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Biomedical subjects

T Yokota

Publications and source records attributed to T Yokota.

At least 19 recordsLinked to original sources
PubMed2003

Down-regulation in human cancers of DRHC, a novel helicase-like gene from 17q25.1 that inhibits cell growth.

Frequent observations of allelic loss in chromosomal band 17q25.1 in a variety of human cancers have suggested that one or more tumor suppressor genes are normally present in this region. Moreover, a locus responsible for hereditary focal non-epidermolytic palmoplantar keratoderma (tylosis oesophageal cancer; TOC), a condition associated with esophageal cancer, has been mapped to the same band. During efforts to sequence, by shot-gun methods, a 1 Mb target region that we had defined as the DNA segment harboring the putative tumor suppressor gene(s) involved in these events, we identified a novel cDNA, DRHC (down-regulated in human cancers), that showed reduced expression in 28 of 95 (29%) cell lines derived from a variety of human cancers. The full-length cDNA, 6275 bp long, was expressed predominantly in thymus and brain. The predicted 1942-amino-acid product exhibited significant sequence homology to yeast enzymes belonging to the DEAD-helicase superfamily, and appeared to be a Uvr/Rep helicase with a DEXDc consensus domain. Transfection of a DRHC expression vector inhibited growth of cancer cells in liquid medium or soft agar. The results suggest that loss of expression of DRHC may play a role in human carcinogenesis.

Blotting, Northern↗
PubMed2003

Exercise training improves ageing-induced decrease in eNOS expression of the aorta.

AIMS: Ageing impairs endothelial function such as the regulation of vascular tone. The release of nitric oxide (NO), which has a potent vasodilator effect and antiatherosclerotic property, is decreased in the aorta of aged rats. Exercise training, however, has been reported to increase the expression of endothelial NO synthase (eNOS) in the aorta of young rats. In aged rats, it is not known whether the expression of eNOS is altered by exercise training. We hypothesized that exercise training would improve the ageing-induced decrease in eNOS expression in vessels, and examined the messenger RNA (mRNA) and protein expression of eNOS in the aorta of sedentary-young rats (sedentary-young group; 4 months old), sedentary-aged rats (sedentary-aged group; 23 months old), and swim-trained aged rats (training-aged group; 23 months old, swimming training for 8 weeks, 5 days week(-1), 90 min day(-1)). RESULTS: Body weight was significantly lower, and citrate synthase activity in the epitrochlearis muscle was significantly higher in the training-aged group compared with the sedentary-aged group. The mRNA expression of eNOS in the aorta was significantly higher in the training-aged group than in the sedentary-aged group, while it was significantly lower in both the sedentary-aged and training-aged groups than in the sedentary-young group. The expression of eNOS protein in the aorta was also significantly higher in the training-aged group than in the sedentary-aged group, while it was also significantly lower in the sedentary-aged group, but not in the training-aged group, than in the sedentary-young group. CONCLUSION: The present results revealed that the production of eNOS in the aorta decreases with ageing, and that the decreased production is increased by exercise training in aged rats, which may produce beneficial effects on the impaired cardiovascular system caused by ageing.

Aging↗
PubMed2003

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Acute Disease↗
PubMed2002

High voltage electrical stimulation of the proximal hypoglossal nerve in normal subjects.

OBJECTIVES: It is often difficult to stimulate the proximal hypoglossal nerve by magnetic occipital stimulation, even in normal subjects. Therefore, we tested an improved method of stimulating the proximal hypoglossal nerve, using high voltage electrical stimulation. METHODS: The proximal hypoglossal nerve was activated by high voltage electrical stimulation using surface electrodes over the occipital skull. The compound muscle action potential (CMAP) was recorded from the lingual muscles using surface electrodes in 10 normal subjects. CMAP and F waves produced by distal hypoglossal nerve stimulation and motor evoked potentials produced by transcranial magnetic stimulation were also recorded. RESULTS: When the anode electrode was placed at the mastoid process and the cathode below the inion, the unilateral proximal hypoglossal nerve was readily stimulated supramaximally in all the subjects. The CMAP latency was the same as that obtained with magnetic occipital stimulation. The central motor conduction time (CMCT) calculated from the proximal CMAP was 4.1+/-0.4 ms in the contralateral corticobulbar tract and 4.4+/-0.4 ms in the ipsilateral. The CMCT calculated from the minimal F wave latency was 3.3+/-0.2 ms. CONCLUSIONS: The high voltage electrical stimulation is a useful method for stimulating the proximal hypoglossal nerve to estimate the CMCT of the corticobulbar tract.

Adult↗
PubMed2002

Prognostic factors of gastric cancer tumours of less than 2 cm in diameter: rationale for limited surgery.

BACKGROUND: A recent trend in the surgical treatment of patients with early gastric cancer in Japan has been to limit surgery to an extent that ensures complete cure and improvement in the patient's quality of life. If a gastric cancer tumour can be completely eradicated by laparoscopic surgery, the patient can be cured of cancer without major operative stress. A small gastric cancer tumour of less than 2 cm in diameter is an indication for laparoscopic surgery, but little is known about what protocol of surgical treatment is appropriate for this type of tumour. PATIENTS AND METHODS: The clinicopathological features of 150 patients with gastric cancer tumour of less than 2 cm in diameter were reviewed retrospectively from hospital records between 1985 and 1995. The results of retrospective analysis of clinicopathological data of 24 patients with advanced cancer were compared with those of 126 patients with early cancer. Univariate and multivariate analyses of patients with small gastric cancer tumours were performed to evaluate the prognostic significance of clinicopathological features. RESULTS: A significant difference was seen between the gross tumour appearances in the two groups; Borrmann type-4 tumours were more common in the advanced group. Lymph-node metastasis, lymphatic vessel invasion and vascular invasion were found more frequently in the advanced cancer group than in the early cancer group. Scirrhous type was more common in the advanced cancer group. In univariate analysis, unfavourable prognostic factors included deep cancer invasion, presence of lymph-node metastasis, lymphatic invasion and vascular invasion. Using Cox's proportional hazard regression model, only nodal involvement emerged as an independent statistically significant prognostic parameter associated with long-term survival. CONCLUSION: Laparoscopic surgery should not be performed on tumours that are Borrmann type in macroscopic appearance and scirrhous-type histologically. Lymph-node metastasis is an independent prognostic factor. We recommend laparoscopic surgery involving local resection of the stomach without lymphadenectomy for small, early gastric cancer tumours that satisfy the criteria mentioned above. However, the validity of this recommendation should be tested by a prospective randomized control trial in the future.

Aged↗
PubMed2002

Pharmacokinetics of a benzodithiin (RD3-0028) following aerosol treatment in rat.

1. RD3-0028, a benzodithiin compound, has potent antiviral activity against respiratory syncytial virus (RSV) in cell culture. The compound also inhibits growth of RSV and improves pathologic changes of interstitial pneumonia in the immunosuppressed mouse when delivered by small-particle aerosol. 2. In the present study, the absorption, distribution and excretion of 14C-RD3-0028 were compared in rat following either a single aerosol treatment or oral administration. 3. The plasma concentration was maintained at the same level from 5 min to 1 h, and decreased with a half-life of 2.2 +/- 0.1 h for 1-8 h. 4. The excretion of radioactivity in the urine and faeces at 24 h after aerosol treatment was 89.3 and 4.5%, respectively, indicating that almost all the radioactivity was rapidly excreted in the urine. The excretion of total radioactivity was 98.9% within 168 h. 5. The concentrations of radioactivity in the lung and trachea following aerosol treatment were higher than those in other tissues, and were detected even at 72 h. 6. These results suggest that the aerosol treatment might be useful for delivering RD3-0028 to the respiratory tract of RSV-infected patients.

Administration, Oral↗
PubMed2001

Age and stage dependency of estrogen receptor expression by lymphocyte precursors.

Sex steroids negatively regulate B lymphopoiesis in adult mice. Paradoxically, lymphocytes arise during fetal life, when estrogen levels are high and maternal lymphopoiesis is suppressed. Here we demonstrate that embryonic B lymphopoiesis was unaffected by estrogen, but sensitive to glucocorticoids. Both fetal and adult precursors contained glucocorticoid receptor transcripts, but only adult precursors expressed estrogen receptor alpha and beta together with the androgen receptor. Fetal hematopoietic cells did not efficiently acquire functional estrogen receptors after transplantation to irradiated adult mice. Sex steroid receptors were also expressed in a stage- and developmental age-dependent fashion in human precursors. A developmental switch in responsiveness of hematopoietic cells to sex steroids may be essential for formation of the immune system.

Age Factors↗
PubMed2001

Delayed-onset ataxia in mice lacking alpha -tocopherol transfer protein: model for neuronal degeneration caused by chronic oxidative stress.

alpha-Tocopherol transfer protein (alpha-TTP) maintains the concentration of serum alpha-tocopherol (vitamin E), one of the most potent fat-soluble antioxidants, by facilitating alpha-tocopherol export from the liver. Mutations of the alpha-TTP gene are linked to ataxia with isolated vitamin E deficiency (AVED). We produced a model mouse of AVED by deleting the alpha-TTP gene, which showed ataxia and retinal degeneration after 1 year of age. Because the brain alpha-TTP functions in maintaining alpha-tocopherol levels in the brain, alpha-tocopherol was completely depleted in the alpha-TTP(-/-) mouse brain, and the neurological phenotype of alpha-TTP(-/-) mice is much more severe than that of wild-type mice when maintained on an alpha-tocopherol-deficient diet. Lipid peroxidation in alpha-TTP(-/-) mice brains showed a significant increase, especially in degenerating neurons. alpha-Tocopherol supplementation suppressed lipid peroxidation and almost completely prevented the development of neurological symptoms. This therapy almost completely corrects the abnormalities in a mouse model of human neurodegenerative disease. Moreover, alpha-TTP(-/-) mice may prove to be excellent animal models of delayed onset, slowly progressive neuronal degeneration caused by chronic oxidative stress.

Animals↗
PubMed2001

Cloning of full-length genomic DNA encoding human FcepsilonRI alpha-chain and its transcriptional regulation.

Two novel exons, named exon 1A and exon 2A, were found at 18.4 and 12.6 kb upstream from the exon known as the first exon of human FcepsilonRI alpha-chain gene. Transcription from the promoter present in the upstream of exon 1A was decreased by mutations introduced into the "first intron" between exon 1A and exon 2A, suggesting the presence of an intronic regulatory element in the intron. Consistent with this, electrophoretic mobility shift assay revealed the presence of a nuclear factor which bound the region in FcepsilonRI alpha-chain positive cells.

Base Sequence↗
PubMed2001

Endogenous nitric oxide-mediated relaxation and nitrinergic innervation in the rabbit prostate: the changes with aging.

BACKGROUND: Nitric oxide (NO) plays the key role in the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation of prostate. We tried to determine whether nitrinergic innervation of the prostate is reduced with aging, and whether a reduction of this innervation alters the relaxant properties of prostatic tissue. METHODS: The prostate isolated from young rabbits at the age of 3 months and aged rabbits at the age of 24 months was used. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of prostate. Nitrinergic nerves were identified histochemically by the presence of NADPH diaphorase reactivity. RESULTS: The prostate weighed 0.34 +/- 0.06 g in the young and 0.78 +/- 0.13 g in the aged (P < 0.01). Electrical stimulation caused frequency-dependent relaxation that was inhibited by N-nitro-L-arginine and increased by L-arginine. Maximum relaxant rates of noradrenaline-induced tone were 41.3 +/- 1.8% and 22.7 +/- 0.6% in the young and the aged (P < 0.01), respectively. Exogenous NO caused concentration-dependent relaxation of the prostate. Both relaxation induced by electrical stimulation and exogenous NO were inhibited by LY83583 (a guanylate cyclase inhibitor). In all specimens, NADPH diaphorase activity was observed in the smooth muscle layer of the prostatic stroma and capsule. However, NADPH diaphorase positive nerves were significantly less in the aged than in the young (P < 0.01). CONCLUSIONS: As a result of these findings, it is suggested that both NO-mediated relaxation and nitrinergic innervation are reduced with aging in this animal model.

Aging↗
PubMed2001

Inhibitory effect of oxcarbazepine on high-frequency firing in peripheral nerve fibers.

We assessed the effects of oxcarbazepine, an antiepileptic derivative of carbamazepine, on discharges in single cutaneous afferent fibers produced by repetitive high-frequency stimulation (mimicking the abnormal excitation of peripheral nerves in neuropathic pain and paresthesia). After intravenous administration of oxcarbazepine, the later responses in the train dropped out without the earlier ones being affected and, thus, the total number of spikes decreased. The latency of the responses to an individual pulse was unchanged. These results, which indicate that oxcarbazepine inhibits the generation of high-frequency firing without affecting impulse conduction, suggest that this drug may be useful against neuropathic pain and paresthesia.

Animals↗
PubMed2001

A novel chordin-like protein inhibitor for bone morphogenetic proteins expressed preferentially in mesenchymal cell lineages.

Chordin is a bone morphogenetic protein (BMP) inhibitor that has been identified as a factor dorsalizing the Xenopus embryo. A novel secreted protein, CHL (for chordin-like), with significant homology to chordin, was isolated from mouse bone marrow stromal cells. Injection of CHL RNA into Xenopus embryos induced a secondary axis. Recombinant CHL protein inhibited the BMP4-dependent differentiation of embryonic stem cells in vitro and interacted directly with BMPs, similar to chordin. However, CHL also weakly bound to TGFbetas. In situ hybridization revealed that the mouse CHL gene, located on the X chromosome, was expressed predominantly in mesenchyme-derived cell types: (1) the dermatome and limb bud mesenchyme and, later, the subdermal mesenchyme and the chondrocytes of the developing skeleton during embryogenesis and (2) a layer of fibroblasts/connective tissue cells in the gastrointestinal tract, the thick straight segments of kidney tubules, and the marrow stromal cells in adults. An exception was expression in the neural cells of the olfactory bulb and cerebellum. Interestingly, the spatiotemporal expression patterns of CHL were distinct from those of chordin in many areas examined. Thus, CHL may serve as an important BMP regulator for differentiating mesenchymal cells, especially during skeletogenesis, and for developing specific neurons.

Alternative Splicing↗
PubMed2001

Identification, tissue expression, and chromosomal position of a novel gene encoding human ubiquitin-conjugating enzyme E2-230k.

Through large-scale human genome mapping and sequencing of a region at chromosome 17q25.1 that is of particular interest because genes associated with breast, ovarian, and esophageal cancer are likely to be located there, we isolated the cDNA of a novel member of the family of ubiquitin-conjugating enzymes. The predicated peptide showed 97% identity in amino-acid sequence to murine ubiquitin-conjugating enzyme E2-230k (Mus UBE2-230k). The human cDNA consisted of 4878 nucleotides with an open reading frame encoding 1138 amino acids; the approximately 5 kb transcript was expressed predominantly in skeletal muscle and heart. The predicted UBE2-230k peptide contained a motif typical of the UBC domain that has been implicated in the ubiquitin-dependent proteolytic system and related pathways.

Amino Acid Sequence↗