Biomedical subjects

S Ishimoto

Publications and source records attributed to S Ishimoto.

At least 19 recordsLinked to original sources

PubMed2005

First measurement of the transverse spin asymmetries of the deuteron in semi-inclusive deep inelastic scattering.

First measurements of the Collins and Sivers asymmetries of charged hadrons produced in deep-inelastic scattering of muons on a transversely polarized 6LiD target are presented. The data were taken in 2002 with the COMPASS spectrometer using the muon beam of the CERN SPS at 160 GeV/c. The Collins asymmetry turns out to be compatible with zero, as does the measured Sivers asymmetry within the present statistical errors.

Journal Article↗

PubMed2002

Spallation ultracold-neutron production in superfluid helium.

The first ultracold-neutron (UCN) production in superfluid helium placed in a spallation neutron source is carried out. A UCN density of 0.7 UCN/cm(3), which can be used in experiments, is achieved for a proton-beam power of 78 W and a He-II temperature of 1.2 K. The present new UCN source is not limited by Liouville's theorem and extraction losses, which were serious problems in the previous sources. The present source has the possibility of extremely high-density UCN production compared with previous UCN sources.

Journal Article↗

PubMed2001

Identification of dual specificity phosphatases induced by olfactory bulbectomy in rat olfactory neuroepithelium.

Dual specificity protein tyrosine phosphatases (dsPTPs) are a subfamily of protein tyrosine phosphatases implicated in the regulation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 mitogen-activated protein kinases (MAPKs) which are target enzymes activated by a wide range of cell-surface stimuli. Like these kinases, a class of dsPTP has been implicated in cell differentiation, regeneration, and apoptosis. In order to isolate dsPTPs which might play an important role in neuronal regeneration and apoptosis in olfactory neuroepithelium, we subcloned DNA fragments amplified by reverse transcription-polymerase chain reaction (RT-PCR), using degenerate oligonucleotide primers based on the conserved amino acid regions within the catalytic domain of dsPTPs, from rat olfactory epithelial RNA 1 and 4 h after an olfactory bulbectomy. The PCR products were subcloned into the pCRII vector, and 23 clones were chosen for further characterization. The sequence of these 23 individual clones revealed that two clones were identical to the rat dsPTP, MKP-3, and the other 21 clones were identical to the rat dsPTP, MKP-1. By Northern analysis, the MKP-1 transcript was induced and peaked 4 h following a bulbectomy. Similar results were obtained with the MKP-3 transcript. These results suggest that MKP-1 and MKP-3 may be involved in the early steps of apoptosis in vivo in rat olfactory neuroepithelium.

Animals↗

PubMed2001

Narrow internal auditory meatus: an idiopathic case confirming the origin and pathway of vestibular evoked myogenic potentials in humans.

OBJECTIVE: To confirm the origin and pathway of vestibular evoked myogenic potentials (VEMPs) in humans. DESIGN: Case study. SETTING: University hospital. PATIENT: A patient with a narrow internal auditory meatus (IAM). MAIN OUTCOME MEASURES: Imaging studies and functional studies concerning the seventh and eighth cranial nerves. RESULTS: Of the 4 nerves in the IAM, all but the cochlear nerve had normal function and normal courses, despite the pronounced narrowing of the IAM. The facial nerve had a normal diameter, but the vestibular nerves were thinner. Imaging revealed that the cochlear nerve was absent or extremely thinned. Both the cochlea and the cochlear nerve showed no function in the affected ear, although the VEMPs were evoked normally. CONCLUSION: Our results definitively support the vestibular origin of VEMPs in humans.

Adult↗

PubMed2001

Fungal mastoiditis in an immunocompetent adult.

Manifest fungal infection of the middle ear, fungal mastoiditis, is a very rare entity, which is almost exclusively seen in immunocompromised patients. The authors present a case of fungal mastoiditis in a 52-year-old woman without immunocompromise. The patient presented with acutely progressing symptoms of hearing loss and dysequilibrium. Bony fistula of the semicircular canal was noted on CT scans and a marginal perforation of the tympanic membrane was also seen. Her hearing recovered following the surgery, which revealed massive granulations and proliferation of fungi but no cholesteatoma in the mastoid cavity. Fungal infection of the middle ear is rare, but can cause serious complications. The possibility should be considered even in immunocompetent patients.

Aspergillosis↗

PubMed1999

[A case of hereditary sensory autonomic neuropathy type II with late onset].

We reported a 22-year-old man with hereditary sensory autonomic neuropathy (HSAN) type II. His initial neurological symptom at the age of 18 years was hypoesthesia on the feet and legs. In spite of late onset and absence of multilating acropathy, we diagnosed this case as HSAN type II because of an absence of sensory nerve action potentials with normal motor nerve conduction velocities and of a total loss of myelinated fibers with a decrease of unmyelinated fibers in the sural nerve. The sweating induced by iontophoretic pilocarpine stimulation was decreased on the dorsum of the foot. In addition, the morphometric analysis of sudomotor nerves around sweat glands showed a decrease of nerve terminals and unmyelinated axons. Because decrease or loss of sweating is one of the cardinal signs in HSAN type II, the quantitative sweating test and morphometric evaluation of the innervation of sweat glands are important for the proof of the autonomic signs.

Adult↗

PubMed1998

Antigen-presenting cells in experimental autoimmune uveoretinitis.

The present study attempts to identify the antigen-presenting cells in the retina, utilizing bone marrow-transplanted chimeric rats. Two types of chimeras were used: one produced by transplanting bone marrow cells from F1 hybrids of Lewis and Brown Norway (BN) into sublethally irradiated Brown Norway rats (LBN/F1-->BN), followed by adoptive transfer of S-antigen-specific T cells obtained from Lewis rats; the second produced by transplanting bone marrow cells from BN rats into sublethally irradiated F1 hybrids (BN-->LBN/F1), followed by adoptive transfer of S-antigen-specific T cells obtained from F1 hybrids. As controls, Lewis, F1 hybrids and BN rats also received adoptive transfer of syngeneic uveitogenic T cell lines. All animals were killed on the seventh day after adoptive transfer and their eyes and pineal glands were analysed immunohistochemically, utilizing antibody directed against Lewis specific MHC class II molecules(OX-3). The analyses revealed the development of uveoretinitis and pinealitis in both types of chimeras and in the Lewis and F1 hybrid rats. BN rats did not develop uveoretinitis. OX-3-positive cells were found in the retina and the pineal glands of both types of chimeras, and in the Lewis and F1 hybrid rats but not in the BN rats. These cells in the retina expressed dendritic morphology and perivascular distribution. Retinal pigment epithelia, Müller cells and the vascular endothelia of both chimeras, the two strains, and the F1 hybrid rats did not demonstrate OX-3-positive staining. These results suggest that the bone marrow-derived cells in the retina and pineal gland may present S-antigen to T cells, initiating the cascade of uveoretinitis and pinealitis.

Adoptive Transfer↗

PubMed1998

Keratinocyte growth factor and its receptor messenger RNA expression in nasal mucosa and nasal polyps.

To examine the potential biologic role of fibroblast growth factors (FGFs) in nasal polyps and nasal mucosa during chronic inflammatory conditions, we investigated messenger RNA (mRNA) expression of three members of the FGF family -- acidic FGF, basic FGF, and keratinocyte growth factor (KGF)-- in nasal polyp tissues, as well as in hyperplastic nasal mucosa. Using the sensitive method reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated that of the examined FGFs, KGF had the most abundant mRNA expression in nasal polyps and nasal mucosa. We also found that significantly higher levels of KGF mRNA were expressed in nasal polyps than in nasal mucosa, whereas mRNA expression of acidic FGF and basic FGF was relatively low in these tissues. In addition, we showed that KGF receptor mRNA was present in most of the nasal mucosa; however, none or little was expressed in nasal polyps. These results suggest that KGF might play an important role in nasal epithelial proliferation and that excessive synthesis of KGF in nasal polyp stroma may contribute to hypertrophy of the nasal mucosa in patients with chronic sinusitis associated with nasal polyposis.

Adult↗

PubMed1998

Role of retinal vascular endothelial cells in development of CMV retinitis.

PURPOSE: Although cytomegalovirus (CMV) retinitis is known to occur in association with retinal microangiopathy in individuals with marked immunodeficiency, glial cells are believed to be the initial target cells in the development of retinitis. Moreover, it has been hypothesized that CMV gains access to the retinal glia because of altered vascular permeability. In an attempt to address the hypothesis, we studied 30 autopsy eyes of AIDS patients with systemic CMV infection, with or without clinically apparent CMV retinitis. METHODS: The autopsy eyes were processed in three ways. First, dual immunohistochemical studies were done by using anti-CMV antibodies for immediate early, early, and late antigens. The retinal cell types infected with the virus were then determined by using anti-GFAP, anti-VonWillebrand's factor, neuronal specific enolase, and leukocyte marker CD68. Second, selected eyes were processed for in situ hybridization with DNA probe specific to CMV. Third, an eye with clinically apparent CMV retinitis was submitted for electron microscopic examination. RESULTS: At the site of retinal necrosis in those eyes with a clinical diagnosis of CMV retinitis, the immunohistochemical, in situ hybridization, and ultrastructural examinations revealed that CMV was present primarily in the Müller cells and in perivascular glial cells. Adjacent to these infected cells, focal areas of positive staining for CMV antigen were seen in the glial cells, neuronal cells, and retinal pigment epithelial cells. At these sites most of the retinal capillaries were devoid of endothelial cells. Few vessels located at the advancing margin of retinal necrosis showed the presence of viral proteins in the endothelial cells. CONCLUSIONS: The present results indicate that retinal vascular endothelial cells could be the initial target in the development of viral retinitis, with subsequent spread of the infection to perivascular glia, Müller cells, and other retinal cells, including the retinal pigment epithelium.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Correlation of titer of antibody to principal neutralizing domain of HIVMN strain with disease progression in Japanese hemophiliacs seropositive for HIV type 1.

With the use of the principal neutralizing determinant (PND) peptide-based ELISA to measure anti-PND antibodies that specifically bound synthetic peptides derived from HIVIIIB, HIVMN, HIVRF, HIVSC, HIVWJM-2, HIVAf1l.con, or HIVAf2.con, type-specific antibodies to the HIVMN peptide were studied in 350 serum specimens from Japanese with hemophilia A who had been injected with known unheated factor VIII concentrates until 1985 and had been infected with HIV-1 subtype B. These antibodies were not found in any of the seronegative sera of hemophiliacs, patients with autoimmune diseases, or normal healthy controls. Further, all hemophiliacs rapidly progressing to AIDS and death among the 95 hemophiliacs in a restricted Nara area had antibody titers of less than 20 and their low levels preceded the rapid progression to the disease state. In contrast, slowly progressing hemophiliacs maintained an antibody titer of more than 100 from the initial stages of viral infection and remained asymptomatic. Sequence analysis of the V3 regions of HIV-1 indicated that the hemophiliacs who maintained a high anti-PNDMN antibody level showed a conserved MN sequence. In contrast, the HIV-infected hemophiliacs with nonreactivity in the ELISA showed sequence changes in the neutralizing epitopes of HIVMN. The dynamic of the serum anti-PNDMN antibody titer appear to be a characteristic indicator of the progression of the HIV-infected status in Japanese hemophiliacs seropositive for HIV-1.

Adult↗

PubMed1997

Oxygen free radical damage in the cornea after excimer laser therapy.

AIMS/BACKGROUND: To evaluate the extent of oxygen radical damage in the cornea after excimer laser ablation. METHODS: The 193 nm argon fluoride excimer laser was programmed for an average fluence of 150 mJ/cm2, with a firing rate of 5 Hz and an ablation zone diameter of 6 mm. Phototherapeutic keratectomy was performed to remove 30 microns of epithelium and 50 microns of stroma from the corneas of New Zealand white rabbits. Oxidative tissue damage after laser was determined by measuring oxidised lipids (conjugated dienes and ketodienes) in corneal lipid extracts, and by fast blue B staining to localise the lipid peroxide in the tissue. RESULTS: Conjugated diene levels were 3.73 (SD 0.56) nmol per hemicornea in ablated corneas and 1.99 (0.33) nmol per hemicornea in normal corneas (p = 0.0044). Ketodiene levels were 2.72 (0.38) nmol per hemicornea in treated corneas and 0.91 (0.12) nmol per hemicornea in normal corneas (p < 0.001). Fast blue B staining disclosed that the tissue damage occurred primarily on the surface of the ablated cornea. CONCLUSION: The presence of lipid peroxidation in the superficial corneal stroma in excimer laser treated corneas was demonstrated. This lipid peroxidation could be from oxygen free radicals generated by the infiltrating polymorphonuclear cells at the site of tissue damage.

Animals↗

PubMed1997

Expression of major histocompatibility complex molecules in rodent retina. Immunohistochemical study.

PURPOSE: In Lewis rats, S-antigen-induced intraocular inflammation, which occurs initially in the retina, is mediated by T cells requiring major histocompatibility complex (MHC)-restricted antigen presentation. In such organ-specific inflammation, antigen presentation may take place at the site of the initial inflammatory response. In the present study an attempt was made to determine the presence of the putative antigen-presenting cells in the retina of rats. METHODS: Six bone marrow chimeras were constructed by transferring 50 x 10(6) donor [Lewis x Brown Norway, (LBN) F1] bone marrow cells into lethally irradiated Brown Norway rats. Three chimeras, 3 Lewis, and 2 Brown Norway rats each received intravenous injections of gamma interferon (IFN-gamma) at a dose of 2 x 10(5) U/rat, 48 and 24 hours before enucleation of the globes. Enucleated globes from the 3 remaining untreated chimeras, 21 additional Lewis rats, and 6 Brown Norway rats served as controls. Retinas from all globes were prepared for either wholemount or cryosectioning and were stained using various primary antibodies, including anti-Lewis MHC class II (OX3), anti-rat MHC class II (OX6), anti-Lewis MHC class I (II-69), anti-rat MHC class I (OX18), anti-macrophage complement receptor 3 (OX42), anti-monocytes/macrophages (ED1, ED2, and ED3), and anti-glial fibrillary acidic protein (GFAP). Fluorescein-conjugated goat anti-mouse and rhodamine-conjugated anti-rabbit immunoglobulins were used to detect the monoclonal or polyclonal antibodies, respectively. All the specimens were examined under Zeiss confocal laser scanning microscopy. The positively stained cells were counted for quantitative analysis. RESULTS: Major histocompatibility complex class II (OX6)-positive cells were demonstrated in the wholemount retinas of IFN-gamma-untreated chimeras, Lewis, and Brown Norway rats. These cells showed a dendritic morphology and increased significantly in number in IFN-gamma-treated Lewis and Brown Norway rats. Expression of Lewis-specific class I (II-69) and class II (OX3) molecules was detected in a few perivascular cells in the retina of chimeric rats treated with IFN-gamma. Most dendritic cells in the retina expressed the macrophage markers, ED1 and OX42, without IFN-gamma treatment. However, vascular endothelia, retinal pigment epithelia, Müller cells, and astrocytes stained neither by Class II molecules nor by macrophage markers. The vascular endothelium and retinal pigment epithelium was found to express constitutively class I molecules (OX18). CONCLUSIONS: A subpopulation of retinal microglia can express MHC class II molecules. Only a few of these are derived from bone marrow. Retinal microglial cells, particularly those derived from bone marrow, may participate in antigen presentation and the subsequent development of retinitis, as seen in S-antigen-induced experimental autoimmune uveoretinitis.

Animals↗

PubMed1997

[Intraocular neovascularization].

To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future.

Adult↗

PubMed1996

Genotypes and multiple infections with hepatitis C virus in patients with haemophilia A in Japan.

Hepatitis C virus (HCV) RNA was tested for, and HCV genotypes determined, in 96 patients with haemophilia A in Japan. Of 88 patients aged > or = 10 years, 74 (84%) were positive for HCV RNA at a frequency higher than that in patients aged less than 10 years (one of eight, 13%, P < 0.001). Genotype I/1a was detected in 30(40%), II/1b in 12 (16%), III/2a in eight (11%), IV/2b in five (7%) and V/3a in 12 (16%); mixed infection with HCV of two different genotypes was identified in the remaining nine (12%). This distribution was markedly different from that in 767 Japanese HCV carriers without haemophilia, in whom II/1b accounted for the majority (68.7%), I/1a was rare (0.5%), V/3a was absent, and mixed infection was observed rarely (1.3%). Mixed infection was transient in all of the seven haemophilic patients who were followed for 1 to 7 years. One of them was infected with genotype II/1b and an unclassifiable genotype, which showed nucleotide sequence similarity to genotype 4c from Zaire (82% homology in the E1 gene) and to 4a from Egypt (91% homology in a part of the NS5b region). In this patient, HCV of genotype II/1b disappeared while that of group 4 survived during a 4-year observation period. These results indicate different epidemiology of HCV genotypes in Japanese haemophiliacs, attributable to HCV contaminating factor VIII imported in the past, and an increased opportunity in haemophiliacs for mixed infection with HCV of different genotypes.

Adolescent↗

PubMed1996

Free radical tissue damages in the anterior segment of the eye in experimental autoimmune uveitis.

PURPOSE: To investigate increased free radical activity and the accumulation and localization of lipid peroxidation in the anterior segment of the eye with uveitis. METHODS: Experimental autoimmune uveitis (EAU) was induced in rats using human S-antigen peptide. Conjugated dienes (CD) and keto-dienes (KD) were then extracted from the cornea, iris-ciliary body and lens of the EAU eyes. The quantity of CD and KD were determined by measuring ultraviolet absorption and estimating by means of a molar extinction coefficient. Frozen sections of EAU eyes were reacted with 3-hydroxy-2-naphthoic acid hydrazide (NAH), and NAH-carbonyl compounds were detected using a confocal laser scanning microscope. Statistical comparisons of CD and KD products between the EAU groups and controls were performed using the Student's t-test. RESULTS: Compared to controls, CD and KD were significantly increased in the cornea and iris-ciliary body of EAU eyes. Lenses of EAU eyes showed a tendency to elevated levels of CD and KD. In EAU, primarily the anterior border layer and the posterior epithelium of the iris--and, to a lesser extent, the trabecular meshwork and corneal endothelium--revealed positive fluorescence staining for peroxidized carbonyl products. No staining was observed on the ciliary epithelium. CONCLUSIONS: Free radicals and lipid peroxidation products are generated in the anterior segment of the eye in EAU. Because the individual tissues in the anterior segment are composed of various levels of fatty acids and different concentrations of antioxidants, the extent of tissue damage from lipid peroxidation may represent a balance between the fatty acid composition and the antioxidant distribution in each of the tissues.

Amino Acid Sequence↗

PubMed1995

[A case of palatal polymorphous low grade adenocarcinoma].

We present a 58-year-old male patient with bilateral cheek swelling and an extraorally protruding tumor who has had deaf mutism since birth. He underwent surgery of the right hard palate 11 years ago. Five years later biopsy was performed for a recurrent lesion diagnosed as pleomorphic adenoma. He refused additional treatment and the size of the tumor subsequently increased slowly. As rapid tumor-growth had been observed since autumn of 1992, he was referred to Tokyo University Hospital. We took meticulous care of this deaf-mute patient, especially from the psychological aspect, which caused him to place great reliance upon us. We performed bilateral maxillectomy with partial resection of the right cheek skin and reconstructed his face and palate successfully using both latissmus dorsi and serratus anterior musculocutaneous free flaps with a rib. Histopathological diagnosis of the tumor was polymorphous low grade adenocarcinoma, which was registered as a definite entity in the WHO Classification in 1991. There was no evidence of local recurrence or metastasis one year postoperatively.

Adenocarcinoma↗

PubMed1995

[An enzyme-linked immunosorbent assay determining anti-principal neutralizing determinant antibodies using synthetic peptides deduced from cDNA sequences of HIV-1 V3 loop domain].

The V3 domain, one of the hypervariable regions of gp 120 in HIV-1 possesses principal type-specific neutralizing determinant (PND). The V3 domain has the epitopes for class I major histocompatibility antigens of cytotoxic-T lymphocyte and helper-T-lymphocyte recognition sites, and also has major determinants for cell tropism towards macrophage, microglia, and human brain-derived fibroblast. Therefore, establishment for the assay of anti-PND antibodies in patients with HIV-1 infection appears to be important for the estimation on developing AIDS in these patients. We here describe a simple enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-PND antibodies found in Japanese hemophiliacs. ELISA was performed using synthetic peptides, each 15 amino acid residues deduced from cDNA sequences of seven HIV-1 V3 domain mutants, which include 5 North-American and European strains (IIIB, MN, RF, SC, and WMJ-2) and 2 African strains (Af1. Con and Af2, Con). The specific antibody binding to each peptide was determined after subtraction of the non-specific binding from the total. In 49 control sera from healthy individuals with HIV-1 antibody negative, the absorbance (M +/- 1SD) at 405 nm was -0.002 +/- 0.064. Then, the cut off value was determined to be M + 4SD. In 48 hemophiliac sera with HIV-1 antibody negative, the absorbance was uniformly less than the cut off value. However, among 44 hemophiliac sera with HIV-1 antibody positive, the anti-PND antibodies were detected in the following frequencies; 2 for IIIB, 20 for MN, 1 for RF, 1 for Af1. Con, and 5 for Af2. Con.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

PubMed1994

The need for organ donation in Hawaii.

Donor organ availability is the primary limiting factor in organ transplantation. The number of patients on the national organ waitlist has increased to more than 32,000, while the number of donors has remained fairly constant at approximately 4,500 per year. In Hawaii, there are 98 patients awaiting organ transplants, and for the past 5 years, the average number of donors per year was 15. The criteria for organ donation, brain death, approaches to donation request, and the management of the multiple organ donor are discussed.

Adolescent↗