase (ALT), 2'5'-oligoadenylate synthetase (2'5'-AS) activity, and beta2-microglobulin in serum were compared between the two groups during the first 2 weeks of IFN therapy. The clearance rate of serum HCV RNA in group A (86.7%) was significantly higher than that in group B (13.3%) at day 3 (p = 0.0006). No accumulation of IFN-beta was shown in serum throughout the therapy. The ratio (day 3/day 1) of 2'5'-AS activity was significantly higher in group A. Multivariate analysis indicated twice-a-day IFN-beta injection therapy led to significantly early clearance of circulating HCV. Twice-a-day IFN-beta injection therapy could induce biologically enhanced antiviral activities and be an efficient induction therapy for eradication of HCV.

Adult↗

Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation.

A CD4(+) T cell subpopulation defined by the expression levels of a particular cell surface molecule (e.g. CD5, CD45RB, CD25, CD62L or CD38) bears an autoimmune-preventive activity in various animal models. Here we show that the expression of CD25 is highly specific, when compared with other molecules, in delineating the autoimmune-preventive immunoregulatory CD4(+) T cell population. Furthermore, although CD25 is an activation marker for T cells, the following findings indicate that immunoregulatory CD25(+)CD4(+) T cells are functionally distinct from activated or anergy-induced T cells derived from CD25(-)CD4(+) T cells. First, the former are autoimmune-preventive in vivo, naturally unresponsive (anergic) to TCR stimulation in vitro and, upon TCR stimulation, able to suppress the activation/proliferation of other T cells, whereas the latter scarcely exhibit the in vivo autoimmune-preventive activity or the in vitro suppressive activity. Second, such activated or anergy-induced CD25(-) spleen cells produce various autoimmune diseases when transferred to syngeneic athymic nude mice, whereas similarly treated normal spleen cells, which include CD25(+)CD4(+) T cells, do not. Third, upon polyclonal T cell stimulation, CD25(+)CD4(+) T cells express CD25 at higher levels and more persistently than CD25(-)CD4(+) T cell-derived activated T cells; moreover, when the stimulation is ceased, the former revert to the original levels of CD25 expression, whereas the latter lose the expression. These results collectively indicate that naturally anergic and suppressive CD25(+)CD4(+) T cells present in normal naive mice are functionally and phenotypically stable, distinct from other T cells, and play a key role in maintaining immunologic self-tolerance.

Animals↗

Combined effects of meropenem and aminoglycosides on Pseudomonas aeruginosa in vitro.

To investigate combinations of antibiotics against Pseudomonas aeruginosa, the in vitro effects of combinations of meropenem with each of three aminoglycosides, arbekacin, amikacin and netilmicin, were evaluated using an agar dilution chequerboard technique. The combinations of meropenem and aminoglycosides were effective against almost all P. aeruginosa strains tested, which included meropenem-resistant strains. Increased synergic effects were observed in combinations that included arbekacin or amikacin. None of the combinations had an antagonistic effect. Most of the synergic and additive effects were achieved at clinically relevant concentrations.

Aminoglycosides↗

Ascending cholangitis as a cause of pyogenic liver abscesses complicated by a gastric submucosal abscess and fistula.

Ruptures of nonamebic (pyogenic) liver abscesses into the thorax and peritoneum are very uncommon; but, hepatoduodenal and hepatocolonic fistulas are ever more rare. We report a case where ascending cholangitis was associated with pyogenic liver abscess formation and a gastric fistula. Drainage into the stomach was demonstrated by gastroduodenal endoscopy for gastric bleeding. After fistula formation, we could successfully treat the inflammation caused by infection of Citrobacter freundii and Candida albicans with intravenous infusion of both antibiotic and antifungal agents.

Aged↗

Enhancement of the cAMP-induced apolipoprotein-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW 264 mouse macrophage cell line cells.

Apolipoprotein (apo) A-I generates high-density lipoprotein (HDL) by removing cellular cholesterol and phospholipid on the interaction with cells as a main source of plasma HDL. The reaction is induced by dibutylyl cyclic (dbc) adenosine monophosphate (AMP) in RAW 264, mouse macrophage cell line cells, and we investigated its pharmacologic modulation using this cell model. Release of cellular cholesterol and choline phospholipid by apoA-I was increased 9.9 and 4.2 times, respectively, by pretreatment of the cells with 300 microM dbcAMP for 24 h. Calmodulin inhibitors, W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) and W5 (N(6-aminohexyl)-1-naphthalenesulfonamide), increased the apoA-I-mediated lipid release by 3 times from the dbcAMP-treated cells. The optimal drug concentrations (80 and 160 microM for W7 and W5, respectively) were not parallel with those reported for in vitro calmodulin inhibition (IC50, 28 and 240 microM for W7 and W5, respectively, toward phosphodiesterase activity), and in fact 40 microM W7 showed much stronger intracellular calmodulin inhibition than did 300 microM W5 using S7AAS2, a fluorescent peptide probe. Other calmodulin inhibitors such as amitriptyline, chlorpromazine, and trifluoperazine showed no effect on the apoA-I-mediated cholesterol release. In contrast to these results, neither dbcAMP nor W7 influenced the diffusion-mediated nonspecific cholesterol efflux to lipid microemulsion. We concluded that W7 and W5 increased the interaction of apoA-I with RAW 264 cells to generate more HDL. The effect did not seem directly correlated to their cal modulin inhibition or modulation of cAMP and protein kinase C.

Animals↗

Proteasome inhibition attenuates renal endothelin-1 production and the development of ischemic acute renal failure in rats.

The objectives of this study were (1) to assess the role of a proteasome-dependent proteolytic pathway in the pathogenesis of acute renal failure (ARF) induced by ischemia-reperfusion, and (2) to determine the involvement of this proteolytic pathway in the enhanced production of renal endothelin-1 (ET-1) in this model of ARF. ARF was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured to test the effectiveness of drugs used. Renal function in untreated ARF rats markedly decreased at 24 h after reperfusion. In addition, a marked increase in renal ET-1 content was evident in the ARF rats, compared to the sham-operated rats. Intraperitoneal injection of a proteasome inhibitor (PSI), N-benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal, at a dose of 1 mg/kg, 1 h before the clamping, significantly attenuated the renal function impairment in the ischemic ARF rats, and the effect was accompanied by a decrease in renal ET-1 content. On the other hand, a calpain inhibitor, calpeptin, had little effect at the same dose. These results suggest that a proteasome-dependent proteolytic pathway is involved in the enhanced production of ET-1 in the kidney and the consequent renal functional damage in ischemic ARF.

Acute Kidney Injury↗

Whole-body energy mapping under physical exercise using positron emission tomography.

We attempted to visualize dynamic adjustment of glucose utilization in humans in the whole-body organs during physical exercise by using three-dimensional positron emission tomography (3D-PET) and [18F]-2-fluoro-deoxy-glucose (FDG). Twelve healthy male volunteers collaborated on the study; six subjects were assigned to the resting control group (C) and the other six to the running group (E). Group E subjects performed running on a flat road for 35 min. After 15 min of running, subjects injected FDG and kept on running thereafter for another 20 min. Group C subjects sat on a comfortable chair in a quiet room for 35 min after the injection of FDG. After scanning by PET, the regions of interest (ROIs) were manually set on brain, heart, thorax, abdomen, lower extremities, and the rest of the body on the corresponding transaxial images. The uptake of FDG in each region was evaluated as the % fraction of FDG accumulation relative to the total amount of whole-body accumulation. The results revealed increase of FDG uptake after running in the lower leg muscles from 24.6 +/- 9.5% to 43.1 +/- 4.7% and in the heart from 2.3 +/- 0.4% to 2.8 +/- 0.6%. The differences were significant (P < 0.05). These increases reflect the rise in energy consumption in leg and heart muscles and were balanced by the reduction of energy consumption in the other part of the body. FDG uptake in the abdominal region reduced from 37.3 +/- 7.2% to 19.7 +/- 4.9%. However, FDG uptake in the brain remained stable, i.e., 11.9 +/- 2.8% at rest and 10.3 +/- 2.5% after exercise. Thus, 3D-PET is a tool to visualize the dynamic adjustment of energy consumption during physical exercise in humans.

Adult↗