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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 163 records · Page 9Linked to original sources

Cold activation of serum complement in patients with chronic hepatitis C: study on activating pathway and involvement of IgG.

It has been documented that the serum complement activities measured by hemolytic assay (CH50) are decreased after storage of sera at a low temperature in some patients with chronic hepatitis C. However, the mechanism of this phenomenon has not been identified yet. Here, we tried to elucidate factors involved in the cold activation of complement (CAC). To clarify what pathway is activated in CAC, we measured complement cleavage products after cold storage of sera. C4d increased significantly after 12 h-storage at cold temperatures in 5 CAC (+) sera compared with 5 CAC (-) (P < 0.01) and 3 control sera (P < 0.05), while Bb did not increase in any of the groups. In order to determine whether IgG or IgG complex is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel beads, and all of them retained hemolytic activities to some extent after cold storage. Column chromatography through Superose 6HR of CAC-positive serum identified the fractions containing molecules that induced CAC in normal serum, which were depleted by treatment with protein G Sepharose. In conclusion, CAC in hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex produced in hepatitis C virus infection may be an important factor in inducing CAC, a common extrahepatic manifestation of hepatitis C.

Adult↗

Removal of polyA tails from full-length cDNA libraries for high-efficiency sequencing.

We have developed a method to overcome sequencing problems caused by the presence of homopolymer stretches, such as polyA/T, in cDNA libraries. PolyA tails are shortened by cleaving before cDNA cloning with type IIS restriction enzymes, such as GsuI, placed next to the oligo-dT used to prime the polyA tails of mRNAs. We constructed four rice Cap-Trapper-selected, full-length normalized cDNA libraries, of which the average residual polyA tail was 4 bases or shorter in most of the clones analyzed Because of the removal of homopolymeric stretches, libraries prepared with this method can be used for direct sequencing and transcriptional sequencing without the slippage observed for libraries prepared with currently available methods, thus improving sequencing accuracy, operations, and throughput.

Animals↗

Ingestion of gelatin has differential effect on bone mineral density and body weight in protein undernutrition.

Malnutrition, particularly protein undernutrition, contributes to the occurrence of osteoporotic fracture by lowering bone mass. In this study, the effects of dietary protein on bone mineral density and body weight in protein undernutrition were compared between gelatin and milk casein. When mice were fed for 10 wk with a low protein diet containing 10(%) casein or 6% casein +4% gelatin, there was no significant difference in the final body weight between the 6% casein+4% gelatin group and the 10% casein group. In contrast, bone mineral content and bone mineral density of the femur were significantly higher in the 6% casein+4% gelatin group than in the 10% casein group. Bone mineral content and bone mineral density did not differ significantly in 14% protein groups between 14% casein and 6% casein +80% gelatin. These results suggest that gelatin has differential effects on bone mineral density and body weight in protein undernutrition.

Animals↗

Sensitive and specific enzyme-linked immunosorbent assay for the diagnosis of Wuchereria bancrofti infection in urine samples.

We developed an enzyme-linked immunosorbent assay (ELISA) that detects filaria-specific immunoglobulin G4 antibodies in unconcentrated urine. The ELISA was positive in 87 of 91 (95.6%) urine samples collected from people with Wuchereria bancrofti microfilariae, antigen, or both. Of 298 urine samples collected in Thailand, Lao People's Democratic Republic, and Japan, where no human filariasis is known, 295 (99.0%) were negative by ELISA. Various intestinal nematode and fluke infections did not interfere with the ELISA. Urine samples with sodium azide could be kept at 37 degrees C for 4 weeks, and the time of urine collection did not influence ELISA results. This ELISA can be used to identify endemic foci of filariasis.

Animals↗

Pre- or post-ischemic treatment with a novel Na+/Ca2+ exchange inhibitor, KB-R7943, shows renal protective effects in rats with ischemic acute renal failure.

We investigated the effects of pre- or post-ischemic treatment with KB-R7943, a new Na+/Ca2+ exchange inhibitor, on ischemic acute renal failure (ARF) in rats, and these were compared with the effects of verapamil. Ischemic ARF was induced by clamping the left renal pedicle for 45-min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function markedly decreased 24 h after reperfusion. Pre-ischemic treatment with KB-R7943 or verapamil attenuated the ARF-induced renal dysfunction. The ischemia/reperfusion-induced renal dysfunction was overcome by post-ischemic treatment with KB-R7943 but not with verapamil. Histopathological examination of the kidney of ARF rats revealed severe renal damage, and suppression of the damage was seen with post-ischemic treatment with KB-R7943. KB-R7943 markedly suppressed the increment of endothelin-1 (ET-1) content in the kidney at 2, 6, and 24 h after reperfusion. No significant changes in Na+/Ca2+ exchanger protein expression in renal tissue were observed with 45-min ischemia, 6 h after reperfusion and KB-R7943 treatment. These results suggest that Ca2+ overload via the reverse mode of Na+/Ca2+ exchange, followed by ET-1 overproduction, seems to play an important role in the pathogenesis of the ischemia/reperfusion-induced ARF. KB-R7943, which is effective in both cases of pre- and post-ischemic treatments, may prove to be an effective therapeutic agent for cases of ischemic ARF.

Acute Kidney Injury↗

18F-FDG PET mapping of regional brain activity in runners.

BACKGROUND: To examine regional metabolic changes in the human brain induced by free running in upright posture. METHODS. EXPERIMENTAL DESIGN: Regional brain changes in glucose uptake induced by running were examined by comparing brain images obtained by positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG). SETTING: The study was conducted at a research institute and involved participation of healthy young volunteers. Data sampling and analysis required special imaging device and special computer hardware/software. PARTICIPANTS: Subjects were 17 healthy male volunteers. They were divided at random into two equal groups, those who ran 4-5 km and the others sat in the room. MEASURES: differences in regional cerebral glucose uptake between runners and control groups were assessed statistically. Plasma glucose level was also measured and global cerebral uptake was estimated. RESULTS: Running was associated with a relative increase of glucose uptake in the temporoparietal association cortex, occipital cortex, premotor cortex and the cerebellar vermis. The highest activity was noted in the temporoparietal association cortex. Activity of the primary sensorimotor cortex was higher in the superomedial part (leg motor area) than the lateral part (thorax and arm). CONCLUSIONS: Running augmented energy consumption in the parieto-occipital region relative to the motor area, probably due to the higher energy consumption necessary for integration of multimodal sensory information than for generation of motor output. Our results indicate that FDG PET is a useful tool for brain mapping under various physiological conditions.

Adult↗

[Mediastinal cystic lesions: CT and MRI findings].

In this article we describe various approaches to the evaluation of mediastinal cystic lesions using CT and MRI. Although cystic lesions generally appear to be uncomplicated and not difficult to diagnose, we consider that there are certain pitfalls in differentiating them from solid lesions. It is important to pay careful attention to the location (including ectopic occurrence), CT attenuation and/or MR intensity, thickness of the wall, tear-drop shape or alternation of shape owing to intrathoracic pressure, and pseudoenhancement. We suggest that MR be recommended when the findings of CT are equivocal, as they were in 32 of our cases.

Adult↗

[Disseminated atypical mycobacteriosis in a patient with chronic myelogenous leukemia].

A 61-year-old woman with a 6-year history of chronic myelogenous leukemia (CML) presented with recurrent fever in July 1996. Bone marrow aspiration, biopsy and chromosome analysis showed that CML was in the chronic phase. Bone marrow biopsy revealed nonspecific inflammatory lesions. Chest X-ray and computed tomography examinations demonstrated interstitial pneumonia. Cultures of gastric juice and bone marrow yielded colonies of Mycobacterium avium complex (MAC), and a diagnosis of disseminated atypical mycobacteriosis was made. Multidrug treatment including rifampicin, ethambutol, clarithromycin and ciprofloxacin was begun. The cultures subsequently became negative and the fever was resolved. However, fever eventually recurred and the patient died of multiple organ failure in October 1997. since disseminated atypical mycobacteriosis complicating hematological disorders worsens the prognosis, its early diagnosis and prompt treatment are important. Although it is often difficult to identify atypical mycobacterium as a causal agent, frequent culturing of atypical mycobacterium from various sources including bone marrow fluid can be helpful for early diagnosis whenever fever of undetermined origin occurs in patients with hematological disorders.

Female↗

Estrogenic influences of estradiol-17 beta, p-nonylphenol and bis-phenol-A on Japanese medaka (Oryzias latipes) at detected environmental concentrations.

Mature male medaka were continuously exposed to 0.005, 0.0-5 or 1.0 ppb of estradiol-17 beta (E2 or 0.1, 10 or 100 ppb of p-nonylphenol (NP) or bis-phenol-A (BPA). Female-specific proteins (Fsp) were induced in medaka exposed to 0.005 ppb of E2, 0.1 ppb of NP, or 10 ppb of BPA. Concentrations of 0.005 pbb of E2 and 0.1 ppb of NP corresponded to concentrations of these chemicals detected in river water in Japan. The abilities of the 3 chemicals to induce Fsp were E2 > NP > BPA. Embryonic medaka were exposed to E2, NP and BPA under conditions of static-renewal for 200-230 days until pre-maturity. Survival ratios of medaka exposed to E2 and NP declined in concentrations more than 25 ppb and 50 ppb, respectively. The groups of medaka exposed to E2 had individuals with testis-ova or abnormal gonad. There was no male in exposure to 1.0 ppb E2. When exposed to 100 ppb of NP or BPA, abnormal gonad was also detected. Abnormal anal fin (female-like) was observed in male exposed to 100 ppb of NP. The LC50 values for each of the 3 chemicals were much higher than the concentrations detected in water in the environment--the 3 chemicals were considered to have no lethal effect on medaka in aquatic environments. However, exposures to E2 or NP at environmental concentrations induced Fsp. BPA also had the ability to affect medaka as an environmental estrogen, although its extrogenic activity was weaker than that of E2 or NP.

Animals↗

Preventive effect of lactacystin, a selective proteasome inhibitor, on ischemic acute renal failure in rats.

To elucidate the role of a proteasome-dependent proteolytic pathway in the pathogenesis of acute renal failure (ARF), we examined the effect of a selective proteasome inhibitor, lactacystin, on ARF induced by ischemia/reperfusion. Ischemic ARF was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in untreated ARF rats markedly decreased at 24 h after reperfusion. Intraperitoneal injection of lactacystin at a dose of 0.1 mg/kg before the occlusion tended to attenuate the deterioration of renal function. The higher dose of lactacystin (1 mg/kg) markedly attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli, and medullary congestion, all of which were markedly suppressed by the higher dose of lactacystin. In addition, endothelin (ET)-1 content in the kidney after the ischemia/reperfusion was significantly increased, being the maximum level at 6 h after the reperfusion, and this elevation was abolished by the higher dose of lactacystin. These results indicate that lactacystin prevents the development of ischemia/reperfusion-induced ARF, and the effect is accompanied by suppression of the enhanced ET-1 production in the kidney, thereby suggesting that a proteasome-dependent proteolytic pathway has a crucial role in the pathogenesis of ischemic ARF, possibly through the enhancement of ET-1 production in postischemic kidneys.

Acetylcysteine↗

[Pachymeningitis with autonomic dysfunctions: a case report].

A 67-year-old man temporarily complained of hearing loss and earache in the left side. Afterwards, hearing impairment in the right, pharyngalgia, dysphagia, and ipsilateral facial weakness occurred, however, otological treatments did not completely improve these symptoms except facial weakness. On admission neurological examination revealed right cranial nerve palsies(IX, X, XII), and severe orthostatic hypotension was noted one month after admission. Cerebrospinal fluid revealed pleocytosis(16/mm3), and increased protein level(91 mg/dl), but bacterial, and tuberculotic cultures were negative. Cranial and neck magnetic resonance imaging with gadolinium administration showed diffuse dural thickening. Autonomic dysfunctions were found in cardiovascular and pupillary systems. Plasma noradrenaline level was normal in supine position but noradrenaline infusion test showed denervation hypersensitivity. Additionally pupils showed hypersensitivity to 1.25% epinephrine. These results suggest that lesions were post-ganglionic afferent fibers in both cardiovascular and pupillary systems. Administration of corticosteroid hormone resulted in dramatic improvement of his clinical symptoms including autonomic dysfunctions. Circulation disorder or infiltration of the inflammatory cells to the autonomic nervous system may be the cause of these dysfunctions in this patient.

Aged↗

[Successful donor lymphocyte infusion for Epstein-Barr virus-associated lymphoproliferative disorder after allogeneic bone marrow transplantation from an HLA 1-locus-mismatched sibling donor in a patient with acute lymphocytic leukemia].

We report a case of Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) after allogeneic bone marrow transplantation (allo-BMT) from a partially mismatched related donor for acute lymphocytic leukemia, which was treated successfully by donor lymphocyte infusion (DLI). A 54-year-old woman in first complete remission from acute lymphocytic leukemia received an unmanipulated bone marrow transplant from an HLA-A 1-locus-mismatched sibling donor after preconditioning with cyclophosphamide and total body irradiation. Prophylaxis against graft-versus-host disease (GVHD) was done with tacrolimus and short-term methotrexate. Skin GVHD (grade I) occurred on day 36, but this subsided spontaneously without treatment. On day 61, rapidly progressive cervical lymphadenopathy with fever developed. Lymph node biopsy revealed lymphoid cell proliferation, which was positive for LCA, L26 and LMP-1. A diagnosis of EBV-LPD was made. After withdrawal of the tacrolimus, DLI (1 x 10(6) CD3 cells/kg) resulted in remission. This case suggests that even in the absence of risk factors such as severe GVHD, intensive immunosuppressive therapy and ATG administration, allo-BMT from an HLA 1-locus-mismatched related donor can be complicated by EBV-LPD, and that reduction of immunosuppressive therapy and DLI can be an effective treatment for it.

Bone Marrow Transplantation↗

Efficient enhancement of priming effect by intermittent treatment with interferon.

To improve the efficacy of interferon (IFN) therapy for chronic hepatitis C, we proposed a therapy with twice-a-day injection of IFNbeta as the induction. To assess its biological enhancement, we compared antiviral activities in vitro using intermittent treatment schedules simulating the clinical condition. FL cells were treated with IFNbeta twice in 12 h interval (Single treatment, 1000 and 0 IU/ml; Double treatment, 500 IU/ml each) and challenged with Sindbis virus. Antiviral activities were determined with 50% cytopathic effect. Activities and mRNA expressions of 2'5'oligoadenylate synthetase (2'5'AS) were also examined. Single treatment showed its peak activity at 9 h, while Double treatment was at 3 h after the second treatment. Double treatment had a significantly higher peak activity. The up-regulated activities of 2'5'AS lasted much longer with Double treatment. The present findings demonstrated Double treatment could induce efficient biological enhancement, which is thought based on the priming effect.

2',5'-Oligoadenylate Synthetase↗

18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies.

Using (18)F-fluorodopa PET and a constant 0.0062 influx rate in the putamen, dementia with Lewy bodies (n = 7) was distinguished from AD (n = 10) with a sensitivity of 86% and a specificity of 100%. A constant 0.0071 influx rate in the caudate yielded a sensitivity of 71% and a specificity of 100% for distinction of the two disorders. Despite a limited sample size, these findings suggest that assessing nigrostriatal dopaminergic function with (18)F-fluorodopa PET may be a useful diagnostic aid in cases of dementia with Lewy bodies while patients are alive.

Aged↗

Repressor activity of Headless/Tcf3 is essential for vertebrate head formation.

The vertebrate organizer can induce a complete body axis when transplanted to the ventral side of a host embryo by virtue of its distinct head and trunk inducing properties. Wingless/Wnt antagonists secreted by the organizer have been identified as head inducers. Their ectopic expression can promote head formation, whereas ectopic activation of Wnt signalling during early gastrulation blocks head formation. These observations suggest that the ability of head inducers to inhibit Wnt signalling during formation of anterior structures is what distinguishes them from trunk inducers that permit the operation of posteriorizing Wnt signals. Here we describe the zebrafish headless (hdl) mutant and show that its severe head defects are due to a mutation in T-cell factor-3 (Tcf3), a member of the Tcf/Lef family. Loss of Tcf3 function in the hdl mutant reveals that hdl represses Wnt target genes. We provide genetic evidence that a component of the Wnt signalling pathway is essential in vertebrate head formation and patterning.

Animals↗

Suppressive effects of DNA vaccines encoding heat shock protein on Helicobacter pylori-induced gastritis in mice.

We investigated the effect of DNA vaccines encoding H. pylori-heat shock protein A and B (pcDNA3.1-hspA and -hspB) on inducing immune responses against H. pylori in mice. C57BL/six mice aged 5 weeks were immunized by single injection of 10 microg of pcDNA3.1-hspA and pcDNA3.1-hspB into intracutaneous tissue. Plasmid DNA lacking the inserted hsp were injected as a control. Three months after vaccination, significant specific antibodies against H. pylori were detected by ELISA in the sera of vaccinated mice. Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1-hspA and mixed IgG1/IgG2a (Th0-like) with pcDNA3.1-hspB. DNA vaccination dramatically suppressed colonies of bacteria in stomach of vaccinated mice (28,400 +/- 21,600/mm(2) for pcDNA3.1-hspA and 6800 +/- 3470/mm(2) for pcDNA3.1-hspB) compared to control mice (128,000 +/- 42,200/mm(2)). Histological analysis of the gastric mucosa demonstrated that the degree of gastritis was significantly lower in the vaccinated mice than in control mice. These results demonstrated that DNA vaccines encoding H. pylori-Hsp induce significant immune response against H. pylori to decrease gastric mucosal inflammation, indicating that a DNA vaccine can be a new approach against H. pylori in humans.

Animals↗

Short-term ethanol exposure alters calbindin D28k and glial fibrillary acidic protein immunoreactivity in hippocampus of mice.

The effects of a short-term ethanol treatment on hippocampus have been studied in mice exhibiting intoxication signs. The alterations of neurons and astrocytes as well as quantitative changes of calbindin D28k-immunoreactivity and glial fibrillary acidic protein-immunoreactivity (GFAP-IR) in selected regions of the dorsal hippocampus were examined using anti-calbindin and anti-GFAP monoclonal anti-body (mAb), respectively. The administration of 6% (v/v) ethanol during first week led to the neuronal death and decrease of the total number of calbindin-IR neurons in the examined brain regions. Moreover, the calbindin positive neurons were shown to have diminished processes following short-term ethanol exposure. These neuronal changes were associated with the increase of the GFAP-IR astrocytes. Hypertrophy of cell bodies and cytoplasmic processes of reactive astrocytes were also seen. In addition, dense, thick and highly-stained GFAP-IR cells with long processes in granular cell layer appeared entering into molecular layer of dentate gyrus. In agreement with the discrepancy percentage of neuronal cell loss and increase of reactive astrocytes detected by calbindin and GFAP-IR using image quantitative analysis, the regional differences in the vulnerability to the neurotoxic effects following short-term ethanol exposure were found: CA3>CA2>CA1>DG. These findings also illustrate the importance of correlation between calbindin and GFAP-IR when determining the morphological alteration of neuron and astroglial following short-term ethanol treatment. The disruption of calbindin and GFAP could affect neuronal-astroglial interaction, resulting in disturbance of behaviors dependent on hippocampus.

Alcoholic Intoxication↗