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Biomedical subjects

S Tani

Publications and source records attributed to S Tani.

At least 19 recordsLinked to original sources
PubMed1999

Delta-induced Notch signaling mediated by RBP-J inhibits MyoD expression and myogenesis.

Signaling induced by interaction between the receptor Notch and its ligand Delta plays an important role in cell fate determination in vertebrates as well as invertebrates. Vertebrate Notch signaling has been investigated using its constitutively active form, i.e. the truncated intracellular region which is believed to mimic Notch-Delta signaling by interaction with a DNA-binding protein RBP-J. However, the molecular mechanism for Notch signaling triggered by ligand binding, which leads to inhibition of differentiation, is not clear. We have established a myeloma cell line expressing mouse Delta1 on its cell surface which can block muscle differentiation by co-culture with C2C12 muscle progenitor cells. We showed that Delta-induced Notch signaling stimulated transcriptional activation of RBP-J binding motif, containing promoters including the HES1 promoter. Furthermore, ligand-induced Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA. Since cycloheximide treatment did not inhibit induction of HES1 mRNA, the HES1 promoter appears to be a primary target of activated Notch. In addition, a transcriptionally active form of RBP-J, i.e. VP16-RBP-J, inhibited muscle differentiation of C2C12 cells by blocking the expression of MyoD protein. These results suggest that HES1 induction by the Delta1/Notch signaling is mediated by RBP-J and blocks myogenic differentiation of C2C12 cells by subsequent inhibition of MyoD expression.

Animals↗
PubMed1999

In vitro susceptibility of Helicobacter pylori to trifluoromethyl ketones.

Heteroaromatic trifluoromethyl ketones (TFMK's) showed strong inhibitory activity against Helicobacter pylori. The MIC50 observed for 2-trifluoroacetonylbenzoxazole (1) is 20-fold more active than metronidazole and is only twice as high as that of clarithromycin. The inhibitory mode of TFMK's on Hp growth was not related to inhibition of urease.

Benzoxazoles↗
PubMed1999

Chromosomal mapping of two RBP-J-related genes: Kyo-T and RBP-L.

We have recently isolated two genes encoding proteins which have either homology or affinity to RBP-J, a transcription factor involved in Notch signaling. Kyo-T interacts with RBP-J and possibly regulates the function of RBP-J. RBP-L has a highly homologous region with RBP-J but the function of RBP-L is unknown. Fluorescence in situ hybridization analysis of human metaphase chromosomes localized Kyo-T and RBP-L to Xq26 and 20q12-13.1, respectively.

Base Sequence↗
PubMed1998

Standardizations of clinical laboratory examinations in Japan.

In this paper we introduce Japanese activities concerning laboratory examinations by illustrating three major categories. The first is the contribution of JCCLS to ISO/TC212 clinical laboratory testing and in vitro diagnostic test systems, with NCCLS and CEN TC140. The second is the establishment and promotion of JLAC Classification and Coding for Clinical Laboratory Tests by The Japan Society of Clinical Pathology. The third is a clinical data exchange format between healthcare facilities using MML/MERIT-9 standard, started as a Ministry research project.

Clinical Laboratory Information Systems↗
PubMed1998

MERIT-9: a patient information exchange guideline using MML, HL7 and DICOM.

To realize clinical data exchange between healthcare providers, there must be many standards in many layers. Terms and codes should be standardized, syntax to wrap the data must be mutually parsable, then transfer protocol or exchange media should be agreed. Among many standards for the syntax, HL7 and DICOM are most successful. However, everything could not be handled by HL7 solely. DICOM is good for radiology images, but, other clinical images are already handled by other 'lighter' data formats like JPEG, TIFF. So, it is not realistic to use only one standard for every area of clinical information. For description of medical records, especially for narrative information, an standard generalized mark-up language, document type definition (SGML DTD) for medical information, called MML (medical markup language) had been created in Japan. It is already implemented in more than ten healthcare providers. However, it is again not realistic to use MML solely for clinical information in various level of detail. Therefore, we proposed a guideline for use of available medical standards to facilitate clinical information exchange between healthcare providers. It is called MERIT-9 (Medical Records, Images, Texts, -Information Exchange). A typical use is HL7 messages, DICOM files, referred from an MML file in a patient record, as external entities. Both MML and MERIT-9 have been research projects of Japanese Ministry of Health and Welfare and the purpose is to facilitate clinical data exchanges. They are becoming to be used in technical specifications for new hospital information systems in Japan.

Community Networks↗
PubMed1998

Characteristics of spontaneous erythema appeared in hairless rats.

The hairless rat (WBN/Kob-Ht), a dominant mutant rat derived from the Wistar strain, rarely develops spontaneous erythema of a progressive nature on its skin. Erythema was first observed at 8 weeks of age and the incidence at 20 weeks of age was about 4% in both males and females. Histopathologically, erythema was characterised by dermatitis induced by an immunological reaction. Areas of erythema in the skin were decreased by treatment with dexamethasone (1 mg/kg) or ciclosporin (25 or 50 mg/kg). These results suggested that erythema on the hairless rat could be used as an animal model of spontaneous dermatitis.

Animals↗
PubMed1998

[Visual defect due to chiasmic compression by the A1 portion of the anterior cerebral artery].

Unilateral nasal hemianopia is highly difficult to notice with bilateral vision intact, and only a few cases has been reported. There are several reported cases of quadrantic hemianopsia caused by cerebral lesions, but the defects were found bilaterally in all cases. There is only one reported case of which an aneurysm was believed to be the cause. We confronted 3 cases of unilateral nasal quadrantic hemianopia. In either case no ophthalmologic disorders could be found but magnetic resonance imaging revealed the compression of the optic chiasma by the A1 portion of the anterior cerebral artery. All three cases are presently under conservative therapy and receive routine evaluations. Nerve fibers from the upper and lower areas of the retina are routed complicatedly in the optic nerve in the periphery of the optic chiasma. From the presentation of the quadrantic hemianopia and from the radiological findings, we diagnosed that the visual defect was caused by vascular compression of the optic chiasma.

Adult↗
PubMed1997

Adenovirus-mediated gene transfer of basic fibroblast growth factor induces in vitro angiogenesis.

To investigate the possibility of adenovirus-mediated gene transfer in the treatment of vascular occlusive diseases, we constructed a replication-deficient recombinant adenovirus vector coding for human basic fibroblast growth factor (bFGF) and examined its effect on the proliferation and differentiation of vascular endothelial cells in vitro. Human umbilical vein endothelial cells (HUVECs) were successfully infected with high efficiency and expressed 18 kD protein which is immunoreactive to anti-bFGF monoclonal antibody. This protein was accumulated mainly in the nuclei of the cells, but was also detected in the culture medium although the complimentary DNA (cDNA) did not contain the classical secreting signal sequence. The proliferation assay of HUVECs infected with bFGF-expressing adenovirus revealed a significant increase in cell number over control. Infection with this virus also enhanced tubular formation of HUVECs on reconstituted basement membrane. Neovascularization and the formation of collateral vessels play important roles in minimizing tissue damage in ischemic disorders. These results imply that the use of bFGF-expressing recombinant adenovirus may be a suitable in vivo gene therapy for ischemic diseases.

Adenoviridae↗
PubMed1997

Antitumor agents--CLXVII. Synthesis and structure-activity correlations of the cytotoxic anthraquinone 1,4-bis-(2,3-epoxypropylamino)-9,10-anthracenedione, and of related compounds.

1,4-Bis-(2,3-epoxypropylamino)-9,10-anthracenedione (3) was synthesized in this laboratory and was found to be a potent antitumor agent. Derivatives of this compound containing anthraquinone, naphthoquinone, and quinone skeletons were also prepared and evaluated for in vitro cytotoxic activity in several cell lines. These molecules were designed as bifunctional antitumor agents with the potential to act as (1) intercalating agents due to their planar backbones, and (2) alkylating agents due to the presence of alkylating moieties in their side chains. Compounds with an anthraquinone skeleton and propylamino side chains containing epoxides or halohydrins as the alkylating species showed greater activity than similar compounds with naphthoquinone or quinone skeletons. Compounds without these alkylating functionalities (e.g., with alkene or amino groups) were generally inactive. Hydroxy substitution on the planar skeleton in conjunction with alkylating side chains gave compounds with the most potent cytotoxic activity. The position of the hydroxy groups and side chains could be varied without substantially affecting activity. Activity was retained when an epoxypropyloxy side chain was substituted for the epoxypropylamino side chain in the parent compound.

Animals↗
PubMed1997

Gastric mucin secretion from cultured rat epithelial cells.

In order to establish the measurement of gastric mucin secreted from cultured mucous cells, rat gastric mucin was purified from secreted mucus with Sepharose CL-4B column chromatography. Gastric mucin was measured by dot blot analysis using an enzyme-linked lectin (soybean agglutinin) assay in a good concentration-dependent manner. Surface epithelial cells were dispersed by limited digestion of a rat everted stomach and collected by density gradient centrifugation with Percoll. These cells were inoculated onto gelled collagen dishes, then cultured in a medium supplemented with 10% fetal calf serum under a 5% CO2 atmosphere in air. Changing the medium after a 2-d culture, the cells were cultured for another 3 d. During the culture, the numbers of cells each day were almost equal, but mucin contents in the cells increased, and then dropped at day 5 after inoculation. At that time, the edge of the cell layer peeled off and the cells adhered to each other. Using 2-d cultured cells, the effects of some secretagogues on mucin secretion were investigated. Carbachol, secretin, CCK-8 and prostaglandin E2 (PGE2) strongly stimulated mucin secretion, and gastrin I weakly did. However, histamine offered no stimulation.

Animals↗
PubMed1997

[Decision support of clinical laboratory test by object-oriented data base].

We have constructed an object-oriented database system, using prescription, lab test result, and disease registry data, transmitted from the order entry system of Hamamatsu University Medical School Hospital. It serves not only numeric data but also semantics of laboratory results. The database system has a feature to categorize each data into structured hierarchies of attributes. By this, the user can retrieve abstract level descriptions such as "prescriptions of anti-inflammation medicines, suppository only", "any kind of gastric ulcer", etc., which is expected to be useful for researchers and students. In transferring order entry data from HIS, HL7-ASTM E1238 standard data formats using the Japan Association of Clinical Pathology lab test item code are utilized, proving this system's transferability to other hospitals. This is the first real use implementation of an object-oriented data base in a clinical setting, and results are promising in terms of providing an intelligent clinical database. Also discussed are future trends of clinical master files, hospital administrative tools, and multi vendor configurations of HIS.

Clinical Laboratory Techniques↗
PubMed1997

Fluorescence properties of quinacrine enantiomers complexed with synthetic double-stranded polyribonucleotides.

The interaction of quinacrine (QAC) enantiomers with poly(A).poly(U) and poly(I).poly(C) has been studied by fluorescence spectroscopy. The fluorescence and fluorescence-excitation spectra of QAC enantiomers complexed with the polyribonucleotides showed a marked dependence on the excitation and emission wavelengths. This behavior of the bound QAC enantiomers was almost independent of the chirality of the cationic side chain and was very similar to that of the bound racemic QAC.

Nucleic Acid Conformation↗
PubMed1996

Phenytoin-induced cerebral thrombosis in rats: cerebral ultrastructure, water content and ischaemic volume in the acute phase.

A new rat model for multifocal cerebral thrombosis has recently been reported (Tani et al., 1994; 1995). Ultrastructural changes in the cerebral neocortex in the acute phase were investigated in order to characterize the early pathological events in this model. A bolus injection of alkaline phenytoin solution (pH 10.8) into one internal carotid artery in the rat caused severe endothelial injury accompanied by thrombosis in the cerebral vasculature within 5 minutes, and severe oedema of the ipsilateral hemisphere within an hour. Cerebral water content was measured by the simple dry-wet method, and cerebral surface area and the surface area and volume of the ischaemic zone were measured using computer-aided image analysis. Good correlations were demonstrated between cerebral water content and cerebral surface area, and between the surface area and volume of the ischaemic zone. We report here that quantitative evaluation of acute cerebral damage induced by phenytoin solution is possible with high reliability using simple image analysis.

Acute Disease↗
PubMed1996

[Acute subdural hematoma caused by professional boxing].

Knockout in boxing entails deliberate production of the state of unconsciousness. Acute subdural hematoma which is the most common acute brain injury in boxing, accounts for 75% of all acute brain injuries and is the leading cause of boxing fatalities. The aim of this study is to evaluate acute subdural hematoma caused by professional boxing by analyzing the content of bouts, the level of consciousness on admission, CT scan, therapy and outcome 3 months after admission. Fifteen boxers who had suffered from acute subdural hematoma were classified into three groups according to the pattern of loss of consciousness. Transient unconsciousness type (Transient type): boxers who had returned to alertness within an hour from the time of injury. Lucid interval type: neurological deterioration appeared with a lucid interval from ten minutes to an hour after knockout. Deterioration of consciousness type (Deterioration type): A state of unconsciousness appeared and worsened from a few minutes after knockout. Analyzing the number of rounds in bouts indicated that the hematoma occurred most frequently in bouts of 10 rounds. All of our subjects presented subdural hematomas without cerebral contusions on CT scan. With regard to the location of the hematomas, 9 hematomas involved the left side, 3 the right, 2 the suboccipit and 1 the interhemisphere. Transient type was found in 7 patients who had GCS scores of 14, 15 on admission. Since CT scan revealed thin subdural hematoma with or without mild midline shift, conservative therapy was carried out in all patients. All patients had a good recovery. Five patients of lucid interval type with an admission GCS score of 4, 6 and 7 demonstrated thicker hematoma compared to that presented by the transient type with significant midline shift on CT scan. All patients required surgery. Outcome of this type was good recovery (n = 2), moderate disability (n = 1), persistent vegetative state (n = 1), death (n = 1). Three patients of deterioration type had GCS scores of 5, 6. Because of subdural hematoma with remarkable midline shift on CT scan, all patients underwent surgery. Outcome was good recovery (n = 1), moderate disability (n = 1), persistent vegetative state (n = 1). Overall outcome was good recovery 66.7%, moderate disability 13.3%, persistent vegetative state 13.3%, death 6.7%. Furthermore, 8 patients who underwent surgery with a GCS score of less than 8 exhibited good recovery 37.5%, moderate disability 25%, persistent vegetative state 25%, death 12.5%. CT scan of lucid interval and deterioration type showed a tendency to show thick subdural hematoma and remarkable midline shift compared to transient type. Outcomes of lucid interval and deterioration type were worse than those of transient type. This result suggests that the influence of repeated head injury and diffuse brain injury might make a difference between these groups. Repeated head injury means that further impacts repeatedly damaged the injured brain after bleeding in the bouts. Overall outcome was better than that published in previous reports and also than that observed in other head injuries, for example, traffic accident and fall. The reasons for this could be that the patients were younger, that there was immediate surgical treatment, and that brain injury without cerebral contusion had contributed to better outcome. Finally, the best medical management intervention seems to be to diagnose and treat the lesions as early as possible after occurrence of subdural hematoma.

Acute Disease↗
PubMed1995

Chronic oral administration of synthetic trypsin inhibitor camostate reduces amylase release from isolated rat pancreatic acini.

In the present study, we examined stimulus-secretion coupling in pancreatic acini prepared from rats given synthetic protease inhibitor camostate at a dose of 200 mg/kg body wt by an orogastric tube once a day for 10 d. Camostate treatment significantly increased pancreatic weight, protein, DNA, and enzyme contents. In acini prepared from the camostate-treated rats, responsiveness to both CCK-8 and carbamylcholine was greatly decreased with no shift in the dose-response curves compared to control acini prepared from saline-treated rats. There were no major changes in the affinity for both high- and low-affinity sites of CCK receptors, but there was a significant reduction in the capacity of low-affinity site based on acinar protein. Responsiveness to secretin in the camostate-treated rat acini was also significantly reduced compared with that in the controls. However, amylase release from the camostate-treated rat acini in response to an increase in intracellular calcium levels induced by the calcium ionophores A23187 or to an increase in intracellular cyclic 3',5'-monophosphate (cyclic AMP) levels caused by 8 bromo cyclic AMP was not significantly different from the control rat acini, suggesting that both Ca(2+)-dependent tyrosine kinase and nucleotide-activated kinases are not impaired. On the other hand, the responsiveness to phorbol ester TPA, which stimulates amylase secretion via a calcium-independent cascade by activating protein kinase C directly, was reduced in the camostate-treated rat acini compared with the controls. These results suggest the possibilities that the reduced amylase secretion in the camostate-treated rats is owing to alterations in both the transmembrane signal transduction and the phosphorylation of regulatory proteins by the Ca(2+)-independent, protein kinase C-dependent mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Induction of cerebral thrombosis with phenytoin in rats.

BACKGROUND AND PURPOSE: This study was conducted to explore whether intra-arterial infusion of phenytoin causes cerebral ischemia and to examine the mechanism of cerebral ischemia induced by phenytoin. METHODS: Ten rats were infused with phenytoin (150 microL, 3.75 mg) retrogradely from the left external carotid artery, followed by perfusion of carbon black transcardially. The removed brain was photographed from above, and the nonperfused area was compared with control rats (n = 10) with the use of an image analyzer. Eight animals with or without phenytoin treatment were perfusion-fixed for transmission electron microscopic analyses of cerebral vasculature. To determine the effect of tissue plasminogen activator (TPA) on phenytoin-infused rat cerebrum, 20 rats were treated with or without TPA (120,000 IU) 5 minutes after the phenytoin infusion (n = 10 each). RESULTS: All rats suffered from respiratory distress 25 to 40 minutes after the injection and received carbon black transcardially. The nonperfused area was seen in the territory of the left internal carotid artery. Thrombi were observed from arterioles to capillaries. Under electron microscopy, endothelial cells were partially exfoliated, and the vascular lumen was obstructed by thrombi predominantly consisting of platelets. Eight rats with TPA survived more than 60 minutes, whereas only 2 rats survived without the treatment (P < .005). Nonperfused areas were 7 +/- 5% and 50 +/- 11% of cerebral surface area in rats with and without TPA treatment, respectively (P < .001). CONCLUSIONS: Intra-arterial infusion of phenytoin results in a nonperfused area in rat cerebrum primarily due to thrombosis of arterioles and capillaries.

Animals↗