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51.
Keiko Funato Teruko Imai Kenichiro Nakashima Masaki Otagiri 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,757(2):229-235
This paper describes a new method of high-performance liquid chromatography with chemiluminescence detection for the analysis of penbutolol (PB) and its main metabolite, 4-hydroxy penbutolol (4-OH PB) in rat plasma. 4-Dimethylaminosulfonyl-7-(N-chloroformylmethyl-N-methyl) amino-2,1,3-benzoxadiazole (DBD-COCl) was used as a fluorogenic labeling reagent. A mixture of hydrogen peroxide and bis[4-nitro-2-(3,6,9-trioxadecyloxycarbonyl)phenyl]oxalate (TDPO) in acetonitrile was used as a post-column chemiluminogenic reagent. The derivatives of PB and 4-OH PB with DBD-COCl were separated by isocratic effluent with 0.01 M imidazole buffer (pH 7.0)–acetonitrile within 10 min. The detection limits of the proposed method for PB and 4-OH PB were 9.9 and 15 fmol on column, respectively. After intravenous administration of PB in rats, its plasma concentration profiles of PB and 4-OH PB were determined by the proposed method. PB was demonstrated to be rapidly metabolized to 4-OH PB at the same rate as cardiac output. 相似文献
52.
Aiko Shinko Takashi Agari Masahiro Kameda Takao Yasuhara Akihiko Kondo Judith Thomas Tayra Kenichiro Sato Tatsuya Sasaki Susumu Sasada Hayato Takeuchi Takaaki Wakamori Cesario V. Borlongan Isao Date 《PloS one》2014,9(7)
In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson’s disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1–2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness and safety. 相似文献
53.
Toll‐like receptors 2 and 3 enhance melanogenesis and melanosome transport in human melanocytes
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Saaya Koike Kenshi Yamasaki Takeshi Yamauchi Mai Inoue Ryoko Shimada‐Ohmori Kenichiro Tsuchiyama Setsuya Aiba 《Pigment cell & melanoma research》2018,31(5):570-584
Because little is known about how the innate immune response influences skin pigmentation, we examined whether Toll‐like receptor (TLR) agonists participate in melanogenesis and melanosome transportation. We observed that TLR2/2 agonist HKLM and TLR3 agonist Poly(I:C) increased the amount of extracellular melanin from primary human epidermal melanocytes. HKLM, but not Poly(I:C), increased the melanogenic genes such as tyrosinase and dopachrome tautomerase. Poly(I:C) increased the expression of Rab27A, a molecule that facilitates melanosome transport to perimembranous actin filament. UVB irradiation induced Rab27A and melanosome transportation in a similar manner of Poly(I:C). SiRNA for TLR3 or Rab27A suppressed the perimembranous accumulation of Gp100‐positive vesicles in melanocytes and decreased melanin transfer to neighboring keratinocytes induced by both Poly(I:C) and UVB. These results suggest that the microenvironment in the epidermis and innate immune stimuli, such as microbiome and ultraviolet represented here by TLR2 and TLR3 agonists, could affect the melanogenesis in human melanocytes. 相似文献
54.
Suleiman M. Saidi Yoshio Lijima William K. Sang Anderson K. Mwangudza Joseph O. Oundo Kenichiro Taga Masanori Aihara Kenichi Nagayama Hiroyuki Yamamoto Peter G. Waiyaki Takeshi Honda 《Microbiology and immunology》1997,41(10):773-778
Diarrheal diseases are major causes of morbidity and mortality among children in developing countries. We have analyzed the causative agents of diarrhea in children under five years of age who resided in rural environments but attended a hospital in Malindi, a coastal town in Kenya. Bacterial diarrhea was found in 239 (27.7%) of 862 patients with diarrhea. Diarrheagenic Escherichia coli, including enteropathogenic, enterotoxigenic, and enterohaemorrhagic strains, was isolated from 119 (13.8%) patients, followed by Salmonella spp. (63 cases, 7.3%) and Shigella spp. (56 cases, 6.5%). Intestinal parasites were found in 109 (12.6%) of the patients. Entamoeba histolytica and Giardia lamblia were found in 67 (7.8%) and 42 (4.9%) of the cases, respectively. Rotavirus was found in 69 (16.1%) of 428 cases, a part of the 862 cases. Significant differences in age distribution were seen in diarrheal cases due to Campylobacter spp., G. lamblia, and rotavirus. No significant seasonal incidence of specific pathogens was found, but the number of diarrheal patients was significantly correlated to rainfall. Drinking water was contaminated with bacteria at concentrations ranging from 103 to 106 CFU/ml in 98% of the households and by coliform bacteria at concentrations of 102 to 105 CFU/ml in 72% of the households. These results suggest that the main routes of infection may be contaminated drinking water and fecal-oral transmission of enteric pathogens. Consequently, we propose that the enhancement of hygienic practice through health education is a feasible control measure of diarrhea in the study area. 相似文献
55.
Kenichiro Inoue Shinichi Ueda Hidekazu Nayeshiro Nobuharu Moritome Hiroyuki Inouye 《Phytochemistry》1984,23(2):312-318
Administration of p13C- and p2H-labelled precursors to Streptocarpus dunnii cell cultures demonstrated that the naphthoquinones formed through aunique prenylation mode are biosynthesized via 4-(2'-carboxyphenyl)-4-oxobutanoic acid, 1,4-dihydroxy-2-naphthoic acid, lawsone and lawsone 2-prenyl ether, and that the anthraquinones are biosynthesized through prenylation of 2-carboxy-4-oxo-1-tetralone at the carboxy-bearing carbon atom to form 2-carboxy-2-prenyl-4-oxo-1-tetralone,or through ipso attack of the prenyl group on the corresponding carbon atom of 1,4-dihydroxy-2-naphthoic acid. 相似文献
56.
Maki Fukami Erina Suzuki Yoko Izumi Tomohiro Torii Satoshi Narumi Maki Igarashi Mami Miyado Momori Katsumi Yasuko Fujisawa Kazuhiko Nakabayashi Kenichiro Hata Akihiro Umezawa Yoichi Matsubara Junji Yamauchi Tsutomu Ogata 《Journal of cellular and molecular medicine》2017,21(10):2623-2626
The human genome encodes ~750 G‐protein‐coupled receptors (GPCRs), including prokineticin receptor 2 (PROKR2) involved in the regulation of sexual maturation. Previously reported pathogenic gain‐of‐function mutations of GPCR genes invariably encoded aberrant receptors with excessive signal transduction activity. Although in vitro assays demonstrated that an artificially created inactive mutant of PROKR2 exerted paradoxical gain‐of‐function effects when co‐transfected with wild‐type proteins, such a phenomenon has not been observed in vivo. Here, we report a heterozygous frameshift mutation of PROKR2 identified in a 3.5‐year‐old girl with central precocious puberty. The mutant mRNA escaped nonsense‐mediated decay and generated a GPCR lacking two transmembrane domains and the carboxyl‐terminal tail. The mutant protein had no in vitro signal transduction activity; however, cells co‐expressing the mutant and wild‐type PROKR2 exhibited markedly exaggerated ligand‐induced Ca2+ responses. The results indicate that certain inactive PROKR2 mutants can cause early puberty by enhancing the functional property of coexisting wild‐type proteins. Considering the structural similarity among GPCRs, this paradoxical gain‐of‐function mechanism may underlie various human disorders. 相似文献
57.
A predictive software system, SOSUI-GramN, was developed for assessing the subcellular localization of proteins in Gram-negative bacteria. The system does not require the sequence homology data of any known sequences; instead, it uses only physicochemical parameters of the N- and C-terminal signal sequences, and the total sequence. The precision of the prediction system for subcellular localization to extracellular, outer membrane, periplasm, inner membrane and cytoplasmic medium was 92.3%, 89.4%, 86.4%, 97.5% and 93.5%, respectively, with corresponding recall rates of 70.3%, 87.5%, 76.0%, 97.5% and 88.4%, respectively. The overall performance for precision and recall obtained using this method was 92.9% and 86.7%, respectively. The comparison of performance of SOSUI-GramN with that of other methods showed the performance of prediction for extracellular proteins, as well as inner and outer membrane proteins, was either superior or equivalent to that obtained with other systems. SOSUI-GramN particularly improved the accuracy for predictions of extracellular proteins which is an area of weakness common to the other methods. 相似文献
58.
When we calculate mortality along a gradient such as size, dividing into size classes and calculating rates for every class
often involves a trade-off: fine class intervals produce fluctuating rates along the gradient, whereas broad ones may miss
some trends within an interval. The same trade-off occurs when we want to illustrate size distribution by a histogram. This
paper introduces nonparametric methods, published in a statistical journal, into forest ecology, in which the fine-class strategy
is used in an extreme way: (1) a smoothly changing pattern is approximated by a fine step function, (2) the goodness-of-fit
to the data and the smoothness along the gradient are formulated as a weighting sum within a Bayesian framework, (3) the Akaike
Bayesian Information Criterion (ABIC) selects the weighting system that most appropriately balances the two demands, and (4)
the values of the step function are optimized by the maximum likelihood method. The nonparametric estimates enable us to represent
various patterns visually and, unlike parametric modeling, calculations do not demand the determination of a functional form.
Mortality and size distribution analyses were conducted on 12-year forest tree monitoring data from a 4 ha permanent plot
in an old-growth warm–temperate evergreen broad-leaved forest in Japan. From trees of 11 evergreen species with a diameter
at breast height (DBH) greater than 5 cm, we found three types of trend with increasing DBH: decreasing, ladle-shaped and
constant mortality. These patterns reflect variations in life history particular to each species. 相似文献
59.
Chin-Hsuan Hsieh Ya-Jan Hsu Chien-Chung Chang Hsin-Chun Liu Kun-Lung Chuang Cheng-Keng Chuang See-Tong Pang Kenichiro Hasumi Soldano Ferrone Shuen-Kuei Liao 《Cancer immunology, immunotherapy : CII》2009,58(3):395-408
In renal cell carcinoma (RCC), HLA class I downregulation has been found in about 40% of the lesions examined. Since only
scanty information is available about the molecular basis of these defects, we have investigated the mechanism(s) underlying
HLA class I antigen downregulation or loss in six RCC cell lines. Five of them express HLA class I antigens although at various
levels; on the other hand, HLA class I antigens are not detectable on the remaining cell line, the RCC52 cell line, belonging
to a sarcomatoid subtype, even following incubation with IFN-γ. β2-microglobulin (β2
m) was not detected in RCC52 cells. Surprisingly, RCC52 cells harbor two mutations in the β
2
m genes in exon 1: a single G deletion (delG) in codon 6, which introduces a premature stop at codon 7, and a CT dinucleotide
deletion (delCT), which leads to a premature stop at codon 55. Analysis of eight clonal sublines isolated from the RCC52 cell
line showed that the two β
2
m gene mutations are carried separately by RCC52 cell subpopulations. The delG/delCT double mutations were detected in two
sublines with a fibroblast-like morphology, while the delCT mutation was detected in the remaining six sublines with an epithelial
cell morphology. Furthermore, loss of heterozygosity (LOH) of the β
2
m gene at STR D15S-209 was found only in the epithelioid subpopulation, indicating loss of one copy of chromosome 15. Immunostaining
results of the tumor lesion from which the cell line RCC52 was originated were consistent with the phenotyping/molecular findings
of the cultured cells. This is the first example of the coexistence of distinct β
2
m defects in two different tumor subpopulations of a RCC, where loss of one copy of chromosome 15 occurs in one of the subpopulations
with total HLA class I antigen loss.
Chin-Hsuan Hsieh, Ya-Jan Hsu and Cheng-Keng Chuang contributed equally to the work. 相似文献
60.
Hisato Kobayashi Kaori Yamada Shinnosuke Morita Hitoshi Hiura Atsushi Fukuda Masayo Kagami Tsutomu Ogata Kenichiro Hata Yusuke Sotomaru Tomohiro Kono 《Genomics》2009,93(5):461-472
In mammals, both the maternal and paternal genomes are necessary for normal embryogenesis due to parent-specific epigenetic modification of the genome during gametogenesis, which leads to non-equivalent expression of imprinted genes from the maternal and paternal alleles. In this study, we identified a paternally expressed imprinted gene, Zdbf2, by microarray-based screening using parthenogenetic and normal embryos. Expression analyses showed that Zdbf2 was paternally expressed in various embryonic and adult tissues, except for the placenta and adult testis, which showed biallelic expression of the gene. We also identified a differentially methylated region (DMR) at 10 kb upstream of exon 1 of the Zdbf2 gene and this differential methylation was derived from the germline. Furthermore, we also identified that the human homolog (ZDBF2) of the mouse Zdbf2 gene showed paternal allele-specific expression in human lymphocytes but not in the human placenta. Thus, our findings defined mouse chromosome 1 and human chromosome 2 as the loci for imprinted genes. 相似文献