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Biomedical subjects

Y Yagi

Publications and source records attributed to Y Yagi.

At least 19 recordsLinked to original sources
PubMed1999

Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein.

A novel protein, human X11-like (human X11L), contains a phosphotyrosine interaction (PI) domain and two PDZ domains and displays 55.2% amino acid homology with the human X11 (human X11). The PI domain of human X11L interacts with a sequence containing the NPXY motif found in the cytoplasmic domain of Alzheimer's amyloid precursor protein. A construct lacking the carboxyl-terminal domain, which comprises two PDZ domains (N + PI), enhances PI binding to APP, whereas another construct lacking an amino-terminal domain relative to PI domain (PI + C) suppresses PI binding to APP. Overexpression of full-length human X11L (N + PI + C) in cells that express APP695 stably decreased the secretion of Abeta40 but not that of Abeta42. However, overexpression of the PI domain alone and the N + PI construct in cells did not affect the secretion of Abeta despite their ability to bind to the cytoplasmic domain of Alzheimer's amyloid precursor protein. These observations suggest that the amino-terminal domain regulates PI binding to APP and that the carboxyl-terminal domain containing PDZ motifs is essential to modulate APP processing. Because expression of the human X11L gene is specific to brain, the present observations should contribute to shedding light on the molecular mechanism of APP processing in Alzheimer's disease.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Diseases associated with ocular surface abnormalities: the importance of reflex tearing.

AIM: To investigate the correlation between tear function tests and ocular surface integrity in patients with dry eye. METHODS: 297 dry eye patients (55 Sjögren's syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and 242 non-Sjögren's syndrome, 41 male and 201 female, average age 53.5 (14.1) years) were examined. The following tear function tests were performed: (1) cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose bengal and fluorescein staining. Correlation analysis was performed between each tear function index and vital staining scores. RESULTS: Among the six tear function tests, the Schirmer test with nasal stimulation correlated most with both of the vital stains (rho = 0.530 for rose bengal and 0.393 for fluorescein). The Schirmer test with or without anaesthesia correlated slightly with rose bengal staining, whereas tear clearance test and tear break up time slightly correlated with fluorescein staining. CONCLUSION: Vital staining of the ocular surface correlates most with reflex tearing measured by the Schirmer test with nasal stimulation.

Dry Eye Syndromes↗
PubMed1998

Detection of activated caspase-3 (CPP32) in the vertebrate nervous system during development by a cleavage site-directed antiserum.

We previously demonstrated that Caspase-3 is highly expressed in dorsal root ganglia and trigeminal ganglia of mouse embryos [T. Mukasa, K. Urase, Y.M. Momoi, I. Kimura, T. Momoi, Specific expression of CPP32 in sensory neurons of mouse embryos and activation of CPP32 in the apoptosis induced by a withdrawal of NGF, Biochem. Biophys. Res. Commun., 231 (1997) 770-774.]. Since, however, Caspases are processed into active form during apoptosis, it is difficult to examine the involvement of activated Caspases in naturally occurring cell death during development by immunohistochemical staining or in situ hybridization method. We prepared a cleavage site-directed antiserum against Caspase-3 (anti-p20/17). This antiserum reacted with fragment (p20/17) of Caspase-3, but not proCaspase-3 (p32), proCaspase-7 (p34) and its cleaved fragment (p24). We examined the relationship between the activation of Caspase-3 and the appearance of the naturally occurring apoptotic cells in the nervous system during development. In the trigeminal ganglia and dorsal root ganglia, the expression of Caspase-3 mRNA was maximal before the appearance of p20/17-positive cells and apoptotic cells. In the mouse brain, many p20/17-positive cells and apoptotic cells were observed in the neuroepithelium in the early developmental stages, but very few p20/17-positive cells were detected in postmitotic neurons in the cerebral cortex although Caspase-3 mRNA was expressed highly. Caspase-3 is activated mainly during apoptosis of neuroepithelial cells in the early developmental stages but not of mature neurons at postnatal stages.

Animals↗
PubMed1998

Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV.

A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1IIIB-WT and retain good activity against a laboratory-derived HIV-1MF delavirdine-resistant variant.

Amino Acid Substitution↗
PubMed1998

Concurrent visual task effects on evoked and emitted auditory p300 in adolescents.

Using an oddball stimulus presentation paradigm, the effects of divided attention on auditory P300s were studied. Auditory attention was either divided or focused, depending on the demands placed on subjects during the performance of a concomitantly presented visual task. Two types of auditory tasks were performed under each of the two auditory attention conditions. In one, subjects responded to infrequently presented high pitched tones (oddball stimuli). In the other they responded to the occasional omission of a stimulus in an otherwise rhythmically presented chain of stimuli. P300s and reaction times were recorded to both the rare tones and the omissions. The Sternberg visual memory task was used to manipulate the subject's auditory attention state. Subjects actively performed the Sternberg task during the divided auditory attention condition, whereas during the focused attention condition they were not required to respond to the visual stimuli. During focused auditory attention, evoked auditory P300s were both larger and faster than their emitted counterparts. During divided attention, auditory P300s were reduced in amplitude but latency was unaffected. Evoked auditory P300s showed evidence of containing P300a as well as P300b components, particularly when attention was shared with the visual task.

Adolescent↗
PubMed1998

Total parenteral nutrition supplemented with medium-chain triacylglycerols prevents atrophy of the intestinal mucosa in septic rats.

Total parenteral nutrition (TPN) is associated with an increased incidence of bacterial translocation (BT) compared with enteral nutrition because of the disuse atrophy of the intestine. In this study, we assessed the effect of adding medium-chain triacylglycerols (MCT) to TPN for the prevention of mucosal atrophy in the intestine. Rats were subjected to either fat-free TPN, TPN with long-chain triacylglycerols (LCT), or TPN with MCT for 5 d and nutrition parameters were evaluated. In another set of rats receiving the same TPN regimen, 0.8 or 0.05 mg/kg endotoxin was administered on day 4. Survival was evaluated and BT to the mesenteric lymph nodes, liver, and systemic blood was measured 24 h later. The mucosal heights of the jejunum and ileum were evaluated concurrently. The survival rate was significantly improved in the MCT group (P < 0.05) at the endotoxin dose of 0.8 mg/kg. The nutrition condition presented by phospholipid, total cholesterol, and total ketone body levels was the best in the MCT group compared to the other groups. The intestinal villous height in the ileum was significantly greater in the MCT group. However, the improvement of BT in MCT group was not statistically significant. In this endotoxin-challenged rat model, survival rate was improved by the supplementation of MCT. This effect may be presented in some part by the improvement in nutrition condition and by the prevention of mucosal atrophy in the intestine.

Animals↗
PubMed1998

[Possibility of prevention of herpes zoster by use of varicella vaccine].

It has been considered that a decline in specific cell-mediated immunity (CMI) for the varicella-zoster virus (VZV) could be responsible for a high incidence of herpes zoster in the elderly. If the strength of CMI for VZV could be increased by immunization of the elderly with a varicella vaccine, herpes zoster might be preventable. We compared the CMI for VZV (using a lymphoproliferative assay and a varicella skin test) and VZV-IgG antibodies in serum before and after 2-3 months of vaccination in 15 subjects more than 40 years old. When the CMI for VZV was measured by the lymphoproliferative assay, a stimulation index (SI) of more than 2.0 was estimated to be positive in this study. The SIs (mean +/- SD) before and after the vaccination were 2.7 +/- 1.8 and 2.7 +/- 1.9, respectively, and no significant difference was noted. On the other hand, the diameter of erythema in the varicella skin test after the vaccination became larger than that before the vaccination in the 10 of 13 subjects. In addition, serum VZV-IgG antibodies increased after vaccination in 6 of 14 subjects. There were no obvious reasons for the discrepancy in the results of the lymphoproliferative assay and the varicella skin test. However, because of the poor response indicated by the assay, only one vaccination for the elderly might not be enough to increase the CMI for VZV. The appropriate age for vaccination should also be considered. Lastly, further investigation of the CMI for VZV before and after vaccination on larger scale is required.

Aged↗
PubMed1998

Interaction between Drosophila EGF receptor and vnd determines three dorsoventral domains of the neuroectoderm.

Neurogenesis in Drosophila melanogaster starts by an ordered appearance of neuroblasts arranged in three columns (medial, intermediate and lateral) in each side of the neuroectoderm. Here we show that, in the intermediate column, the receptor tyrosine kinase DER represses expression of proneural genes, achaete and scute, and is required for the formation of neuroblasts. Most of the early function of DER is likely to be mediated by the Ras-MAP kinase signaling pathway, which is activated in the intermediate column, since a loss of a component of this pathway leads to a phenotype identical to that in DER mutants. MAP-kinase activation was also observed in the medial column where esg and proneural gene expression is unaffected by DER. We found that the homeobox gene vnd is required for the expression of esg and scute in the medial column, and show that vnd acts through the negative regulatory region of the esg enhancer that mediates the DER signal, suggesting the role of vnd is to counteract DER-dependent repression. Thus nested expression of vnd and the DER activator rhomboid is crucial to subdivide the neuroectoderm into the three dorsoventral domains.

Animals↗
PubMed1998

Airway responsiveness to acetylcholine in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs in vivo and in vitro.

The characteristics of airway responsiveness to acetylcholine (ACh) in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs were clarified in vivo and in vitro. We measured the change in ventilatory mechanics in response to ACh inhalation by means of the bodyplethysmograph and the contractile responses of isolated trachea to ACh and carbachol (CCh). Further, muscarinic receptor subtypes involved these responses were identified. The basal values for ventilatory mechanics in BHS were not significantly different from those in BHR. Respiratory resistance to ACh was progressively increased in a time- and dose-dependent manner in BHS. The contractile responses of tracheal smooth muscle to ACh in BHS were significantly greater than those in BHR, but CCh-induced responses in BHS and BHR were similar. ACh- and CCh-induced contractions were mediated via M3 receptors. These results suggested that the falling-down of BHS in response to ACh inhalation was caused by the strong constriction of the airway and the reduction in ventilation. Moreover, the airway hyperresponsiveness to ACh in BHS might be partly dependent on the change in acetylcholinesterase activity.

Acetylcholine↗
PubMed1998

[The intratumoral levels of thymidylate synthetase and folate in gastric and colon cancer].

Currently, biochemical modulation for 5-fluorouracil (5-FU) is one of the most successful chemotherapy for both colo-rectal and gastric cancer. The purpose of this study is to evaluate the significance of measuring intratumoral thymidylate synthetase (TS) and folate (FH4) levels as predictive parameters for the successful treatment. Samples were collected from 16 advanced colo-rectal and 21 advanced gastric cancer. TS and tetrahydrofolate levels in the specimens were measured by binding assay. Results showed that there were no significant difference in TS levels between the different pathologic types of carcinoma. On the other hand, well (3.94 +/- 1.75 p mol/g) and moderately (5.95 +/- 2.69 p mol/g) differentiated carcinoma showed lower FH4 levels compared to poorly differentiated carcinoma (9.58 +/- 5.27 p mol/g). In conclusion, biochemical modulation by cisplatin or leucovorin, which elevates intratumoral folate levels, is more needed for well and moderately differentiated carcinoma. Finally, measuring TS levels can also be important because two cases who responded to cisplatin/5-FU chemotherapy showed low TS levels compared to the others who had lower response.

Adenocarcinoma↗
PubMed1997

Effect of the maze procedure for atrial fibrillation on atrial and brain natriuretic peptide.

We studied plasma levels of atrial and brain natriuretic peptides at rest and after exercise before and after intracardiac surgery with and without the maze procedure in patients with chronic heart failure secondary to valvular heart disease. The present study found that an increased response of both cardiac natriuretic peptides is attenuated with resulting water retention after the maze procedure.

Atrial Fibrillation↗
PubMed1997

Pharmacological profile of JTE-522, a novel prostaglandin H synthase-2 inhibitor, in rats.

OBJECTIVE AND DESIGN: The antinociceptive, antipyretic, and anti-inflammatory effects of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, were examined in rats. MATERIALS: Sheep seminal vesicle PGHS-1 and placenta PGHS-2 were used for in vitro assay, while for in vivo experiments, male rats (4-8 weeks old) were used. TREATMENT: JTE-522 and reference compounds (0.01-100 microM) were subjected to enzyme assay. JTE-522 (0.3-30 mg/kg) and indomethacin (0.3-10 mg/kg) were administered orally. RESULTS: JTE-522 inhibited PGHS-2 (IC50: 0.64 microM) without affecting PGHS-1 activity at 100 microM. In rats with yeast-induced hyperalgesia, JTE-522 showed a dose-dependent antinociceptive effect (ED50: 4.4 mg/kg). In rats with yeast-induced pyrexia, JTE-522 significantly reversed the pyrexic response (ED50: 3.9 mg/kg). Orally administered JTE-522 dose-dependently inhibited carrageenin-induced rat paw edema (ED30: 4.7 mg/kg). In rats with adjuvant-induced arthritis, JTE-522 showed a significant inhibitory effect at daily doses of 0.3-3 mg/kg. JTE-522 did not cause severe gastric lesions at oral doses up to 300 mg/kg. CONCLUSIONS: Our results indicate that the selective PGHS-2 inhibitor JTE-522 may represent a novel type of anti-inflammatory drug without adverse effects on the gastrointestinal tract. JTE-522 may thus be a promising agent for treating both acute inflammatory disease and chronic inflammatory diseases such as rheumatoid arthritis.

Administration, Oral↗
PubMed1997

Role of the Drosophila EGF receptor in determination of the dorsoventral domains of escargot expression during primary neurogenesis.

BACKGROUND: Primary neurogenesis in the central nervous system of insects and vertebrates occurs in three dorsoventral domains in each side of the neuroectoderm. Among the three dorsoventral domains of the Drosophila neuroectoderm, the medial and lateral columns express the zinc-finger gene escargot (esg), whereas the intermediate column does not. We studied esg expression as a probe to investigate the mechanism of neuroectoderm patterning. RESULTS: The effect of dorsoventral patterning genes on esg expression was studied. decapentaplegic, snail and twist were found to repress esg expression outside the neuroectoderm. The expression of esg in the intermediate column is normally repressed, but was de-repressed when the EGF receptor homologue (DER) activity was either elevated or reduced. A neurogenic enhancer of esg was identified, and was shown to be separable into a distal region that promotes ubiquitous expression in the neuroectoderm and a proximal region that represses the intermediate expression. CONCLUSIONS: decapentaplegic, snail, twist and an activator act through the distal region to initiate transcription of esg in the neuroectoderm. We propose that the combination of opposing gradients of DER and its ligand creates a peak of DER activity in the intermediate column where DER represses esg transcription through the proximal repressor region. These two kinds of regulation establish the early esg expression that prefigures the neuroectoderm patterning.

Animals↗