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排序方式: 共有166条查询结果,搜索用时 15 毫秒
101.
4-(p-Sulphamoylphenyl)androstenedione (3) and 6α-p-sulphamoylphenyl analogues 12-14 were synthesised and tested as aromatase inhibitors as well as oestrone sulphatase inhibitors in human placental microsomes. All of the p-sulphamoylphenyl compounds synthesised were powerful inhibitors of aromatase with apparent Ki values ranging between 30 and 97 nM. In addition, the aromatase inhibitory activities of 6α-p-hydroxyphenyl compounds 9-11, which may be produced from their respective sulphamoylphenyl compounds by action of oestrone sulphatase, were also high in a range of 23 and 75 nM of the Ki values. On the other hand, all of the sulphamoylphenyl compounds were poor inhibitors of oestrone sulphatase with more than about 200 μM of IC25 values. Although the present findings of the oestrone sulphatase inhibition are disappointing, such attempts may be valuable to develop a new class of drugs having a dual function, aromatase inhibitor and oestrone sulphatase inhibitor, for the treatment of oestrogen-dependent breast cancer. 相似文献
102.
Watari K Tojo A Nagamura-Inoue T Nagamura F Takeshita A Fukushima T Motoji T Tani K Asano S 《FEBS letters》2000,466(2-3):367-371
In order to elucidate molecular events in BCR/ABL-induced transformation, we adopted a polymerase chain reaction (PCR)-based technique of differential display and compared mRNA expression in human factor-dependent cells, TF-1, with that in factor-independent cells, ID-1, which were established from TF-1 cells by transfection of BCR/ABL. Cloning and sequencing of a gene which was upregulated in ID-1 cells revealed that the gene was identical to a melanoma antigen, PRAME. Our present study demonstrated that PRAME was markedly expressed in primary leukemic cells with chronic myeloid leukemia (CML) in blastic crisis and Philadelphia (Ph)+-acute lymphoblastic leukemia (ALL), in which BCR/ABL played an important role as a pathogenic gene. Moreover, comparison of PRAME expression among CD34+ cells with CML in blastic, accelerated, and chronic phases revealed a higher expression in CML in advanced phases. Thus PRAME was considered to be a good candidate for a marker of Ph+-leukemic blast cells as well as a new target antigen of leukemic blast cells that cytotoxic T cells can recognize. 相似文献
103.
104.
New polyhydroxylated sterols, stylisterol A-C (1-3), and a novel 5,19-cyclosterol, hatomasterol (4) were isolated from the Okinawan sponge Stylissa sp. Structural determinations of these compounds were made by spectroscopic analysis and chemical conversion. Assessment of cytotoxicity toward HeLa cells was also determined. 相似文献
105.
Cholesterol is an important structural component of membranes as well as a precursor for steroid hormone, bile acid and regulatory oxysterol biosynthesis. Recent observations revealed that cholesterol plays an important role in signaling and the regulation of intracellular vesicular trafficking. Studies on Niemann-Pick type C disease, a fatal neuro-visceral cholesterol storage disorder, led to the elucidation of a sterol-modulated vesicular trafficking pathway. Mutations in the NPC1 gene, which cause the majority of cases of Niemann-Pick type C disease, result in the accumulation of free cholesterol in lysosomes and associated defects in glycolipid sorting. NPC1 has a sterol-sensing domain that presumably recognizes free sterols in the protein's environment and participates in the movement of cholesterol out of lysosomes. The compartment containing NPC1 is a subset of late endosomes; it is highly mobile, travels along microtubules, emitting flexible tubules. The movements of this compartment require an intact NPC1 sterol-sensing domain and are dramatically suppressed when free cholesterol accumulates in the late endosomes. Two other proteins involved in sterol trafficking enter into the NPC1 compartment, NPC2 also known as HE1, a secreted sterol-binding glycoprotein, and MLN64, a StAR-related lipid transfer (START) domain protein, which can bind cholesterol and promote its movement from donor to acceptor membranes. Mutations in NPC2 cause a rarer form of Niemann-Pick type C disease, establishing its importance in intracellular sterol movement. NPC2, NPC1 and MLN64 may act in an ordered sequence to sense cholesterol, effect sterol movement, and consequently, influence the process of vesicular trafficking. 相似文献
106.
In vertebrates, certain Hox genes are known to control cellular identities along the anterior-posterior (A-P) axis in the developing hindbrain. In mouse Hoxa3 mutants, truncation of the glossopharyngeal (IXth) nerve or the fusion of the IXth and vagus (Xth) nerves was reported, although its underlying mechanism is largely unknown. To elucidate the mechanism of the IXth nerve defects, we reexamined the phenotype of Hoxa3 mutant embryos. In Hoxa3 mutants, we observed an abnormal caudal stream of the migrating Hoxa3-expressing neural crest cells at the prospective IXth nerve-forming area. Dorsomedial migration of the placode-derived neuronal precursor cells of the IXth nerve was also affected. Motor neurons at rhombomere 6 (r6), where those of the IXth nerve were positioned, often projected axons to the Xth nerve. In summary, the Hoxa3 gene has crucial roles in ensuring the correct axon projection pattern of all three components of the IXth nerve, i.e., motor neurons and sensory neurons of the proximal and distal ganglia. 相似文献
107.
H Takami E Furuya K Tagawa Y Seo M Murakami H Watari H Matsuda H Hirose Y Kawashima 《Journal of biochemistry》1988,104(1):35-39
The subcellular compartmentalization of adenosine 5'-triphosphate (ATP) in isolated perfused rat heart and its relation to energy depletion in ischemia were examined by 31P nuclear magnetic resonance (31P-NMR) spectroscopy and chemical analyses. The signal intensities of the beta-phosphate of ATP and creatine phosphate in the 31P-NMR were standardized by the intracellular volume ratio measured with 23Na-NMR to determine the actual content of each. During aerobic perfusion the ATP content determined by NMR (13.7 +/- 2.2 mumol/g dry weight) was significantly lower than that found by chemical analysis (22.4 +/- 0.7 mumol/g dry weight), while the creatine phosphate contents determined by the two methods were the same. During ischemia at 33 degrees C, the signal of the beta-phosphate of ATP in the 31P-NMR spectrum decreased progressively, disappearing completely after 16 min. But at this time 5.7 +/- 1.7 mumol/g dry weight of myocardial ATP was still detected by chemical analysis. These results indicated that there were two different compartments of intracellular ATP in the heart, only one of which is detectable by 31P-NMR spectroscopy, and that during ischemia the ATP that is detectable, which seems to be the free ATP in the cytosol, decreased more rapidly than the ATP in the other compartment. 相似文献
108.
Rui Kano Yuka Nakamura Toshihiro Watari Shinichi Watanabe Hisashi Takahashi Hajime Tsujimoto Atsuhiko Hasegawa 《Current microbiology》1998,37(4):236-239
Nucleotide sequences of chitin synthase 1 (CHS1) gene of dermatophytes, Arthroderma benhamiae, A. simii, A. vanbreuseghemii, Trichophyton mentagrophytes var. interdigitale (T. interdigitale), and T. rubrum were analyzed for their phylogenetic relationship. About 620-bp genomic DNA fragments of the CHS1 gene were amplified from these dermatophytes by polymerase chain reaction (PCR) and sequenced. The CHS1 nucleotide sequences of these five dermatophytes showed more than 90% similarity between the species. The phylogenetic analysis
of their sequences revealed that A. benhamiae, A. simii, A. vanbreuseghemii, and T. rubrum were genetically distinct from one another, but T. interdigitale was genetically very close to A. vanbreuseghemii. On the other hand, a specific restriction endonuclease site of HinfI was present in the CHS1 gene fragment of T. rubrum but not in those of A. benhamiae, A. simii, A. vanbreuseghemii and T. interdigitale. The molecular analysis of CHS1 genes will provide useful information for the identification of these Trichophyton species and the understanding of their evolution.
Received: 6 March 1998 / Accepted: 4 May 1998 相似文献
109.
Mammal Research - The small Indian mongoose, Urva auropunctata, is one of the most notorious invasive species in the world. In Japan, the mongoose was introduced to Amami, Kyushu (Kiire region),... 相似文献
110.
Hiroshi Watari Yoshinori Isogai Hiroyasu Nlshikawa 《Journal of theoretical biology》1980,83(2):209-214
The maximum slope of the plot, appearing in the paper of Watari & Isogai (1976), was derived algebraically as a function of allosteric constants c and αmor βm (= cαm), and the relation between L, c, and αmor βm, was also obtained, where are concentrations of unligated R and T states respectively, KRand KT are microscopic dissociation constants, and Fm is the ligand concentration at the maximum slope of the plot. When the maximum slope is increased by one, the value becomes Hill constant, n. Nomographs which enable easier estimation of allosteric constants, L and c, were constructed from the two given values, the maximum slope of the plot, n ? 1, and αmor βm, in the cases where the maximum number of ligands, N, was 2 and 4. In the nomograph, log c is plotted against log L2cN keeping the value of the maximum slope of the plot and that of αmor βm constant. These nomographs show that the representation is symmetrical in the cases of L2cN > 1 and L2cN < 1. 相似文献