Search PubMed⌕ Search

Biomedical subjects

K Ishii

Publications and source records attributed to K Ishii.

At least 37 records · Page 2Linked to original sources
PubMed2005

A novel DNA vaccine based on ubiquitin-proteasome pathway targeting 'self'-antigens expressed in melanoma/melanocyte.

Cancer vaccine that targets 'self'-antigens expressed at high levels in tumor cells is a potentially useful immunotherapy, but immunological tolerance often defeats this strategy. Here, we describe the use of a naked DNA vaccine encoding a self tumor antigen, tyrosinase-related protein 2, to whose N-terminus ubiquitin is fused in a 'nonremovable' fashion. Unlike conventional DNA vaccines, this vaccine broke the tolerance and induced protective immunity to melanoma in C57BL/6 mice, as evaluated by tumor growth, survival rate and lung metastasis. The protective immunity was cancelled in the proteasome activator PA28alpha/beta knockout mice. Moreover, this vaccination exhibited therapeutic effects on melanoma implanted before vaccination. Our findings provide evidence for the first time that naked DNA vaccines encoding a ubiquitin-fused self-antigen preferentially induce the main effector CD8+ T cells through efficient proteolysis mediated by the ubiquitin-proteasome pathway, and lead the way to strategies aimed at targeting tissue differentiation antigens expressed by tumors.

Animals↗
PubMed2005

Endoscopic resection of cystic lesions in the lumbar spinal canal: a report of two cases.

We report excellent outcomes in two patients with cystic lesions in the lumbar spinal canal who underwent resection using the METRx micro-endoscopic discectomy (MED) system. Pathological examinations revealed the diagnoses of a synovial cyst and a discal cyst, respectively. Both of them were allowed to walk the next day after surgery with complete pain relief. Micro-endoscopic surgery provides excellent visualization of the spinal canal and allows minimally invasive removal of the pathological lesions. This technique can be an effective alternative to conventional open surgery for cystic lesions in the lumbar spine.

Adult↗
PubMed2005

Function of sigma1 receptors in Parkinson's disease.

OBJECTIVE: The objective of this study was to investigate the mapping of sigma1 receptors in Parkinson's disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients. MATERIALS AND METHODS: We studied seven normal volunteers and six PD patients. The low density of dopamine transporters and the normal or high density of dopamine receptors were confirmed in the putamen of all patients using [11C]CFT and [11C]RAC PET. A dynamic series of PET data acquisition was performed with arterial blood sampling. We computed the binding potential (BP) of [11C]SA4503. RESULTS: In PD patients, the BP was significantly lower on the more affected than the less affected side of the anterior putamen, although there was no significant difference with respect to the BP between patients and controls. CONCLUSIONS: Release of dopamine is reduced asymmetrically in the putamen of early PD. [11C]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD.

Adult↗
PubMed2005

Severe haemodynamic stress in selected subtypes of patients with moyamoya disease: a positron emission tomography study.

BACKGROUND: The optimum management of patients with moyamoya disease remains controversial. OBJECTIVES: To examine retrospectively the correlation between the degree of haemodynamic stress and the clinical presentation by measuring cerebral haemodynamics and metabolism using positron emission tomography (PET). METHODS: 57 patients with moyamoya disease (mean age 32 years, range 12 to 64), classified into five groups according to clinical manifestations, underwent PET measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMR(O2)), and oxygen extraction fraction (OEF) using (15)O labelled gases. The regional values in patient groups were compared with a normal group. RESULTS: CBF in non-symptomatic patients, patients presenting with transient ischaemic attacks (TIA), and patients with haemorrhagic onset (H) was not significantly lower than in normal controls in any region. CBV in the TIA group and in patients with infarction associated with TIA (I/TIA) was significantly higher than in the controls in most regions. OEF in the frontal, parietal, and temporal cortex was significantly higher in the I/TIA group than in the controls. Patients in the H group and those with a permanent deficit with infarction (PD group) had decreased metabolism with normal OEF. Multivariate analysis to test the distribution of the three dimensional vector (CBF, CBV, OEF) showed significant differences between every possible pair among the six groups except NS v H and H v PD in the frontal cortex. CONCLUSIONS: The haemodynamic status of moyamoya disease is not uniform, and severe haemodynamic stress occurs in selected subgroups of patients.

Adolescent↗
PubMed2005

Evaluation of average amount of cerebral blood flow measured by brain perfusion index in patients with neuropsychiatric systemic lupus erythematosus.

We used the brain perfusion index (BPI), an indicator of the average amount of cerebral blood flow (CBF), to evaluate the usefulness of the average amount of CBF for neuropsychiatric systemic lupus erythematosus (NPSLE). Of the seventy three SLE patients examined in this study (total 100 scans), 16 patients (23 scans) had already been diagnosed with NPSLE based on clinical symptoms indicative of central nervous system involvement. In addition, 12 patients (17 scans) exhibited the antiphospholipid antibody syndrome (APS). BPI is significantly influenced by age and we therefore used the BPI ratio (ratio of age predicted BPI to measured BPI value) for each assessment. The mean BPI value of 100 scans was 11.2 +/- 2.79, and the mean BPI ratio was 0.99 +/- 0.24 in all SLE patients. The mean BPI ratio among NPSLE (0.84 +/- 0.19) was significantly lower than that of the non-NPSLE patients (1.04 +/- 0.24) (P < 0.0005). However, there was no difference in the mean BPI ratio between APS patients (0.98 +/- 0.24) and non-APS patients (0.99 +/- 0.25). These results indicate that the mean CBF assessed by the BPI ratio using SPECT is of use in the evaluation of central nervous system involvement in SLE patients.

Adolescent↗
PubMed2005

Immunohistochemical localization of senescence marker protein-30 (SMP30) in the submandibular gland and ultrastructural changes of the granular duct cells in SMP30 knockout mice.

Senescence Marker Protein-30 (SMP30) is a calcium-regulating protein that decreases in an androgen-independent manner as aging occurs. An enzyme-labeled antibody technique has demonstrated that SMP30 localized to the ducts (granular, intercalated, and striated ducts) of mouse submandibular glands. Immunoelectronmicroscopy demonstrated that the granular duct cells were strongly positive for SMP30, but that pillar cells in the granular duct were negative for the protein. In SMP30-knockout (KO) mice, the granular ducts were smaller in diameter. Swelling of mitochondria in the granular duct cells was observed; however, this phenomenon was not observed in the pillar cells. After administration of alpha-isoproterenol, a beta-adrenergic stimulant, a large numbers of small secretory granules were present in the granular duct cells and an expansion of the rough endoplasmic reticulum in SMP30-wild type (WT) mice; in contrast, little change was observed in SMP30-KO mice. These results suggest that SMP30 may be closely related to a signal transduction pathway in the granular duct cells of submandibular glands.

Animals↗
PubMed2005

Stimulation of catecholamine biosynthesis via the PKC pathway by prolactin-releasing peptide in PC12 rat pheochromocytoma cells.

We have previously shown that prolactin-releasing peptide (PrRP) stimulates catecholamine release from PC12 cells (rat pheochromocytoma cell line). However, it is not known whether PrRP also affects catecholamine biosynthesis. Thus, we examined the effect of PrRP on catecholamine biosynthesis in PC12 cells. PrRP31 (>10 nM) and PrRP20 (>100 nM) significantly increased the activity and expression level of tyrosine hydroxylase (TH), a rate-limiting enzyme, in catecholamine biosynthesis. However, the PrRP20-stimulated TH activity was markedly weaker than that of PrRP31. PrRP31 (>1 nM) and PrRP20 (>10 nM) significantly induced an increase in the level of PKC activity. Both Ro 32-0432 (a protein kinase C inhibitor) and H89 (a protein kinase A inhibitor) effectively suppressed the PrRP31 (100 nM)-induced TH mRNA level. Next, we examined the effect of PrRP on mitogen-activated protein kinases (MAPKs). PrRP31 (1 microM) significantly induced an increase in the activity of extracellular signal-related kinases (ERKs) and the stress-activated protein kinase/c-jun N terminal kinase (SAPK/JNK). In contrast to ERKs and JNK, PrRP31 did not affect P38 MAPK activity. Consistent with these findings, pretreatment of cells with the MEK-1-inhibitor, PD-98059 (50 microM), significantly inhibited the PrRP31 (100 nM)-induced increase in TH mRNA. These results indicate that PrRP stimulates catecholamine synthesis through both the PKC and PKA pathways in PC12 cells.

Animals↗
PubMed2004

A new cytochemical method for ultrastructural localization of Co2+ in rat hippocampal CA1 pyramidal neurons in vitro.

This paper describes new cytochemical method for the ultrastructural localization of Co(2+) following blockade of synaptic transmission. In the CA1 region of rat hippocampal slices, electrical stimulation of the Schaffer collaterals elicited field excitatory postsynaptic potentials (fEPSPs). The fEPSPs were completely blocked within 2 min after the addition of Co(2+) (2 mM). The slice was then fixed and precipitated Co(2+) was examined by means of a solution containing 2.5% glutaraldehyde and 10 mM K(3)[Fe(3+)(CN)(6)] in 90 mM NaCl. Electron spectroscopic imaging confirmed Co in the precipitate. The precipitates were found as clusters on the membranes of the fine apical dendrites and their spine heads of CA1 pyramidal neurons. No clustered precipitate was found when slices were treated: (1) without Co(2+); (2) after recovery from the Co(2+)-induced blockade of fEPSPs; (3) without electrical stimulation of the Schaffer collaterals; and (4) with dl-2-amino-5-phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione. After administrating glutamate (5 mM) in the presence of tetrodotoxin (1 microM) and Co(2+), precipitates were found on dendritic membranes and spine heads. These results indicate that the Schaffer collaterals stimulation induces the binding of Co(2+) on CA1 pyramidal neuron membrane.

2-Amino-5-phosphonovalerate↗
PubMed2004

High sensitivity search for nu;e's from the sun and other sources at KamLAND.

Data corresponding to a KamLAND detector exposure of 0.28 kton yr has been used to search for nu;(e)'s in the energy range 8.3<E(nu;(e))<14.8 MeV. No candidates were found for an expected background of 1.1+/-0.4 events. This result can be used to obtain a limit on nu;(e) fluxes of any origin. Assuming that all nu;(e) flux has its origin in the Sun and has the characteristic 8B solar nu(e) energy spectrum, we obtain an upper limit of 3.7 x 10(2) cm(-2) s(-1) (90% C.L.) on the nu;(e) flux. We interpret this limit, corresponding to 2.8 x 10(-4) of the standard solar model 8B nu(e) flux, in the framework of spin-flavor precession and neutrino decay models.

Journal Article↗
PubMed2004

Ultrasound assessment of venous blood flow before and after laser therapy: approach to understanding the pathophysiology of twin-twin transfusion syndrome.

OBJECTIVE: To estimate direction and volume of blood exchange between the donor twin and recipient twin by ultrasound assessment of blood flow in the umbilical vein before and after selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS). METHODS: Forty-one TTTS patients underwent Doppler examination of the umbilical vein before and 24 h after SLPCV. The diameter and mean time-averaged velocity of the umbilical vein were estimated. Total umbilical venous flow (TUVF) was calculated as follows: TUVF (mL/min) = mean time-averaged velocity (cm/s) x mean cross-sectional area (cm2) x 60 (s). RESULTS: TUVF was significantly higher in the recipient (111.2 mL/min) than in the donor twin (44.8 mL/min) before SLPCV (P < 0.0001). However, TUVF was no different between the recipient and the donor twin after SLPCV (93.1 vs. 70.7 mL/min, recipient and donor twin, respectively, P = 0.11). The donor twin's TUVF increased after surgery (P < 0.0001), while the recipient twin's TUVF decreased (P = 0.041). The median postoperative increase in the donor twin's TUVF of 25.9 mL/min had a corresponding decrease of TUVF in the recipient twin of 18.1 mL/min (P = 0.27). CONCLUSIONS: Our data suggest that untreated TTTS is characterized by excessive umbilical venous blood flow in the recipient twin relative to the donor twin. Laser surgery results in concordant changes in umbilical venous flow in opposite directions between the donor and recipient twins, eliminating the initial imbalance. Our results lend support to the fundamental hypothesis of unbalanced blood flow exchange (net flow from donor to recipient) between monochorionic twins as the cause for TTTS and that laser surgery eliminates the pathophysiological cause.

Blood Flow Velocity↗
PubMed2004

IL-18 gene therapy develops Th1-type immune responses in Leishmania major-infected BALB/c mice: is the effect mediated by the CpG signaling TLR9?

IL-18 regulates either Th1 or Th2 responses depending on the cytokine microenvironment. Administration of recombinant IL-18 (rIL-18) alone does not promote Th1 response, but rather induces Th2 response and exacerbates Leishmania major infection in susceptible BALB/c mice. Here, we treated BALB/c mice with an IL-18-expressing plasmid by using a gene gun weekly after L. major infection. This gene therapy resulted in improved pathogenic process and preferential induction of Th1 responses by inducing the expression of IL-12 p40, but treatment with rIL-18 did not. Notably, simultaneous administration of rIL-18 with an empty plasmid vector rendered BALB/c mice resistant to the infection, despite the fact that treatment with either rIL-18 alone or the plasmid vector alone did not influence the susceptibility. The synergistic role of the vector with rIL-18 was found to depend on CpG motifs, which enhanced expression of proinflammatory cytokines, especially IL-12, from APCs through Toll-like receptor (TLR) 9 ligation. Treatment with methylated plasmid vector in which CpG was disrupted could no longer prevent the disease development in coadministration with rIL-18. Taken together, IL-18 gene therapy was shown to develop Th1-type protective immunity in L. major-infected BALB/c mice without the requirement of exogenous IL-12, probably via CpG-TLR9 signaling pathway.

Animals↗
PubMed2004

High prevalence rate of Helicobacter pylori resistance to clarithromycin during long-term multiple antibiotic therapy for chronic respiratory disease caused by non-tuberculous mycobacteria.

BACKGROUND: Helicobacter pylori resistance to clarithromycin, probably due to the frequent use of this antibiotic for the treatment of other diseases, is the greatest obstacle against its eradication. AIM: To clarify the prevalence of clarithromycin-resistant H. pylori in patients with non-tuberculous mycobacterial lung disease receiving multiple antibiotic treatment, including clarithromycin. METHODS: We enrolled 88 patients with non-tuberculous mycobacterial lung disease; 29 underwent upper gastrointestinal endoscopy for the diagnosis of H. pylori infection prior to treatment, and 60 underwent it during treatment. The diagnosis of H. pylori infection was confirmed by histological examination, urease test and microaerobic bacterial culture. The minimum inhibitory concentration of clarithromycin was determined and the DNA was analysed for each of the isolated H. pylori strains. RESULTS: Patients during the treatment had a high prevalence rate of clarithromycin-resistant H. pylori (100%). Analysis of DNA of the clarithromycin-resistant H. pylori isolates revealed point mutations at A2142G or A2143G. Moreover, a linear correlation was found between the total cumulative dose of clarithromycin and the minimum inhibitory concentration. CONCLUSION: All patients with non-tuberculous mycobacterial lung disease being treated long-term with multiple antibiotics, including clarithromycin, harboured clarithromycin-resistant H. pylori in the stomach. Therefore, eradication of H. pylori before commencement of long-term therapy including clarithromycin should be recommended.

Anti-Bacterial Agents↗
PubMed2004

Genetic mapping of quantitative trait loci affecting body weight, egg character and egg production in F2 intercross chickens.

Phenotypic measurements of chicken egg character and production traits are restricted to mature females only. Marker assisted selection of immature chickens using quantitative trait loci (QTL) has the potential to accelerate the genetic improvement of these traits in the chicken population. The QTL for 12 traits (i.e. body weight (BW), six for egg character, three for egg shell colour and two for egg production) of chickens were identified. An F2 population comprising 265 female chickens obtained by crossing White Leghorn and Rhode Island Red breeds and genotyped for 123 microsatellite markers was used for detecting QTL. Ninety-six markers were mapped on 25 autosomal linkage groups, and 13 markers were mapped on one Z chromosomal linkage group. Eight previous unmapped markers were assigned to their respective chromosomes in this study. Significant QTL were detected for BW on chromosomes 4 and 27, egg weight on chromosome 4, the short length of egg on chromosome 4, and redness of egg shell colour (using the L*a*b* colour system) on chromosome 11. A significant QTL on the Z chromosome was linked with age at first egg. Significant QTL could account for 6-19% of the phenotypic variance in the F2 population.

Analysis of Variance↗
PubMed2004

Recombinant fibrinogen, gamma275Arg-->Cys, exhibits formation of disulfide bond with cysteine and severely impaired D:D interactions.

BACKGROUND AND OBJECTIVES: Analysis of dysfibrinogens has provided useful information aiding our understanding of molecular defects in fibrin polymerization. We have already reported impaired fibrin polymerization in a variant fibrinogen (gammaArg275Cys), the Cys being located in the D:D interface. Since this substitution occurred in a heterozygous individual, interpretation of the functional analysis was complicated. We tried to resolve this complication by synthesizing a recombinant variant fibrinogen. METHODS: A variant gamma-chain expression plasmid was transfected into Chinese hamster ovary cells expressing normal human fibrinogen Aalpha- and Bbeta-chains. The recombinant variant fibrinogen (gamma275C) was purified using an immunoaffinity column, and we compared its structure and functions with those of normal recombinant fibrinogen (gamma275R) and plasma variant fibrinogen. RESULTS: Mass analyses showed the existence of disulfide-linked Cys in both patient and recombinant variant fibrinogens. Functional analyses indicated that both fibrin polymerization and gamma-gamma dimer formation were markedly impaired in the variant fibrinogen. The impairments were much more pronounced in gamma275C than in plasma variant fibrinogen. In addition, scanning electron microscopic observation of fibrin clots made from gamma275C revealed less dense fibrin fiber bundles and larger fiber diameter than in those made from gamma275R, and also the existence of many aberrant fibrin fibers with tapered ends. CONCLUSIONS: These results indicate that gammaArg275 has an important residue affecting the structure and function of the gamma-chain C-terminal domain. However, the variant D:D interface can interact with that of the normal fibrinogen existing in a heterozygous patient with dysfibrinogenemia.

Amino Acid Substitution↗
PubMed2004

Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy.

OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.

Adult↗
PubMed2003

The LPS receptor (CD14) links innate immunity with Alzheimer's disease.

To rapidly respond to invading microorganisms, humans call on their innate immune system. This occurs by microbe-detecting receptors, such as CD14, that activate immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide receptor CD14 with Alzheimer's disease, a severe neurodegenerative disease resulting in dementia. We demonstrate that this key innate immunity receptor interacts with fibrils of Alzheimer amyloid peptide. Neutralization with antibodies against CD14 and genetic deficiency for this receptor significantly reduced amyloid peptide induced microglial activation and microglial toxicity. The observation of strongly enhanced microglial expression of the LPS receptor in brains of animal models of Alzheimer's disease indicates a clinical relevance of these findings. These data suggest that CD14 may significantly contribute to the overall neuroinflammatory response to amyloid peptide, highlighting the possibility that the enormous progress currently being made in the field of innate immunity could be extended to research on Alzheimer's disease.

Alzheimer Disease↗