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121.
Shoji M Kanai M Matsubara E Tomidokoro Y Shizuka M Ikeda Y Ikeda M Harigaya Y Okamoto K Hirai S 《Neurobiology of aging》2001,22(2):209-215
Decreased levels of cerebrospinal fluid (CSF) Abeta42 is a diagnostic marker of Alzheimer's disease. To clarify the biological basis of this marker, the physiological alterations of CSF Abeta40 and Abeta42 by aging were studied. CSF samples from 92 normal subjects between 8 and 89 years old were measured using a specific ELISA for Abeta40 and Abeta42(43). High concentrations of Abeta40 and Abeta42(43) in the young group, under 29 years old, changed to be at low concentrations in the adult group between 30 and 59 years old. Subsequently, the levels increased again with age. Third order regression analysis showed a significant correlation between the levels of Abeta40 and age (Y = - 169 X(3) + 3.1X(2)- 0.02X + 4135; P < 0.034) and between the levels of Abeta42(43) and age (Y = - 46 X(3) + 0.9 X(2)- 0.005X + 992; P < 0.005). The levels of CSF Abeta40 and Abeta42(43) were physiologically regulated to show a U-shaped natural course in normal aging. These findings suggested that the physiological increase of Abeta42(43) over 59 years of age is selectively inhibited in Alzheimer's disease. 相似文献
122.
123.
Kajiya H Okamoto F Fukushima H Okabe K 《Pflügers Archiv : European journal of physiology》2003,445(6):651-658
Although calcitonin is well known to be a potent inhibitor of bone resorption, it remains unknown how it regulates osteoclastic H(+) transport. In this study, we examined the effects of calcitonin on H(+) extrusion in cultured rat resorbing osteoclasts using an intracellular pH (pHi) indicator, BCECF [2'7'-bis-(2-carboxyethyl)- 5-carboxyfluorescein]. Resorbing osteoclasts were identified by their formation of resorbing pits on calcium phosphate-coated quartz coverslips. Both basal pHi and H(+) extrusion activity were significantly higher compared to non-resorbing osteoclasts. Two types of H(+)-extruding systems were identified by pharmacological and immunocytochemical means: a bafilomycin-A(1)-sensitive and an amiloride-sensitive system [H(+) extrusion mediated by a vacuolar type proton pump (V-ATPase) and by a Na(+)/H(+) exchanger (NHE), respectively]. Calcitonin inhibited both H(+) extrusion activities in a dose-dependent manner and this action was mimicked by protein kinase A (PKA) activators, but not by protein kinase C (PKC) activators. Pretreatment with PKA inhibitors completely suppressed calcitonin-induced inhibition, whereas neither PKC inhibitors nor calcium chelators suppressed it. These results indicate that calcitonin inhibits H(+) extrusion generated by V-ATPase and NHE via PKA activation. These inhibitory mechanisms of H(+) transport by calcitonin are important for the regulation of bone resorption. 相似文献
124.
Nobuhiko Okamoto Mashiro Nakayama Chie Narahara Han-suk Kim Masashi Fujioka Isao Imada Tatsuya Arai Soichiro Toda 《Journal of human genetics》1997,42(3):441-444
Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol
and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation,
postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including
triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level
was found by GC/MS. 相似文献
125.
Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice. 总被引:5,自引:2,他引:5 下载免费PDF全文
The production and roles of endogenous gamma interferon (IFN-gamma), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in both lethal and nonlethal infections of Staphylococcus aureus were investigated in mice. In the case of nonlethal infection, although no bacteria were detected in the bloodstreams, bacteria that colonized and proliferated persistently for 3 weeks were found in the kidneys. All mice given lethal injections died within 7 days, and large numbers of bacteria were detected in the bloodstreams, spleens, and kidneys. The first peaks of IFN-gamma, TNF, and IL-6 were observed in the bloodstreams and spleens of the mice with nonlethal and lethal infections within 24 h. Thereafter, in the nonlethal cases, IFN-gamma, TNF, and IL-6 peaked again in the spleens and kidneys during the period of maximum growth of bacteria in the kidneys, although only IL-6 was detected in the sera. In contrast, in the case of lethal infection, the titers of IFN-gamma and IL-6 in the sera and TNF in the kidneys peaked before death. Effects of in vivo administration of monoclonal antibodies (MAbs) against IFN-gamma and TNF on the fates of S. aureus-infected mice were studied. In the nonlethal infections, anti-TNF alpha (anti-TNF-alpha) MAb-treated mice, but not anti-IFN-gamma MAb-treated mice, died as a result of worsening infection, suggesting that endogenous TNF plays a protective role in host resistance to S. aureus infection. In the mice that received lethal doses, injection of anti-TNF-alpha MAb accelerated death. However, although injection of anti-IFN-gamma MAb inhibited host resistance of the infected mice early in infection, most of the animals survived the lethal infection by injection of anti-IFN-gamma MAb, suggesting that endogenous IFN-gamma plays a detrimental role in S. aureus infection. Thus, this study demonstrated that IFN-gamma and TNF play different roles in S. aureus infection. 相似文献
126.
K Imai N Yuasa H Iwakiri K Nakamura H Hihara T Ishita A Inamoto I Okamoto K Ohta M Maeda 《Avian pathology》1992,21(1):119-126
Pathogenicity of two isolates of Marek's disease virus (MDV), MS1 and MS2, from chickens was examined in two genetically different strains of chickens, MD-susceptible P-2 chickens and less susceptible PDL-1 chickens. The isolates induced an early mortality syndrome unassociated with lymphoproliferative lesions in P-2 chickens. There were no significant differences in pathogenicity between our isolates and the Md/5 strain of very virulent MDV (vvMDV) in both P-2 and PDL-1 chickens. Protective indices of turkey herpes virus (HVT) vaccine against challenge with MS1 or MS2 in P-2 chickens were 54% and 28%, respectively, whereas HVT gave more than 80% protection in PDL-1 chickens. These results indicate that the two isolates could be classified as vvMDV. In contrast, a bivalent vaccine composed of HVT and serotype 2 MDV, and CVI988 vaccine gave good protection against challenge with the isolates in P-2 chickens; however, the best protection was given by the CBI988 vaccine. This is the first report of isolation of vvMDV in Japan. 相似文献
127.
9株YONBAN相关TTV变异株全基因序列测定及其结构、分型的研究 总被引:1,自引:2,他引:1
目的:对9个TTV新分离株全基因序列测定,基因结构及基因分型的研究。方法:从9名TTV第4基因群感染阳性的婴儿血清中抽提取其DNA,用long inverted PCR扩增出全基因组,克隆和测定全基因组序列,并对测序结果进行计算机分析。结果:首次次测定了TTV第4基因群共9个新分离株的全基因序列,其中8个分离株代表核基因群首次报道的8个新基因型。结论:TTV基因组核酸序列具有高度异质性及基因型的高度多样性,但是,其独特的转录特性和基因组的基本结构在各自的基因群及基因型中十分保守。 相似文献
128.
129.
Nishimura Hiroyuki; Hattori Susumu; Ueda Genjiro; Abe Masaaki; Yang Kwangseok; Nozawa Shingo; Okamoto Hiroshi; Zhang Danqing; Tsurui Hiromichi; Hirose Sachiko; Shirai Toshikazu 《International immunology》1995,7(7):1115-1123
Using two mAb, one specific to the alternative exon 6-dependentepitope of CD45 molecules(JH6.2) and one a natural thymocytotoxicautoantibody (NTA) with an unknown reactive epitope (NTA260),we subdivided splenic CD4+ T cells from 2-month-old BALB/c miceinto five phenotypically distinct subsets. CD45RC+NTA260–(SI) cells were phenotypically analogous to CD4+ T cells predominatingin newborn mice and produced a significant amount of IL-2, butnot so IL-4, IL-10 or IFN- when stimulated with immobilizedanti-CD3 mAb in vitro. They appeared to consist mainly of naiveThP cells. The CD45RC+;NTA260+ (S II) subset also produced IL-2,but not other cytokines; however, the IL-2 levels produced weremuch higher than seen with the S I subset, thereby suggestingthe predominance of further maturated ThP cells. The D45RC–NTA260+(S III) subset mainly produced IL-4, IL-10, IFN- and less IL-2,and contained memory cells that helped the secondary antibodyresponse to a recall antigen, and hence contained Th2 and probablya mixture of Th0 and Th1 cells. The CD45RC–NTA260–(S IV) subset was a poor responder to the immobilized anti-CD3mAb. The CD45RCbrightNTA260dull(S V) subset consisted of a smallnumber of cells that were phenotypically analogous to activatedCD4+ T cells. While an age-associated decrease in the proportionof S I and less markedly in S II and in turn increase in S IIIsubsets of CD4+ T cells occurred in normal BALB/c mice, autoimmunedisease-prone (NZBxNZW)F1 mice showed a marked age-associateddecrease in the proportion of not only S I, II but also IIIsubsets. As aged (NZBxNZW)F1 mice carry CD4+ T helper cellsfor IgG anti-DNA antibody production, such age-associated polarizationto the S IV subset appears to be critical in the pathogeneslsof autoimmune disease in these mice. 相似文献
130.
Yoshitaka Saito Terutaka Ozawa Akinori Nishiyama 《Pflügers Archiv : European journal of physiology》1990,417(4):382-390
Kinetic properties of the Na+-H+ antiport in the acinar cells of the isolated, superfused mouse lacrimal gland were studied by measuring intracellular pH (pHi) and Na+ activity (aNai) with the aid of double-barreled H+- and Na+-selective microelectrodes, respectively. Bicarbonate-free solutions were used throughout. Under untreated control conditions, pHi was 7.12±0.01 and aNai was 6.7±0.6 mmol/l. The cells were acid-loaded by exposure to an NH
4
+
solution followed by an Na+-free N-methyl-d-glucamine (NMDG+) solution. Intracellular Na+ and H+ concentrations were manipulated by changing the duration of exposure to the above solutions. Subsequent addition of the standard Na+ solution rapidly increased pHi. This Na+-induced increase in pHi was almost completely inhibited by 0.5 mmol/l amiloride and was associated with a rapid, amiloride-sensitive increase in aNai. The rate of pHi recovery induced by the standard Na+ solution increased in a saturable manner as pHi decreased, and was negligible at pHi 7.2–7.3, indicating an inactivation of the Na+-H+ antiport. The apparent K
m for intracellular H+ concentration was 105 nmol/l (pH 6.98). The rate of acid extrusion from the acid-loaded cells increased proportionally to the increase in extracellular pH. Depletion of aNai to less than 1 mmol/l by prolonged exposure to NMDG+ solution significantly increased the rate of Na+-dependent acid extrusion. The rate of acid extrusion increased as the extracellular Na+ concentration increased following Michaelis-Menten kinetics (V
max was 0.55 pH/min and the apparent K
m was 75 mmol/l at pHi 6.88). The results clearly showed that the Na+-H+ antiport activity is dependent on the chemical potential gradient of both Na+ and H+ ions across the basolateral membrane, and that the antiporter is asymmetric with respect to the substrate affinity of the transport site. The data agree with the current model of activation and inactivation of the antiporter by an intracellular site through changes in the intracellular Na+ and H+ concentrations. 相似文献