Biomedical subjects

Takao Arai

Publications and source records attributed to Takao Arai.

14 recordsLinked to original sources

PubMed2006

Isolation and identification of a cytopathic activity in Tannerella forsythia.

Interactions between pathogens and host induce human disorders including periodontitis, disintegration of the tooth supporting tissues. Tannerella forsythia has been linked to the periodontitis and several cytopathic reagents have been found in the bacterium; however, its contribution to the disease remains unclear. Biochemical approach to explore the cytopathic effect revealed two distinct activities in T. forsythia (ATCC 43037) extract; one detaches adherent cells from substratum and another arrests cells at G2. An executor of former activity, forsythia detaching factor (FDF) was identified; its genomic sequence and peptidase activity revealed that FDF is a substantial form of putative PrtH; prtH gene was hypothetically identified directly from a DNA fragment of the bacterium and its native product has never been shown. Since FDF was found in the bacterial culture supernatant, its activity implies a contribution to the disintegration of tissues although the mechanism how FDF disturbs cellular anchors remains elusive.

Amino Acid Sequence↗

PubMed2006

Novel drug delivery system using thermoreversible gelation polymer for malignant glioma.

Many approaches to local tumor treatment have been reported and their efficacy demonstrated in patients with malignant glioma. We studied thermoreversible gelation polymer (TGP) as a novel drug delivery system (DDS) for treating this type of tumor. TGP exhibits sol-gel transition i.e., is water-soluble in the sol phase below the chosen sol-gel transiting temperature and water-insoluble in the gel phase above this temperature. We conjugated doxorubicin with TGP to prepare doxorubicin-TGP (DXR-TGP), then studied the kinetics of doxorubicin release from TGP and the antitumor activity of DXR-TGP in vitro and in vivo. The diffusive speed of doxorubicin from TGP was 9.4x10(-7) cm(2)/s and doxorubicin was reliably released from TGP. DXR-TGP showed antitumor activity against the human glioma cell lines T98G and U87MG and in a subcutaneous tumor model in nude mice. Pathologically, detection of the proliferation marker Ki-67 was considerably lower in the DXR-TGP group than in the control group (30-40% vs. 60-70%, respectively). This is to the best of our knowledge the first report of TGP as a novel drug delivery system, and further we provide evidence that TGP exhibits potential for use as a novel DDS for malignant glioma.

Animals↗

PubMed2006

[Intraoperative photodynamic diagnosis for spinal ependymoma using 5-aminolevulinic acid: technical note].

OBJECTIVE: The fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is a well established method for the treatment of brain tumor, especially malignant glioma. However, there is no report on photodynamic diagnosis (PDD) for spinal tumor. In the present study, we evaluated the usefulness of PDD for spinal ependymoma using 5-ALA. METHODS: Three patients with spinal ependymoma received oral doses of 5-ALA (20 mg/kg body weight) 2 hours before anesthesia induction. Intraoperatively, fluorescence was observed with a 420 nm sharp cut filter after excitation with a violet semiconductor laser (405 nm) and was verified by analysis of fluorescent spectra. Residual fluorescent samples taken from the tumor cavity were examined histologically RESULTS: Fluorescence peaked at 636nm in the removed tumors in all cases. Fluorescent tissue tended to exist at the cranial and caudal portion in the tumor cavity or around the anterior median fissure. The residual fluorescent tissue was not detected after removal of the tumor in case 1. The residual fluorescent tissue was composed of tumor cells and ependymal lining in case 2 or the infiltrated inflammatory cells and vascular endothelial cells in case 3. Postoperative magnetic resonance (MR) imaging showed no residual tumor in any of the cases. CONCLUSION: The results of this study indicate the usefulness of 5-ALA-induced tumor fluorescence in guiding resection of spinal ependymoma. 5-ALA-induced porphyrin fluorescence may label spinal ependymomas easily and clearly enough to enhance the completeness of tumor removal.

Adult↗

PubMed2005

[Radionuclide cisternography for patients suspected of having intracranial hypotension].

We evaluated radionuclide cisternography for the diagnosis of intracranial hypotension in terms of the rate of appearance of abnormal findings in 23 patients, their correlation with therapy, and the most suitable scanning method and timing for visualization of leakage. During the first hour after injection, dynamic lumbar images or consecutively repeated whole-body images were acquired. Whole body images then were acquired at 1, 5, and 24 hours. Until 5 hours after injection, patients were kept in bed resting. Visualization of the leakage (direct finding) and that of the bladder (indirect finding) were observed in 78.3% (18/23) and 60.9% (14/23), respectively. Leakage was visualized most frequently at 5 hours after injection. There were three cases in which the leakage was only visualized at 24 hours. Therefore, there must be cases that show intermittent CSF leakage. To avoid overlooking these cases, a 24-hour whole-body image is also important. The appropriate procedure of radionuclide cisternography is very important to detect CSF leakage, and our procedure proved to be more effective for detecting the abnormal findings.

Accidents, Traffic↗

PubMed2004

Protective properties of neoechinulin A against SIN-1-induced neuronal cell death.

Peroxynitrite (ONOO-) is thought to be involved in the neurodegenerative process. To screen for neuroprotective compounds against ONOO- -induced cell death, we developed 96-well based assay procedures for measuring surviving cell numbers under oxidative stress caused by 3-(4-morpholinyl) sydnonimine hydrochloride (SIN-1), a generator of ONOO-, and sodium N,N-dietyldithiocarbamate trihydrate (DDC), an inhibitor of Cu/Zn superoxide (O2-) dismutase. Using these procedures, we obtained a microbial metabolite that rescued primary neuronal cells from SIN-1-induced damage, but not from DDC-induced damage. By NMR analysis, the compound was identified as neoechinulin A, an antioxidant compound that suppresses lipid oxidation. We found that the compound rescues neuronal cells such as primary neuronal cells and differentiated PC12 cells from damage induced by extracellular ONOO-. However, non-neuronal cells, undifferentiated PC12 cells and cells of the fibroblast cell line 3Y1 were not rescued. Neoechinulin A has scavenging, neurotrophic factor-like and anti-apoptotic activities. This compound specifically scavenges ONOO-, but not O2- or nitric oxide (NO). Similar to known neuroprotective substances such as nerve growth factor and extracts of Gingko biloba leaves, neoechinulin A inhibits the SIN-1-induced activation of caspase-3-like proteases and increases NADH-dehydrogenase activity. These results suggest that neoechinulin A might be useful for protecting against neuronal cell death in neurodegenerative diseases.

Alkaloids↗

PubMed2004

[An autopsy case with cerebral histoplasmoma: case report].

Histoplasma capsulatum infection is, for the most part, asymptomatic or of little clinical consequence. Disseminated infection due to H. capsulatum is rather uncommon. Clinically apparent infection of central nervous system (CNS) is rare, and involves in 10 to 50% of patients with disseminated histoplasmosis. Although CNS histoplasmosis is frequently fetal or only discovered as an autopsy, some patients can be effectively treated with anti-fungal agents. We describe a 44-year-old civil man who is engineering contractor with headache without evidence of systemic infection. Magnetic resonance imaging showed enhancing masses in the third and forth ventricles, right interpeduncular cistern, and right cerebello-pontine angle. After biopsy of what was presumed to be a malignant lymphoma, the patient died of rapidly progressive multiple cerebral infarctions. The autopsy revealed the CNS histoplasmoma disseminating systemically. And we finally diagnosed him as histoplasmoma by gene analysis. It was extremely difficult to make a diagnosis based on his physical and radiological findings because it should be included in the differential diagnosis of a well or ring enhanced lesion. It is very important to ask patients about their birthplace, past illness, occupation, and where they had traveled. In the present case, the patient working for the construction has visited many countries including the African Continent and Central America. Clinicians should maintain a high index of suspicion in patients who are from any area endemic for histoplasmosis. The clinical, radiological and pathological features of this infection were reviewed in this report.

Adult↗

PubMed2003

Dissociation of DNA polymerase alpha-primase complex during meiosis in Coprinus cinereus.

Previously, the activity of DNA polymerase alpha was found in the meiotic prophase I including non-S phase stages, in the basidiomycetes, Coprinus cinereus. To study DNA polymerase alpha during meiosis, we cloned cDNAs for the C. cinereus DNA polymerase alpha catalytic subunit (p140) and C. cinereus primase small subunit (p48). Northern analysis indicated that both p140 and p48 are expressed not only at S phase but also during the leptotene/zygotene stages of meiotic prophase I. In situ immuno-staining of cells at meiotic prophase I revealed a sub population of p48 that does not colocalize with p140 in nuclei. We also purified the pol alpha-primase complex from meiotic cells by column chromatography and characterized its biochemical properties. We found a subpopulation of primase that was separated from the pol alpha-primase complex by phosphocellulose column chromatography. Glycerol gradient density sedimentation results indicated that the amount of intact pol alpha-primase complex in crude extract is reduced, and that a smaller complex appears upon meiotic development. These results suggest that the form of the DNA polymerase alpha-primase complex is altered during meiotic development.

Blotting, Northern↗

PubMed2002

Assay-based quantitative analysis of PC12 cell differentiation.

Differentiation of PC12 cells has been quantified by measurement of neurite length. However, this procedure is not suitable for large numbers of samples, for example in 96-well tissue culture plates. For this reason, we established three simple and quantitative methods for nerve growth factor-induced differentiation of PC12 cells cultured in 96-well plates. Firstly, because neuronal markers, including neurofilament proteins and beta-tubulin isotype III, are increased during PC12 cell differentiation, we developed cell enzyme-linked immunoabsorbent assays (ELISA)-based procedures that measure the amount of these proteins. Secondly, because lactate dehydrogenase (LDH) is down-regulated and mitochondrial NADH-dehydrogenase activity is increased during PC12 cell differentiation, we established procedures to measure changes in LDH and NADH dehydrogenase. We found that the cell ELISA and cell counting assays could be used to determine the degree of PC12 cell differentiation caused by nerve growth factor, basic fibroblast growth factor and epidermal growth factor. However, neither LDH nor NADH-dehydrogenase activities changed during Thy-1 antibody-induced differentiation. These findings show that in addition to the cell ELISA procedures, the LDH and NADH-dehydrogenase procedures are useful for characterization of growth factor-induced PC12 cell differentiation.

Analysis of Variance↗

PubMed2002

Optimal inversion time for acquiring flow-sensitive alternating inversion recovery images to quantify regional cerebral blood flow.

The purpose of this study was to correlate regional cerebral blood flow (rCBF) measured by I-123-IMP and flow-sensitive alternating inversion recovery (FAIR) studies with different inversion time (TI) values to find out the optimum TI that gives comparable rCBF and images on FAIR study. Nine patients with symptoms and signs of internal carotid or major cerebral arterial stenosis were enrolled in this study. Both I-123-IMP single photon emission computed tomography (SPECT) and FAIR images were acquired in all patients. Single-slice FAIR images (with different TI values) were acquired using a 1.5-T MRI unit. The rCBF was calculated from all I-123-IMP and FAIR images. Receiver operating characteristics (ROC) analysis was performed to detect hypoperfused segments on FAIR images. The rCBF calculated from FAIR and I-123-IMP studies were compared and correlated with each other. The ROC analysis showed no significant differences among the readers or TI values, but a trend of higher sensitivity, specificity, and accuracy was observed with TI of 1400 ms. The rCBF values of FAIR and I-123-IMP studies significantly correlated with each other. The FAIR images with TI value of 1400 ms gave more comparable CBF. A TI value of 1400 ms might be optimum for 1.5-T MR strength to get high quality FAIR images and comparable CBF.

Aged↗

PubMed2002

CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV.

We raised monoclonal antibodies against senile plaque (SP) amyloid and obtained a clone 9D2, which labeled amyloid fibrils in SPs and reacted with approximately 50/100 kDa polypeptides in Alzheimer's disease (AD) brains. We purified the 9D2 antigens and cloned a cDNA encoding its precursor, which was a novel type II transmembrane protein specifically expressed in neurons. This precursor harbored three collagen-like Gly-X-Y repeat motifs and was partially homologous to collagen type XIII. Thus, we named the 9D2 antigen as CLAC (collagen-like Alzheimer amyloid plaque component), and its precursor as CLAC-P/collagen type XXV. The extracellular domain of CLAC-P/collagen type XXV was secreted by furin convertase, and the N-terminus of CLAC deposited in AD brains was pyroglutamate modified. Both secreted and membrane-tethered forms of CLAC-P/collagen type XXV specifically bound to fibrillized Abeta, implicating these proteins in beta-amyloidogenesis and neuronal degeneration in AD.

Alzheimer Disease↗

PubMed2002

Development of atopic dermatitis-like skin lesions in STAT6-deficient NC/Nga mice.

Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by elevation of plasma levels of total IgE, infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 T cells. However, the role of Th2 cells in the pathogenesis of AD is not fully understood. In this study we examined the NC/Nga (NC) mouse model of AD and established STAT6-deficient (SATA6(-/-)) NC mice to investigate the relevance of IL-4-mediated immune responses. Surprisingly, these mice elicited AD-like skin lesions at equivalent frequency and time of onset compared with normal NC littermates. Histological features of the lesion in STAT6(-/-) NC mice fulfilled the criteria for the pathogenesis of AD, although these mice fail to produce IgE and Th2 cytokines. The lymph nodes proximal to the regions of skin that developed lesions exhibited massive enlargement elicited by the accumulation of activated IFN-gamma-secreting T cells. Moreover, caspase I, IL-18, IL-12, and IFN-gamma are found to be highly expressed at the skin lesion, occurring simultaneously with elevation of eotaxin 2 and CCR3 expression. Therefore, the Th2-mediated immune response is not necessary for the development of AD-like skin disease in NC mice. The skin microenvironment that favored IFN-gamma production tightly correlates with the skin disease in NC mice through the infiltration of eosinophils.

Animals↗

PubMed2002

The IL-4 production capability of different strains of naive CD4(+) T cells controls the direction of the T(h) cell response.

The qualitative nature of an immune response raised against infectious pathogens depends upon the phenotypes of T(h) cell subsets, which secrete distinct types of cytokines. Genetic background is known to greatly influence the nature of the T(h) cell response. However, the precise nature of this influence still remains unclear. In the present study, we demonstrate that CD62L(+), CD44(low) and CD4(+) naive T cells from BALB/c mice are capable of producing significant amounts of IL-4, while naive T cells from B10.D2 mice exhibit no IL-4 production. The addition of exogenous IL-4 into the B10.D2 induction culture recovered T(h)2 development, thereby indicating that the potential of naive T cells to secrete IL-4 at primary activation is likely to substantially influence development of T(h)2. Regulation of the IL-4 gene in naive T cells differs from that in cells committed towards becoming T(h)2 cells, based on the observation that naive T cells from STAT6-deficient mice having a BALB/c background produce detectable amounts of IL-4. The IL-4 promoter region was found to be equally histone acetylated in both BALB/c and B10.D2 naive T cells by primary TCR activation. Interestingly, the expression levels of transcription factors NF-AT and GATA-3, which regulate promoter activity, differ between BALB/c and B10.D2 cells. These results suggest that the differences in expression level between the two transcriptional factors may affect the potential of naive T cells to secrete IL-4, which may subsequently influence the development of T(h) cell phenotypes.

Animals↗

PubMed2002

Quantitative measurement of regional cerebral blood flow with flow-sensitive alternating inversion recovery imaging: comparison with [iodine 123]-iodoamphetamin single photon emission CT.

BACKGROUND AND PURPOSE: Flow-sensitive alternating inversion recovery (FAIR) MR imaging is a technique for depicting cerebral perfusion without contrast enhancement. Our purpose was to determine whether quantification at FAIR imaging can be used to assess regional cerebral blood flow (rCBF) in a manner similar to [iodine 123]-iodoamphetamin ((123)I-IMP) single photon emission CT (SPECT). METHODS: Nine patients with internal carotid or major cerebral arterial stenosis underwent (123)I-IMP SPECT and FAIR imaging (single section, different TIs, 1.5 T) at rest and after acetazolamide (Diamox) stress. FAIR and (123)I-IMP rCBF values were compared and correlated. Receiver operating characteristic analysis was conducted to detect hypoperfused segments on FAIR images. RESULTS: rCBF values of normally perfused segments were 41.53 and 51.91 mL/100 g/min for pre- and post-acetazolamide (123)I-IMP studies, respectively. Corresponding values for pre- and post-acetazolamide FAIR images, respectively, were 46.64 and 59.60 mL/100 g/min with a TI of 1200 milliseconds and 53.23 and 68.17 mL/100 g/min with a TI of 1400 milliseconds. (123)I-IMP and FAIR results were significantly correlated, with both pre- and post-acetazolamide images. Sensitivity (86%) in detecting hypoperfused segments was significantly higher with post-acetazolamide images (TI, 1400 milliseconds), and specificity (82-85%) and accuracy (80-82%) were higher with all pre- and post-acetazolamide images (all TIs). CONCLUSIONS: The significant correlation, high specificity and accuracy in detecting hypoperfused segments, similar increases in flow on both post-acetazolamide images, and absence of the need for contrast enhancement suggest that FAIR imaging, like nuclear medicine study, is complementary to routine MR imaging in the assessment of cerebral perfusion.

Acetazolamide↗

PubMed2002

[A case of falcotentorial meningioma with visual allesthesia].

Visual allesthesia, in which visual images are transposed from one homonymous half-field of visual field to another, is a rare phenomenon. Palinopsia is the persistence or recurrence of visual images after the exciting stimulus object has been removed. Some authors have reported these phenomena, but these pathophysiology has not been understood. We report a right-handed 63-year-old woman, with a right falcotentorial meningioma. She paroxysmally experienced illusory transpositions of objects viewed in the right homonymous visual field into the left, and she recognized her face in it. The illusory images were palinoptic, persisting for up to a few minutes after the real objects were no longer in view. Administration of anticonvulsant medications resulted in the decrease of frequency of this phenomenon. Radiological and surgical findings revealed that the tumor was compressing the very localized visual cortex, especially the Brodmann's area 18 and 19. After resection of the tumor, visual allesthesia and palinopsia completely disappeared. These areas are associated with memory and recognition of visual images as visuopsychic area. This case provides some insight into the mechanisms of this phenomenon, and we consider that it could be caused by seizure activity in this lesion.

Female↗