Search PubMed⌕ Search

Biomedical subjects

J Itoh

Publications and source records attributed to J Itoh.

At least 19 recordsLinked to original sources

Definitive experimental evidence for two-band superconductivity in MgB2.

The superconducting-gap of MgB2 has been studied by high-resolution angle-resolved photoemission spectroscopy. The results show that superconducting gaps with values of 5.5 and 2.2 meV open on the sigma band and the pi band, respectively, but both the gaps close at the bulk transition temperature, providing a definitive experimental evidence for the two-band superconductivity with strong interband pairing interaction in MgB2. The experiments validate the role of k-dependent electron-phonon coupling as the origin of multiple-gap superconductivity as well as the high transition temperature of MgB2.

Journal Article↗

Spinal epidural metastasis from pineal germinoma.

A 16-year-old boy first presented with a pineal tumour identified by neuroimaging but without positive serum or cerebrospinal fluid markers. The tumour disappeared after 50 Gy cranial irradiation. One year later he returned with spinal epidural metastasis from the pineal germinoma and required emergency surgery. Intraoperative findings showed that the spinal tumour had originated from cerebrospinal fluid dissemination and had passed through the spinal nerve sleeve. The pathologic diagnosis of the tumour was of a pure germinoma metastasis. An epidural tumour frequently requires emergency diagnosis and treatment. Attention should be paid to the possibility of this rare but serious clinical situation caused by a metastasis from a pineal germinoma.

Adolescent↗

Characterization of tissue- and cell-type-specific expression of a novel human septin family gene, Bradeion.

Expression changes in subsets of genes occur in the course of altering cell fates, i.e., aging, cell death, and carcinogenesis. These changes simultaneously provide the good candidate as a biomarker for monitoring cancer. We have identified a novel human septin family gene, Bradeion, from adult brain cDNA library by a monoclonal antibody CE5. Northern blot and in situ hybridization analysis showed that Bradeion has two distinct transcripts, approximately 2.2 and 1.7 kb length (alpha and beta, respectively) mainly in brain and slightly in heart, and no expression in any fetal organs. Haplotype analysis placed the gene location at 17q23. The gene contains GTPase motifs highly conserved in the septin family genes that are essential for cytokinesis and cell separation. The transcript of beta form lacks a hydrophobic region, which suggests that this form arises from a single Bradeion gene through unique RNA splicing. Interestingly, this brain-specific Bradeion gene is also expressed in two human cancers, colorectal cancer and malignant melanoma. Ectopic expression of normal Bradeion alpha and beta transcripts were confirmed both in patients' tumor samples and in in vitro cultured human cancer cell lines. Thus the Bradeion provides valuable tools as a tumor-specific and selective marker.

Amino Acid Sequence↗

Histopathological analyses of silent pituitary somatotroph adenomas using immunohistochemistry, in situ hybridization and confocal laser scanning microscopic observation.

To characterize the morphological and functional aspects of silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are considered to be a useful strategy for endocrinological identification of silent somatotroph adenomas, we examined three silent somatotroph adenomas histopathologically. The adenomas were investigated by immunohistochemistry, including the highly sensitive catalyzed signal amplification system, the non-radioisotopic in situ hybridization method, and confocal laser scanning microscopy. GH production and GH-immunopositive secretory granules in the adenoma cells were demonstrated histopathologically, and the adenomas were interpreted as being densely granulated somatotroph adenomas. Endocrinological identification of silent somatotroph adenomas in combination with paradoxical responses of GH in TRH or GnRH provocation tests may elucidate the increasing number of silent somatotroph adenomas that have been regarded as mammotroph or clinically inactive adenomas. One should be aware of the differences between the previously reported silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, a somatotroph adenomas with paradoxical and the silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, and the silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are densely granulated somatotroph adenomas.

Adenoma, Chromophobe↗

Three-dimensional imaging of hormone-secreting cells and their microvessel environment in estrogen-induced prolactinoma of the rat pituitary gland by confocal laser scanning microscopy.

This study focused on the three-dimensional imaging of hormone-secreting cells and their microvascular environment in estrogen-induced prolactinoma of the rat pituitary gland. Adult female Wistar-Imamichi rats were injected with estradiol dipropionate and killed 7 weeks later. Some rats given estrogen for 7 weeks also were injected with bromocriptine before killing. To obtain a detailed three-dimensional image of microvessels, dialyzed fluorescein isothiocyanate (FITC)-conjugated gelatin was injected into the left ventricle of the rat heart. After the perfusion, the pituitary glands were resected and subjected to immunohistochemistry (IHC). To evaluate the effects of estrogen and bromocriptine, IHC was performed with antibodies against prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH). With the combination, microvessels and cells containing PRL, ACTH, and GH could be clearly identified by confocal laser scanning microscopy (CLSM). The PRL cells increased in number and became hypertrophic after prolonged exposure to estrogen. With bromocriptine administration after estrogen treatment, however, PRL cells decreased in number and became atrophic. The current study revealed that estrogen and bromocriptine had significant effects on PRL secretion and the microvascular environment. Therefore, this technique (FITC injection and IHC) with CLSM is suitable for the three-dimensional imaging of hormone-secreting mechanisms under various conditions.

Adrenocorticotropic Hormone↗

Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease.

BACKGROUND: Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn's disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms. AIMS: To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. PATIENTS AND METHODS: Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-x(L), and Bax, and mean fluorescence intensity measured by flow cytometry. RESULTS: Compared with PBT, the expression level of Bcl-2 and Bax, but not Bcl-x(L), was significantly greater in LPT, resulting in lower Bcl-x(L)/Bax ratios. In PBT, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-x(L), but correlation with Bcl-2 was absent in LPT. Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-x(L)/Bax ratio. The significant correlation of Bcl-x(L) to Bax was preserved in CD, but not UC, LPT. CONCLUSIONS: Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-x(L)/Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.

Adolescent↗

Lecithinized copper, zinc-superoxide dismutase ameliorates prolonged hypoxia-induced injury of cardiomyocytes.

Recent studies have suggested that prolonged hypoxia results in increased production of reactive oxygen species in cardiomyocytes, which leads to apoptosis of these cells. We previously showed that lecithinized recombinant human copper, zinc-superoxide dismutase (rhSOD) showed increased bioavailability through greater membrane affinity and a longer half-life than unmodified SOD. The purpose of this study was to investigate whether lecithinized SOD plays a protective role against hypoxic injury in cardiomyocytes. Cultured rat cardiomyocytes incubated with lecithinized SOD (100 U/ml), unmodified SOD (100 U/ml), or vehicle alone were subjected to hypoxia for up to 72 h. Lecithinized SOD, but not unmodified SOD, was successfully delivered intracellularly, which was verified by Western blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized SOD significantly suppressed hypoxia-induced cell damage. Since lecithinized SOD also suppressed hypoxia-induced DNA fragmentation, the improved cell survival provided by lecithinized SOD is thought to be mediated by its antiapoptotic effect. In summary, lecithinization resulted in a facilitated rhSOD delivery into cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to prolonged hypoxia.

Animals↗

Effect of calcium in assay medium on D value of Bacillus stearothermophilus ATCC 7953 spores.

The D value of commercial biological indicator spore strips using Bacillus stearothermophilus ATCC 7953 was increased by higher calcium concentrations in assay media. The calcium concentration in assay media varied among the manufacturers. The calcium concentration in assay media is an important factor to consider to minimize the variation of D value.

Bacteriological Techniques↗

Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing.

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac(-)](p)) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (-15 cmH(2)O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac(-)](p) for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 (P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise (P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WL(max)) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity (P < 0.01) except for MBF at 70% WL(max), whereas the increase in MAP for N2 was attenuated compared with that in C2 (P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac(-)](p) might be caused, at least partially, by the increased MBF.

Adult↗

A new approach to three-dimensional reconstructed imaging of hormone-secreting cells and their microvessel environments in rat pituitary glands by confocal laser scanning microscopy.

There has been considerable interest in the relationship between hormone- secreting endocrine cells and their microvessels in human pituitary gland. However, microcirculatory networks have rarely been studied in three dimensions (3D). This study was designed to visualize and to reveal the relationship between hormone-secreting endocrine cells and their microvessel environment in 3D, using rat pituitary glands under various (hyper/hypo) experimental conditions by confocal laser scanning microscopy (CLSM). Female adult Wistar rats were used after bilateral adrenalectomy or ACTH administration for 2 weeks. Clear 3D reconstructed images of ACTH cells, the microvessel network and counterstained nuclei were obtained at a maximal focus depth of 1 mm by CLSM without any background noise. In the hyperfunctional state, slender cytoplasmic processes of hypertrophic stellate ACTH cells frequently extended to the microvessels. In the hypofunctional state, ACTH cells appeared atrophic and round with scanty cytoplasm, and cytoplasmic adhesions to microvessel network patterns were inconspicuous. Therefore, 3D reconstructed imaging by CLSM is a useful technique with which to investigate the microvessel environment of hormone-secreting cells and has the potential to reveal dynamic hormone-secreting pathways.

Adrenalectomy↗

Differentiation of necrotic cell death with or without lysosomal activation: application of acute liver injury models induced by carbon tetrachloride (CCL4) and dimethylnitrosamine (DMN).

We investigated the relationship between DNA degradation and lysosome activity (loss of lysosomal integrity) in necrotic cell death induced by carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN): coagulation necrosis and hemorrhagic necrosis, respectively. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) and enzyme histochemistry for acid phosphatase were performed in both models and results were analyzed by light microscopy, electron microscopy, and confocal laser scanning microscopy (CLSM). In the CCl(4)-injected liver, TUNEL staining was closely associated with release of lysosomal enzymes into the cytoplasm, and intranuclear deposition of lysosomal enzymes took place at an early stage of subcellular damage. In the DMN-injected liver, TUNEL-positive nuclei tended to have well-preserved lysosomes and centrally localized TUNEL signals. It was assumed that acute hepatocellular damage in the CCl4-injected liver would be characterized by necrotic cell death with lysosome activation and that damage in the DMN-injected liver would be necrotic cell death without lysosome activation. In the DMN-injected liver, DNA degradation may be selectively induced in the nuclear center, in which heterochromatin (including inactive chromatin) is believed to be a target. We concluded that necrotic cell death, i.e., DNA degradation, would be at least divided into two types, with/without association with lysosome activation, represented by necrotic cell death in the CCl4-injected liver and that in the DMN-injected liver.

Acid Phosphatase↗

Zinc distribution in the small-intestinal digesta of pigs fed skim milk powder or defatted soybean flour.

Zinc distribution in the small-intestinal digesta was studied in pigs fed a skim milk powder (SMP)-based or defatted soybean flour (DSF)-based diet. Ten pigs were fed experimental diets for 30 d. Serum and femoral zinc concentrations were lower in the DSF group than in the SMP group, suggesting the lower zinc availability in the DSF diet than in the SMP diet. In the digesta of small intestine, zinc solubility was higher in the SMP group than in the DSF group. A gel permeation high-performance liquid chromatography showed that the SMP group exhibited four zinc peaks in the chromatogram of the supernatant of digesta. The chromatogram in the DSF group showed four zinc peaks corresponding to those of the SMP group. However, the first zinc peak was smaller and the second peak was larger in the DSF group than in the SMP group. Dietary treatment did not affect the other peaks of zinc. Although the high solubility of zinc in the digesta of SMP group is considered to result in the high availability of zinc, the difference of zinc distribution in the liquid phase of digesta may partly affect zinc availability.

Animals↗

Three-dimensional imaging of tumor angiogenesis.

OBJECTIVE: To three-dimensionally visualize the microvessel environment of tumor angiogenesis by confocal laser scanning microscopy (CLSM). STUDY DESIGN: To reveal underlying mechanisms of tumor angiogenesis, a 7, 12-dimethylbenz(a) anthracene-induced rat cancer model was used. For demonstrating tumor vasculature, fluorescence injection method (FITC-conjugated gelatin solution) was employed. FITC gelatin was injected into the left ventricle of the rat heart. After complete perfusion, the mammary glands were resected, fixed under ice cold conditions and subjected to immunohistochemistry (IHC) for tumor cells. The LSM-410 (Carl Zeiss, Jena, Germany) was employed on thick sections (300-2,000 microns) to elucidate detailed microvessel networks (MVN) and tumor cells. RESULTS: Tumor vasculature on thick sections was clearly detected by CLSM at the maximum focus depth of 2,000 microns. Three-dimensional (3-D), reconstructed images of normal mammary glands showed regular and linear MVN. In DMBA-induced mammary cancer, vascular density of MVN was markedly increased and showed an anastomosing, irregular MVN pattern. Furthermore, focal segmentation and tortuous, branching patterns of microvessels were also seen. CONCLUSION: Application of the fluorescence injection method and IHC using CLSM was very useful for studying the 3-D relationship between tumor angiogenesis and neoplastic epithelial changes. These results suggest that application of this technique is ideal for studying 3-D imaging of tumor angiogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance.

Crohn's disease (CD) is a condition characterized by excessive numbers of activated T cells in the mucosa. We investigated whether a defect in apoptosis could prolong T cell survival and contribute to their accumulation in the mucosa. Apoptotic, Bcl-2+, and Bax+ cells in tissue sections were detected by the TUNEL method and immunohistochemistry. T cell apoptosis was induced by IL-2 deprivation, Fas Ag ligation, and exposure to TNF-alpha and nitric oxide. TUNEL+ leukocytes were few in control, CD, and ulcerative colitis (UC) mucosa, with occasional CD68+ and myeloperoxidase+, but no CD45RO+, apoptotic cells. Compared with control and UC, CD T cells grew remarkably more in response to IL-2 and were significantly more resistant to IL-2 deprivation-induced apoptosis. CD T cells were also more resistant to Fas- and nitric oxide-mediated apoptosis, whereas TNF-alpha failed to induce cell death in all groups. Compared with control, CD mucosa contained similar numbers of Bcl-2+, but fewer Bax+, cells, while UC mucosa contained fewer Bcl-2+, but more Bax+, cells. Hence, the Bcl-2/Bax ratio was significantly higher in CD and lower in UC. These results indicate that CD may represent a disorder where the rate of T cell proliferation exceeds that of cell death. Insufficient T cell apoptosis may interfere with clonal deletion and maintenance of tolerance, and result in inappropriate T cell accumulation contributing to chronic inflammation.

Abatacept↗

Pathogenesis of inflammatory bowel disease.

In spite of expanding knowledge of cellular and molecular mechanisms of intestinal inflammation, the etiology and pathogenesis of inflammatory bowel disease (IBD) remain obscure. The link between the environment and IBD is still circumstantial, but definite progress is occurring in defining genetic susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The notion that normal enteric flora play a role in initiating or maintaining IBD is gaining momentum. Some components of the flora may act as noxious agents, whereas others (probiotics) seem to have a protective effect. The importance of the mucosal immune system to IBD is established, and evidence is accumulating that nonimmune components, such as epithelial, mesenchymal, and endothelial cells, also contribute to gut inflammation. The effect of cytokines in intestinal immunity is being elucidated by studies on their molecular mechanism, particularly the activation of nuclear factor (NF)-kappaB. Finally, the beneficial effects of cytoprotective prostaglandins and cell adhesion molecule (CAM) blockade promise novel therapeutic opportunities derived from an improved understanding of IBD pathogenesis.

Journal Article↗