Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 235 records · Page 13Linked to original sources

PubMed1995

Coexpression of trk family members and low-affinity neurotrophin receptors in rat dorsal root ganglion neurons.

We examined the colocalization of trk family and low-affinity neurotrophin receptor (LANR) mRNAs by means of in situ hybridization histochemistry in rat dorsal root ganglion (DRG) neurons. About 35-40%, 5%, and 15-20% of DRG neurons were positive for trkA, trkB, and trkC mRNAs, respectively. Each member of the trk family was coexpressed with LANR. The trkB mRNA-expressing neurons essentially lacked trkA and trkC mRNAs, and most of trkA and trkC mRNAs-expressing neurons (85-90%) belonged to different subpopulations, suggesting that they are involved in different functions.

Animals↗

PubMed1995

Myocardial action potential prolongation by calcium channel activation under calcium free-EGTA condition in rats: developmental and regional variations.

1. Prolongation of action potentials upon the addition of isoproterenol, forskolin, isobutylmethyl-xanthine (IBMX) and dibutyril cAMP (dbcAMP) under Ca-free EGTA condition was examined in isolated myocardial preparations from neonatal and adult rats, whose action potential configuration greatly differ. 2. The prolongation of the action potential was previously suggested to be produced by persistent sodium influx through calcium channel due to the lack of calcium-mediated inactivation of calcium channels under such experimental condition. 3. Preparations used were papillary muscles and free walls of the right and left ventricles from neonatal and adult rats. 4. In adult preparations, the prolongation produced by isoproterenol, forskolin and IBMX in the right free wall was smaller than those in the other three regions, while no regional difference was observed with dbcAMP. 5. The degree of prolongation by all of the four drugs were smaller in the neonate than in the adult. No regional difference was observed with any of the drugs in the neonate. 6. Our present results suggest that contribution of calcium-mediated inactivation of calcium channels to the repolarization of rat myocardium may increase postnatally to produce the developmental shortening of its action potential. Also, regional difference in the cAMP related mechanisms may appear postnatally.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Augmentation of specific tumor killing activity by tumor-infiltrating lymphocytes (TIL) in the presence of TNF-SAM2.

The effect of TNF-SAM2 on cytotoxic activity of tumor-infiltrating lymphocytes (TIL) was investigated. TIL were prepared from 11 human cancer patients. They were propagated by double in vitro stimulation with anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 weeks. The cytotoxic activity of TIL was tested with standard 4h 51Cr-release assays in the presence or the absence of TNF-SAM2. In the presence of TNF-SAM2 (500U/ml), the mean cytotoxic activity against autologous tumor cells was significantly augmented compared to that in its absence. However, the fact that cytotoxic activity against K562 and Daudi showed no difference whether substance was present or not, indicates that LAK and NK activity were not affected by TNF-SAM2. Direct cytotoxicity by exogenously added TNF-SAM2 to tumor cells was measured in 9 out of 11 cases and this revealed that cytotoxicity solely by TNF-SAM2 was seen in 3 tumors. However, there was no correlation between the augmentation of cytotoxicity by TIL in the presence of TNF-SAM2 and the cytotoxicity shown by TNF-SAM2 alone. These results suggested that TIL therapy combined with administration of exogenous TNF may exert a synergistically stronger therapeutic effect on cancer.

Cytotoxicity, Immunologic↗

PubMed1995

Different localization of tau protein kinase I/glycogen synthase kinase-3 beta from glycogen synthase kinase-3 alpha in cerebellum mitochondria.

We examined the subcellular distribution of two glycogen synthase kinase-3 (GSK-3) isoforms in rat cerebellum. Results from immunoelectron microscopy and subcellular fractionation revealed that one isoform, tau protein kinase I/GSK-3 beta (TPKI/GSK-3 beta), was present in mitochondria, but GSK-3 alpha was not. Although the two GSK-3 isoforms seem to have similar properties, the difference of subcellular localization observed here suggests that TPKI/GSK-3 beta fulfills some specific function in mitochondria.

Animals↗

PubMed1995

Correlation among secondary structure, amyloid precursor protein accumulation, and neurotoxicity of amyloid beta(25-35) peptide as analyzed by single alanine substitution.

Structure-neurotoxicity relationships of amyloid beta (25-35) peptide were studied by replacing each amino acid with Ala. In contrast to the general tendency in hydrophobicity-toxicity relationships, replacement of Asn27 yielded a more hydrophobic but less toxic analog and that of Met35 gave a less hydrophobic but more toxic one. Sedimentation profiles and CD spectra indicated that peptide aggregation via intermolecular beta-sheet formation is essential for the neurotoxicity of amyloid beta (25-35) peptide. The correlation between neurotoxicity and amyloid precursor protein accumulation suggested that the latter is one of the pathways of the neuronal death caused by amyloid beta protein.

Alanine↗

PubMed1995

Inhibition by differentiation-inducing agents of wild-type p53-dependent apoptosis in HL-60 cells.

The product of the p53 tumor-suppressor gene has been shown to function in apoptosis and cell cycle regulation. However, there is little information regarding the regulation of apoptosis in cell differentiation. We investigated the relationship between p53-dependent apoptosis and differentiation induction using human promyelocytic leukemia HL-60 cells transfected with pMAMneo expression vectors containing dexamethasone-inducible wild-type p53 (wt-p53) cDNA inserts. Continuous exposure of the pMAMneo/wt-p53 transfectants to 1 microM dexamethasone for more than 24 h caused overexpression of wt-p53 followed by cell death with morphological changes typical of apoptosis. Using the wt-p53-inducible HL-60 cells, we examined the effects of differentiation inducers on the wt-p53-dependent apoptosis. All-trans retinoic acid (all-trans RA) at 1 nM or granulocyte macrophage colony-stimulating factor (GM-CSF) at 35 pM inhibited the wt-p53-induced apoptosis over a 42-h treatment. The apoptosis inhibition by GM-CSF, but not all-trans RA, was abolished by specific inhibitors of protein kinase C. These results suggest that extracellular signals involved in the differentiation induction could modulate the wt-p53-dependent apoptosis through protein kinase C-dependent and independent pathways.

Apoptosis↗

PubMed1995

Functional domains of Pho81p, an inhibitor of Pho85p protein kinase, in the transduction pathway of Pi signals in Saccharomyces cerevisiae.

The PHO81 gene is thought to encode an inhibitor of the negative regulators (Pho80p and Pho85p) in the phosphatase (PHO) regulon. Transcription of PHO81 is regulated by Pi signals through the same PHO regulatory system. Elimination of the PHO81 promoter or its substitution by the GAL1 promoter revealed that stimulation of the PHO regulatory system requires both increased transcription of PHO81 and a Pi starvation signal. The predicted Pho81p protein contains 1,179 amino acids (aa) and has six repeats of an ankyrin-like sequence in its central region. The minimum amino acid sequence required for Pho81p function was narrowed down to a 141-aa segment (aa 584 to 724), which contains the fifth and sixth repeats of the ankyrin-like motif. The third to sixth repeats of the ankyrin-like motif of Pho81p have significant similarities to that of p16INK4, which inhibits activity of the human cyclin D-CDK4 kinase complex. Deletion analyses revealed that the N- and C-terminal regions of Pho81p behave as negative and positive regulatory domains, respectively, for the minimal 141-aa region. The negative regulatory activity of the N-terminal domain was antagonized by a C-terminal segment of Pho81p supplied in trans. All four known classes of PHO81c mutations that show repressible acid phosphatase activity in high-Pi medium affect the N-terminal half of Pho81p. An in vitro assay showed that a glutathione S-transferase-Pho81p fusion protein inhibits the Pho85p protein kinase. Association of Pho81p with Pho85p or with the Pho80p-Pho85p complex was demonstrated by the two-hybrid system.

Amino Acid Sequence↗

PubMed1995

Acute subarachnoid hemorrhage: MR imaging with fluid-attenuated inversion recovery pulse sequences.

PURPOSE: To evaluate the usefulness of fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging sequences in the detection of acute subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: MR imaging with FLAIR sequences was performed with a 0.5-T superconducting unit in 20 patients (aged 30-72 years) with acute SAH due to a ruptured aneurysm and in 27 control subjects (aged 32-72 years). FLAIR images were obtained 2 hours to 2 days after ictus. Findings were evaluated and compared with computed tomographic (CT) findings. RESULTS: In all patients, acute SAH was clearly demonstrated as an area with signal intensity that was high relative to that of the normal cerebrospinal fluid and surrounding brain parenchyma at FLAIR imaging. This sequence was especially useful in demonstration of acute SAH in the posterior fossa, which was difficult to show at CT because of beam-hardening artifacts. In a double-blind comparison, no FLAIR images acquired in control subjects were confused with those acquired in control subjects were confused with those acquired in patients. CONCLUSION: FLAIR sequences reliably provide diagnostic images in patients with acute SAH.

Acute Disease↗

PubMed1995

Endothelin-1 contributes to antigen-induced airway hyperresponsiveness.

Endothelin A (ETA)-receptors mediate ET-1 contractions of ovine airway smooth muscle. Therefore, the ETA-receptor antagonist, BQ-123, was used to test the hypothesis that ET-1 contributes to antigen-induced airway responses in sheep allergic to Ascaris suum. We first established the protective effect of BQ-123 by demonstrating that BQ-123 given as an aerosol (0.3 or 1.0 mg/kg in 3 ml buffer) or by continuous intravenous infusion (100 micrograms.kg-1.min-1) significantly blocked the bronchoconstriction to aerosolized ET-1 (0.2-200 micrograms/ml). To determine whether ET-1 contributed to antigen-induced airway responses, BQ-123 was given either as an intravenous infusion (100 micrograms.kg-1.min-1) beginning 30 min before and continuing for 8 h after antigen challenge or as an aerosol (1 mg/kg in 3 ml buffer) 30 min before and 4, 8, and 24 h after antigen challenge. Neither treatment with intravenous infusion nor aerosolized BQ-123 blocked the immediate antigen-induced bronchoconstriction, but both treatments significantly reduced the late response (approximately 50%). The treatments with aerosolized BQ-123 also blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol seen 24 h after challenge. Subsequently, we found that sheep developed airway hyperresponsiveness to inhaled carbachol at 4 and 24 h after ET-1 challenge, an effect that was blocked by aerosolized BQ-123. We conclude that in allergic sheep 1) aerosolized ET-1 causes bronchoconstriction, in part, by stimulation of ETA-receptors, 2) ET-1 is released in the airways after antigen challenge, and 3) this peptide contributes to the severity of the allergic responses, probably by increasing airway smooth muscle responsiveness.

Administration, Inhalation↗

PubMed1995

Survey of Pseudomonas aeruginosa contamination in human beings and laboratory animals.

Several serotypes of Pseudomonas (P.) aeruginosa were isolated from the oral cavities of researchers, but no positive cases were found among the animals they had contacted or in the environment. These results indicated that researchers are not a source of P. aeruginosa infection for animals. However, P. aeruginosa was detected on the hands of researchers and animal caretakers after they finished their work. The same serotype of P. aeruginosa was found in the animals and the environment. These findings demonstrated that the researchers and the animal caretakers were contaminated with P. aeruginosa by the animals, and then became infective vehicles.

Animal Husbandry↗

PubMed1995

MR diagnosis of subacute and chronic subarachnoid hemorrhage: comparison with CT.

OBJECTIVE: The purpose of our study was to compare the value of MR imaging with CT in the diagnosis of subarachnoid hemorrhage in the subacute and chronic stages (> 3 days after the hemorrhagic episode). MATERIALS AND METHODS: We performed 42 MR examinations using a 0.5-T unit in 37 patients with subarachnoid hemorrhage caused by a ruptured aneurysm. Examinations were done 4-75 days after the ictus. We obtained 40 T1-weighted, 11 proton density-weighted, 15 T2-weighted, and 28 moderately T2-weighted images. CT was also performed in all patients within 24 hr of the MR examination. Confirmation of the presence of subarachnoid hemorrhage at the time of the MR examination was made by CSF examination using lumbar puncture or surgical findings. RESULTS: In the subacute and chronic stages, subarachnoid hemorrhage was seen as an area of high signal intensity on T1-weighted, proton density-weighted, T2-weighted, and moderately T2-weighted MR images in 63%, 90%, 25%, and 92% of cases, respectively. On CT scans, subarachnoid hemorrhage was seen as an area of high attenuation in only 46% of cases. Especially in the chronic stage, subarachnoid hemorrhage was seen as an area of high signal intensity more frequently by MR imaging than by CT (90% on T1-weighted images; 100% on proton density-weighted images; 25% on T2-weighted images; 100% on moderately T2-weighted images; and 10% on CT scans). High-signal-intensity subarachnoid hemorrhage was demonstrated by MR imaging until a maximum of 39 days after the ictus, whereas high-attenuation subarachnoid hemorrhage was demonstrated by CT until a maximum of 17 days after the ictus. CONCLUSIONS: Our findings show that MR imaging is superior to CT for the diagnosis of subacute and chronic subarachnoid hemorrhage. MR imaging is especially useful for the diagnosis of chronic subarachnoid hemorrhage.

Acute Disease↗

PubMed1995

[Clinical analysis on 40 cases of primary aldosteronism--long-term follow-up of blood pressure].

Forty cases of primary aldosteronism after adrenalectomy were observed from 1975 to 1993 at Yokohama City University hospital. All of them had adrenocortical adenoma producing aldosterone. These cases are evaluated retrospectively on localization, surgical approach and long term follow up blood pressure. These patients were from 26 to 65 years old (average 46.6), and consisted of 11 males and 29 females. Fourteen adenomas were located on the right adrenal gland, 25 on left, and one case had adenomas on bilateral adrenal glands. On localization study, 39 cases had been correctly diagnosed by combined diagnostic method of selective adrenal venous sampling, selective adrenal venography, adrenal scintigraphy, X-ray CT, and MRI, with each diagnostic values being 65.8%, 69.0%, 72.5%, 96.9%, 100% respectively. This analysis suggests that, in almost cases, it is enough to diagnose the laterality by adrenal scintigraphy, X-ray CT and MRI. Selective venous catheterization is not always necessary to know the laterality of the tumor. For surgical approach to the adrenal gland, 16 adenomas were removed through anterior subcostal incision (transabdominal approach) from 1975 to 1988, and 24 cases through lumbar oblique incision or dorsal incision (extra peritoneal approach) from 1986 to 1993. This analysis reveals that lumbar oblique and dorsal incision provided us superior surgical approach to the adrenal gland. Thirty-eight cases had been followed after adrenalectomy for more than one year (average 57.6 months). Blood pressure had been normalized in 28 cases, but 10 cases had remained hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1995

Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons.

Using in situ hybridization and the retrograde tracer, Fluorogold, we examined the expression of preprotachykinin (PPT) mRNA in the rat dorsal root ganglion neurons projecting to the gracile nucleus. Seven days after unilateral sciatic nerve transection, some medium- to large-sized neurons in the rat dorsal root ganglia projecting to the gracile nucleus express PPT mRNA, whereas very few gracile nucleus-projecting neurons on the contralateral side express PPT mRNA. Immunohistochemistry revealed an increase in substance P (SP) immunoreactivity in the gracile nucleus and large myelinated fibers in the dorsal root 2 weeks after unilateral sciatic nerve transection. The results suggest that medium to large DRG cells that project to the gracile nucleus express PPT mRNA de novo in response to peripheral nerve injury, and increased SP is transported to the gracile nucleus through large myelinated fibers. To determine whether the increased SP might affect the excitability of the gracile nucleus neurons postsynaptically, Fos expression after electrical stimulation of the injured sciatic nerve was examined. Multiple injections of the NK-1 receptor antagonist, CP-96,345, suppressed stimulus-induced Fos expression in gracile nucleus neurons including thalamic relay neurons. The inactive enantiomer, CP-96,344, had no effect on stimulus-induced Fos expression. These data indicate that the de novo synthesized SP in the lesioned primary afferent neurons may be involved in an augmentation of excitability in the dorsal column-medial lemniscus sensory pathway. This hyperexcitability may play a role in the pathogenesis of abnormal neuropathic sensations following peripheral nerve injury.

Animals↗

PubMed1995

Role of cytoskeleton and acidification of endocytic compartment in asialoglycoprotein metabolism in isolated rat hepatocyte couplets.

The process of receptor-mediated endocytosis is common to a variety of species and cell types. One of the best characterized receptor-ligand systems is the hepatocyte receptor for asialoglycoproteins. We investigated the morphological features of the uptake and intracellular transport of gold-conjugated asialofetuin in isolated rat hepatocyte couplets. We assessed the effects of colchicine, lumicolchicine, cytochalasin B, and chloroquine on the uptake and intracellular transport of asialoglycoproteins. Isolated rat hepatocyte couplets were incubated with gold-conjugated asialofetuin, and transmission electron micrographs of these cells were analyzed to determine the density and distribution of gold particles in the peripheral and pericanalicular areas. Results were analyzed morphometrically. Colchicine significantly inhibited the uptake and intracellular transport of asialoglycoproteins, but did not affect membrane fusion of endocytic compartments in the peripheral area. Lumicolchicine and cytochalasin B had minimal effects on these processes. Chloroquine inhibited the uptake of asialoglycoproteins, but did not affect the intracellular transport of asialoglycoproteins. Results suggest that the microtubule is essential for intracellular movement of endocytosed asialoglycoproteins and receptor recycling, and that endocytic structures in the peripheral regions can fuse in the absence of intact microtubules. We also found that uptake and intracellular transport of asialoglycoproteins were independent of the microfilaments, and the pH gradient in endocytic compartments was important in receptor-mediated endocytosis of asialoglycoproteins.

Acids↗

PubMed1995

Effects of extracellular matrices on tube formation of cultured rat hepatic sinusoidal endothelial cells.

To determine the effects of extracellular matrices on the function and morphology of hepatic sinusoidal endothelial cells, isolated rat hepatic sinusoidal endothelial cells were cultured in three-dimensional fashion on collagen gel containing various extracellular matrix components. Cells cultured on type I collagen gel with or without type IV collagen formed a cobblestone appearance on the surface of the gel. Cells cultured on laminin-containing type I collagen gel invaded the gel and exhibited three-dimensional tube formation with a decreased number of characteristic endothelial pores. Morphometrically, there was a significant relationship between the length of the tube formed and the concentration of laminin in the type I collagen gel. Cells cultured on Matrigel, which contains high concentrations of laminin, type IV collagen, fibroblast growth factor, tissue plasminogen activator, and other growth factors, formed a great number of tubes into a network on the surface of the gel, as is observed in the situ hepatic sinusoidal endothelial cells. Ultrastructurally, tube-forming endothelial cells cultured on Matrigel had many endothelial pores on the cell surface, with tubes (approximately 10 microns in diameter) formed by two or three hepatic sinusoidal endothelial cells. These results indicated that extracellular matrix components, especially laminin, induced the formation of tubes in cultured rat hepatic sinusoidal endothelial cells. Tube-forming sinusoidal endothelial cells cultured on Matrigel could provide more advantages than the two-dimensional culture model for investigating the function and morphology of these cells in vitro.

Animals↗

PubMed1995

Evaluation of cerebral infarction with iodine 123-iomazenil SPECT.

UNLABELLED: This study evaluates ischemic damage to central benzodiazepine (BZD) receptor binding in the brain with [123]iomazenil SPECT in relation to CT hypodense lesions and blood flow abnormalities. METHODS: Nine patients with middle cerebral artery territory infarction were studied. Iomazenil images obtained 180 min postinjection were analyzed for BZD receptor binding. The cortical infraction, visualized as CT hypodense area on CT, the peri-infarct area, visualized as normodensity surrounding the infarction on CT, the intrahemispheric remote area and the cerebellum were analyzed by taking the ratio of the lesion to contralateral mirror region (L/C ratio). CT during the chronic stage and perfusion images obtained during the smallest time difference between the two studies were used for comparative analysis. RESULTS: The mean L/C ratio of iomazenil uptake was 0.53 +/_ 0.08, 0.79 +/- 0.07, 0.98 +/- 0.03 and 1.00 +/- 0.04 in the infarct, peri-infarct and remote areas and the cerebellum, respectively. The infarct and peri-infarct areas showed significant decrease compared with unity. The corresponding mean L/C ratio for blood flow was 0.52 +/- 0.08, 0.73 +/- 0.07, 0.83 +/- 0.09, and 0.80 +/- 0.07, respectively. In all areas, the ratios were significantly decreased compared with unity. There was significant difference between the L/C ratio for blood flow and iomazenil in the remote area and the cerebellum. CONCLUSION: Iodine-123-iomazenil SPECT imaging may provide new information on ischemic damage to the brain, particularly neurons.

Aphasia, Broca↗

PubMed1995

Carbon-11-methionine PET evaluation of intracerebral hematoma: distinguishing neoplastic from non-neoplastic hematoma.

UNLABELLED: We evaluated whether PET with L-methyl-11C-methionine (11C-methionine) was clinically useful in distinguishing neoplastic from non-neoplastic intracerebral hematoma. METHODS: We examined eight patients with neoplastic (n = 4) or non-neoplastic (n = 4) intracerebral hematomas between 5 and 68 days after the bleeding episode using PET with 11C-methionine (Met-PET). RESULTS: Carbon-11-methionine accumulated in the area surrounding the hematoma in both groups, except in one patient with an acute hypertensive hematoma. Between 22 and 45 days after the ictus, non-neoplastic hematomas showed increased 11C-methionine accumulation largely in accordance with the contrast-enhanced areas on CT or MR images; whereas between 14 and 68 days after bleeding, neoplastic hematomas showed increased 11C-methionine accumulation that extended beyond the contrast-enhanced areas on CT or MR images. The intensity of 11C-methionine accumulation in tumor tissue was greater than that in non-neoplastic hematomas. CONCLUSION: Preliminary results suggest that Met-PET can distinguish neoplastic from non-neoplastic hematomas on the basis of differences in lesion extent compared with CT or MR findings.

Adult↗

PubMed1995

Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid.

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.

Animals↗