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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 145 records · Page 8Linked to original sources
PubMed2000

Progress reports on immune gene therapy for stage IV renal cell cancer using lethally irradiated granulocyte-macrophage colony-stimulating factor-transduced autologous renal cancer cells.

There is no effective treatment for patients with stage IV renal cell cancer (RCC), although the introduction of new therapy is imminent. Cancer gene therapy is currently considered to be one of the most promising therapeutic modalities in the field of cancer treatment. Based on the results of animal studies, vaccination using autologous granulocyte-macrophage colony-stimulating factor-transduced renal cancer cells appears promising. Before initiating a clinical study using an ex vivo gene-transduced autologous cell vaccine-based immunogene therapy for RCC in Japan, in 1992 we initially planned a Japanese version of a clinical protocol in collaboration with a US group. In 1993, the original protocol was refined. We performed five preclinical qualification studies using RCC nephrectomy specimens from patients in 1997, and the results showed that preparation of RCC cells for autologous vaccines at the Clinical Cell Technology Facility, Research Hospital of the Institute of Medical Science, University of Tokyo, was feasible. Subsequently in August 1998, the Ministry of Health and Welfare and the Ministry of Education, Science, Culture, and Sport approved our clinical protocol. We have recruited two patients with stage IV RCC to our study so far. Here we report the background to the initiation of cancer gene therapy in Japan.

Adult↗
PubMed2000

Molecular basis of cardiac hypertrophy.

Cardiac hypertrophy is an adaptive process to an increased hemodynamic overload. When cardiomyocytes cultured on silicone dishes were stretched, second messengers such as protein kinase C (PKC), Raf-1 kinase, and mitogen-activated protein (MAP) kinases were activated, which were followed by increased protein synthesis. Moreover, pretreatment with an angiotensin II (AngII) type 1 receptor antagonist dimished an increase in protein synthesis, MAP kinase activity, and c-fos gene expression induced by the stretching of cardiomyocytes. These suggest the linkage of the cardiac renin-angiotensin system to the formation of pressure-overload hypertrophy. Indeed, in the stretch-conditioned medium the levels of AngII concentration were increased. Also, mechanical stretch enhanced endothelin (ET)-1 release from the cardiomyocytes and activated the Na(+)/H(+) exchanger independently of these vasoactive peptides. In the second part, we examined AngII-induced signaling pathways both in cardiac myocytes and in cardiac fibroblasts. AngII-evoked signal transduction pathways differed between cell types. In cardiac fibroblasts AngII activated MAP kinases through a pathway including the Gbetagamma subunit of Gi protein, Src, Shc, Grb2, and Ras, while Gq and PKC activation was necessary in cardiac myocytes. We further explored norepinephrine (NE)-induced signaling pathways in cardiac myocytes. NE activated Raf-1 kinase and MAP kinases and increased amino acid uptake in cardiomyocytes of neonatal rats. beta-adrenoceptor (AR) stimulation as well and alpha1-AR stimulation was involved in NE-induced MAP kinase activation. It is noteworthy that unlike in other cell types not only PKC activation but also protein kinase A (PKA) activation increased the activities of Raf-1 kinase and MAP kinases in cardiac myocytes and induced cell growth. Finally, we observed that beta-AR-induced activation of MAP kinases is dependent on both Gs/cAMP/PKA and Gi/Src/Ras signaling pathways and that phosphorylation of beta-AR is critical to the cross talk between these signaling pathways.

Animals↗
PubMed2000

Structure and function of a pyrimidine/purine-biased sequence from the 5'-flanking region of the basidiomycete Lentinus edodes gene priA.

The priA gene of the basidiomycete Lentinus edodes possesses a pyrimidine (CT)-rich stretch (26 bp) that includes a short (6-bp) repeat, the elements of which form a mirror repeat at and near the transcriptional initiation sites. A DNA fragment that included this sequence was inserted into pBR322, and the resulting plasmids were introduced into Escherichia coli. Analysis of the susceptibility of these pBR322 derivatives to cleavage by S1 nuclease, following isolation from E. coli, indicated the formation of an open, S1-sensitive structure within and just downstream of the CT/AG-biased sequence. Replacement of two dTMP residues in one of the repeat elements by dGMP resulted in the elimination of the S1-cleavable open structure from the plasmids. To analyze the effect of the CT/AG-biased sequence from priA in the basidiomycete Coprinus cinereus, the integrating vectors pLC2 and pLC2mutCT were used; these contained the wild-type priA promoter and the mutant priA promoter with the aforementioned mutation in the mirror repeat, respectively. The Streptomyces-derived bialaphos resistance gene (bar) was fused downstream of the promoters, and the resulting plasmids, pLC2-bar and pLC2mutCT-bar, were introduced into C. cinereus. Transformants carrying pLC2mutCT-bar grew significantly more slowly on bialaphos-containing agar plates and contained a noticeably lower level of the bar transcript when compared with the transformants obtained with pLC2-bar. These results suggest that an unusual structure induced by the CT/AG-biased sequence is required for efficient gene expression from the priA promoter.

Base Sequence↗
PubMed2000

Adrenergic inhibition of endogenous acetylcholine release on postganglionic cardiac vagal nerve terminals.

OBJECTIVE: The aim was to examine the adrenergic modulation of endogenous acetylcholine (ACh) release from vagal nerve terminals in the in vivo heart. METHODS: Using dialysis technique in anesthetized cats, we investigated the influence of exogenous noradrenaline on dialysate ACh response. Dialysis probes were implanted in the left ventricular myocardium and perfused with Krebs-Henseleit buffer containing eserine (10(-4) M) at 3 microl/min. Dialysate ACh concentration was measured as an index of ACh release from cardiac vagal nerve terminals. The dialysate ACh response to vagal nerve stimulation was examined before and after local administration of noradrenaline (10(-5) M) through dialysis probes. RESULTS: Noradrenaline significantly attenuated the dialysate ACh response to vagal nerve stimulation (10 Hz) from 9.5+/-1.8 to 5.4+/-1.2 nM (n=7). In the presence of the alpha-adrenergic antagonist phentolamine (10(-4) M), noradrenaline did not attenuate the dialysate ACh response (from 9.8+/-2.7 to 9.4+/-2.8 nM, n=6). The N-type Ca2+ channel blocker omega-conotoxin GVIA (10(-5) M) significantly attenuated the dialysate ACh response from 9.6+/-1.2 to 4.5+/-0.7 nM (n=8). In the presence of omega-conotoxin GVIA, noradrenaline did not attenuate the dialysate ACh response (from 3.8+/-1.4 to 3.5+/-1.3 nM, n=7). CONCLUSIONS: Our results suggest the presynaptic adrenergic inhibition of ACh release on postganglionic cardiac vagal nerve terminals. Adrenergic inhibition of Ca2+ influx through the N-type Ca2+ channels could play a predominant role in the decrease in ACh release.

Acetylcholine↗
PubMed2000

Troglitazone has a reducing effect on thromboxane production.

Effects of troglitazone, an antidiabetic thiazolidinedione that enhances insulin sensitivity, on thromboxane (TX) production were assessed in human erythroleukemia (HEL) cells and human platelets. Measurement of TX was performed by using the gas chromatography/selected ion monitoring (GC/SIM) method. We found that troglitazone reduced the TX production from HEL cells and human platelets. Furthermore, troglitazone also reduced arachidonic acid (AA)-induced TX production from HEL cell and thrombin-induced TX release from platelets. In addition, we compared the effect of troglitazone with that of alpha-tocopherol and BRL 49653. Other thiazolidinedione compound BRL 49653 had effects similar to troglitazone, but alpha-tocopherol had no effect on TX production. Our findings suggest that the thiazolidinedione group had an antithrombotic effect and was beneficial in preventing vascular complications often observed in diabetes mellitus.

Arachidonic Acid↗
PubMed2000

Epigallocatechin gallate increase the prostacyclin production of bovine aortic endothelial cells.

We describe the effect of (-) epigallocatechin gallate (EGCg), one of catechins known in tea, on the prostacyclin (PGI) production by bovine aortic endothelial cells. The amounts of 6-keto-PGF(1alpha) and Delta(17)-6-keto-PGF(1alpha), stable metabolites of PGI(2) and PGI(3), released in culture medium were measured using gas chromatography/selected ion monitoring (GC/SIM). The prostacyclin production of endothelial cells was increased by EGCg in a dose- and time-dependent manner. The effect by EGCg was stronger than any other catechins (catechin, epicatechin, epigallocatechin, and epicatechin gallate). When endothelial cells incubated with EGCg and arachidonic acid (AA) or eicosapentaenoic acid (EPA), PGI(2), and PGI(3) production were increased greater than those incubated with AA or EPA alone. Furthermore, gallic acid, that also has a pyrogallol structure, increased PGI(2) production. These observations indicate that catechins increase the prostacyclin production and that the pyrogallol structure is significant to this function.

Animals↗
PubMed2000

Unusual occipital condyle fracture with multiple nerve palsies and Wallenberg syndrome.

A 52-year-old male presented with an extremely rare fracture of the occipital condyle involving the jugular foramen with marked medial rostrad displacement of the fragments. He had ipsilateral VII through XII nerves palsies and Wallenberg syndrome. Conservative treatment did not improve the cranial nerve palsies. A high-resolution CT-scan is essential to visualize these fractures.

Accidents, Occupational↗
PubMed2000

Evaluation of the pharmacological activity of extracts from amomi semen on the gastrointestinal tracts.

We have investigated the effects of methanolic and alcoholic extracts from Amomi Semen on gastric secretion, as well as gastrointestinal propulsion or the prokinetic activities. The methanolic extract from Amomi Semen dose dependently decreased the volume output, acid output, and pepsin output in rat's gastric juice with increasing pH value, while the alcoholic extract had no influence on basal gastric acid secretion. Furthermore, the alcoholic extract improved the L-dopa to induce a delay of gastrointestinal transit in mice, while the methanolic extract did not improve it. However, both extracts had no influence on gastrointestinal transit in intact mice. These results suggest that Amomi Semen has an inhibitory effect on gastric acid secretion and that it has effects as the gastrointestinal prokinetics rather than propulsion. The present study pharmacologically elucidates a belief that Amomi Semen has been used in Chinese medicine for the treatment of gastrointestinal dyspepsia, which includes hyperchlorhydria, stomachache, abdominal distention, anorexia, gastric atony, etc.

Animals↗
PubMed2000

The perfusion defect seen with SPECT in West syndrome is not correlated with seizure prognosis or developmental outcome.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

Cerebral Cortex↗
PubMed2000

Systematic approach to dipole localization of interictal EEG spikes in children with extratemporal lobe epilepsies.

OBJECTIVES: To assess the reliability of dipole localization based on residual variances (RV), using equivalent current dipole analysis of interictal EEG spikes in children with extratemporal lobe epilepsy. METHODS: Four pediatric patients with extratemporal lobe epilepsy were studied. Digital EEG was recorded from 19 scalp electrodes. Computer programs for spike detection and clustering analysis were used to select spikes. Dipoles were calculated 5 times for each spike using different initial guesses by the moving dipole model. Standard deviation (SD) of the dipole positions was calculated at each time point in the 5 trials. RESULTS: We analyzed the dipoles at 1097 time points from 4 patients. Among 106 time points with RV < 2%, the SD was < 1 mm in 78 (74%), while in those with SD > 1 mm the dipole positions varied between 2.8 and 52.6 mm. Of dipoles with RV < 1%, 26 of 27 (96%) had an SD < 1 mm; the one dipole with SD > 1 mm varied within 2.5 mm. The dipole localizations with RV < 2% corresponded to the epileptogenic zones identified on intracranial invasive video EEG and intraoperative ECoG. CONCLUSIONS: The systematic approach of equivalent current dipole analysis using spike detection, clustering analysis, and an RV < 2% as a standard is useful for identifying extratemporal epileptic regions.

Adolescent↗
PubMed2000

Multiple equivalent current dipole source localization of visual event-related potentials during oddball paradigm with motor response.

Event-related potentials (ERPs) during a visual oddball paradigm with button-pressing responses were recorded in 12 right-handed subjects from 32 scalp electrodes. The single equivalent current dipole (ECD) of the target C1 (weak occipito-parietal negativity from 30-80 ms) was consistently located at the primary visual cortex. From the 4-ECD localization of the target P1/N1 (temporally coincident frontal positivity and occipito-temporal negativity), it was suggested that this complex reflected activities from distributed sources along both dorsal occipito-parietal and ventral occipito-temporal areas. The stable multiple ECD solutions for the target P3b were chosen as those including the left primary motor and/or sensorimotor dipole and satisfying goodness-of-fit (GOF) of more than 98% and confidence limit (CL) of less than 1 mm. The obtained frontal dipoles were discussed in terms of visual working memory and sustained attention in reference to the previous PET, fMRI and MEG studies. The distributed multiple ECDs may suggest that P3 should be interpreted as being the embodiment of the cortico-limbic-thalamic network which involves Halgren and Marinkovic's emotional and behavioral model and Mesulam's attentional circuit.

Adult↗
PubMed2000

Application of a method incorporating differential centrifugation for selective isolation of motile actinomycetes in soil and plant litter.

The present paper describes a simple enrichment technique which enables rapid and selective isolation of diverse zoosporic actinomycete genera directly from soil and plant litter. This technique, designated the rehydration and centrifugation (RC) method, consists of immersing the air-dried source material in 10 mM phosphate buffer containing 10% soil extract, letting the preparation stand at 30 degrees C for 90 min, followed by centrifugation of the fluid at 1,500 x g for 20 min. Portions of the supernatant containing actinomycete zoospores are plated on the humic acid-vitamin agar which is supplemented with nalidixic acid and trimethoprim as the selective inhibitors for Gram-negative bacteria and bacilli. The phosphate buffer-soil extract solution significantly promoted liberation of motile zoospores from the source material. The centrifugation stage greatly eliminated streptomycetes and other non-motile actinomycetes from the liquid phase, thereby facilitating selective growth of rare, motile actinomycetes on the isolation plates subsequent to inoculation. Ten different soil and leaf-litter samples, taken from fields, forests, and stream banks, were examined. The RC method consistently achieved preferential isolation of motile actinomycetes in all samples, which accounted for 37-86% of the total microbial population recovered. The most frequently isolated motile actinomycetes were Actinoplanes and Dactylosporangium. Strains of Actinokineospora, Catenuloplanes and Kineosporia were also recovered, depending on the nature of the samples examined. Other motile actinomycetes that were occasionally isolated in small numbers included Actinosynnema, Geodermatophilus and Sporichthya.

Actinomycetales↗