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991.
Two morphological types of appendages, an anchor-like appendage and a peritrichate fibril-type appendage, have been observed on cells of an adhesive bacterium, Acinetobacter sp. strain Tol 5, by use of recently developed electron microscopic techniques. The anchor extends straight to the substratum without branching and tethers the cell body at its end at distances of several hundred nanometers, whereas the peritrichate fibril attaches to the substratum in multiple places, fixing the cell at much shorter distances. 相似文献
992.
Four trans-planaramineplatinum(II) complexes code named YH9, YH10, YH11 and YH12 each of the form trans-PtL(NH(3))Cl(2), where L=2-hydroxypyridine and 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine for YH9, YH10, YH11 and YH12, respectively, have been synthesized and the activity of the compounds against human cancer cell lines, cell uptake, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied. The compound having imidazo(1,2-alpha)pyridine ligand as one the carrier ligands in the trans-configuration is found to be significantly more active than cis-platin against ovarian A2780(cisR) cancer cell line corresponding with higher Pt-DNA binding. All other compounds have resistance factors less than that for cis-platin in the A2780 and A2780(cisR) cell lines. A greater prevention of BamH1 digestion with increasing concentration of the compounds indicates that as the compounds bind with nucleobases in DNA, the DNA conformation is changed sufficiently so as to prevent BamH1 digestion at the specific GG site. Gel electrophoresis results also indicate that as the compounds bind to DNA, unwinding of supercoiled form I DNA takes place to change it from the negatively supercoiled form I through relaxed circular form I to the positively supercoiled form I. 相似文献
993.
The reactions of platinum(II) complexes with thiol containing molecules are highly relevant to the mechanism of action of platinum-based drugs. This work presents the electrospray mass spectrometry (ESMS) and NMR results on the reactions of [Pt(l-MetH-S,N)Cl(2)] (l-MetH: l-methionine) with gamma-glutathione (GSH) and l-cysteine (l-Cys) at different pH and different molar ratios. Polymeric species such as [Pt(2)(micro-SG-S)(2)(Met-S,N)(2)], [Pt(3)(micro-SG-S)(4)(Met-S,N)(2)], [Pt(4)(micro-SG-S)(6)(Met-S,N)(2)] and [Pt(5)(micro-SG-S)(8)(Met-S,N)(2)] (l-Met: deprotonated l-methionine) were detected and were stable for long hours. For both reactions, the polymerization extent decreased with the increase of pH. For the reaction of l-Cys, only mononuclear complex [Pt(l-Met-S,N)(l-Cys-S,N)] was observed when pH>9. The observation and identification of polymeric (higher than binuclear) adducts of Pt(II)/GSH and Pt(II)/l-Cys appears to be unprecedented. 相似文献
994.
Photosystem II (PSII) is a multisubunit chlorophyll–protein complex that drives electron transfer from water to plastoquinone using energy derived from light. In green plants, the native form of PSII is surrounded by the light-harvesting complex (LHCII complex) and thus it is called the PSII–LHCII supercomplex. Over the past several years, understanding of the structure, function, and assembly of PSII and LHCII complexes has increased considerably. The unicellular green alga Chlamydomonas reinhardtii has been an excellent model organism to study PSII and LHCII complexes, because this organism grows heterotrophically and photoautotrophically and it is amenable to biochemical, genetic, molecular biological and recombinant DNA methodology. Here, the genes encoding and regulating components of the C. reinhardtii PSII–LHCII supercomplex have been thoroughly catalogued: they include 15 chloroplast and 20 nuclear structural genes as well as 13 nuclear genes coding for regulatory factors. This review discusses these molecular genetic data and presents an overview of the structure, function and assembly of PSII and LHCII complexes. 相似文献
995.
Ohtaki H Dohi K Yofu S Nakamachi T Kudo Y Endo S Aruga T Goto N Watanabe J Kikuyama S Shioda S 《Regulatory peptides》2004,123(1-3):61-67
It has been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in preventing neuronal cell death and is also a potent vasodilator. Cerebral hypotension and hypoperfusion during cerebral ischemia and neurodegenerative diseases are well known as some of the negative factors which aggravate neuronal cell death. Nevertheless, the effect of PACAP on the cerebral circulation was not understood well. Therefore, in the present study, we determined the mean arterial blood pressure (MBP), regional cerebral blood flow (rCBF) and cerebral oxygen content (pO2) in mice, and estimated the therapeutically useful doses of PACAP. Under barbiturate anesthesia, polyethylene tubes were inserted into mice to monitor MBP and to administer PACAP (5 x 10(-13)-5 x 10(-8) mol/kg) or vasoactive intestinal peptide (VIP; 5 x 10(-12) and 5 x 10(-9) mol/kg). Then, MBP, rCBF and cerebral pO2 were simultaneously measured in the mice. PACAP (5 x 10(-10)-5 x 10(-9) mol/kg) injections transiently decreased MBP, and cerebral pO2. PACAP (5 x 10(-8) mol/kg) injections produced a long-lasting potent decline of MBP, rCBF and cerebral pO2. Therefore, PACAP should be applied at low doses which do not influence the MBP and cerebral circulation to determine the therapeutically useful doses of PACAP for neuroprotection. 相似文献
996.
Hu YJ Dolan ME Bae R Yee H Roy M Glickman R Kiremidjian-Schumacher L Diamond AM 《Biological trace element research》2004,101(2):97-106
Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously implicated in the risk and development of lung
and breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in squamous cell carcinomas of the head and neck. The frequency
of a polymorphism at codon 198 resulting in either a leucine or a proline at that position was surveyed by comparing 133 DNA
samples obtained from head and neck tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs exhibited fewer
pro/leu heterozygotes as compared to DNA obtained from the cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic alanine repeat sequences in the same gene.
The analysis revealed an approximately 42% reduction in heterozygosity in the DNA from the tumor samples. In order to assess
loss of heterozygosity (LOH) at the GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and microscopically normal tissues adjacent to the tumor,
derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues
at the tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly
linked to it, is an early event in the development of this type of malignancy.
Author to whom all correspondence and reprint requests should be addressed. These authors contributed equally to this work. 相似文献
997.
Enzymatic enantioselective transcyanation of silicon-containing aliphatic ketone with (S)-hydroxynitrile lyase from Manihot esculenta 总被引:2,自引:0,他引:2
(S)-Hydroxynitrile lyase from Manihot esculenta (MeHNL) was shown for the first time to be able to catalyze the enantioselective transcyanation of acetyltrimethylsilane (ATMS) with acetone cyanohydrin to form (S)-2-trimethylsilyl-2-hydroxyl-propionitrile in an aqueous/organic biphasic system. To better understand the reaction, various influential variables were examined. The most suitable organic phase, optimal buffer pH, aqueous phase content, shaking rate, temperature, concentration of ATMS, acetone cyanohydrin and crude enzyme were diisopropyl ether (DIPE), 5.4, 13% (v/v), 190 rpm, 40°C, 10 mM, 20 mM, and 35 U/ml, respectively, under which the initial reaction rate, substrate conversion and product enantiomeric excess (e.e.) were 19.5 mM/h, 99.0% and 93.5%, respectively. A comparative study demonstrated that silicon atoms in the substrate had a great effect on the reaction, and that ATMS was a much better substrate for MeHNL than its carbon analogue 3,3-dimethyl-2-butanone (DMBO) with respect to the initial reaction rate, substrate conversion and product e.e. MeHNL has greater affinity towards ATMS than its carbon analogue as indicated by the much lower Km. The activation energy of MeHNL-catalyzed transcyanation of ATMS was also markedly lower than that of DMBO. The silicon effect on the reaction was rationalized on the basis of the special characteristics of silicon atoms and the catalytic mechanism of MeHNL. 相似文献
998.
Davidoff AJ Mason MM Davidson MB Carmody MW Hintz KK Wold LE Podolin DA Ren J 《American journal of physiology. Endocrinology and metabolism》2004,286(5):E718-E724
We recently identified cardiomyocyte dysfunction in the early stage of type 2 diabetes (i.e., diet-induced insulin resistance). The present investigation was designed to determine whether a variety of clinically relevant interventions are sufficient to prevent and reverse cardiomyocyte dysfunction in sucrose (SU)-fed insulin-resistant rats. Subsets of animals were allowed to exercise (free access to wheel attached to cage) or were treated with bezafibrate in drinking water to determine whether these interventions would prevent the adverse effects of SU feeding on cardiomyocyte function. After 6-8 wk on diet and treatment, animals were surgically prepared to assess whole body insulin sensitivity (intravenous glucose tolerance test), and isolated ventricular myocyte mechanics were evaluated (video edge recording). SU feeding produced hyperinsulinemia and hypertriglyceridemia, with euglycemia, and induced characteristic whole body insulin resistance. Both exercise and bezafibrate treatment prevented these metabolic abnormalities. Ventricular myocyte shortening and relengthening were slower in SU-fed rats (42-63%) compared with starch (ST)-fed controls, and exercise or bezafibrate completely prevented cardiomyocyte dysfunction in SU-fed rats. In separate cohorts of animals, after 5 wk of SU feeding, animals were either switched back to an ST diet or given menhaden oil for an additional 7-9 wk to determine whether the cardiomyocyte dysfunction was reversible. Both interventions have previously been shown to have favorable metabolic effects, and both improved myocyte mechanics, but only the ST diet reversed all indications of cardiomyocyte dysfunction induced by SU feeding. Thus phenotypic changes in cardiomyocyte mechanics associated with early stages of type 2 diabetes were found to be both preventable and reversible with clinically relevant treatments, suggesting that the cellular processes contributing to this dysfunction are modifiable. 相似文献
999.
Itoh K Satoh Y Kadota Y Oheda Y Kuwahara J Shimmoto M Sakuraba H 《Neurochemistry international》2004,44(6):447-457
Human neuroblastoma GOTO cell lines were established that stably express recombinant human lysosomal protective protein/cathepsin A (PPCA) cDNA by transfection. Intracellular cathepsin A (acid serine carboxypeptidase) activity increased four-fold compared with in those of the parent and mock-transfected cell lines. The immunoreactive 54 kDa precursor/zymogen and mature 32/20 kDa two-chain forms were produced in the cells. The amount of the latter form expressed in the GOTO cells was significantly larger than those in the PPCA-overexpressing CHO cell lines previously established. The intracellular proteins showed a typical lysosomal granular distribution and the glycosylated 54 kDa precursor was secreted into the culture medium without the addition of an alkalizing agent. The PPCA-overexpressing cell lines also retained the ability to differentiate bi-directionally as well as the parent cells; into neuronal cells on induction by dibutyryl cAMP in serum-free medium and into Schwannian cells on induction by bromodeoxyuridine. During the course of differentiation into neuronal and Schwannian cells, the intracellular cathepsin A activity further increased two and five times, respectively, which was associated with an increase in the expression of the 32/20 kDa two-chain form. The glycosylated precursor proteins were taken up via the mannose 6-phosphate receptors, and the cathepsin A, alpha-neuraminidase and beta-galactosidase (beta-Gal) activities deficient in the fibroblasts derived from a patient with PPCA deficiency (galactosialidosis) were restored. These results suggest that the bi-directional differentiation of GOTO cell lines stably expressing the recombinant human PPCA gene could be a model system for analyzing the functions of PPCA in peripheral neuronal cells and Schwannian cells as well as the recombinant PPCA could be a useful source for enzyme replacement therapy (ERT) for galactosialidosis patients. 相似文献
1000.
Zhang HC Ye H Conway BR Derian CK Addo MF Kuo GH Hecker LR Croll DR Li J Westover L Xu JZ Look R Demarest KT Andrade-Gordon P Damiano BP Maryanoff BE 《Bioorganic & medicinal chemistry letters》2004,14(12):3245-3250
A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3beta and selectivity versus PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3beta (IC(50)=7 and 26 nM, respectively) and exhibited excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3beta. 相似文献