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71.
The ETV6 (TEL) locus at chromosome band 12p 13 is a major site of translocations in acute leukemia, particularly in childhood acute lymphoblastic leukemia (ALL). In cases with translocations involving ETV6, the normal ETV6 allele is often deleted. In addition, loss of heterozygosity of ETV6 is frequently observed in childhood'ALL. Thus, it has been suggested that ETV6 may have an anti-oncogenic role to play, in addition to its oncogenic role. We have described an unusual case of ALL in which ETV6 is found fused to the ABL gene; ABL is normally activated by fusion to the BCR gene in the 9:22 translocation. We expanded the primary cells from this ETV6/ABL rearranged case of ALL in SCID animals and analyzed them for expression of both ETV6/ABL and the normal ETV6 mRNA. We found that both the rearranged and normal ETV6 mRNAs are expressed in the expanded cell population. Furthermore, sequence analysis of the ETV6 PCR product revealed no point mutations which would influence the amino acid sequence. Thus, deletion of the second ETV6 allele is not necessary for the transformation to leukemia by ETV6/ABL.  相似文献   
72.
The majority of early-onset familial Alzheimer's disease (FAD) is associated with mutations in the presenilin-1 (PS1) gene. We describe a novel Polish PS1 mutation of Pro117Leu, associated with the earliest average age of onset and death so far reported in a PS-linked, FAD kindred. Human kidney 293 and mouse neuroblastoma N2a cells were stably transfected with wild-type and PS1 P117L. There was a significant increase in the amyloid beta42/40 ratio in the N2a P117L PS1 transfected cells compared with N2a transfected with wild-type PS1. What role PS has in the pathogenesis of AD remains to be determined, however, the severity of the clinical picture associated with this PS1 mutation stresses the importance of presenilin.  相似文献   
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Phenotypical properties of single-gene reassortants of attenuated cold-adapted strain A/Leningrad/135/47/57 (H2N2) and strain A/PR8/34 virulent for laboratory animals were studied. Only the group of reassortants inheriting NS gene from cold-adapted virus was fully attenuated for various animals species, similarly as reassortants with 6/2 genomic formula containing all the 6 internal protein genes from strain A/Leningrad/134/47/57. Reassortant 25A-1 single-gene for NS was temperature-sensitive (ts) on mammalian cells but formed plaques at 40 degrees C on chicken kidney cells. Reassortants with genomic formula 6/2 were temperature-sensitive in all types of cells used. Reassortant 25A-1 could synthesize normal amounts of polypeptides in MDCK cells at 39 degrees C, whereas protein synthesis of reassortants with 6/2 genomic formula was noticeably reduced at this temperature. Hence, a similar level of attenuation of both reassortant groups appears to be due to various molecular mechanisms. Possible role of NS2 gene mutation in attenuation of strain A/Leningrad/134/47/57 and its reassortants is discussed.  相似文献   
75.
The dendritic localization of mRNAs has been proposed to underlie the structural and functional polarity of neurons, as well as certain aspects of synaptic plasticity. Even though there is no conclusive evidence that such a localization is a physiological requirement, studies of mRNA localization in relation to function in other cell types and recent experiments on synaptic plasticity suggest that this proposal may be correct.  相似文献   
76.
We have investigated whether hypoxia and muscle contractions stimulate glucose transport in perfused rat muscle to the same extent, additively and with the same sensitivity to the microbial products calphostin C and wortmannin. Hindlimb glucose uptake increased gradually from 3.4+/-0.5 to a maximal level of 12.7+/-0.6 micromol g-1 h-1 (n=11) after 50 min of hypoxia. Compared with hypoxia, the effect of maximal electrical stimulation of the sciatic nerve on muscle glucose uptake was more than two-fold higher (27+/-2 micromol g-1 h-1 (n=14)). This was due to a higher contraction- vs. hypoxia-induced glucose transport rate in oxidative fibers. The stimulatory effect of hypoxia and electrical stimulation was not additive. Contraction-induced muscle glucose transport was inhibitable by both calphostin C and wortmannin in the micromolar range, whereas the effect of hypoxia was totally insensitive to these drugs. Our data suggest that diacylglycerol/phorbol ester-sensitive protein kinase C is involved in stimulation of muscle glucose transport by contractions and that in contrast to the prevailing concept, hypoxia and contractions do not stimulate muscle glucose transport by the same signaling mechanism.  相似文献   
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In the 14, 3 and 90 day-experiments with tail-suspended rats, histochemical determination of myosin ATP-ase activity in m. soleus and m. gastrocnemius preincubated in acid and neutral media was followed by measurement of the cross-sectional areas (CSAs) of muscular fibers (MF) and calculation of the percentage of various types of MF. By day 30 of testing atrophy in m. soleus reached maximum and stabilized. By that time, MF CSAs were less than in the control by 69, 62, and 68% in MF-I, -IIA and -IIC, respectively. Slow MF underwent the transformation into fast and intermediate. In slow MF this process peaked by day 3 when the number of these fibers decreased by 28% as compared to the control, and stabilized. The transformation of intermediate fibers into the fast ones was progressing simultaneously. This process was not finished by day 90. Atrophy of m. gastrocnemius was less pronounced than in m. soleus. On day 14 of experiment, MF CSAs, except for IIB, were by 30% smaller than in the control. Type IIB MF were less affected as their CSAs decreased by only 17% as compared with the control. On day 90, CSAs in both slow and IIC-type fast MFs remained approximately same as in the rats investigated on day 14. Fast MF CSAs either tended to (IIA) or regained (IIB) the norm. Hence, atrophy in m. gastrocnemius stabilized earlier than in m. soleus. Besides, longer suspension led to a partial or complete reconstruction of two out of three types of fast fibers. The percent ratio of MFs was unchanged; however, during the ATP-ase determination slow IB-type MFs assumed th color typical of fast MFs.  相似文献   
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