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Biomedical subjects

C Sasaki

Publications and source records attributed to C Sasaki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Protective effect of ginkgo extract on rat brain with transient middle cerebral artery occlusion.

It has been empirically known that Ginkgo extract is useful for reducing many symptoms associated with cerebral blood flow (CBF) insufficiency, but its mechanisms have been uncertain. In the present study, therefore, we gave Ginkgo extract to rats with per os digestion, and investigated its effect on CBF and ischemic brain damage with middle cerebral artery occlusion (MCAO). The treatment with Ginkgo extract (10 mg 100 g-1 rat) increased CBF in the normal condition, but the degree of increase in CBF was lesser during and after MCAO. TTC staining showed that infarct volume was reduced with Ginkgo treatment. TUNEL and HSP72 immunostaining confirmed the protective effect of Ginkgo treatment reducing numbers of TUNEL and HSP72 positive cells. Immunohistochemical analysis showed that caspase-3 expression was less abundant in Ginkgo treated rats. The present results suggest that Ginkgo extract contains a substance which increases normal CBF and reduces ischemic brain damage.

Animals↗
PubMed2000

Temporal profile of cytochrome c and caspase-3 immunoreactivities and TUNEL staining after permanent middle cerebral artery occlusion in rats.

Although apoptotic pathways play important roles in ischemic neuronal injury, exact mechanism of apoptotic enzyme cascade has not been fully studied. Immunohistochemical stainings for cytochrome c and caspase-3, and histochemical staining for a terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end-labeling method (TUNEL) were examined in a rat model of permanent middle cerebral artery (MCA) occlusion. Cytochrome c was strongly induced in neurons of the ischemic penumbra from 3 h after MCA occlusion, and caspase-3 began to be induced in the same area from 3 h with a peak at 8 h. Neuronal cells in MCA area became TUNEL positive at delayed time, reaching a peak at 24 h. Thus, the peak of induction of cytochrome c preceded that of caspase-3, and these two peaks were also precedence of the peak of DNA-fragmentation. Western blot analysis showed cytosolic expression of cytochrome c from mitochondria. This study demonstrated 1. Rapid release of cytochrome c from mitochondria to the cytosol, mainly in neurons of the cortex at 3 h after ischemia. 2. Subsequent peaks of caspase-3 and TUNEL in this order. These temporal profiles suggest a serial cascadic activation of apoptotic pathways in neuronal death after permanent MCA occlusion of rats.

Animals↗
PubMed2000

Expression, purification and crystallization of human tau-protein kinase I/glycogen synthase kinase-3beta.

Human tau-protein kinase I (TPK-I; also known as glycogen synthase kinase-3beta, GSK-3beta) is a serine/threonine protein kinase. Full-length TPK-I/GSK-3beta was expressed in Escherichia coli as a fusion protein with a 6xHis tag at the C-terminus and was crystallized using the hanging-drop vapour-diffusion method. Prismatic crystals of dimensions 0.4 x 0.2 x 0.1 mm were obtained using 12-15%(w/v) polyethylene glycol 6000 as a precipitant at 278 K. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 82.9, b = 86.1, c = 178.1 A measured at 100 K, diffract to 2.3 A resolution and seem to contain two enzyme molecules per asymmetric unit.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Reduction of tyrosine kinase B and tyrosine kinase C inductions by treatment with neurotrophin-3 after transient middle cerebral artery occlusion in rat.

Infarct volume and immunoreactivities for trkB and trkC in rat brain were compared at 24 h after 90 min of transient middle cerebral artery occlusion (MCAO) between animal groups with or without neurotrophin-3 (NT-3, 10 microg/250 g animal). Treatment of rat brain with topical application of NT-3 significantly reduced infarct volume (P = 0.02) and trkB and trkC inductions. These data suggest that NT-3 reduced the ischemic injury along with the reduction of trkB and trkC inductions.

Administration, Topical↗
PubMed1999

Immunoreactive Akt, PI3-K and ERK protein kinase expression in ischemic rat brain.

In order to clarify the role of protein kinases in ischemic brain injury, the spatiotemporal expression of immunoreactive serine-threonine kinase Akt, phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK) were examined at 3, 8, or 24 h after permanent middle cerebral artery occlusion (MCAO) in rats. Weak staining for these protein kinases was found in both cortical and caudate neurons in sham controls. The staining for Akt-1 and PI3-K was increased at 3-8 h in the ischemic penumbral region and declined at 24 h. A slight induction of these kinases was observed in the ischemic core region. Robust expression of ERK was noted at 3-8 h in most neurons in the area of ischemia. At 24 h, ERK continued to be expressed in the ischemic penumbra, but decreased in the ischemic core. These findings suggest that the signaling for Akt and PI3-K are different from the ERK dependent signal transduction during ischemic brain injury.

Animals↗
PubMed1999

Topical application of neurotrophin-3 attenuates ischemic brain injury after transient middle cerebral artery occlusion in rats.

In order to examine the effect of neurotrophin-3 (NT-3) on ischemic brain injury, NT-3 was topically applied to brain surface just after 90 min of middle cerebral artery occlusion (MCAO) in rats. NT-3 significantly reduced the infarct size at 24 h of reperfusion. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick labeling (TUNEL) staining and immunohistochemical study for caspase-3 and heat shock protein 72 (HSP72) showed that NT-3 treatment decreased the number of cells with DNA fragmentation and caspase-3 and HSP72 expressions. These data suggest that NT-3 protects neuronal cells from ischemic injury, and it is possibly associated with inhibition of DNA fragmentation.

Administration, Topical↗
PubMed1999

Induction of glial cell line-derived neurotrophic factor receptor proteins in cerebral cortex and striatum after permanent middle cerebral artery occlusion in rats.

In an attempt to elucidate whether glial cell line-derived neurotrophic factor (GDNF) receptors are induced after ischemic brain injury, possible expression of immunoreactive GDNF receptor-alpha1 (GFRalpha-1) and c-ret (RET) was examined at 3, 8, or 24 h after permanent middle cerebral artery occlusion (MCAO) in rats. Immunohistochemical study showed that both GFRalpha-1 and RET staining cells which were not detected in sham control brain, were present in the ipsilateral cortex and caudate at 3 to 8 h after permanent MCAO, and then decreased but remained to some extent at 24 h. Positive cells for both GDNF receptors were predominantly in cortical neurons of ischemic penumbral area. Western blot analysis confirmed the induction of those receptors after permanent MCAO. This rapid induction of GFRalpha-1 and RET, which correlates with the similar induction of GDNF under these conditions, may play a role in the early response to ischemic brain injury.

Animals↗
PubMed1999

Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury after transient middle cerebral artery occlusion in rats.

To examine a possible protective effect of exogenous glial cell line-derived neurotrophic factor (GDNF) gene expression against ischemic brain injury, a replication-defective adenoviral vector containing GDNF gene (Ad-GDNF) was directly injected into the cerebral cortex at 1 day before 90 minutes of transient middle cerebral artery occlusion (MCAO) in rats. 2,3,5-Triphenyltetrazolium chloride staining showed that infarct volume of the Ad-GDNF-injected group at 24 hours after the transient MCAO was significantly smaller than that of vehicle- or Ad-LacZ-treated group. Enzyme-linked immunosorbent assay (ELISA) for immunoreactive GDNF demonstrated that GDNF gene products in the Ad-GDNF-injected group were higher than those of vehicle-treated group at 24 hours after transient MCAO. Immunoreactive GDNF staining was obviously detected in the cortex around the needle track just before or 24 hours after MCAO in the Ad-GDNF group, whereas no or slight GDNF staining was detected in the vehicle group. The numbers of TUNEL, immunoreactive caspase-3, and cytochrome c-positive neurons induced in the ipsilateral cerebral cortex at 24 hours after transient MCAO were markedly reduced by the Ad-GDNF group. These results suggest that the successful exogenous GDNF gene transfer ameliorates ischemic brain injury after transient MCAO in association with the reduction of apoptotic signals.

Adenoviruses, Human↗
PubMed1998

Maturation of rat dendritic cells during intrahepatic translocation evaluated using monoclonal antibodies and electron microscopy.

Specific populations of hepatic sinusoidal cells were stained with monoclonal antibodies that recognize monocytes/macrophages (ED1), tissue macrophages (Kupffer cells) (ED2), MHC class II (Ia) antigen (MRC OX6), and dendritic cells/gamma,delta T-cells (MRC OX62) and analyzed by light and electron microscopy. The majority of ED1(+) and/or ED2(+) cells were localized to the hepatic parenchyma, whereas OX6(+) and/or OX62(+) cells were more densely distributed within Glisson's sheath than in the hepatic parenchyma. Double-immunoperoxidase staining of normal liver for ED1, ED2, and OX6 identified dendritic cells (DC) of two different phenotypes, ED1(+)ED2(-)OX6(+) and ED1(-)ED2(-)OX6(+). DC can be classified into three different types based on ultrastructural characteristics. The first type (type I) is characterized by one or more long cytoplasmic processes and a well-developed lysosomal system. The second type (type II) has an inconspicuous lysosomal system, abundant hyaloplasm, and characteristic short cytoplasmic processes. The third type (type I-II) has cytologic features intermediate between those of type I and type II DC. At the electron-microscopic level, these three cell types are found in the sinusoidal lumen, whereas the majority of type II DC are located in the space of Disse and Glisson's sheath. Furthermore, some OX6-labeled elongated DC appeared to traverse the lumen of sinusoids through endothelial pores to enter the space of Disse. One hour after intravenous injection of latex particles (0.81 micrometer in diameter), numerous latex-laden dendritic cells (ED1(+)OX6(+), type I and type I-II) were detected in the lumen of hepatic sinusoids, but not in the space of Disse or Glisson's sheath. These findings suggest that normal rat liver contains resident dendritic cells which downregulate phagocytic activity and mature into potent accessory cells during migration from the portal vein toward the central vein. These DC then traverse the sinusoidal lumen to the hepatic lymph system via the space of Disse.

Animals↗
PubMed1996

Successful treatment of mucosal melanosis of the lip with normal pulsed ruby laser.

Melanosis of the lip is not rare in Orientals. Although it causes cosmetic problems, treatment of this pigmentary disorder is often neglected because a satisfactory tool for complete removal of mucosal melanosis has not yet been developed. The pulsed ruby laser, which has a wavelength of 694 nm and a short pulse duration of 1-2 msec, selectively damages pigmented cells in the skin. In this study, six Japanese patients with labial melanosis, manifested as labial lentigo and Peutz-Jeghers syndrome, were successfully treated with the pulsed ruby laser. The therapy achieved rapid results without producing changes in mucosal texture or recurrence after operation.

Adolescent↗
PubMed1996

[A fluoroscopic analysis of the catheters abnormally placed in the epidural space].

In order to know how the catheters are placed abnormally in the epidural space, we inserted the epidural catheters under fluoroscopy. The catheter was placed straightly upward when the epidural puncture was done in the center of epidural space. When the puncture site was nearly close to the side wall of epidural space, we could not insert catheter at all. When the tip of the needle was near the side wall and the inserting catheter slipped upward, catheter was placed straight. When the catheter wedged at the side wall, it made loop and curled or kinked. We thought that the cause of abnormal location of the catheters in epidural space is the right angle between the wall of the epidural space and the direction of catheter.

Adult↗
PubMed1995

Crystal structure of Ustilago sphaerogena ribonuclease U2 at 1.8 A resolution.

The crystal structure of purine-specific ribonuclease (RNase) U2 from Ustilago sphaerogena has been solved by the molecular replacement methods using RNase T1 as a search model. The structure, with 114 amino acid residues, 141 water molecules, and a sulfate ion, is refined to an R factor of 0.143 at 1.8 A resolution. As evidenced by the electron densities, residues 49 and 50 are revised to Glu 49 and Asp 50, respectively, and also Asp 45 is identified as a beta-isomerized form to L-isoaspartate with a beta-peptide linkage. RNase U2 consists of a beta-hairpin at residues from 7 to 14, a 4.4-turn alpha-helix from 16 to 32, a central beta-sheet with five strands, and a protruding beta-turn from 74 to 77. As for the catalytic site residues, His 41, Glu 62, and Arg 85 are located as constituents of the central beta-sheet, and Tyr 39 and His 101 are situated at either end of the beta-sheet. The side chains of Tyr 39, Glu 62, Arg 85, and His 101 are hydrogen-bonded to the sulfate ion which marks the RNA phosphate position. Though the side chain of His 41 is pointing away from the sulfate, small conformational adjustments of His 41 enable the side chain to interact with either the phosphate or the ribose group of RNA. The loop region from Tyr 44 to Asp 50 is ascribed to the base recognition site where Glu 49 is involved in adenine recognition. beta-Isomerized Asp 45 suggests that this region is conformationally flexible and alterable.

Amino Acid Sequence↗
PubMed1995

[Effect of physical activity on physical fitness among workers].

We conducted a cross-sectional study to clarify the effects of physical activity on physical fitness. Physical fitness tests were offered to workers of companies manufacturing automobile parts from December, 1992 to December, 1993. The subjects were 1,217 male and 600 female workers who participated in the physical fitness test. From this group, we analyzed 1,048 male and 522 female workers who answered a physical activity questionnaire. The questionnaire included age, sex, working posture, physical activity during working time and physical activity during leisure time. The physical fitness tests were composed of grip strength, standing trunk flexion, foot balance with closed eyes, jumping reaction time and step tests. We classified the subjects into low performance group and high performance group for each test. In addition, we classified the subjects into different groups by age (16-29 years old, 30-49 years old old and 50-69 years old), by working posture (standing and sitting), as well as by activity levels during working time and leisure time physical activities (inactive and active). Thus, we examined potential risk factors for the physical fitness by a multiple logistic regression model. The results were as follows: 1. Standing work was a significant risk factor for grip strength, foot balance with closed eyes and jumping reaction time in male workers, and standing trunk flexion, foot balance with closed eyes, jumping reaction time and the step test in female workers. 2. Physical activity during working time was not related to physical fitness in male and female workers. 3. Inactivity during leisure time was a significant risk factor for standing trunk flexion, foot balance with closed eyes, jumping reaction time and the step test in male workers, and grip strength and foot balance with closed eyes in female workers. 4. Young age (16-29 years old) was a significant risk factor for grip strength, standing trunk flexion, foot balance with closed eyes, jumping reaction time and the step test in male and female workers. Middle age (30-49 years old) was a significant risk factor for foot balance with closed eyes and jumping reaction time in male workers, and standing trunk flexion, foot balance with closed eyes, jumping reaction time and the step test in female workers.

Adolescent↗
PubMed1989

Randomized clinical trial of mitomycin C as an adjunct to radiotherapy in head and neck cancer.

A randomized prospective clinical trial was carried out to assess the usefulness of the addition of mitomycin C to radiation therapy used alone or in combination with surgery for the treatment of squamous cell carcinoma of the head and neck region. One hundred and twenty patients with biopsy proven tumor of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx were randomly assigned to receive or not receive mitomycin C; all other aspects were similar in the two treatment groups. One hundred and seventeen patients were evaluable with a median follow-up time of greater than 5 years. Acute and chronic normal tissue radiation reactions were equivalent in the two treatment groups. Hematologic and pulmonary toxicity were observed in the drug treated patients. Actuarial disease-free survival at 5 years was 49% in the radiation therapy group and 75% in the radiation therapy plus mitomycin C group, p less than 0.07. Local recurrence-free survival was 66% in the radiation therapy group and 87% in the radiation therapy plus mitomycin C group, p less than 0.02. The findings demonstrate that mitomycin C can be administered safely as an adjunct to radiation therapy in the treatment of head and neck cancer. The drug improves local tumor control without enhancing normal tissue radiation reactions.

Adult↗
PubMed1989

X-ray analysis of a thrombin inhibitor-trypsin complex.

The three-dimensional structure of a thrombin inhibitor-trypsin complex has been determined by an X-ray analysis at 2.5 A resolution. The result has given experimental support to the mechanisms previously proposed by the authors for the selective inhibition of trypsin, thrombin, factor Xa, and plasmin by inhibitors with an arginine or lysine backbone. The differences in the amino acid sequences at the positions corresponding to Ilc63, Leu99, and Ser190 of trypsin give each enzyme different binding affinities toward inhibitors and result in the selective inhibition. Furthermore, the X-ray analysis has revealed a novel type of interaction between the inhibitor and trypsin. The hydrogen bonds between the inhibitor main chain and trypsin Gly216 play an essential role in the complex formation.

Crystallization↗
PubMed1988

A predicted tertiary structure of a thrombin inhibitor-trypsin complex explains the mechanisms of the selective inhibition of thrombin, factor Xa, plasmin, and trypsin.

The tertiary structure of a thrombin inhibitor-trypsin complex has been predicted by a molecular modelling considering the van der Waals interactions between the inhibitor and the enzyme. The selective inhibition of trypsin, thrombin, factor Xa, and plasmin exhibited by arginine and lysine derivatives has been clearly explained based on the predicted structure and the homology in the amino acid sequences of these enzymes. The differences in the amino acid sequences at the positions corresponding to Ile63, Leu99, and Ser190 of trypsin give each enzyme different binding affinities toward inhibitors and result in the selective inhibition. The X-ray analysis of the inhibitor-trypsin complex is in progress to prove the predicted structure.

Amino Acid Sequence↗
PubMed1988

Sinonasal tumors and inflammatory tissues: differentiation with MR imaging.

The magnetic resonance (MR) and computed tomographic (CT) images of 53 patients with sinonasal tumors were analyzed and compared for accuracy in tumor mapping. the findings were confirmed by means of either surgery or biopsy. The MR images of 60 patients with inflammatory disease were also studied, and the findings were confirmed at surgery. Forty-seven additional MR images were also examined of patients with tumors showing histologic characteristics similar to those found in the sinonasal tumor group but occurring elsewhere in the head and neck, excluding the orbit. This study concludes that nearly 95% of sinonasal tumors have an intermediate T2 signal, while only 5% have bright T2 signals. This small latter group is composed almost exclusively of some minor salivary gland tumors and some neuromas. The inflammatory tissues all had bright T2 signals. The distinction between sinonasal tumors and inflammatory tissues was best accomplished with T2-weighted studies, and MR imaging was more accurate than CT.

Diagnosis, Differential↗