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91.
Izumi T Sakaguchi J Takeshita M Tawara H Kato K Dose H Tsujino T Watanabe Y Kato H 《Bioorganic & medicinal chemistry》2003,11(12):2541-2550
Structural modification of imiquimod (1), which is known as an interferon-alpha (IFN-alpha) inducer, for the aim of finding a novel and small-molecule tumor necrosis factor-alpha (TNF-alpha) suppressor and structure-activity relationship (SAR) are described. Structural modification of a imiquimod analogue, 4-amino-1-[2-(1-benzyl-4-piperidyl)ethyl-1H-imidazo[4,5-c]quinoline (2), which had moderate TNF-alpha suppressing activity without IFN-alpha inducing activity, led to a finding of 4-chloro-2-phenyl-1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline (10) with potent TNF-alpha suppressing activity. The relation between conformational direction of 2-(4-piperidyl)ethyl group at position 1 and TNF-alpha suppressing activity is also demonstrated by NMR. 相似文献
92.
93.
Takamoto K Kawada M Usui T Ishizuka M Ikeda D 《Biochemical and biophysical research communications》2003,308(4):866-871
Nephrotoxicity is known to be a major clinical side effect of aminoglycoside antibiotics. Aminoglycosides cause damage to proximal tubular cells in kidney, however the mechanism of toxicity is still unclear. In order to elucidate the mechanism of nephrotoxicity, we studied the effect of aminoglycoside antibiotics on glucose transport systems in vitro and in vivo. As a result, we found that the aminoglycosides significantly reduced Na(+)/glucose cotransporter (SGLT1)-dependent glucose transport and also down-regulated mRNA and protein levels of the SGLT1 in pig proximal tubular LLC-PK(1) cells. To obtain evidence about SGLT1 down-regulation in vivo, we studied the mRNA expression of SGLT1 using gentamicin C-treated murine kidney and found that gentamicin C down-regulated SGLT1 in vivo as well as in vitro. Furthermore, the gentamicin C-treated mice showed significant rise in urinary glucose excretion. These results indicate that one of the mechanisms of aminoglycoside nephrotoxicity is the down-regulation of SGLT1, which causes reduction in glucose reabsorption in kidney. 相似文献
94.
95.
Honda T Shimizu K Fukuhara A Irie K Takai Y 《Biochemical and biophysical research communications》2003,306(1):104-109
Cadherins are key Ca(2+)-dependent cell-cell adhesion molecules at adherens junctions (AJs) in fibroblasts and epithelial cells, whereas claudins are key Ca(2+)-independent cell-cell adhesion molecules at tight junctions (TJs) in epithelial cells. The formation and maintenance of TJs are dependent on the formation and maintenance of AJs. Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules which comprise a family of four members, nectin-1, -2, -3, and -4, and are involved in the formation of AJs in cooperation with cadherins, and the subsequent formation of TJs. We show here that the velocity of the formation of the E-cadherin-based AJs is increased by overexpression of nectin-1 and is reduced by addition of the nectin-1 inhibitors to the medium in L cells stably expressing E-cadherin and Madin-Darby canine kidney cells. Moreover, the velocity of the formation of the claudin-based TJs is increased by overexpression of nectin-1 and is reduced by addition of the nectin-1 inhibitors to the medium in Madin-Darby canine kidney cells. These results indicate that nectins regulate the velocity of the formation of the E-cadherin-based AJs and the subsequent formation of the claudin-based TJs. 相似文献
96.
97.
We investigated the nucleotide variation of a conifer, Cryptomeria japonica, and the divergence between this species and its closest relative, Taxodium distichum, at seven nuclear loci (Acl5, Chi1, Ferr, GapC, HemA, Lcyb, and Pat). Samples of C. japonica were collected from three areas, Kantou-Toukai, Hokuriku, and Iwate. No apparent geographic differentiation was found among these samples. However, the frequency spectrum of the nucleotide polymorphism revealed excesses of intermediate-frequency variants, which suggests that the population was not panmictic and a constant size in the past. The average nucleotide diversity, pi, for silent sites was 0.00383. However, values of pi for silent sites vary among loci. Comparisons of polymorphism to divergence among loci (the HKA test) showed that the polymorphism at the Acl5 locus was significantly lower. We also observed a nearly significant excess of replacement polymorphisms at the Lcyb locus. These results suggested possibilities of natural selection acting at some of the loci. Intragenic recombination was detected only once at the Chi1 locus and was not detected at the other loci. The low level of population recombination rate, 4Nr, seemed to be due to both low level of recombination, r, and small population size, N. 相似文献
98.
West–east contrast of phenology and climate in northern Asia revealed using a remotely sensed vegetation index 总被引:4,自引:0,他引:4
The phenology of the vegetation covering north Asia (mainly Siberia) and its spatial characterstics were investigated using remotely sensed normalized difference vegetation index (NDVI) data. The analysis used the weekly averaged NDVI over 5 years (1987-1991) using the second-generation weekly global vegetation index dataset (0.144 degrees x 0.144 degrees spatial resolution). In the seasonal NDVI cycle, three phenological events were defined for each pixel: green-up week (NDVI exceeds 0.2), maximum week, and senescence week (NDVI drops below 0.2). Generally there was a west-early/east-late gradient in the three events in north Asia. In the zonal transect between 45 degrees and 50 degrees N, the timing of green-up, maximum, and senescence near 60 degrees E (Kazakh) was about 3.4, 8.7, and 13.4 weeks earlier than near 110 degrees E (Mongolia) respectively. It has been suggested that vegetation near Kazakh only flourishes during a short period when water from snow melt is available from late spring to early summer. In Mongolia, abundant water is available for the vegetation, even in midsummer, because of precipitation. In the 50-60 degrees N zonal transect, the green-up and maximum near 40 degrees E were about 3.8 and 3.9 weeks earlier than near 115 degrees E, respectively. As for the week of senescence, there was no clear west-east trend. This west-to-east phenological gradient was related to the weekly cumulative temperature (over 0 degrees C). Weeks in which the cumalative temperature exceeded 40 degrees C and 140 degrees C had a similar west-east distribution to green-up and maximum NDVI. 相似文献
99.
Kawada T Zheng C Yanagiya Y Uemura K Miyamoto T Inagaki M Shishido T Sugimachi M Sunagawa K 《American journal of physiology. Heart and circulatory physiology》2002,282(3):H1149-H1156
A transfer function from baroreceptor pressure input to sympathetic nerve activity (SNA) shows derivative characteristics in the frequency range below 0.8 Hz in rabbits. These derivative characteristics contribute to a quick and stable arterial pressure (AP) regulation. However, if the derivative characteristics hold up to heart rate frequency, the pulsatile pressure input will yield a markedly augmented SNA signal. Such a signal would saturate the baroreflex signal transduction, thereby disabling the baroreflex regulation of AP. We hypothesized that the transfer gain at heart rate frequency would be much smaller than that predicted from extrapolating the derivative characteristics. In anesthetized rabbits (n = 6), we estimated the neural arc transfer function in the frequency range up to 10 Hz. The transfer gain was lost at a rate of -20 dB/decade when the input frequency exceeded 0.8 Hz. A numerical simulation indicated that the high-cut characteristics above 0.8 Hz were effective to attenuate the pulsatile signal and preserve the open-loop gain when the baroreflex dynamic range was finite. 相似文献
100.
Kai K Komine K Komine Y Kuroishi T Kozutsumi T Kobayashi J Ohta M Kitamura H Kumagai K 《Microbiology and immunology》2002,46(3):187-194
Lactoferrin (Lf) may play a key role in the clearance of microorganisms from a host. To study in vitro the bactericidal mechanisms of Lf during nonlactating periods, we investigated whether the effects of Lf were influenced by bovine mammary gland secretory cells (MGSC) and fresh normal bovine serum (NBS) as a source of complement. Phagocytic killing tests demonstrated that a phagocytic mixture of unopsonized Staphylococcus aureus (S. aureus) and MGSC in the presence of Lf reduced bacterial growth, compared with that of unopsonized S. aureus and MGSC without Lf. The opsonization with Lf and fresh NBS together resulted in more than a 95% reduction in CFU. The activation of complement induced by Lf also resulted in increased deposition of C3 on S. aureus, and the phagocytic activity of MGSC was augmented by opsonization with Lf and fresh NBS. Inhibition of C3 deposition by Lf was not induced in the presence of Mg-EGTA, but was induced by the addition of bovine Lf antiserum. These results strongly suggest that Lf induces the activation of complement in fresh NBS mainly through an alternative pathway. The results demonstrated a Lf-dependent, antibody-independent and complement-mediated phagocytic killing of S. aureus, and implied that Lf was synergistically capable of activating both the alternative pathway of the bovine complement cascade and phagocytosis by phagocytes. 相似文献