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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 127 records · Page 7Linked to original sources
PubMed2000

Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV).

The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human cells. In this study we have analyzed endothelial cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic stem cells and bone marrow stromal cells for PERV transmission. We now provide evidence for primary human endothelial cells, vascular fibroblasts, and mesangial cells to be susceptible to PERV transmission. PERV infection was productive in endothelial cells and mesangial cells. Our data confirm and extend former reports concerning the PERV infection of human cells. The PERV infection of different primary human cells represents further significant evidence for a viral risk during xenotransplantation. In this context, special attention should be directed towards productive infection of human endothelial cells: in the setting of xenotransplantation this cell type will have close contact with porcine cells and PERV particles.

Animals↗
PubMed2000

Experimental study on skin sensitization potencies and cross-reactivities of hair-dye-related chemicals in guinea pigs.

In screening patch testing of hairdressers with occupational contact dermatitis, multiple positive reactions to hair dye-related chemicals, such as p-phenylenediamine (PPD), p-toluenediamine x 2HCl (PTD) and p-aminophenol (PAP), a fabric dye p-aminoazobenzene (PAB), and a tar dye Sudan III, were frequently encountered. To investigate individual skin sensitization potency and the cross-reactivities among above chemicals, a guinea pig maximization test with the above 5 chemicals was performed. In each group, 6 animals were induced with one of the chemicals at 0.1% concentration by intradermal injection and at 1.0% by topical application. The animals were challenged with all 5 chemicals in concentrations of dilution by 10 from 0.1% to 0.001%. Under the conditions of 0.1% challenges, similar sensitization potencies were observed in PPD (6/6), PTD (6/6), PAP (5/6) and PAB (6/6) groups, but no positive reactions were elicited in the Sudan III group. The cross-reactivities to PPD were confirmed in the animals challenged with PTD (6/6), PAP (6/6), PAB (6/6) and Sudan III (3/6). In the PTD-induced group, positive responses to cross-challenges were elicited by PPD (5/6), PAP (3/6), PAB (5/6) and Sudan III (1/6). The cross-reactivities to PAP were observed only with PPD (2/5) and PAB (5/5). PAB-induced animals responded only to PPD (1/6). The results indicate that all these chemicals except Sudan III are strong sensitizers. Their cross-reactivities are different in sensitized conditions, respectively. The cross-reactivities to PPD were higher than those to PTD, PAP and PAB.

Aminophenols↗
PubMed2000

Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.

Adult↗
PubMed2000

FK506-induced intractable leukoencephalopathy following allogeneic bone marrow transplantation.

FK506-related leukoencephalopathy has been reported to be reversible and readily treated by discontinuation or reduction of FK506. We describe two pediatric cases of FK506-related leukoencephalopathy following allogeneic bone marrow transplantation, which could not be readily controlled. These cases show that FK506-related leukoencephalopathy is not always reversible, and patients may develop epilepsy. Bone Marrow Transplantation (2000) 25, 331-334.

Acute Disease↗
PubMed2000

Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat.

Phthalate esters, now regarded as endocrine disruptors, are widely used in the plastics industry. In particular, di-(2-ethylhexyl) phthalate (DEHP) is produced in large quantities, and is used in blood storage bags, catheters and haemodialysis instruments. Previous studies have demonstrated that treatment of rats with DEHP induces testicular atrophy with liver enlargement, although the precise nature and mechanism of the action of DEHP on these organs remains unclear. In the present study, we produced an experimental model of DEHP-induced spermatogenic disturbance in rats by feeding them a DEHP-containing diet. Liver enlargement occurred in rats fed either a 1 or 2% DEHP-containing diet. However, testicular atrophy accompanied by aspermatogenesis was induced by feeding with the 2% but not with the 1% DEHP-containing diet. This suggests that the critical DEHP dose for gonadotoxicity is higher than that for hepatotoxicity. Using the 2% DEHP-dose, the effect of simultaneous administration of antioxidant vitamins (= vitamins C and E) was next examined. It was found that the vitamin supplementation significantly prevented the testicular injury. The results suggest that antioxidant vitamins can protect the testes from DEHP-toxicity.

Animals↗
PubMed2000

Increase of brain-derived neurotrophic factor gene expression in NG108-15 cells by the nuclear isoforms of Ca2+/ calmodulin-dependent protein kinase II.

We have reported that the delta3 isoform of Ca2+/ calmodulin-dependent protein kinase II (CaM kinase II) is abundant in the nucleus in cerebellar granule cells. To examine the possibility that the nuclear isoforms of CaM kinase II are involved in the expression of brain-derived neurotrophic factor (BDNF), we transiently overexpressed the delta3 isoform in NG108-15 cells. The quantitative RT-PCR analysis revealed that rat cerebellum and NG108-15 cells expressed the exon IV-containing mRNA of BDNF (exon IV-BDNF mRNA) more than the exon III-BDNF mRNA. Treatment of NG108-15 cells with Bay K 8644 increased both exon III- and exon IV-BDNF mRNAs, and overexpression of the 83 isoform potentiated the expression of the exon IV-BDNF mRNA. The potentiation was not observed in the cells that were overexpressed with either the 61 isoform, a nonnuclear isoform, or the inactive mutant of the delta3 isoform. We constructed the luciferase reporter gene following the promoter upstream of exon IV and confirmed that overexpression of the delta3 isoform increased luciferase gene expression. Double-immunostaining of NG108-15 cells with the antibodies to CaM kinase II and BDNF clearly showed that BDNF was highly expressed in the cells that were overexpressed with the delta3 isoform or the alphaB isoform, another nuclear isoform of CaM kinase II. These results suggest that the nuclear isoforms of CaM kinase II are involved in the expression of BDNF.

Animals↗
PubMed2000

Identification of the isoforms of Ca(2+)/Calmodulin-dependent protein kinase II in rat astrocytes and their subcellular localization.

Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) occurs in astrocytes as well as in neurons in brain. We have reported that CaM kinase II is involved in the regulation of cytoskeletal proteins and gene expression in astrocytes. In this study, we identified all isoforms of CaM kinase II in astrocytes and examined their subcellular localization. When we amplified the isoforms of four subunits by RT-PCR followed by the "nested" PCR, totally 10 isoforms were obtained. Immunoblot analyses with five types of antibodies against CaM kinase II indicated that the most abundant isoform was delta2. Immunostaining suggested that the delta2 isoform was localized predominantly at the Golgi apparatus. The localization of the delta2 isoform at the Golgi apparatus was also observed in NG108-15 cells. We overexpressed all isoforms that contained the nuclear localization signal to examine their nuclear targeting in NG108-15 cells. In contrast to the alphaB and delta3 isoforms that entered the nucleus, as reported, the gammaA isoform was excluded from the nucleus in the transfected NG108-15 cells. These results suggest that the 15-amino acid insertion following the nuclear localization signal inhibits the nuclear targeting of the gammaA isoform.

Amino Acid Sequence↗
PubMed2000

Effects of box weight, vertical location and symmetry on lifting capacities and ratings on category scale in Japanese female workers.

The aim was to clarify the effects of box weight, vertical location and symmetry on the lifting capacities and subjective burden in Japanese female workers with manual material handling tasks. Sixteen healthy females were tested. They performed 12 different lifting tasks (three heights * two weights * two symmetries). It is difficult for Japanese women to exert dynamic force in lifting a 15-kg weight from the elbow to the shoulder level. A remarkable increase was observed in heart rate and category scale with ratio properties (CR-10) on large muscle group in lifting a 15-kg weight as compared with lifting a 10-kg one. Judging from calculation of the Recommended Weight Limit using the application manual by the National Institute for Occupational Safe and Health, it was also suggested that lifting the 15-kg weight from the elbow to the shoulder level was difficult for female workers. Not only peak force, but also the average upward acceleration and peak velocity were lower in asymmetric liftings than those in symmetric liftings. CR-10 for the left back and right thigh were also higher in 90 degrees right lateral plane lifting than in the mid-sagittal plane. Thus, asymmetric lifting was supposed to impose higher stress on the back contralaterally and thigh ipsilaterally to the location of the weight.

Adult↗
PubMed2000

Resistance induction in barley coleoptile cells by intracellular pH decline.

Cytoplasmic acidification in suspension-cultured plant cells has been characterized as a common intracellular response of some kinds of plant cells to elicitors. Expression of various defense genes in these cells has been increased by the cytoplasmic acidification itself without treatment by elicitors. It is not evident, however, whether or not cells with acidified cytoplasm actually exhibit resistance to the pathogen because of the lack of an adequate infection system between cultured plant cells and some pathogens. Using barley coleoptiles rather than suspension-cultured cells, we demonstrated both detection of cellular pH decline and increased resistance to Blumeria graminis. The cytoplasmic pH of barley coleoptile cells floated on 1 mM citrate buffer (CB), pH 4.0, became 0.5 unit lower than that of cells floated on 1 mM CB, pH 8.0, within 30 min after treatment. The penetration efficiency of B. graminis into the coleoptile was decreased in a pH-dependent manner; that is, when the coleoptiles were floated on 1 mM CB, pH 8.0, the penetration efficiency of the fungi was about 80%. In contrast, when the coleoptiles were floated on acidic buffers, the penetration efficiency decreased in parallel the decline of pH and the penetration efficiency reached 0% when coleoptiles were floated on 1 mM CB, pH 4.0. Morphogenesis of appressoria on the coleoptiles floating on CB was not influenced. The lowered penetration efficiency at lower pH was partially cancelled when the barley coleoptiles were irradiated with UV for 5 min prior to B. graminis inoculation. These findings suggest that the decline in cytoplasmic pH in barley coleoptile cells increases resistance to the pathogenic fungus B. graminis.

Cytoplasm↗
PubMed2000

Reproductive toxicity of 1-bromopropane, a newly introduced alternative to ozone layer depleting solvents, in male rats.

1-Bromopropane has been newly introduced as an alternative to ozone-depleting solvents. We aimed to clarify its dose-dependent reproductive toxicity in male rats. Thirty-six Wistar male rats were randomly divided into 4 groups of 9. The groups were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 12 weeks. Epididymal sperm indices were evaluated after a 12-week exposure. The testes, epididymides, seminal vesicle, prostate, and other organs were weighed and examined histopathologically. Spermatogenic cells, in stage VII seminiferous tubules, and retained spermatids, at the basal region of stages IX-XI seminiferous epithelium, were counted. Plasma testosterone levels were measured by radioimmunoassay. The testicular weight did not significantly change, but the weight of epididymides, seminal vesicle, and prostate dose-dependently decreased. The weight of seminal vesicle decreased significantly at the lowest concentration of 200-ppm and over. 1-Bromopropane induced a dose-dependent decrease in the epididymal sperm count and in motility, as well as an increase in tailless sperm and sperm with an immature head shape. The spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids did not decrease significantly at stage VII. Retained, elongated spermatids near the basement membrane at the postspermiation stages IX-XI increased dose-dependently. Plasma testosterone levels significantly decreased at the 800-ppm dosage. 1-Bromopropane caused failure of spermiation. Its reproductive toxicity is different from that of 2-bromopropane, which specifically impairs spermatogonia. Thus, this solvent may have serious reproductive toxic effects in men, and should be used very cautiously in the workplace.

Administration, Inhalation↗
PubMed2000

1-Bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure.

1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace.

Administration, Inhalation↗
PubMed2000

Testosterone-dependent primer pheromone production in the sebaceous gland of male goat.

To test the hypothesis that the primer pheromone responsible for inducing the "male effect" is produced in the sebaceous gland androgen dependently, we examined the correlation between morphological changes of sebaceous glands and the pheromone activity in skin samples taken from castrated goats that had been treated with testosterone. Five castrated goats were implanted s.c. with testosterone capsules to maintain physiological levels of plasma testosterone for four weeks. Skin samples were obtained from the head region on Day 0 (the day of testosterone implant), Day 7, Day 14, Day 28 (the day of testosterone removal), Day 36, Day 42, and Day 56. Matched blood samples were also collected for measurement of testosterone concentration. The pheromone activity of the ether-extracts of the upper dermal layer containing sebaceous glands was assessed by its stimulatory effect on the hypothalamic GnRH pulse generator, which was monitored for changes of specific multiple unit activity (MUA) in ovariectomized estradiol-primed goats as described previously. The sebaceous gland enlarged during the testosterone treatment but reduced in size after testosterone removal. The pheromone activity first appeared in 2 out of 5 goats on Day 7 and in all the 5 goats by Day 28. Fourteen days after testosterone removal (Day 42), the pheromone activity was no longer detectable in any of the 5 goats. In short, the sebaceous gland size and the pheromone activity shifted almost in parallel. The present results provide strong support for the view that the primer pheromone is produced testosterone dependently in the sebaceous gland of the male goat.

Animals↗
PubMed2000

Lichen planus with involvement of all twenty nails and the oral mucous membrane.

A 57-year-old man had had deformities of all ten fingernails for one and a half years before presentation and deformities of all ten toenails for the previous six months. The surfaces of the nails were rough, with excessive longitudinal striations. The bases of the nails were slightly hypertrophic, and the tips were atrophic and itchy. A longitudinal nail biopsy including the nail matrix revealed the typical histology of lichen planus. Reticulated pigmentation, maceration, and erosion on the buccal mucous membrane were also discovered. Histological analysis of the buccal mucous membrane revealed lichen planus intermingled with eosinophils. Immunological blood analysis revealed elevated CD4+ T cells and CD4/CD8 ratio. He worked as a tinsmith and had dental metal. The metal series patch test revealed positive reactions to chromate and tin. Treatment with systemic steroids was quite effective in treating the nail lesions.

Atrophy↗
PubMed2000

In vitro antitumor activity, intracellular accumulation, and DNA adduct formation of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum (II) suspended in lipiodol.

SM-11355, cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum (II), is a lipophilic platinum complex under clinical development that targets primary hepatocellular carcinoma using Lipiodol as a carrier. SM-11355 was compared with cisplatin (CDDP) using an in vitro evaluation system capable of examining the release characteristics and the cytotoxicity of drugs suspended in Lipiodol. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) and CDDP suspended in Lipiodol (CDDP/Lipiodol) showed cytotoxic activity against rat ascites hepatoma AH-109A cells in a dose-dependent manner. Their IC50 values following 7-day exposure were 22.3 and 0.40 microg/ml, respectively. Following the subsequent 7-day exposure, from day 7 to day 14 after preparation of the suspension, SM-11355/Lipiodol showed an almost equivalent activity, but CDDP/Lipiodol did not show any activity at all. SM-11355/Lipiodol showed a sustained release into the culture medium over the course of a 14-day exposure. Following the exposure to CDDP/Lipiodol, the platinum concentration in the medium was at its maximum on the first day and remained constant thereafter. Intracellular platinum uptake and formation of platinum-DNA adducts were dependent on the release characteristics of each drug suspension. For SM-11355/Lipiodol, the drug release, intracellular drug uptake, and formation of platinum-DNA adducts over the course of the subsequent 7-day exposure were similar to those observed during the first 7 days. DPC, one of the compounds released from SM-11355/Lipiodol, was taken up by cells and showed formation of platinum-DNA adducts. Thus, this study suggests that SM-11355/Lipiodol may release active platinum compound(s) that bind to nuclear DNA and mediate the cytotoxic activity of SM-11355/Lipiodol.

Animals↗
PubMed2000

Cytotoxicity of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)]-platinum (II) suspended in Lipiodol in a newly established cisplatin-resistant rat hepatoma cell line.

The cytotoxic activity of cis-[((1R,2R)-1,2-cyclohexanediamine-N, N')bis(myristato)]platinum (II) (SM-11355) was evaluated in a cisplatin (CDDP)-resistant tumor cell line, and compared with that of CDDP. H4-II-E / CDDP with acquired resistance to CDDP was established by continuous exposure of a rat hepatic tumor line, H4-II-E, to increasing concentrations of CDDP over 12 months. Compared with the parental cell line, this cell line exhibited an 8.8-fold increase in resistance to CDDP and was not cross-resistant to 1,2-diaminocyclohexane platinum (II) dichloride (DPC). There were no differences in sensitivity to six non-platinum antitumor drugs between H4-II-E and H4-II-E / CDDP, which suggests that H4-II-E / CDDP is not multidrug-resistant. Intracellular platinum accumulation and the formation of a platinum-DNA adduct following CDDP exposure were significantly reduced in H4-II-E / CDDP compared to the parental cell line. The acquired CDDP resistance in H4-II-E / CDDP appeared to be predominantly due to reduced CDDP uptake. H4-II-E / CDDP was also resistant to CDDP suspended in Lipiodol (CDDP / Lipiodol), but was not cross-resistant to SM-11355 suspended in Lipiodol (SM-11355 / Lipiodol). Also, there were no differences in intracellular platinum accumulation or the formation of platinum-DNA adducts after SM-11355 / Lipiodol exposure between H4-II-E and H4-II-E / CDDP. These results suggest that acquired CDDP resistance in H4-II-E / CDDP does not influence the cytotoxic activity of SM-11355 / Lipiodol.

Animals↗