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Biomedical subjects

T Ohno

Publications and source records attributed to T Ohno.

At least 91 records · Page 5Linked to original sources

Transient prevention of ethanol-induced gastric lesion by capsaicin due to release of endogenous calcitonin gene-related peptide in rats.

Pre-exposure of the rat gastric mucosa to capsaicin reduced the mucosal lesion by 50% ethanol to 1/4. Treatment with an antagonist of calcitonin gene-related peptide (CGRP), CGRP (8-37), nullified the effect of capsaicin. During constant perfusion of the gastric lumen with physiological saline + pepstatin, the CGRP level was not increased by 50% ethanol, but it showed a peak (802.5 +/- 145.7 pg/2 min) after 1.6 mM capsaicin. Four minutes after capsaicin, the CGRP level was kept at a high level and the gastric lesion was markedly reduced by re-exposure of the mucosa to 50% ethanol. At 20-30 min after capsaicin, the CGRP levels returned to the resting level and the reddened area by 50% ethanol was not reduced. It was concluded that capsaicin transiently prevented the mucosal lesion through CGRP release.

Animals↗

The tumor cells in nodular lymphocyte-predominant Hodgkin disease are clonally related to the large cell lymphoma occurring in the same individual. Direct demonstration by single cell analysis.

Large cell lymphoma (LCL) sometimes occurs concurrently or subsequently in patients with nodular lymphocyte-predominant Hodgkin disease (NLPHD). Although there is evidence of a clonal relationship between LCL and NLPHD, there has been no direct demonstration that the lymphocytic and histiocytic (L&H) cells in NLPHD are related to the tumor cells in LCL. We identified 2 cases of NLPHD with an associated LCL. Single L&H cells, the Reed-Sternberg cell variants in NLPHD, were isolated from immunostained tissue sections by micromanipulation, and the immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of the cells was amplified by the polymerase chain reaction (PCR). The products were compared with those obtained from microdissected LCL cells using polyacrylamide gel electrophoresis and nucleotide sequencing. The IgH CDRIII sequences from the L&H cells were related to each other, but also showed nucleotide substitutions, consistent with a germinal center origin. The sequences from the L&H cells also were related to those from the corresponding LCL cells. We have provided direct evidence through sequence analysis of the IgH CDRIII that the L&H cells are clonally related to the corresponding LCL arising in 2 cases of NLPHD.

Adult↗

Quantitative trait loci for body weight in the intercross between SM/J and A/J mice.

We performed a genome-wide quantitative trait locus (QTL) analysis of body weight at 10 weeks of age in a population of 321 intercross offspring from SM/J and A/J mice, progenitor strains of SMXA recombinant inbred strains. Interval mapping revealed two significant QTLs, Bwq3 (body weight QTL3) and Bwq4, on Chromosomes (Chrs) 8 and 18 respectively, and five suggestive QTLs on Chrs 2, 6, 7, 15 and 19. Bwq3 and Bwq4 explained 6% of the phenotypic variance. The SM/J alleles at both QTLs increased body weight, though the SM/J mouse was smaller than the A/J mouse. On the other hand, four of the five suggestive QTLs detected had male-specific effects on body weight and the remainder was female-specific. These suggestive QTLs explained 5-6% of the phenotypic variance and all the SM/J alleles decreased body weight.

Alleles↗

Blood and liver lipid concentrations in EDS shrews exhibiting spontaneous non-insulin dependent diabetes mellitus (NIDDM).

The EDS (early-onset diabetes in suncus) colony was developed as a new laboratory colony of the musk shrew and is characterized by a high incidence of early-onset spontaneous non-insulin dependent diabetes mellitus (NIDDM). We examined blood lipid (triglyceride [TG], total cholesterol [TC], phospholipid [PL], free fatty acid [FFA]) and liver lipid (TG, TC, PL) concentrations to investigate the features of lipid metabolism in these animals. All lipid concentrations examined both in blood and liver of the diabetic shrews had a tendency toward higher values than those in non-diabetic shrews. The PL concentration was the only parameter that barely showed a significant difference. Values for all blood lipid concentrations in diabetic shrews at 7-9 months tended to be higher than those of 2-month-old diabetic shrews, although the difference was not significant. These findings indicate that diabetic EDS shrews exhibit a much milder defect of lipid metabolism induced by NIDDM than other rodent models.

Animals↗

Diabetic cataract of the musk shrew (Suncus murinus, Insectivora) exhibiting spontaneous non-insulin dependent diabetes mellitus (NIDDM).

The EDS colony, developed as a new laboratory colony of the musk shrew, is characterized by a high incidence of early-onset spontaneous non-insulin dependent diabetes mellitus (NIDDM). In this colony, a few diabetic shrews exhibited a cataract at 1 month after the onset of diabetes, and all diabetic shrews had bilateral cataracts at 5 months after the onset of diabetes. In contrast, cataractous animals were never observed among non-diabetic shrews. These results suggest that the cataract in the EDS colony is a diabetic complication.

Animals↗

Adrenal glands in small smooth-tailed tree shrew (Dendrogale murina).

Adrenal glands of small smooth-tailed tree shrews (Dendrogale murina), four males and two females, caught and fixed in Thailand were observed macroscopically and histologically. They were located at the cranio-medial sides of the kidney. They were elongated in shape and consisted of a cortex and medulla. The cortex could be subdivided into three zones by the cell arrangement and the morphology of nuclei, cytoplasm and cell strands, like in other mammalian species. The tree shrew seemed to share more morphological characteristics with some laboratory rodents than some of non-human primates.

Adrenal Glands↗

The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) induces lethality of human carcinoma cells by generation of reactive oxygen species.

2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) is an isocoumarin derivative that has recently entered clinical trials for evaluation as a p.o.-bioavailable, antiangiogenic molecule. NM-3 induces endothelial cell death at low microM concentrations by a nonapoptotic mechanism. The present studies have assessed the direct effects of NM-3 on human carcinoma cells. The results demonstrate that NM-3 treatment is associated with the generation of reactive oxygen species and loss of clonogenic survival. In concert with these findings, we show that exposure to NM-3 is associated with increases in expression of the p53 tumor suppressor. In human MCF-7 and ZR-75-1 breast cancer cells, NM-3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G1-S-phase, and necrotic cell death. Moreover, human PA-1 ovarian carcinoma and HeLa cervical carcinoma cells respond to NM-3 with the induction of apoptosis by a reactive oxygen species-dependent mechanism. These findings demonstrate that NM-3 has direct effects on carcinoma cells at clinically achievable concentrations and that this agent could be effective in targeting both the tumor and its vasculature.

Antineoplastic Agents↗

Psychophysiological correlates of social skills deficits in persons with schizophrenia.

Social skill deficits in schizophrenia profoundly affect patients' life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.

Adult↗

Coordination control of intramolecular electron transfer in boronate-bridged zinc porphyrin-diimide molecules.

Three sets of dyads, in which a zinc-porphyrin (ZP) electron donor is connected to an aromatic diimide electron acceptor,either pyromellitimide (PI) or naphthalene-1,8:4,5-tetracarboxylic acid diimide (NI), via a boronate-ester bridge, a piperidine bridge, and a 1,3-dioxolane bridge, respectively, were prepared for the purpose of control of intramolecular electron transfer (ET) by acid-base reactions at the connecting bridge. Boronate-ester bridge is a Lewis acidic site and confers a chance to regulate intramolecular ET reaction upon base coordination. This has been demonstrated by suppression of photoinduced ET from ZP to PI or NI in highly electron-pair donating solvents or upon addition of a fluoride anion. To extend this strategy to control of ET-path selectivity, we prepared triad 18, which consists of a ZP donor bearing NI and PI acceptors at similar distances through a boronate-ester bridge and an acetal bridge, respectively. Photoexcitation of 18 in a free form led to intramolecular ET from (1)()ZP preferentially to NI, but the ET path was completely switched toward PI in F(-)-coordinated form without a serious drop in the rate, constituting a novel ET-switching molecular system.

Journal Article↗

Molecular evolutionary analysis of the complete nucleotide sequence of hepatitis B virus (HBV) in a case of HBV infection acquired through a needlestick accident.

To elucidate needlestick transmission of hepatitis B virus (HBV), strains isolated from 1 physician who acquired HBV infection through a needlestick accident and 3 patients with chronic hepatitis B (donor patients A, B, and C) were tested using molecular evolutionary analysis based on full-length HBV genomic sequences. Nucleotide sequences of these isolates were aligned with 55 previously reported full-length genomic sequences. Genetic distances were estimated using the 6-parameter method, and phylogenetic trees were constructed using the neighbor-joining method. Strains isolated from patient A and the recipient pair were clustered within a closer range of evolutionary distances than were strains recovered from the recipient pair and patients B and C. Furthermore, strains from patient A and the recipient were also clustered on the S gene sequences of HBV. These results demonstrated that patient A alone was the source of direct transmission to the recipient. This approach can be used to investigate the transmission route of HBV.

Adult↗

A sequence-ready BAC clone contig of human chromosome 10p15 spanning the loss of heterozygosity region in glioma.

Deletion of chromosome 10 is one of the most common chromosomal alterations in glioma. At 10p15, the telomeric region of the short arm of chromosome 10, loss of heterozygosity (LOH) has been frequently observed by microsatellite analysis, suggesting the presence of a tumor suppressor gene. We examined LOH in 34 gliomas on chromosome 10, and frequent LOH on 10p was detected on 10p15, in agreement with deletion mapping studies on chromosome 10. We then constructed a bacterial artificial chromosome (BAC) clone contig covering the critical region, which spanned the interval between D10S249 and D10S533 on 10p15. The map contained 68 BAC clones connected by 74 sequenced tag sites (STSs) and covered approximately 2.7 Mb, with one gap. A total of 74 STSs, including 6 microsatellite markers, 29 expressed sequenced tags (ESTs), and 39 BAC end STSs, were physically arranged. Twenty-eight ESTs were mapped in the interval between D10S249 and D10S559 (approximately 1200 kb), and another EST was mapped in the interval between D10S559 and D10S533 (approximately 1300 kb). This sequence-ready BAC clone contig map will be a basic resource for high-quality sequencing and positional cloning of the putative tumor suppressor gene at 10p15 in glioma.

Base Sequence↗

Ultrasound facilitates transduction of naked plasmid DNA into colon carcinoma cells in vitro and in vivo.

One approach to improve the efficacy of in vivo gene therapy, with the aim at enhancing expression of the transgene, involves utilization of mechanical forces to facilitate transduction of DNA into cells. In this study, we evaluated the feasibility of mechanical insonation in gene transfers with naked DNA plasmid loading both in vitro and in vivo. We used an ultrasound probe, which can focus the ultrasonic beam in the exit zone of the probe. The reporter pcDNA3-lacZ plasmid, containing Escherichia coli lacZ or the beta-galactosidase gene (beta-gal), and the neomycin 3'-phosphotransferase gene (neo), was used for evaluation of transfer efficiency. Expression of beta-gal in MC38 murine colon carcinoma cells was measured after insonation of 20 W/cm2 with continuous 1.0-MHz wave exposure. In a transient assay, significant numbers of cells were transduced with the beta-galactosidase gene. After cells were treated with geneticin, we also observed a difference in colonogenicity between noninsonated and insonated groups. When MC38 cells were implanted in syngeneic mice and plasmid was injected, the insonation that followed facilitated beta-galactosidase expression. These results indicate that insonation represents a potential approach for gene therapy when combined with naked DNA plasmid injection.

Adenocarcinoma↗

Simultaneous analysis of anthranilic acid derivatives in pharmaceuticals and human urine by high-performance liquid chromatography with isocratic elution.

A high-performance liquid chromatographic (HPLC) method for simultaneous determination of mefenamic acid (MFA), flufenamic acid (FFA) and tolfenamic acid (TFA) is presented for application to pharmaceuticals and human urine. Isocratic reversed-phase HPLC was employed for quantitative analysis using tetra-pentylammonium bromide (TPAB) as an ion-pair reagent. Urine samples were purified by solid-phase extraction using a silica-based strong anion-exchanger, Bond-Elut SAX cartridge. The HPLC assay was carried out using a Wakosil ODS 5C18 column (5 microm, 150x4.6 mm I.D.). The mobile phase consisted of 1.9 g of TPAB dissolved in 1:1 of a mixture of acetic acid-sodium acetate buffer solution, pH 5.0, and acetonitrile (11:9, v/v). The calibration curves of MFA, FFA and TFA showed good linearity in the concentration range of 33-167 microg/ml with a wavelength of 280 nm for pharmaceuticals, and in the low concentration range (1.7-30.1 microg/ml) with a wavelength of 230 nm for biological fluids. The correlation coefficients were better than 0.9999 in all cases. The lower limits of detection (defined as a signal-to-noise ratio of about 3) were approximately 2 ng for MFA, 3.5 ng for FFA and 2.5 ng for TFA. The procedure described here is rapid, simple, selective and is suitable for routine analysis of pharmaceuticals and pharmacokinetic studies in human urine samples.

Calibration↗

Apraxic agraphia due to thalamic infarction.

The authors report a patient of pure apraxic agraphia with normal praxis due to left thalamic infarction. 15O-gas-PET showed reduced oxygen metabolism in the left thalamus and the left dorsolateral premotor area, while MRI and 11C-fulumazenil-PET showed no remarkable lesions in the frontal cortex. The patient's word imaging remained normal. The authors hypothesize that thalamic destruction causes pure apraxic agraphia by exerting a remote effect on left dorsolateral premotor area and blocking somewhere between graphemic area and motor programming.

Aged↗

Tumor formation suppressed in gammadeltaT knock-out mice.

Tumor formation was examined in mice in which the beta-chain gene of alphabetaT was knocked out (alphabetaT-KO mice) or the delta-chain gene of gammadeltaT was knocked out (gammadeltaT-KO mice). Development of Hepa 1-6 cell hepatoma was observed in six of six alphabetaT-KO mice, in four of six wild-type mice, and in only one of six gammadeltaT-KO mice. These results imply that gammadeltaT cells play a role in suppression of killer cell activity in tumor-bearing mice.

Animals↗

Binding of human mitochondrial transcription factor A, an HMG box protein, to a four-way DNA junction.

Mitochondrial transcription factor A (mtTFA), the only known transcription factor in mitochondria, is also implicated in maintenance of mitochondrial genome although little is elucidated about its molecular basis. mtTFA is a member of HMG box proteins family. Some HMG proteins bind with high affinity to four-way DNA junctions that mimic a Holliday structure, a putative intermediate in DNA recombination. To explore possible involvement of a Holliday-like structure in the maintenance of mitochondrial genome, we examine the binding of recombinant human mtTFA to a synthetic four-way DNA junction. The human mtTFA binds to the four-way DNA junction with an approximately 10-fold higher affinity than to the corresponding linear duplex DNA and with essentially the same affinity as to a 40-mer DNA containing the human mitochondrial light strand promoter sequence. The mtTFA binds to the four-way as a monomer. Both of the two HMG box domains of human mtTFA are required for the high affinity binding to the four-way junction.

Base Sequence↗

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Journal Article↗