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151.
Das B Rudra S Yadav A Ray A Rao AV Srinivas AS Soni A Saini S Shukla S Pandya M Bhateja P Malhotra S Mathur T Arora SK Rattan A Mehta A 《Bioorganic & medicinal chemistry letters》2005,15(19):4261-4267
Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate. 相似文献
152.
Chintamani Jai Parakash Singh Mahesh K Mittal Sunita Saxena Anju Bansal Ashima Bhatia Pranjal Kulshreshtha 《World journal of surgical oncology》2005,3(1):1-9
Background
Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery.Methods
30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC) by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT) chemotherapy (CT) or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC®) for quantification of these cells.Results
In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21) whereas pneumonectomy led to a decrease (5/8) of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase). In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia adenocarcinoma were observed. The increase of CEC preceded clinical detection by six months.Conclusion
We consider, therefore, that patients with adenocarcinoma and a continuous increase of CEC after complete resection for lung cancer are at an increased risk of early relapse. 相似文献153.
Fowler AS Tiwari KN Campbell SR Secrist JA 《Nucleosides, nucleotides & nucleic acids》2005,24(5-7):533-537
N4-Acetyl-1-(2, 3-di-O-acetyl-4-thio-beta-D-arabinofuranosyl) cytosine (2) was synthesized in three steps from 1-(4-thio-beta-D-arabinofuranosyl) cytosine (1). The reaction of this partially blocked 4'-thio-ara-C derivative 2 with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one gave the 5-phosphitylate derivative 3, which on reaction with pyrophosphate gave the 5'-nucleosidylcyclotriphosphite 4. Product 4 was then oxidized with iodine/pyridine/water and deblocked with concentrated ammonium hydroxide to provide the desired 4'-thio-ara-C-5'-triphosphate 5. This triphosphate 5 was converted to 4'-thio-ara-C -5'-monophosphate 6 by treatment with snake venom phosphodiesterase I. The details of the synthesis, purification, and characterization of both nucleotides are described. 相似文献
154.
1-(2-Fluoro-2-deoxy-beta-D-drabinofuranosyl) uracil (5) and 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)cytosine (6) were synthesized as reported earlier. Both of these compounds were converted into 2'-fluoro-2'-deoxy-3'-C-ethynyl and 3'-C-vinyl-beta-D-lyxofuranosyl nuclearsides (16-19) by a multistep sequence. All these new nucleosides were evaluated against seven human tumor cell lines in vitro. 相似文献
155.
Kobrinsky E Tiwari S Maltsev VA Harry JB Lakatta E Abernethy DR Soldatov NM 《The Journal of biological chemistry》2005,280(13):12474-12485
Voltage-gated Ca(v)1.2 channels are composed of the pore-forming alpha1C and auxiliary beta and alpha2delta subunits. Voltage-dependent conformational rearrangements of the alpha1C subunit C-tail have been implicated in Ca2+ signal transduction. In contrast, the alpha1C N-tail demonstrates limited voltage-gated mobility. We have asked whether these properties are critical for the channel function. Here we report that transient anchoring of the alpha1C subunit C-tail in the plasma membrane inhibits Ca2+-dependent and slow voltage-dependent inactivation. Both alpha2delta and beta subunits remain essential for the functional channel. In contrast, if alpha1C subunits with are expressed alpha2delta but in the absence of a beta subunit, plasma membrane anchoring of the alpha1C N terminus or its deletion inhibit both voltage- and Ca2+-dependent inactivation of the current. The following findings all corroborate the importance of the alpha1C N-tail/beta interaction: (i) co-expression of beta restores inactivation properties, (ii) release of the alpha1C N terminus inhibits the beta-deficient channel, and (iii) voltage-gated mobility of the alpha1C N-tail vis a vis the plasma membrane is increased in the beta-deficient (silent) channel. Together, these data argue that both the alpha1C N- and C-tails have important but different roles in the voltage- and Ca2+-dependent inactivation, as well as beta subunit modulation of the channel. The alpha1C N-tail may have a role in the channel trafficking and is a target of the beta subunit modulation. The beta subunit facilitates voltage gating by competing with the N-tail and constraining its voltage-dependent rearrangements. Thus, cross-talk between the alpha1C C and N termini, beta subunit, and the cytoplasmic pore region confers the multifactorial regulation of Ca(v)1.2 channels. 相似文献
156.
Tummala H Jung C Tiwari A Higgins CM Hayward LJ Xu Z 《The Journal of biological chemistry》2005,280(18):17725-17731
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration, paralysis, and death. Mutant Cu,Zn-superoxide dismutase (SOD1) causes a subset of ALS by an unidentified toxic property. Increasing evidence suggests that chaperone dysfunction plays a role in motor neuron degeneration in ALS. To investigate the relationship between mutant SOD1 expression and chaperone dysfunction, we measured chaperone function in central nervous system tissue lysates from normal mice and transgenic mice expressing human SOD1 variants. We observed a significant decrease in chaperone activity in tissues from mice expressing ALS-linked mutant SOD1 but not control mice expressing human wild type SOD1. This decrease was detected only in the spinal cord, became apparent by 60 days of age (before the onset of muscle weakness and significant motor neuron loss), and persisted throughout the late stages. In addition, this impairment of chaperone activity occurred only in cytosolic but not in mitochondrial and nuclear fractions. Furthermore, multiple recombinant human SOD1 mutants with differing biochemical and biophysical properties inhibited chaperone function in a cell-free extract of normal mouse spinal cords. Thus, mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of ALS-linked mutant SOD1 proteins. 相似文献
157.
Alkyl 2,3-unsaturated C-glycopyranosides have been prepared by Ferrier rearrangement of acyl or alkyl protected glycals catalyzed by HClO(4)-SiO(2). 相似文献
158.
Andrew CR Kemper LJ Busche TL Tiwari AM Kecskes MC Stafford JM Croft LC Lu S Moënne-Loccoz P Huston W Moir JW Eady RR 《Biochemistry》2005,44(24):8664-8672
The heme coordination chemistry and spectroscopic properties of Rhodobacter capsulatus cytochrome c' (RCCP) have been compared to data from Alcaligenes xylosoxidans (AXCP), with the aim of understanding the basis for their different reactivities with nitric oxide (NO). Whereas ferrous AXCP reacts with NO to form a predominantly five-coordinate heme-nitrosyl complex via a six-coordinate intermediate, RCCP forms an equilibrium mixture of six-coordinate and five-coordinate heme-nitrosyl species in approximately equal proportions. Ferrous RCCP and AXCP both exhibit high Fe-His stretching frequencies (227 and 231 cm(-)(1), respectively), suggesting that factors other than the Fe-His bond strength account for their differences in heme-nitrosyl coordination number. Resonance Raman spectra of ferrous-nitrosyl RCCP confirm the presence of both five-coordinate and six-coordinate heme-NO complexes. The six-coordinate heme-nitrosyl of RCCP exhibits a fairly typical Fe-NO stretching frequency (569 cm(-)(1)), in contrast to the relatively high value (579 cm(-)(1)) of the AXCP six-coordinate heme-nitrosyl intermediate. It is proposed that NO experiences greater steric hindrance in binding to the distal face of AXCP, as compared to RCCP, leading to a more distorted Fe-N-O geometry and an elevated Fe-NO stretching frequency. Evidence that RCCP has a more accessible distal coordination site than in AXCP stems from the fact that ferric RCCP readily forms a heme complex with exogenous imidazole, whereas AXCP does not. A model is proposed in which distal heme-face accessibility, rather than the proximal Fe-His bond strength, determines the heme-nitrosyl coordination number in cytochromes c'. 相似文献
159.
BACKGROUND: Initially described as a pleural tumor, solitaryfibrous tumor of the parotid gland (SFT) is rare and has been reported at a wide range ofanatomic sites. Although cases of SFT arising in the parotid gland have been previously described, a review of the literature failed to reveal cytology-based reports of this entity. CASE: A 42-year-old man presented with a right parotid mass that had gradually enlarged over 3 years. He was otherwise asymptomatic. Fine needle aspiration biopsy of the mass showed a hypercellular smear composed of spindle cells in both clusters and isolated forms, with ovoid nuclei, evenly distributed chromatin, inconspicuous nucleoli and scant to moderate cytoplasm with focally wispy, collagenous, intercellular material. The background was hemorrhagic, without chondromyxoid matrix or inflammatory cells. There was no evidence of a myoepithelial component. A diagnosis of spindle cell neoplasm was rendered. Histologic examination of the total parotidectomy specimen revealed a SFT arising in the parotid gland. The diagnosis was supported by immunohistochemical studies. CONCLUSION: SFT is a well-circumscribed neoplasm composed of short, spindled, plump cells with scanty cytoplasm growing in a haphazard or "patternless" pattern. Tumor cells are intimately admixed with collagenous stroma. Hemangiopericytomalike vessels are frequently seen. Although SFT rarely occurs in the salivary gland and a definitive diagnosis based on cytologic preparations alone is difficult, the diagnosis of SFT can be considered when cytologic examination reveals a hypercellular smear composed of isolated, cohesive clusters of spindled, fibroblastlike cells associated with a collagenous component in ahemorrhagic background. The preoperative magnetic esonance image findings of a highly vascular neoplasm support the diagnosis. 相似文献
160.
Octopamine acts as an important neurotransmitter and neuromodulator in arthropods, mollusks, and nematodes. In mammals, however, no definite function for this amine has yet been described. By virtue of this difference in the neurophysiological requirement of the mammalian host and nematodes, octopamine offers good opportunity for exploring this area deeply with a view to identify a unique target for filarial chemotherapy. Results of the present study indicated that Acanthocheilonema viteae, the rodent filarial parasite, utilized tyrosine as a precursor for producing octopamine and some other biogenic amines. Octopamine exhibited specific saturable binding with the membrane prepared from the anterior portion of the filariid. This amine induced concentration dependent increase in the membrane potential which possibly caused tonic paralysis of the filariid. The rate of micro filarial release by the female worms also declined in the presence of this amine. The study thus provided preliminary evidences for the presence of an octopamine neurotransmitter system and also about some of the roles it plays in A. viteae. 相似文献