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Biomedical subjects

K Matsuno

Publications and source records attributed to K Matsuno.

At least 109 records · Page 6Linked to original sources

Reduction of 4-cyclohexyl-1-[(1R)-1,2-diphenylethyl]-piperazine-induced memory impairment of passive avoidance performance by sigma 1 receptor agonists in mice.

Intraperitoneal administration of 4-cyclohexyl-1-[(1R)-1,2-diphenylethyl]-piperazine (CDEP) immediately after the training session produced significant memory impairment in the mouse passive avoidance performance. Interestingly, this memory impairment was alleviated by subcutaneous administrations of sigma receptor agonists, (+)-N-allylnormetazocine ((+)-SKF-10,047), (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) and 1,3-di(2-tolyl)guanidine (DTG) immediately after the training session. In particular, the remarked recovery for this memory impairment was produced by (+)-SKF-10,047. A receptor binding study showed that CDEP possessed high affinities for both sigma 1 and sigma 2 receptor subtypes (IC50 1.4 +/- 0.3 nM for sigma 1 receptor subtype, 1.8 +/- 0.3 nM for sigma 2 receptor subtype), while (+)-SKF-10,047 had a high selectivity for the sigma 1 receptor subtype. These findings suggest that the sigma receptor, particularly sigma 1 receptor subtype, may play an important role in the CDEP-induced impairment of learning and memory processes.

Animals↗

Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers.

Matrilysin is one of matrix metalloproteinases, which is supposed to have a specific role in tumor progression. Expression of matrilysin was investigated in gastric and esophageal cancers by an immunohistochemical examination. Matrilysin was expressed in all esophageal squamous cell carcinomas (13/13) and in the majority of gastric adenocarcinomas (31/35, 89%). The positive staining was observed in tumor cells of cancerous tissues. In gastric cancers, there were significant statistical correlations between matrilysin expression at the invasive front and nodal metastasis or advanced stage. These results suggest that overexpression of matrilysin has an important role in the progression of upper gastrointestinal cancers.

Disease Progression↗

[New technology of automated blood cell differential counting].

Examination of stained peripheral blood films for evaluation of erythrocyte and platelet morphology and leukocyte differential count provides considerable data for diagnosis of various diseases including hematologic disorders. Since 1980, the use of an automated leukocyte differentiation analyzer has become common in large clinical laboratories. We surveyed the principles, performance, and characteristics of the newest automated leukocyte differential instruments, GEN.S system (Coulter), SE-9000/RAM-1 (Toa), CELL-DYN 4000 (Dainabot), ADVIA120 (Bayer-Sankyo), VEGA RETIC LC-141 (Horiba), and MICROX HEG-120N (Omron). We also compared the differentiated function of GEN.S system and CELL-DYN 4000. Automated leukocyte differentiation using two instruments correlated well with a reference method for leukocyte differential counting proposed by the National Committee for Clinical Laboratory Standards (NCCLS) H20-T (eye-count differential). The sensitivities of the suspect flag in GEN.S system and CELL-DYN 4000 were 79.3% and 83.5%, and the specificities of the two instruments were 100% and 94.9%, respectively.

Humans↗

[Detection of parafoveal scotoma by multifocal electroretinograms].

We investigated the relation between multifocal electroretinograms (M-ERGs) and artificial parafoveal scotoma. M-ERGs were recorded from normal subjects using a circular piece of black paper attached to a monitor. Lower response density around the 10 to 15 degree parafovea region was not observed up to 3 degree scotoma (visual angle), but was detected above 5 degree scotoma in field topography of M-ERGs. The shape of the scotoma in field topography was not circular but somewhat oval. The results from two cases of parafoveal retinal degeneration were in good accordance with this basic study in normal subjects. We proved that detection of parafoveal scotoma by M-ERG is limited in comparison with the results obtained by automated static perimetry.

Electroretinography↗

Protection from cadmium cytotoxicity by N-acetylcysteine in LLC-PK1 cells.

N-acetylcysteine (NAC) has been known not only to stimulate synthesis of glutathione but also to affect the gene regulation. In our study, effects of NAC on the cytotoxicity of cadmium (Cd) were examined in LLC-PK1 cells. Preincubation and subsequent incubation with 1 mM NAC almost completely suppressed Cd-induced cellular damage evaluated either by trypan blue exclusion or lactate dehydrogenase leakage. This almost complete protection required the presence of NAC during Cd exposure. Treatment with 1 mM NAC increased the intracellular glutathione level approximately 2-fold. Inhibition of this increase by buthionine sulfoximine did not abolish the protection by NAC. One mM NAC also suppressed Cd-induced increase of c-Fos protein although NAC alone did not change the protein content. The inhibition of transcriptions by actinomycin D did not affect the protection by NAC. Thus, NAC-induced protection appeared to be independent of glutathione level or the transcriptional activation of genes including c-fos. However, treatment with NAC markedly lowered the uptake of Cd into cells although it did not affect the efflux clearly. Addition of NAC during the exposure to Cd suppressed Cd-induced cellular damage but the suppression decreased when the duration of the exposure without NAC increased. These results suggest that NAC-induced protection against Cd cytotoxicity is mainly due to the lowered uptake of Cd into the cells.

Acetylcysteine↗

[Recent advance of prognostic factor in human colorectal cancer].

It has become clear that cancers develop and progress through the accumulation of various genetic alterations. Among various human malignancies, none is better understood at the molecular genetic level than colorectal cancer. Colorectal cancer is one of the commonest malignant tumors and has a relatively poor prognosis. Recent advances in the molecular genetics of colorectal cancer have stimulated attempts to evaluate the prognostic significance of specific genetic alterations in this tumor. Although conventional pathological staging has served as the standard measure of prognosis in colorectal cancer, certain molecular genetic markers are now considered to be useful for predicting the behavior of cancer and the clinical outcome of patients. We have described the recent advances in prognostic factors of colorectal cancer, such as oncogenes, tumor suppressor genes, chromosomal deletions, adhesion molecules, proteinases, DNA replication error, and others. The latest improvements in detecting these molecular markers have made it possible to apply them to the clinical setting with relative ease. Some of these markers are considered to be susceptible to, or modifiable by, direct therapeutic intervention. For instance, matrix metalloproteinases could be targets for therapeutic intervention using their inhibitors. We hope that these molecular genetic markers with prognostic significance play an important role in disease management of patients with colorectal cancer in future.

Cell Adhesion Molecules↗

A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation.

The migration pathways for dendritic cells (DC) from the blood are not yet completely resolved. In our previous study, a selective recruitment of DC progenitors from the blood to the liver was suggested. To clarify the role of the hepatic sinusoids in the migration of blood DC, relatively immature DC and mature DC were isolated from hepatic and intestinal lymph, and intravenously transferred to allogeneic hosts. It was then possible to detect small numbers of DC within secondary lymphoid tissues either by immunostaining for donor type major histocompatibility complex class I antigen or, at much higher sensitivity, for bromodeoxyuridine incorporated by proliferating cells (mainly T lymphocytes), which responded to the alloantigen presented by the administered DC. The intravenously injected DC accumulated in the paracortex of regional lymph nodes of the liver via a lymph-borne pathway. Intravenously injected fluorochrome-labeled syngeneic DC behaved similarly. In contrast, very few DC were found in spleen sections and were hardly detectable in other lymph nodes or in other tissues. An in situ cell binding assay revealed a significant and selective binding of DC to Kupffer cells in liver cryosections. It is concluded that rat DC can undergo a blood-lymph translocation via the hepatic sinusoids, but not via the high endothelial venules of lymph nodes. Hence the hepatic sinusoids may act as a biological concentrator of blood DC into the regional hepatic nodes. Kupffer cells may play an important role in this mechanism.

Animals↗

Persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, in prolonging hepatic allografts in rats pretreated with a donor-specific blood transfusion.

A single intravenous injection of freshly heparinized blood from a donor-specific blood transfusion (DST) seven days before transplantation significantly prolongs the subsequent survival of hepatic allografts from ACI(RT1a) to LEW(RT1(1)) rats. We used W3/25 (anti-CD4) and OX22 (anti-CD45RC: an isoform of leukocyte-common antigen [CD45R]) monoclonal antibodies to investigate the cellular identity of hepatic allograft infiltrates following transplantation. The number of CD4+ and CD45RC+ cells in untreated allografts increased equally over time by day seven. However, in DST-treated hepatic allografts, CD4+ and CD45RC+ cells also increased over time by day 14, but the increment in the number of CD4+ cells was significantly greater than that in CD45RC+ cells. While the number of CD4+ cells remained persistently elevated in the hepatic allografts of rats pretreated with DST, they did not initiate rejection. Fluorescence-activated cell sorter (FACS) analysis revealed that the accumulated CD4+ T cells could be divided into two subsets, CD45RC- CD4+ and CD45RC+ CD4+ T cells, and that the ratio of CD45RC- CD4+/CD45RC+ CD4+ T cells in the hepatic allografts of recipients pretreated with DST was significantly greater than that in untreated allografts. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated that CD45RC- CD4+ T cells expressed interleukin (IL)-4 and IL-10 messenger RNA (mRNA), but not IL-2 and interferon gamma (IFN-gamma). The pattern of messenger RNA expression in hepatic allograft infiltrates from animals pretreated with DST provides compelling evidence for the selective in vivo preservation of T-helper (Th2)-specific cytokines in the rat system. Our studies show that CD45RC leukocyte-common antigen expression can define different populations of hepatic infiltrating CD4+ T cells. A persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, is characteristic of hepatic allografts with a prolonged survival in DST-pretreated rats.

Animals↗

Reduction of the scopolamine-induced impairment of passive-avoidance performance by sigma receptor agonist in mice.

We examined the ameliorating effects of several sigma receptor agonists on scopolamine-induced memory impairment in mice. Scopolamine was administered IP 30 min before the training session. Each sigma receptor agonist was administered 60 min before or immediately after the training session, or 60 min before the retention test in the passive-avoidance performance experiments. (+)-N-Allylnormetazocine ((+)-SKF-10,047), a prototype sigma 1 receptor agonist, showed an ameliorating effect on the scopolamine-induced memory impairment in these 3 administration schedules, and (-)-SKF-10,047, a stereoisomer with low affinity for the sigma 1 receptor subtype, failed to reduce this memory impairment in mice. In addition, 1,3-di(2-toly1)guanidine (DTG) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperizine ((+)-3-PPP), nonselective sigma receptor agonists, did not affect this memory impairment. Physostigmine, an acetylcholinesterase (AChE) inhibitor, alleviated the scopolamine-induced memory impairment in all these drug administration schedules. In addition, (+)-SKF-10,047-induced antiamnesic effect was antagonized by the concurrent administration of haloperidol, a sigma receptor antagonist, or N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy) phenyl)ethylamine monohydrochloride (NE-100), a selective sigma 1 receptor antagonist. These findings indicate that the sigma 1 receptor agonist has ameliorating effects on all phases of learning and memory processes. This profile of sigma 1 receptor agonist is similar to that of an AChE inhibitor.

Acetylcholinesterase↗

SA4503, a novel cognitive enhancer, with sigma 1 receptor agonistic properties.

We found a potent and selective sigma 1 (sigma 1) receptor ligand, SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride). This compound had a high affinity for sigma 1 receptor subtype (IC50 = 17 +/- 1.9 nM), but a low affinity for sigma 2 receptor subtype (IC50 = 1800 +/- 310 nM). The present study examines the effect of this compound on the central cholinergic functions, since sigma receptor has been reported to interact with the central cholinergic neurons. SA4503 elicited the increase in extracellular acetylcholine level in rat frontal cortex, while it did not affect the striatal acetylcholine level. On the other hand, tetrahydroaminoacridine (THA), an acetylcholinesterase (AChE) inhibitor, increased the extracellular acetylcholine level in both regions. Although both compounds had anti-amnesic effect against scopolamine-induced memory impairment, THA also induced catalepsy in rats. These results suggest that SA4503 may be a novel cognitive enhancer, with sigma 1 receptor agonistic properties. In addition, SA4503 does not cause striatal cholinomimetic side-effects, which is different from THA.

Acetylcholine↗

Biodynamics for the emergence of energy consumers.

What is unique to biodynamics in vivo or dynamics leading to the emergence of biological organizations is a frozen aggregate of degrees of freedom in motion that can change its constituent members in time. Association and dissociation of degrees of freedom in the frozen aggregate is information-generative, in the sense that their realization proceeds in a contingent manner, with no unique pattern being predetermined. In particular, dissociation of some of the degrees of freedom from the parental aggregate becomes information-generative when the dissociative interaction initiated by thermal agitation originating in the ambient takes significantly longer time than the interval of the inverse thermal frequency. For instance, ATP hydrolysis with the help of myosin following the preceding association of an ATP molecule with the myosin happens to be a case of such a dissociative interaction, in which the duration of the interaction is far greater than the inverse of thermal frequency. One dominant mode of biodynamics in vivo is to effectively materialize a heat engine by preparing a local region with a temperature lower than that of the surroundings, thereby letting the duration time of the dissociative interaction be far greater than the inverse of thermal frequency. Evolutionary emergence of most primitive biological organizations would coincide with a de novo appearance of a heat engine that could hold thermal agitations from the surroundings locally there and could act upon the latter accordingly.

Adenosine Triphosphate↗

Molecular semantics and the origin of life.

The physical origin of life addresses itself to a semantic process on material grounds, in which causation toward contextualization is at work. Physically semantic process of whatever kind is specific in that every material participant is searching and modifying the material context to be fitted in. Fundamental to the physical semantics is the process of measurement proceeding internally among the constituent material participants, whereas the molecular syntax alone as embodied in the form of the quantum-mechanical equation of motion supplemented independently by exogenous boundary conditions cannot cope with the material process underlying the origin. A basic physical attribute of the phenomenon called life is variable duration, in contrast to invariant duration of Galilean inertia. In fact, moleculars replication thought as a harbinger of the phenomenon of life is a concrete form of variable duration and could be established unless internal measurement being instrumental to physically semantic process is forcibly eliminated by some external means. Physical experiments on the onset of molecular replication could become feasible only when external controllability over the intended experiments even at nano-meter scales is abandoned so as to save the room of internal measurement on the part of participating molecules.

Biological Evolution↗

Involvement of IMP dehydrogenase activity in induction of sporulation of Bacillus cereus.

IMP dehydrogenase activity of B. cereus increased parallel to cell growth in YE-EMM, where B. cereus did not sporulate. When B. cereus was cultured in a modified G medium, a sporulation medium, the activity reached the highest level at 6 hr and decreased thereafter. After induction of sporulation by nutritional shift down in 1/100 G medium, the enzyme activity decreased to about 5% compared with exponentially growing cells at 1 hr of resuspension. The sporulation rate of B. cereus was over 90% in the modified G medium and 1/100 G medium. Sporulation was strongly inhibited by mycophenolic acid at 1 mM, when the drug was added at 0 and 1 hr of resuspension in 1/100 G medium. Intracellular GTP concentration of B. cereus decreased to the lowest level about 1 hr of resuspension. Although GTP increased to about 50% of the exponentially growing cells at 2 hr of resuspension in control cells, the concentration did not increase in the presence of 1 mM mycophenolic acid.

Bacillus cereus↗

Sigma 1 receptor subtype is involved in the facilitation of cortical dopaminergic transmission in the rat brain.

Our previous studies have shown that three sigma (sigma) receptor ligands, (+)-N-allylnormetazocine ((+)-SKF-10,047), (+/-)-pentazocine and 1,3-di(2-tolyl)guanidine (DTG) differently regulated the dopamine (DA) transmission in the rat brain. In the present study, we attempted to clarify the role of sigma 1 receptor subtype in the regulation of DA transmission using a novel and selective sigma 1 receptor agonist, 1-(3,4-dimethoxyphenethyl)-4(3-phenylpropyl)piperazine dihydrochloride (SA4503) in the rat brain. Acute administration of SA4503 (1.0 mg/kg, p.o.) significantly increased DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the rat frontal cortex, but not in the other six regions, hippocampus, striatum, midbrain, cerebellum, medulla/pons and hypothalamus. The increase of cortical DA level elicited by SA4503 was fully reversed by N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) (0.25 mg/kg, p.o.), a putative sigma 1 receptor antagonist. In addition, SA4503 (1.0 mg/kg, p.o.) showed an increase of cortical L-3,4-dihydroxyphenylalanine (L-DOPA) accumulation under the inhibition of dopa decarboxylase activity with m-hydrobenzylhydrazine (NSD-1015), suggesting that SA4503 has activated the cortical DA synthesis rate. These results suggest that the sigma 1 receptor subtype plays an important role in the facilitation of cortical DA transmission. In addition, this phenomenon is partially involved in the augmentation of DA synthesis rate.

3,4-Dihydroxyphenylacetic Acid↗

Regulated crosslinked actin filaments and the decoupling between their ATPase activity and sliding motility.

Troponin-tropomyosin complex from skeletal muscles was observed to regulate sliding movement of actin filaments on myosin molecules in a manner independent of their ATPase activity. When actin molecules were crosslinked with DSS (disuccinimidyl suberate), the myosin ATPase activity in the presence of the modified actin filaments complexed with both troponin and tropomyosin was only 10% less than that in the case of unmodified actin, and the ATPase activation was independent of calcium ions. In contrast, the sliding velocity of the modified actin filaments on myosin molecules decreased to zero below pCa 6.5. The present results indicate that troponin-tropomyosin complex regulates contractile movement of actomyosin systems through direct alternation of a mechanochemical property of the thin filaments, not through a decrease in the ATPase activity of the myosin molecules.

Actin Cytoskeleton↗