Biomedical subjects

Y Itoh

Publications and source records attributed to Y Itoh.

At least 73 records · Page 4Linked to original sources

PubMed2001

Its8, a fission yeast homolog of Mcd4 and Pig-n, is involved in GPI anchor synthesis and shares an essential function with calcineurin in cytokinesis.

In fission yeast, calcineurin is required for cytokinesis and ion homeostasis; however, most of its physiological roles remain obscure. To identify genes that share an essential function with calcineurin, we screened for mutations that confer sensitivity to the calcineurin inhibitor FK506 and high temperature and isolated the mutant its8-1. its8(+) encodes a homolog of the budding yeast MCD4 and human Pig-n that are involved in glycosylphosphatidylinositol (GPI) anchor synthesis. Consistently, reduced inositol labeling of proteins suggested impaired GPI anchor synthesis in its8-1 mutants. The temperature upshift induced a further decrease in inositol labeling and caused dramatic increases in the frequency of septation in its8-1 mutants. BE49385A, an inhibitor of MCD4 and Pig-n, also increased the septation index of the wild-type cell. Osmotic stabilization suppressed these morphological defects, indicating that cell wall weakness caused by impaired GPI anchor synthesis resulted in abnormal cytokinesis. Furthermore, calcineurin-deleted cells exhibited hypersensitivity to BE49385A, and FK506 exacerbated the cytokinesis defects of the its8-1 mutant. Thus, calcineurin and Its8 may share an essential function in cytokinesis and cell viability through the regulation of cell wall integrity.

Amino Acid Sequence↗

PubMed2001

Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. I. Effect on the cerebral infarction and edema at the acute stage of permanent middle cerebral artery occlusion in rats.

The effect of a novel Na+/Ca2+ channel blocker NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] on the cerebral infarction, edema and brain energy metabolism was investigated in rats after permanent middle cerebral artery occlusion (MCAO). The infarction and brain water content were evaluated at 48 h and 24 h after MCAO, respectively. A single bolus injection of NS-7 (0.03125-0.25 mg/kg) immediately after MCAO produced a dose-dependent reduction in the infarct volume as well as edema both in the cerebral cortex and striatum. Glycerol (4 g/kg) also decreased water content both in the occluded and non-occluded brain, but it did not reduce the size of cerebral infarction. Unlike glycerol, NS-7 did not change the water content in non-occluded brain. Moreover, a significant protective action was still observed even when NS-7 was injected once at 12 h after occlusion. In addition, NS-7 significantly reversed the decrease in tissue ATP content observed at 3 h but not at 0.5 h after MCAO. These findings suggest that a Na+/Ca2+ channel blocker NS-7 protects cerebral tissues against ischemic insults by improving the disturbance of cerebral energy metabolism and suppressing the cerebral edema.

Adenosine Diphosphate↗

PubMed2001

Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. II. Effect on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of permanent middle cerebral artery occlusion in rats.

We have previously shown that NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] reduces the size of cerebral infarction measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h after permanent middle cerebral artery occlusion (MCAO) in rats. To determine whether NS-7 improves the pathological and behavioral changes at the chronic stage of MCAO, the effect of this compound on the cerebral infarction as well as the neurological and cognitive impairments was investigated 7 days after MCAO. Single or five daily injections of NS-7 (0.125-0.5 mg/kg, i.v.) significantly reduced the infarct volume and improved the neuronal dysfunction including the hind leg paralysis, walking disability and motor incoordination, and the deficit of passive avoidance task, although the neuroprotective efficacy was not different among these dosing regimens. On the other hand, the effects of single versus repeated injections of NS-7 at 0.1 or 0.2 mg/kg on the neurological symptoms were compared at 4 weeks after MCAO. At a lower dose, repeated but not single injection of NS-7 significantly improved the neurological symptoms, although the single injection was effective at a higher dose. From these findings, it is suggested that NS-7 reverses the behavioral and cognitive dysfunction observed at the chronic stage of cerebral ischemia by suppressing the cerebral infarction.

Animals↗

PubMed2001

Mechanical behaviour of condenser microphone in mechanomyography.

Condenser microphones (MIC) have been widely used in mechanomyography, together with accelerometers and piezoelectric contact sensors. The aim of the present investigation was to clarify the mechanical variable (acceleration, velocity or displacement) indicated by the signal from a MIC transducer using a mechanical sinusoidal vibration system. In addition, the mechanomyogram (MMG) was recorded simultaneously with a MIC transducer and accelerometer (ACC) during voluntary contractions to confirm the mechanical variable reflected by the actual MMG and to examine the influence of motion artifact on the MMG. To measure the displacement-frequency response, mechanical sinusoidal vibrations of 3 to 300 Hz were applied to the MIC transducer with different sizes of air chambers (5, 10, 15 and 20 mm in diameter and 15, 20 or 25 mm long). The MIC transducer showed a linear relationship between the output amplitude and the vibration displacement, however, its frequency response declined with decreasing diameter and decreasing length of the air chamber. In fact, the cut-off frequency (-3dB) of the MIC transducer with the 5-mm-diameter chamber was 10, 8 and 4 Hz for the length 15, 20 and 25 mm, respectively. The air chamber with at least a diameter of 10 mm and a length of 15 mm is recommended for the MIC transducer. The sensitivity of this MIC transducer arrangement was 92 mV microm(-1) when excited at 100 Hz. During voluntary contraction, the amplitude spectral density function of the MMG from the MIC transducer resembled that of the double integral of the ACC transducer signal. The angle of the MIC transducer was delayed by 180 degrees in relation to the ACC transducer signal. The sensitivity of the MIC transducer was reduced to one-third because of the peculiar volume change of air chamber when the MMG was detected on the surface of the skin. In addition, the MIC transducer was contaminated by a smaller motion artifact than that from the ACC transducer. The maximal peak amplitude of the MIC and ACC transducer signal with the motion artifact was 7.7 and 12.3 times as much as the RMS amplitude of each signal without the motion artifact, respectively. These findings suggest that the MIC transducer acts as a displacement meter in the MMG. The MIC transducer seems to be a possible candidate for recording the MMG during dynamic muscle contractions as well as during sustained contractions.

Biomechanical Phenomena↗

PubMed2001

Morphologic features of human chorionic gonadotropin- or alpha-fetoprotein-producing germ cell tumors of the central nervous system: histological heterogeneity and surgical meaning.

Our study of germ cell tumors (GCT) of the central nervous system (CNS) investigated the relationship between tumor histology and patient serum titers of human chorionic gonadotropin (HGC) and alpha-fetoprotein (AFP). Thirty-five patients were enrolled. Their serum titers of HCG (mlU/ml) and/or AFP (ng/ml) before initial treatment were available, as were tumor specimens obtained before the administration of adjuvant therapy. They were divided into three groups, depending on whether HCG alone (group H), AFP alone (group A), or both HCG and AFP (group HA) were detected. Each group was subdivided into three groups: patients in group I had H, A, and/or HA titers below 9.9; patients in group II/III had titers from 10.0 to 999; and those in group IV had titers of 1000 or more. Serial sections of tissue specimens were repeatedly stained, mainly with hematoxylin and eosin (H-E) stain, HCG immunostain, and AFP immunostain. There were seven patients in the H-I group and five in H-II/III. Of these 12 patients, 11 had germinomas (G) and one had an embryonal carcinoma (EC). Five patients were included in group A: one was classified as A-II/III and had a germinoma, and the remaining four patients were in A-IV and had yolk sac tumors (YST) or mixed GCT consisting mainly of YST or EC (MXGCT-YST, EC). The HA group consisted of 18 patients. Three were classified as HA-I and had germinomas; nine HA-II/III patients had T or MXGCT-T; and six HA-IV patients had choriocarcinoma (CC), YST, MXGCT-CC, or MXGCT-YST. Throughout the study, the situations for the elevated serum titers could be elucidated in only four cases (three in group A-IV and one in group HA-IV). These results led to the conclusion that serologic evaluation is superior to morphologic evaluation in diagnosing marker-producing GCTs. From a diagnostic perspective, the role of surgery is to verify the HCG- and AFP-immunonegative tissue in patients with G, T, and EC.

Adolescent↗

PubMed2001

Aortic valve replacement in a heavily calcified "porcelain" aorta.

Although a heavily-calcified so-called "porcelain" aorta is encountered infrequently, its association presents a formidable problem in cardiac surgery. Here we describe a case of severe aortic stenosis and coronary artery disease combined with the circumferentially calcified aorta. The patient was a 63-year-old man who successfully underwent double coronary artery bypass grafting and aortic valve replacement during hypothermic perfusion through the right axillary artery with endoaortic balloon occlusion, followed by minimal endarterectomy of the calcified plate along the aortotomy, and closure of the aorta buttressed with bovine pericardium under circulatory arrest.

Aortic Diseases↗

PubMed2001

An Aspergillus nidulans uvsC null mutant is deficient in homologous DNA integration.

The Aspergillus nidulans uvsC gene was identified as a homolog of RAD51 and recA of Saccharomyces cerevisiae and Escherichia coli, respectively, whose role in genetic recombination and recombinational repair has been extensively studied. Like many other filamentous fungi, A. nidulans shows no bias towards either homologous or ectopic integration of exogenous DNA. Therefore it is a unique and useful organism for the study of the mechanisms of DNA integration. Homologous integration of a 1.7-kb argB gene was not detected in 50 transformants obtained from a uvsC null mutant. In contrast, the frequency of homologous integration in uvsC+ control strains varied from 41 to 86%. Another feature observed with the uvsC null mutant was that an increased number of transformants had undergone ectopic integrations at multiple sites in the genome. These results are consistent with the established function of Rad51/RecA, and further indicate the involvement of redundant pathways in integration of exogenous DNA. This study provides direct evidence for the involvement of uvsC in exogenous DNA integration and should contribute to the improvement of genetic manipulations in general, but particularly in fungi.

Aspergillus nidulans↗

PubMed2001

The therapeutic effect of lipo PGE1 on diabetic neuropathy-changes in endothelin and various angiopathic factors.

A high blood concentration of endothelin (ET)-1 may participate in the onset and progress of diabetic microangiopathy, resulting in neuropathy. We examined the therapeutic effects of prostaglandin E1 (PGE1), which possesses both a peripheral vasodilating action and inhibition of platelet aggregation, on diabetic microangiopathy. Increases in both skin temperature and peripheral never conduction velocity in diabetic patients were recorded four weeks after Lipo PGE1 administration. A quantitative decrease in urinary albumin concentration was also observed, suggesting its efficacy of action was on diabetic nephropathy. Lipo PGE1 administration reduced the elevated circulating plasma ET-1 levels in the diabetic patients. As an increase in ET-1 concentrations is thought to correlate with the onset and progress of diabetic microangiopathy, the reduction of plasma ET-1 concentration by Lipo PGE1 administration may be one reason for the improvement in diabetic neuropathy and nephropathy.

Adult↗

PubMed2001

Intracellular cytokine profile of CD14 positive cells in patients with hematologic malignancies and solid tumors during hematologic recovery phase after intensive chemotherapy designed to mobilize peripheral blood stem cells.

We studied intracellular cytokines in monocytes by flow cytometry from 28 patients with hematologic malignancies and solid tumors to analyze the role of monokines in the hematologic recovery phase for peripheral blood stem cell harvest. The patients were divided into three groups: the first group, A, had a documented infection; the second group, B, had fever of unknown origin; and the third group, C, was afebrile. We found an increase in intracellular IL-1alpha, IL-6, IL-8 and TNF-alpha positive monocytes as CD14 positive gated cells cultured with lipopolysaccharide in all groups, but no increase was found with medium only when cultured for 4 h. We also found an increase in intracellular IL-1a, IL-6, IL-8 and TNF-alpha positive monocytes cultured with autologous serum for 4 h, but only in group A. The rate of intracellular cytokine positive cells was higher in monocytes cultured with only autologous serum from group A patients compared to those cells from the other groups; the data concerning IL-1a, IL-6 and TNF-alpha reached statistical significance (P < 0.05). However, increasing intracellular cytokine levels in the control group of patients exhibiting only infectious disease were observed. Thus, it appear that pro-inflammatory intracellular cytokine levels in monocytes are only related to microbial infections.

Adult↗

PubMed2001

In vitro and in vivo expression of protoporphyrin IX induced by lipophilic 5-aminolevulinic acid derivatives.

We estimated the expression level of protoporphyrin IX (PpIX) induced by lipophilic 5-aminolevulinic acid (ALA) derivatives and observed its histological distribution by fluorescence microscopy. In vitro PpIX expression in Hepe2 cells was the highest when induced by ALA pentyl ester. This level was 2.8-fold higher than that induced by ALA after 4 h incubation and 2.5-fold higher than that after 24 h incubation. The differences between ALA pentyl ester and ALA were significant at both time points (P<0.01). In HeLa cells, ALA butyl ester showed the highest induction of PpIX, which was 2.6-fold higher than ALA after 4 h incubation and 3.5-fold higher after 24 h incubation. The differences were significant at both time points (P<0.01). In mice with squamous cell carcinoma, the in vivo expression of PpIX in the tumors was highest with ALA methyl ester, which was 1.3-fold higher than ALA. The difference was significant (P<0.01). The expression of PpIX by means of fluorescence microscopy was highest by ALA methyl ester. Under in vitro conditions, PpIX expression was efficiently induced by long chain ALA esters, while better in vivo PpIX induction was obtained with short chain ALA esters. In this study, ALA methyl ester was found to be the best among the ALA derivatives in inducing PpIX expression in vivo, and would be more effective in treatment of skin cancers than ALA.

Aminolevulinic Acid↗

PubMed2001

Recovery of 18F from [18O] water by electrochemical method.

An electrochemical method for producing 18F sources for the slow positron beam was applied to the recovery of 18F from H2(18)O water. The 18F of activities 150-227 mCi (5.55-8.40 GBq) was electro-deposited on a graphite rod and then emitted into pure water. The best result of the efficiency for the electro-deposition for 5 min was 97% and that for the electro-emission for 5 min was 89%. The H2(18)O water is expected to be reused much more easily by this method than by the ion exchange resin method. The metal impurities contained in the 18F solution were considerably reduced by using this method.

Journal Article↗

PubMed2001

False positive reaction in ELISA for IgM class anti-M2 antibody and its prevention.

Anti-M2 of anti-mitochondrial antibodies is recognized as the specific autoantibody detected in sera from patients with primary biliary cirrhosis (PBC). The IgG class and IgM class of this antibody can be separately measured using each ELISA. In the present study, false positive reactions were found in some sera from non-PBC patients such as acute hepatitis A, syphilis and rheumatoid arthritis using the IgM anti-M2 ELISA. They showed an increase of polyclonal IgM, and positivity for IgM anti-cardiolipin or rheumatoid factors, respectively. So, we developed a means to prevent these false positive reactions. First, dilutions of test sera at 1:1000-fold were carried out in addition to the original method at 1:100-fold. Secondly, some blocking reagents were added into the buffer system. By serum dilution, non-specific bindings disappeared in most samples other than showing an increase in polyclonal IgM. Moreover, the addition of suitable blocking reagents such as fetal bovine serum (FBS) and skimmed milk into the buffer system could prevent these non-specific bindings. From these findings, the procedure of optical serum dilution and the addition of suitable blocking reagents successfully prevented false positive reactions in this IgM anti-M2 ELISA.

Journal Article↗

PubMed2001

Retreatment with interferon-alpha at dosages or period increased by 1.3 times is effective for treatment for transient responders and non-responders in chronic hepatitis C patients.

The objectives of retreatment with interferon (IFN) in chronic hepatitis C (CH-C) patients are sustained response and a reduction in the risk of hepatocellular carcinoma (HCC). However, it is still unclear, as to which patients are candidates for retreatment with IFN. Eighteen transient responders (TRs) and 15 non-responders (NRs) to IFN therapy in CH-C received retreatment with IFNalpha. Of the 18 TRs, five showed sustained disappearance of hepatitis C virus, two showed sustained biochemical response, 10 continued as TR and one was a NR. Of the 15 NRs, six showed a TR while nine continued as NRs. Responsive cases, which included the virologically or biochemically sustained and transient responders, received either a dose of IFN 1.3 times greater or were treated for a period of 1.3 times longer in the retreatment than the original treatment. We submit that IFN treatment consisting of either a time period or a dosage 1.3 times those of the original IFN administration may be beneficial in the case of TR and NR in chronic hepatitis C patients.

Journal Article↗

PubMed2001

Development of a new enzyme-linked immunosorbent assay for the detection of anti-M2 in primary biliary cirrhosis.

We developed a new enzyme-linked immunosorbent assay (ELISA) for the detection of antimitochondrial antibody (AMA)-M2 in sera from patients with primary biliary cirrhosis (PBC), using 2-oxo-acid dehydrogenase complex (2-OADC) purified from porcine myocardium as the antigen source. The immunoreactivity was tested in a total of 354 sera, including 63 sera from patients with PBC by our ELISA. In the sera, indirect immunofluorescence for AMA, former ELISA for anti-pyruvate dehydrogenase complex (PDC) and immunoblot assay were performed, respectively. Of the 63 sera from patients with PBC, 51 sera (81.0%) were positive for anti-M2 in the new ELISA. Thirty-eight of the 63 sera (60.3%) were positive for anti-PDC in the former ELISA; the difference was significant between them (P=0.011). None of the 291 control sera from healthy volunteers showed reactivity against 2-OADC in the new ELISA. Moreover, in comparison with the results of immunoblot analysis, sensitivity and specificity in our ELISA to the sera from patients with PBC were 100 and 92.3%, respectively. Our results indicate that the new ELISA for anti-M2 using 2-OADC is simple, rapid and sensitive enough for the detection of AMA specific to PBC.

Journal Article↗

PubMed2001

Megastigmane glycosides and an acylated triterpenoid from Eriobotrya japonica.

Two new megastigmane glycosides, eriojaposides A (1) and B (2), and a new acylated triterpenoid (3) were isolated along with nine known compounds from a leaf extract of Eriobotrya japonica. The structures of 1--3 were characterized as (6R,9R)-3-oxo-alpha-ionyl-9-O-beta-xylopyranosyl-(1' '-->6')-beta-glucopyranoside, (6R,9R)-3-oxo-alpha-ionyl-9-O-alpha-rhamnopyranosyl-(1' '-->6')-beta-glucopyranoside, and 3 alpha-trans-feruloyloxy-2 alpha-hydroxyurs-12-en-28-oic acid, respectively, on the basis of spectral and chemical evidence.

Asia↗

PubMed2001

Chicken spindlin genes on W and Z chromosomes: transcriptional expression of both genes and dynamic behavior of spindlin in interphase and mitotic cells.

Contigs of genomic clones covering about 480 kb on the terminal region of the short arm of chicken W chromosome were obtained. By applying the exon trapping procedure on this whole region, a chicken homolog of spindlin gene, chSpin-W, was identified and subcloned. A counterpart gene, chSpin-Z, was found near the centromere on the long arm of Z chromosome. Although protein-coding regions of both genes are nearly identical, a part of the 3'-untranslated region is sufficiently different to distinguish the transcript of chSpin-W. Both chSpin-W and chSpin-Z are transcribed in early embryos. chSpin-Z is transcribed in various tissues of adult chickens, while chSpin-W is transcribed most prominently in ovarian granulosa and thecal cells. When female chicken embryonic fibroblasts were transfected with a cDNA construct for red fluorescent protein or green fluorescent protein-fused spindlin or FLAG-tagged spindlin, the expressed spindlin was co-localized with SUMO-1 in nuclear dots, ND10, in interphase cells, while the expressed spindlin was localized on entire chromosomes during mitosis. The localization of spindlin in ND10 reappeared after mitosis in daughter cell nuclei. A C-terminal region of spindlin was suggested to be required for the localization of spindlin to ND10.

Amino Acid Sequence↗

PubMed2001

Electrophysiological and neurochemical evidence for voltage-dependent Ca(2+) channel blockade by a novel neuroprotective agent NS-7.

The effects of a neuroprotective agent 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride (NS-7) on the Ca(2+) currents in rat dorsal root ganglion neurones and on the depolarization-evoked nitric oxide synthesis, which was estimated from cyclic GMP formation in slices of the rat cerebral cortex, were investigated, and its mode of action was compared with those of typical Ca(2+) channel blockers. In rat dorsal root ganglion neurones, NS-7 (0.3-100 microM) inhibited the whole-cell Ba(2+) currents (IBa) in a voltage-dependent manner, in which the compound more potently blocked the IBa elicited from the holding potential of -40 mV than that induced from -80 mV. In slices of rat cerebral cortex, KCl-evoked nitric oxide synthesis was markedly inhibited by omega-conotoxin GVIA and omega-agatoxin IVA, but only slightly attenuated by nifedipine, suggesting that the response is mediated predominantly through activation of N-type and P/Q-type Ca(2+) channels. NS-7 (1-100 microM) inhibited the KCl-stimulated nitric oxide synthesis in a manner dependent on the intensity of the depolarizing stimuli. Moreover, weak but significant inhibitory effect of NS-7 was observed even after wash-out. Similar voltage-dependent inhibition of the KCl response was observed by a limited concentration (10 microM) of verapamil. These findings indicate that NS-7 in several concentrations blocks Ca(2+) channel in a voltage-dependent manner.

Animals↗

PubMed2001

Photodynamic therapy of acne vulgaris with topical delta-aminolaevulinic acid and incoherent light in Japanese patients.

BACKGROUND: Photodynamic therapy (PDT) is useful for treatment of epidermal neoplasia but may also have a role in the treatment of inflammatory dermatoses. OBJECTIVES: To study the effect of PDT in patients with acne. METHODS: Three men and 10 women who suffered from intractable acne vulgaris were treated using PDT with topical delta-aminolaevulinic acid (ALA) and polychromatic visible light. Twenty per cent ALA in an oil-in-water emulsion was applied to the lesions for 4 h with a light-shielding dressing. The lesions were then exposed to polychromatic visible light at 600-700 nm using a halogen light source of energy intensity 17 mW cm-2 and a total energy dose of 13 J cm-2. RESULTS: All patients had apparent improvement of facial appearance and reduction of new acne lesions at 1, 3 and 6 months following PDT treatment. The adverse effects were discomfort, burning and stinging during irradiation, oedematous erythema for 3 days after PDT, epidermal exfoliation from the fourth to the 10th day, irritation and hypersensitivity to physical stimulation for 10 days after PDT, and pigmentation or erythema after epidermal exfoliation; the treated lesions returned to normal skin conditions within 1 month. CONCLUSIONS: PDT was beneficial in the treatment of acne. As a photoactivating light source, polychromatic visible light was thought to be better for use with acne patients than laser light because of its cost-effectiveness, uniform illumination and time-efficiency in treating large areas.

Acne Vulgaris↗