Search PubMed⌕ Search

Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 451 records · Page 25Linked to original sources

Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson's disease and progressive supranuclear palsy.

We measured brain acetylcholinesterase activity in 16 patients with Parkinson's disease (PD), 12 patients with progressive supranuclear palsy (PSP), and 13 age-matched controls, using N-methyl-4-[11C]piperidyl acetate and positron emission tomography. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. In PD patients, there was a significant reduction (-17%) of cerebral cortical k3 compared with normal controls, whereas there was only a nonsignificant reduction (-10%) of cortical k3 in PSP patients. However, there was a prominent reduction (-38%) of thalamic k3 in PSP patients compared with normal controls, whereas there was only a nonsignificant reduction (-13%) of thalamic k3 in PD patients. The results suggest that there is a loss of cholinergic innervation to the cerebral cortex in association with cholinergic innervation to the thalamus in PD, whereas there is a preferential loss of cholinergic innervation to the thalamus in PSP. When the thalamic to cerebral cortical k3 ratio was taken for each subject, PD and PSP were separated, suggesting that positron emission tomography measurement of acetylcholinesterase activity may be useful for differentiating the two similar disorders.

Acetylcholinesterase↗

[Three cases of semi-invasive pulmonary aspergillosis occurring in healthy or diabetic individuals].

We encountered three cases of suspected semi-invasive pulmonary aspergillosis, occurring in healthy or diabetic patients. Radiographic findings disclosed cavity formation in 2 of the patients, but only nodular lesions in 1. The beta-D glucan level was elevated in 1 patient, but was within the normal range in the other 2. Morphological findings indicated that all 3 patients had pulmonary aspergillosis. Following the oral administration of FLCZ to 1 patient and ITCZ to the other 2 for about 2 months, the radiographic lesions resolved and hematologic inflammatory reactions cleared up. Gefter et al and Sider et al have defined 2 types of aspergillosis that occur in mildly immuno-compromised or healthy individuals: the semi-invasive type, which destroys pulmonary tissue without vascular invasion and leads to cavity formation; and the locally invasive type, which is characterized by nodular or massive radiographic lesions without cavity formation. Semi-invasive aspergillosis was diagnosed in all 3 of the cases we reported.

Adult↗

[Three cases of multiple liver metastases of gastric cancer responding to tegafur/low-dose CDDP/CPT-11 combination chemotherapy].

We report 3 cases of multiple liver metastases of gastric cancer responding to tegafur/low-dose CDDP/CPT-11 combination chemotherapy. One course of the chemotherapeutic regimen consisted of tegafur 1,200 mg/body/24 hr civ (days 1-12) + CDDP 10 mg/body one shot i.v. (days 1-5, 8-12) + CPT-11 100 mg/body one shot i.v. (day 13). The patient underwent 2 courses. The 2nd course was done on days 16-28, and the CPT-11 dose was increased as 125 mg/body. The outcome obtained was a 3 PR response. In general, a poor nutritional state is often seen in cases of multiple liver metastases of gastric cancer. Chemotherapy with low toxicity and high efficacy is required in such cases. Our regimen is an effective means of treatment for both primary lesion of gastric cancer, and multiple liver metastases, allowing a good postchemotherapeutic quality of life.

Adenocarcinoma↗

Actin degradation concomitant with Fusobacterium necrophorum subsp. necrophorum adhesion to bovine portal cells.

The effects of Fusobacterium necrophorum subsp. necrophorum on cellular actin were investigated using tissue-cultured bovine portal cells. Fluorescence studies revealed the appearance of intense fluorescent spots on the cellular actin and the spots increased in a time dependent manner. Sodium dodecyl sulphate polyacrylamide gel electrophoresis profiles manifested partial or complete degradation of actin preparation after treatment with the bacterial cells. These findings suggest that the bacterial cell wall may contribute to the degradation of the cellular actin during the initial stage of the infection caused by F. necrophorum subsp. necrophorum.

Actins↗

Inhibitory effect of calcium-binding protein regucalcin on protein kinase activity in the nuclei of regenerating rat liver.

The effect of Ca2+-binding protein regucalcin on protein kinase activity in the nuclei of normal and regenerating rat livers was investigated. Protein kinase activity in the nuclei isolated from normal rat liver was significantly increased by addition of Ca2+ (500 microM) and calmodulin (10 microg/ml) in the enzyme reaction mixture. Nuclear protein kinase activity was significantly decreased in the presence of EGTA (1.0 mM), trifluoperazine (TFP; 20 microM), dibucaine (10(-4) M), or staurosporine (10(-7) M), indicating that Ca2+-dependent protein kinases are present in the nuclei. Protein kinase activity was significantly elevated in the liver nuclei obtained at 6 to 48 h after a partial hepatectomy. Hepatectomy-increased nuclear protein kinase activity was significantly decreased in the presence of EGTA (1.0 mM), TFP (20 microM), or staurosporine (10(-7) M) in the enzyme reaction mixture. The presence of regucalcin (0.1-0.5 microM) caused a significant decrease in protein kinase activity in the nuclei obtained from normal and regenerating rat livers. Meanwhile, the nuclear protein kinase activity from normal and regenerating livers was significantly elevated in the presence of anti-regucalcin monoclonal antibody (50-200 ng/ml). The present study suggests that regucalcin plays a role in the regulation of protein kinase activity in the nuclei of proliferative liver cells.

Animals↗

Glutathione downregulates the phosphorylation of I kappa B: autoloop regulation of the NF-kappa B-mediated expression of NF-kappa B subunits by TNF-alpha in mouse vascular endothelial cells.

Nuclear factor-kappa B (NF-kappa B) regulates gene expression upon immune and inflammatory responses. It has been demonstrated that redox regulation by thiols is involved in the signal-transduction cascade. In this study, we examined the effect of glutathione (GSH) on the NF-kappa B activity and the expression of NF-kappa B subunits induced by tumor necrosis factor-alpha (TNF-alpha) using mouse vascular endothelial cells. GSH inhibited the serine phosphorylation of I kappa B-alpha by TNF-alpha, leading to the downregulation of NF-kappa B-DNA binding activity followed by decreased expression of p65/p50 and I kappa B mRNAs. The regulation of the autoregulatory loop for the NF-kappa B activation and the expression of NF-kappa B subunits may be important in endothelial cells in response to cytokines.

Animals↗

Ipsilateral dominance of human olfactory activated centers estimated from event-related magnetic fields measured by 122-channel whole-head neuromagnetometer using odorant stimuli synchronized with respirations.

The aim of this study was to measure and analyze olfactory event-related magnetic fields using a whole-cortex biomagnetometer (122-channel SQUID gradiometer). Amyl-acetate gas (approx. 1%) was administered for 300 msec into either the right or left nostril in synchronization with respiration using a mask and an optical fiber sensor. Clear olfactory event-related magnetic fields were asymmetrically obtained on both sides of the forehead in all six subjects. The generators of olfactory magnetic fields were estimated at two regions located fairly asymmetrivally near the bilateral frontal deep areas. The goodness-of-fit was better for the two-dipole model than the one-dipole model in all experiments. In almost all subjects the latency and intensity of ipsilateral olfactory magnetoencephalography (MEG) responses were shorter and larger than those of the contralateral responses, respectively. These results suggest that the olfactory MEG responses on the ipsilateral side are generally larger and more dominant than those on the contralateral side in the human olfactory system.

Brain Mapping↗

Mouse placental cells secrete soluble leptin receptor (sOB-R): cAMP inhibits sOB-R production.

The aims of this study were to identify whether mouse placenta secretes soluble OB-R (sOB-R) and to find the regulating factor of OB-R expression. Total RNAs were extracted from placenta and decidua, and OB-R expression was assessed by Northern blot analysis. Decidua did not express OB-R mRNA. However, OB-R mRNA expression was detectable in the placenta on day 13 of pregnancy, and then it increased and reached a peak on day 17 of pregnancy. Mouse placental cells from day 12 of pregnancy were cultured and OB-R gene expression was assessed by Northern blot analysis. OB-R mRNA expression was detectable from the second day of culture and reached a peak on the third day of culture. To determine whether placental cells release sOB-R, supernatant of cultured placental cells was subjected to Western blot analysis. sOB-R was detected in the medium by the second day of culture and sOB-R release increased up to the fourth day of culture. Addition of leptin to the medium did not affect expression of OB-R mRNA. However, 8-bromo cAMP inhibited both steady-state levels of OB-R mRNA and the amount of sOB-R protein in the medium in a dose- and time-dependent manner. These results suggest that trophoblast cells differentiate, express, and release sOB-R both in vivo and in vitro and that cAMP is one of several potent regulators of sOB-R secretion by the mouse placenta.

8-Bromo Cyclic Adenosine Monophosphate↗

dE2F2, a novel E2F-family transcription factor in Drosophila melanogaster.

Mammalian E2F transcription factors comprise a family of proteins encoded by distinct genes which function in the form of heterodimers with DP proteins. In Drosophila melanogaster, only a single E2F-related transcription factor, dE2F, has been reported. We have now identified and characterized a cDNA encoding another E2F family member in Drosophila, termed dE2F2. The predicted amino acid sequence shares 38.8% identity with dE2F, including the QKRRIYDITNVLEGI motif which is highly conserved in mammalian E2F family members and dE2F. The 18 amino acids, located in the carboxy-terminal region of the mammalian E2F family, sufficient for binding to pRb are also conserved in dE2F2. Band mobility shift analyses with glutathione S-transferase fusion proteins revealed dE2F2 binding to E2F-recognition sites to be dependent on the presence of dDP protein, in apparent contrast to dE2F. Furthermore, cotransfection experiments in Kc cells demonstrated dE2F2 repression of the PCNA gene promoter activity, while dE2F caused activation, the target site for the repression being identical to the dE2F-recognition site.

Amino Acid Sequence↗

The DNA replication-related element (DRE)/DRE-binding factor system is a transcriptional regulator of the Drosophila E2F gene.

Two mRNA species were observed for the Drosophila E2F (dE2F) gene, differing with regard to the first exons (exon 1-a and exon 1-b), which were expressed differently during development. A single transcription initiation site for mRNA containing exon 1-b was mapped by primer extension analysis and numbered +1. We found three tandemly aligned sequences, similar to the DNA replication-related element (DRE; 5'-TATCGATA), which is commonly required for transcription of genes related to DNA replication and cell proliferation, in the region upstream of this site. Band mobility shift analyses using oligonucleotides containing the DRE-related sequences with or without various base substitutions revealed that two out of three DRE-related sequences are especially important for binding to the DRE-binding factor (DREF). On footprinting analysis with Kc cell nuclear extracts and a glutathione S-transferase fusion protein with the N-terminal fragment (1-125 amino acid residues) of DREF, all three DRE-related sequences were found to be protected. Transient luciferase expression assays in Kc cells demonstrated that the region containing the three DRE-related sequences is required for high promoter activity. We have established transgenic lines of Drosophila in which ectopic expression of DREF was targeted to the eye imaginal disc cells. Overexpression of DREF in eye imaginal disc cells enhanced the promoter activity of dE2F. The obtained results indicate that the DRE/DREF system activates transcription of the dE2F gene.

Animals↗

Inhibition of Ca2+/calmodulin-dependent phosphatase activity by regucalcin in rat liver cytosol: involvement of calmodulin binding.

The regulatory effect of regucalcin on Ca2+/calmodulin-dependent phosphatase activity and the binding of regucalcin to calmodulin was investigated. Phosphatase activity toward phosphotyrosine, phosphoserine, and phosphothreonine in rat liver cytosol was significantly increased by the addition of Ca2+ (100 microM) and calmodulin (0.30 microM). These increases were clearly inhibited by the addition of regucalcin (0.50-1.0 microM) into the enzyme reaction mixture. The cytosolic phosphoamino acid phosphatase activity was significantly elevated by the presence of anti-regucalcin monoclonal antibody (0.2 microg/ml), suggesting that endogenous regucalcin in the cytosol has an inhibitory effect on the enzyme activity. This elevation was prevented by the addition of regucalcin (0.50 microM). Purified calcineurin phosphatase activity was significantly increased by the addition of calmodulin (0.12 microM) in the presence of Ca2+ (1 and 10 microM). This increase was completely inhibited by the presence of regucalcin (0.12 microM). The inhibitory effect of regucalcin was reversed by the addition of calmodulin with the higher concentration (0.36 microM). Regucalcin has been demonstrated to bind on calmodulin-agarose beads by analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The present study demonstrates that regucalcin inhibits Ca2+/calmodulin-dependent protein phosphatase activity in rat liver cytosol, and that regucalcin can bind to calmodulin.

Animals↗

Messenger RNA differential display reverse-transcriptase-polymerase-chain-reaction analysis of a progestogen-suppressive gene in a human endometrial-cancer cell line.

Progestogen suppresses the progression of endometrial cancer and has an important effect on the secretory change of human endometrium. We characterized the progestogen-induced alterations of gene expression in a human endometrial-cancer cell line using a mRNA differential-display reverse-transcriptase-polymerase-chain-reaction (DDRT-PCR) method. After 5-day incubation of Ishikawa endometrial-cancer cells, with or without 100 nM medroxyprogesterone acetate (M PA), total RNA was isolated from confluent cells. We identified 8 candidate genes by mRNA differential display by screening up to approximately 3,000 mRNA species. Among these, 2 genes named T21A and T21B showed a decrease in mRNA by MPA treatment when analyzed by Northern blot. Nucleotide sequence showed that clone T21A was part of human mitochondrial short-chain enoyl-CoA hydratase cDNA. The other clone, T21B, showed no homology with any known nucleotide sequences. Northern-blot analysis using T21A and T21B clones as probes showed a decrease in mRNA in human endometrium from the luteal stage, with high serum estradiol and progesterone levels, as compared with that from the early follicular stage, with low serum estradiol and progesterone levels, and that from the pre-ovulatory stage with high serum estradiol and low progesterone levels. These findings suggest that mRNA DDRT-PCR could be used to identify the candidate genes regulated by progestogen in human endometrial cancer and in normal human endometrium.

Antineoplastic Agents, Hormonal↗

Mast cells can secrete vascular permeability factor/ vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression.

Vascular permeability factor/vascular endothelial cell growth factor (VPF/VEGF) can both potently enhance vascular permeability and induce proliferation of vascular endothelial cells. We report here that mouse or human mast cells can produce and secrete VPF/VEGF. Mouse mast cells release VPF/VEGF upon stimulation through Fcepsilon receptor I (FcepsilonRI) or c-kit, or after challenge with the protein kinase C activator, phorbol myristate acetate, or the calcium ionophore, A23187; such mast cells can rapidly release VPF/VEGF, apparently from a preformed pool, and can then sustain release by secreting newly synthesized protein. Notably, the Fc epsilonRI-dependent secretion of VPF/VEGF by either mouse or human mast cells can be significantly increased in cells which have undergone upregulation of Fc epsilonRI surface expression by a 4-d preincubation with immunoglobulin E. These findings establish that at least one cell type, the mast cell, can be stimulated to secrete VPF/VEGF upon immunologically specific activation via a member of the multichain immune recognition receptor family. Our observations also identify a new mechanism by which mast cells can contribute to enhanced vascular permeability and/or angiogenesis, in both allergic diseases and other settings.

Animals↗

Fine structure of hepatitis B virus surface antigen produced by recombinant yeast: comparison with HBsAg of human origin.

The ultrastructure of hepatitis B virus surface antigen (HBsAg) particles produced by recombinant yeast cells was examined using high-resolution negative staining, and ice embedding, electron microscopy. With negative staining, the HBsAg particles were spherical to slightly ovoid with a mean diameter of 27.5 nm and consisted of many subunits each 4 nm in diameter. Subunits were marked with a minute central pore. With ice embedding, particles were mostly spherical to ovoid, with a mean diameter of 23.7 nm and a 7-8 nm thick cortex surrounding an electron translucent core. Human HBsAg particles, examined using the same methods, were smaller, apparently because of molecular differences in polypeptide structure.

Electrophoresis, Polyacrylamide Gel↗

Regulation of ferritin synthesis and iron regulatory protein 1 by oxygen in mouse peritoneal macrophages.

Ferritin is an intracellular iron storage protein whose synthesis is regulated post-transcriptionally by a mechanism that involves binding of cytoplasmic iron regulatory protein (IRP) to iron-responsive element (IRE) in the 5' untranslated region of ferritin mRNA. In this study, we have shown that in mouse peritoneal macrophages, the synthesis of ferritin was enhanced and the IRE binding activity of IRP-1 was diminished when the oxygen tension was decreased. Iron is known to induce ferritin synthesis and even in the presence of a low concentration of iron, synthesis of ferritin was enhanced and the activity of IRP-1 was decreased under hypoxia. The enhanced synthesis of ferritin under hypoxia was abolished by the addition of O2(-)-generating agents but not H2O2. The decreased activity of IRP-1 under hypoxia was reversed by adding O2(-)-generating agents. These data suggest that O2- generated in the cell is involved in alterations of ferritin synthesis and the activity of IRP-1 by oxygen.

Animals↗

Auditory evoked off-response: its source distribution is different from that of on-response.

Offset auditory responses were investigated by electroencephalography mainly in the 1970s, but since then no particular attention has been paid to them. Among the studies using magnetoencephalography (MEG) devices there are, to our knowledge, only three studies of the auditory off-response, and no significant variance has ever been observed between the source locations of on- and off-responses elicited from pure tones. We measured auditory evoked magnetic fields (AEFs) to various frequency pure tone stimulation in 5 healthy subjects with a 122-channel helmet-shaped magnetometer, and compared the distributions of the source locations of auditory N100m-Off (magnetic off-response around 100 ms) with those of N100m-On. Their spatial distributions were quite close to each other, and yet they were significantly different.

Acoustic Stimulation↗

Different adhesive characteristics and VLA-4 expression of CD34(+) progenitors in G0/G1 versus S+G2/M phases of the cell cycle.

We identified the cell cycle status of CD34(+) cells of steady-state bone marrow (BM) and peripheral blood (PB) obtained from healthy volunteers, and those of apherasis PB samples collected from healthy donors who had been administered granulocyte colony-stimulating factor (G-CSF). More than 10% of CD34(+) cells in BM were in S+G2/M phase. In contrast, regardless of whether G-CSF treatment was performed, less than 2% of CD34(+) cells in PB were cycling. BM CD34(+) cells showed greater VLA-4 expression and adherence to stromal cells than PB CD34(+) cells. In addition, when cycling and dormant BM CD34(+) cells were analyzed separately, the cells in S+G2/M phase expressed more VLA-4 and adhered to the stromal cell monolayer more efficiently than the cells in G0/G1 phase. Furthermore, this adhesion of CD34(+) cells to the stromal cell layer was almost completely inhibited by anti-VLA-4 antibody. Taken together, these results suggest that CD34(+) progenitors in G0/G1 phase of the cell cycle differ from those in S+G2/M phase in adhesiveness mediated by VLA-4 in the hematopoietic microenvironment.

Adult↗