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Biomedical subjects

T Chiba

Publications and source records attributed to T Chiba.

At least 379 records · Page 21Linked to original sources

Inhibitory effect of pyridobenzazoles on virus replication in vitro.

Twelve species of pyridobenzazoles and pyrimidobenzimidazole were examined as inhibitors of the replication of respiratory syncytial virus (RSV) in HeLa cells. From the pyridobenzazoles studied, 2-benzamido-4-cyano-1-oxo-1H,5H-pyrido[1,2-alpha]benzimidazol emerged as a potent inhibitor of the RSV. Based on its inhibitory effect on the cytopathogenicity of the RSV in HeLa cells, the 50% effective dose was found to be 0.95 micrograms/ml. The cytotoxicity of this compound for HeLa cells was examined by monitoring the incorporation of radiolabeled uridine into cellular RNA. The selectivity index was ca. 30, the same as Virazole.

Antiviral Agents↗

Systemic capillary leak syndrome associated with multiple myeloma of IgG kappa type.

A case of systemic capillary leak syndrome in a 67-year-old woman is reported. The patient suddenly presented with severe edema and hypotension associated with an increased hematocrit and a decreased level of serum albumin, suggesting capillary hyperpermeability. The patient had IgG kappa monoclonal gammopathy in association with not only a slight increase in plasma cells in the bone marrow but also several punched out lesions in the skull, indicating multiple myeloma. Although most of the cases of systemic capillary leak syndrome reported previously were accompanied by monoclonal gammopathy, this appears to be the first case in which capillary leak syndrome developed in a patient with multiple myeloma.

Aged↗

Observation of apical part and nerve terminals of human vestibular hair cells.

The human vestibular sensory epithelia of macula utriculi in 3 cases of acoustic neurinoma were examined by conventional and intermediate voltage electron microscopes. The apical part and the nerve terminals of hair cells were studied by means of a computer-aided three-dimensional (3-D) reconstruction technique. The sensory epithelia were fairly well preserved. Most type I and all type II hair cells appeared as those described in the other reports. However, some type I hair cells were incompletely surrounded by nerve calyces and received direct contacts from the efferent nerve endings. These type I hair cells were also innervated by a few neighbouring afferent nerve calyces. The stereocilia and the cuticular plate of type I hair cells differed from those of type II hair cells. The mean diameter of type I hair cell stereocilia was 488 +/- 59 nm and that of type II hair cells was 373 +/- 21 nm. The cuticular plate of type I hair cells resembled a cone and was about several times as thick as that of type II hair cells which was similar to a flat disc.

Cell Membrane↗

Atypical innervation pattern of human vestibular hair cells.

Human vestibular sensory epithelia of macula utriculi were examined in 3 cases with acoustic neurinoma by intermediate voltage electron microscope. The innervation pattern of vestibular hair cells was studied by means of computer aided three-dimensional reconstruction technique. The sensory epithelia were fairly well preserved. Most of type I and all of type II hair cells appeared normal. However, some type I hair cells were incompletely surrounded by nerve calyces and received direct contact from the efferent nerve endings. These type I hair cells were also innervated by a few neighboring afferent nerve calyces. These atypical type I hair cells constituted 5-8% of the total number of hair cells.

Culture Techniques↗

Proteolytic activity of NS3 serine proteinase of hepatitis C virus efficiently expressed in Escherichia coli.

The serine proteinase of hepatitis C virus (HCV) non-structural protein NS3 was efficiently expressed in an active form as a fused protein with oligohistidine in Escherichia coli. The recombinant fusion protein was purified to near homogeneity by affinity chromatography on a metal chelation column. Trans-cleavage activity of this protein was investigated by using the substrate NS5 protein expressed in insect cells. The purified serine proteinase trans-cleaved the partially purified NS5 protein. In contrast, the NS3 proteins with mutations at the proposed catalytic site, Ser1165 or His1083, lost the trans-cleavage activity. Analysis of the authentic enzyme and variants with site-directed mutations provides a useful tool for understanding the structure-function relationship of the NS3 serine proteinase. We then developed an in vivo trans-cleavage assay system by coexpression of the NS3 proteinase and the NS5 substrate in E coli, and examined the effect of known inhibitors of serine proteinase. Inhibition of its proteolytic activity by N-p-tosyl-L-lysine chloromethyl ketone (TLCK) was observed, but only at high concentrations. The in vitro and in vivo trans-cleavage assays for NS3 serine proteinase will facilitate efficient testing for inhibitors of the replication of HCV and specific treatment for hepatitis C.

Baculoviridae↗

Inspiratory activity responses to lung inflation and ventral medullary surface cooling of glossopharyngeal nerve (stylopharyngeal muscle branch) and its motoneuron distribution in the rat.

Inspiratory (I) discharges of the phrenic (Phr) and glossopharyngeal (stylopharyngeal muscle branch, IX) nerves were compared in the urethane anesthetized, vagi-intact and artificially ventilated rat in which respiratory rhythm was generated in synchrony with cyclic changes in airway pressure (P(aw)) produced by a ventilator. Observations were made during respiratory suppression due to excess lung inflation and bilateral cooling of the ventral medullary surface (VMS). In the control condition, regular rhythmic I bursts appeared at low baseline P(aw) phase (lung deflation) and ceased when P(aw) increased (lung inflation) in each ventilator cycle. Increase in baseline P(aw) (P(aw) > 8 cmH2O, excess lung inflation) suppressed the initiation of rhythmic I discharge. However, threshold baseline P(aw) for suppressing I bursts was higher in the IX than in the Phr nerve, and regular rhythmic I activity remained in the IX even after cessation of Phr bursts. During VMS cooling, I bursts disappeared first in the Phr and subsequently in the IX nerve and emerged always first in the IX during recovery. The results suggest that I activity of the IX (stylopharyngeal) motoneurons, which are located in the rostral part of the nucleus ambiguus, are less suppressed than that of Phr motoneurons by vagal afferents arising probably from slowly adapting pulmonary stretch receptors or by a reduction in respiratory drive from VMS. These differential responses of Phr and IX motoneurons may be ascribed to differences in activation or inhibition processes between two motoneuron groups despite both being driven by a common rhythm generator.

Action Potentials↗

[Study on peripheral blood stem cells mobilized by different chemotherapies with granulocyte-colony stimulating factor in ovarian cancer].

A new therapeutic strategy for advanced ovarian cancer is to administer ultra-high doses of anticancerous drugs, followed by peripheral blood stem cell transplantation (PBSCT) to recover normal marrow functions. There are, however, no clear regimens to induce mobilization of peripheral blood stem cells (PBSCs). We therefore used three different chemotherapies and granulocyte colony-stimulating factor (G-CSF) to produce a rebound increase in PBSCs during myelosuppression by apheresis. Eleven patients with advanced ovarian cancer (FIGO Stage; IIc-1, IIIc-5, IV-4, Recurrence-1) received chemotherapy with CEP (cyclophosphamide: 500-750mg/m2, epirubicin: 50-70mg/m2, cisplatin: 70mg/m2), CEE (cyclophosphamide: 2,000mg/m2, epirubicin: 50mg/m2, etoposide: 300mg/m2, and PEC salvage (cisplatin: 75mg/m2, etoposide: 300mg/m2, cyclophosphamide: 1,000mg/m2) followed by lenograstim (G-CSF; 2 micrograms/kg subcutaneous injection daily for 14-18 days) to mobilize PBSCs. A range of 0-38.2 x 10(4) (mean +/- S.D.; 11.1 +/- 5.0 x 10(4) colony forming unit granulocyte-macrophage (CFU-GM)/kg in the CEP regimen (n = 15), 1.6-40.8 x 10(4) (mean +/- S.D.; 12.3 +/- 3.6 x 10(4) CFU-GM/kg in the CEE regimen (n = 11), and 8.6-11.4 x 10(4) (mean +/- S.D.; 10.0 +/- 2.0 x 10(4) CFU-GM/kg in the PEC salvage regimen (n = 2) were recruited by a single apheresis. Although the CEE regimen to mobilize PBSCs was much more efficient than the CEP regimen, a large number of PBSCs showing 38.2 x 10(4) CFU-GM/kg were mobilized by the CEP regimen with a dose-escalation of cyclophosphamide 750mg/m2 and epirubicin 70mg/m2. The number of CFU-GM/kg correlated well with that of CD34+ (r = 0.693).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Classification for bronchial asthma from the viewpoint of autonomic nerve function and airway hyperreactivity].

In the present study, patients with asthma ware evaluated in order to find out if the emotional stress itself causes their asthmatic attack or not, and to elucidate the mechanisms underlining it. 41.8% of the 55 patients demonstrated asthmatic attack during hypnosis evaluated their symptoms and significant decrease in their air flow. The non-responders showed significant increase ind the serum DBH level (p < 0.05) during the hypnosis compared with their baseline value, while the responders did not show any significant change in the serum concentration. However, the responders shows significant increase in serum histamine concentration during (p < 0.01) and 40 min (p < 0.05) after the hypnosis. These data suggest that the increased sympathetic nerve activity during the hypnosis suppresses the release of chemical mediators from inflammatory cells and autonomic nerve terminals in the airways.

Asthma↗

Expression of CDK5 (PSSALRE kinase), a neural cdc2-related protein kinase, in the mature and developing mouse central and peripheral nervous systems.

CDK5 is a cdc2-related protein kinase that is known to be highly expressed in mature brain. In this study, we obtained a mouse CDK5 cDNA by screening an adult mouse cDNA library. Northern blot analysis demonstrated that the mouse CDK5 mRNA was expressed especially highly in brain, and moderately in kidney, testis and ovary. In brain the expression of CDK5 is already seen at embryonal 12.5 days (E12.5), and it gradually increases through the embryonal stage. After birth, the expression is maintained at a high level to adulthood. In situ hybridization demonstrated that the expression of CDK5 mRNA was distributed in neurons throughout the brain, spinal cord and peripheral ganglia, especially in the hippocampal pyramidal cells, cerebellar Purkinje cells, cortical neurons, olfactory mitral cells, mesencephalic and motor trigeminal nuclei and trigeminal ganglion. In any portion, no apparent expression was observed in glia. During development, the expression of CDK5 was already seen at E12.5 intensely in trigeminal and dorsal root ganglia, and moderately and diffusely in the central nervous system. The expression pattern of CDK5 is quite in contrast with that of CDC2. The fact that CDK5 is expressed in terminally differentiated non-dividing neurons predicts an alternative function(s) in addition to controlling the cell cycle.

Aging↗

Nitric oxide synthase containing neurons in the carotid body and sinus of the guinea pig.

The morphology and function of the carotid sinus and carotid body have been extensively studied, but our knowledge of their transmitter(s) is still incomplete. Nitric oxide (NO) recently has been identified as a novel messenger molecule in a number of neuronal and non-neuronal tissues. Nitric oxide synthase (NOS) has been demonstrated in many neurons of the autonomic nervous system. The present study examines the distribution of NOS in the carotid sinus and body. The carotid sinus and body of newborn guinea pigs were removed for histochemical examination of NOS using the NADPH-diaphorase method. In the carotid body, many nerve fibers enveloping the glomus cells were positive for NOS. In addition, some glomus cells were positive for NOS. In the carotid sinus, NADPH-d positive fibers were distributed unevenly in the adventitia and media. These results indicate the possibility that nitric oxide plays a role in both arterial chemoreception and baroreception.

Amino Acid Oxidoreductases↗

Nitric oxide synthase-immunoreactive nerve fibers in the nasal mucosa of the rat.

An immunohistochemical study was performed to detect the localization of nitric oxide synthase (NOS) in the rat nasal mucosa by light and electron microscopy. NOS-immunoreactive nerve fibers were observed around blood vessels and seromucous glands. They were found in the subepithelial layer and even within the epithelium. But no NOS-immunoreactivity was found in the olfactory neuroepithelium. Electron microscopy showed that NOS-immunoreactive nerve profiles were in close contact with the cytolemma of respiratory epithelial cells and acinar cells of seromucous glands. NOS-immunoreactive axon varicosities were located at a considerable distance from the smooth muscle of arterioles and small veins as well as the endothelial cells of venules and capillaries. We confirmed that NOS-containing nerves innervated the epithelium, blood vessels and seromucous glands of the nasal mucosa. These findings, collectively, suggested the possibility that nitric oxide participated in the sensory function of the epithelium, the secretory activities of the nasal gland, and the regulation of vascular tone and vascular permeability in the nasal mucosa.

Amino Acid Oxidoreductases↗

Distribution of mRNA for CCK-B receptor in the brain of Mastomys natalensis: abundant expression in telencephalic neurons.

The distribution of cholecystokinin B (CCK-B) receptors in the Mastomys brain was studied using Northern blot analysis and in situ hybridization technique. By Northern blot analysis using 32P-labeled cDNA probe, the cortex had the highest hybridization signal of CCK-B receptor mRNA in the brain. The olfactory bulb and hippocampus showed a moderate level of signals. In situ hybridization using 35S-labeled cRNA probes revealed a wide and region-specific distribution of CCK-B receptor mRNA in the telencephalon. Throughout the cerebral cortex, labeled cells were found in all layers, with higher intensities in layers II, V and VI. Pyramidal cells of the layer II of the piriform cortex showed the highest level of signals in the brain. In the hippocampus, most of the pyramidal cells of the Ammon's horn were labeled, although labeled cells were not detected in other layers. Distinct signals were also detected in the various amygdaloid nuclei, caudate-putamen, reticular thalamic nucleus, hypothalamic ventromedial nucleus and inferior colliculus. This distribution pattern may further support the prominent existence of CCK-B receptors in the brain particularly in the telencephalon.

Animals↗

p53 mutations in flat- and polypoid-type colorectal tumors detected by temperature-gradient gel electrophoresis.

Reports of cases of flat-type colorectal tumors are increasing in Japan, but almost nothing has been elucidated about the genetic abnormalities of these tumors. In this study, we have examined p53 mutations in six cases of colon cancer cell lines, 22 cases of flat-type colorectal tumors, and 27 cases of polypoid-type colorectal tumors using the polymerase chain reaction (PCR) and temperature-gradient gel electrophoresis (TGGE); the latter has recently been developed as a screening method for gene mutations. p53 mutations were observed in four colon cancer cell lines, six flat-type colorectal tumors, and three polypoid-type colorectal tumors, all of which were analyzed by direct sequencing. These mutations were observed only in adenomas with high-grade dysplasia and in colorectal cancers but not in adenomas with low-grade dysplasia. These observations suggest that p53 gene mutations are involved in flat-type as well as polypoid-type colorectal tumors at relatively later stages of carcinogenesis and that TGGE seems to be useful as one of the rapid screening methods.

Adenoma↗