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151.
Shue HJ Chen X Shih NY Blythin DJ Paliwal S Lin L Gu D Schwerdt JH Shah S Reichard GA Piwinski JJ Duffy RA Lachowicz JE Coffin VL Liu F Nomeir AA Morgan CA Varty GB 《Bioorganic & medicinal chemistry letters》2005,15(17):3896-3899
A series of novel five- and six-membered ring urea derivatives have been described as potent and selective NK1 receptor antagonists. Several compounds in this series exhibited good oral activity and brain penetration. Syntheses of these compounds are also described herein. 相似文献
152.
153.
Hasegawa U Nomura SM Kaul SC Hirano T Akiyoshi K 《Biochemical and biophysical research communications》2005,331(4):917-921
We report here a novel carrier of quantum dots (QDs) for intracellular labeling. Monodisperse hybrid nanoparticles (38 nm in diameter) of QDs were prepared by simple mixing with nanogels of cholesterol-bearing pullulan (CHP) modified with amino groups (CHPNH2). The CHPNH2-QD nanoparticles were effectively internalized into the various human cells examined. The efficiency of cellular uptake was much higher than that of a conventional carrier, cationic liposome. These hybrid nanoparticles could be a promising fluorescent probe for bioimaging. 相似文献
154.
Sunil?Kumar Koel?ChaudhuryEmail author Prasenjit?Sen Sujoy?K?Guha 《Journal of nanobiotechnology》2005,3(1):9
Atomic force microscopy (AFM) has emerged as the only technique capable of real-time imaging of the surface of a living cell
at nano-resolution. Since AFM provides the advantage of directly observing living biological cells in their native environment,
this technique has found many applications in pharmacology, biotechnology, microbiology, structural and molecular biology,
genetics and other biology-related fields. AFM has also proved to be a valuable tool for reproductive biologists. An exhaustive
review on the various applications of AFM to sperm cells is presented. AFM has been extensively applied for determining the
structural and topological features of spermatozoa. Unstained, unfixed spermatozoa in their natural physiological surroundings
can be imaged by this technique which provides valuable information about the morphological and pathological defects in sperm
cells as three-dimensional images with precise topographical details. Sperm head defects and the acrosome at the tip of the
head responsible for fertilization, can be examined and correlated with the lack of functional integrity of the cell. Considerable
amount of work is reported on the structural details of the highly condensed chromatin in sperm head using AFM. Detailed information
on 3D topographical images of spermatozoa acquired by AFM is expected to provide a better understanding of various reproductive
pathways which, in turn, can facilitate improved infertility management and/or contraceptive development. 相似文献
155.
Samaiya A Deo SS Thulkar S Hazarika S Kumar S Parida DK Shukla NK 《World journal of surgical oncology》2005,3(1):3-7
BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients. 相似文献
156.
Diseases of specific fibrocartilaginous joints are especially common in women of reproductive age, suggesting that female hormones contribute to their etiopathogenesis. Previously, we showed that relaxin dose-dependently induces matrix metalloproteinase (MMP) expression in isolated joint fibrocartilaginous cells. Here we determined the effects of relaxin with or without beta-estradiol on the modulation of MMPs in joint fibrocartilaginous explants, and assessed the contribution of these proteinases to the loss of collagen and glycosaminoglycan (GAG) in this tissue. Fibrocartilaginous discs from temporomandibular joints of female rabbits were cultured in medium alone or in medium containing relaxin (0.1 ng/ml) or beta-estradiol (20 ng/ml) or relaxin plus beta-estradiol. Additional experiments were done in the presence of the MMP inhibitor GM6001 or its control analog. After 48 hours of culture, the medium was assayed for MMPs and the discs were analyzed for collagen and GAG concentrations. Relaxin and beta-estradiol plus relaxin induced the MMPs collagenase-1 and stromelysin-1 in fibrocartilaginous explants--a finding similar to that which we observed in pubic symphysis fibrocartilage, but not in articular cartilage explants. The induction of these proteinases by relaxin or beta-estradiol plus relaxin was accompanied by a loss of GAGs and collagen in joint fibrocartilage. None of the hormone treatments altered the synthesis of GAGs, suggesting that the loss of this matrix molecule probably resulted from increased matrix degradation. Indeed, fibrocartilaginous explants cultured in the presence of GM6001 showed an inhibition of relaxin-induced and beta-estradiol plus relaxin-induced collagenase and stromelysin activities to control baseline levels that were accompanied by the maintenance of collagen or GAG content at control levels. These findings show for the first time that relaxin has degradative effects on non-reproductive synovial joint fibrocartilaginous tissue and provide evidence for a link between relaxin, MMPs, and matrix degradation. 相似文献
157.
Activation of wild type p53 function by its mortalin-binding, cytoplasmically localizing carboxyl terminus peptides 总被引:6,自引:0,他引:6
Kaul SC Aida S Yaguchi T Kaur K Wadhwa R 《The Journal of biological chemistry》2005,280(47):39373-39379
The Hsp70 family member mortalin (mot-2/mthsp70/GRP75) binds to a carboxyl terminus region of the tumor suppressor protein p53. By in vivo co-immunoprecipitation of mot-2 with p53 and its deletion mutants, we earlier mapped the mot-2-binding site of p53 to its carboxyl terminus 312-352 amino acid residues. In the present study we attempted to disrupt mot-2-p53 interactions by overexpression of short p53 carboxyl-terminal peptides. We report that p53 carboxyl-terminal peptides (amino acid residues 312-390, 312-352, 323-390, and 323-352) localize in the cytoplasm, whereas 312-322, 337-390, 337-352, and 352-390 locate mostly in the nucleus. Most interestingly, the cytoplasmically localizing p53 peptides harboring the residues 323-337 activated the endogenous p53 function by displacing it from p53-mortalin complexes and relocating it to the nucleus. Such activation of p53 function was sufficient to cause growth arrest of human osteosarcoma and breast carcinoma cells. 相似文献
158.
Bi Y Stuelten CH Kilts T Wadhwa S Iozzo RV Robey PG Chen XD Young MF 《The Journal of biological chemistry》2005,280(34):30481-30489
Extracellular matrix glycoproteins and proteoglycans bind a variety of growth factors and cytokines thereby regulating matrix assembly as well as bone formation. However, little is known about the mechanisms by which extracellular matrix molecules modulate osteogenic stem cells and bone formation. Using mice deficient in two members of the small leucine-rich proteoglycans, biglycan and decorin, we uncovered a role for these two extracellular matrix proteoglycans in modulating bone formation from bone marrow stromal cells. Our studies showed that the absence of the critical transforming growth factor-beta (TGF-beta)-binding proteoglycans, biglycan and decorin, prevents TGF-beta from proper sequestration within the extracellular matrix. The excess TGF-beta directly binds to its receptors on bone marrow stromal cells and overactivates its signaling transduction pathway. Overall, the predominant effect of the increased TGF-beta signaling in bgn/dcn-deficient bone marrow stromal cells is a "switch in fate" from growth to apoptosis, leading to decreased numbers of osteoprogenitor cells and subsequently reduced bone formation. Thus, biglycan and decorin appear to be essential for maintaining an appropriate number of mature osteoblasts by modulating the proliferation and survival of bone marrow stromal cells. These findings underscore the importance of the micro-environment in controlling the fate of adult stem cells and reveal a novel cellular and molecular basis for the physiological and pathological control of bone mass. 相似文献
159.
Helms MN Liu L Liang YY Al-Khalili O Vandewalle A Saxena S Eaton DC Ma HP 《The Journal of biological chemistry》2005,280(49):40885-40891
Whole cell voltage clamp experiments were performed in a mouse cortical collecting duct principal cell line using patch pipettes back-filled with a solution containing phosphatidylinositol 3,4,5-trisphosphate (PIP(3)). PIP(3) significantly increased amiloridesensitive current in control cells but not in the cells prestimulated by aldosterone. Additionally, aldosterone stimulated amiloridesensitive current in control cells, but not in the cells that expressed a PIP(3)-binding protein (Grp1-PH), which sequestered intracellular PIP(3). 12 amino acids from the N-terminal tail (APGEKIKAKIKK) of gamma-epithelial sodium channel (gamma-ENaC) were truncated by PCRbased mutagenesis (gammaT-ENaC). Whole cell and confocal microscopy experiments were conducted in Madin-Darby canine kidney cells co-expressing alpha- and beta-ENaC only or with either gamma-ENaC or gamma(T)-ENaC. The data demonstrated that the N-terminal tail truncation significantly decreased amiloride-sensitive current and that both the N-terminal tail truncation and LY-294002 (a PI3K inhibitor) prevented ENaC translocation to the plasmamembrane. These data suggest that PIP(3) mediates aldosterone-induced ENaC activity and trafficking and that the N-terminal tail of gamma-ENaC is necessary for channel trafficking, probably channel gating as well. Additionally, we demonstrated a novel interaction between gamma-ENaC and PIP(3). 相似文献
160.
The function of the middle ear is to resolve the acoustic impedance mismatch between the air in the ear canal and the fluid of the inner ear. Without this impedance matching, very little acoustic energy would be absorbed into the cochlea. The first step in this process is the tympanic membrane (TM) converting sound in the ear canal into vibrations of the middle ear bones. Understanding how the TM manages its task so successfully over such a broad frequency range should lead to more satisfactory and less variable TM repairs (myringoplasty). In addition, understanding the mechanics of the TM is necessary to improve the coupling between ossicular prostheses and the TM. Mathematical models have played a central role in helping the research community understand the mechanics of the eardrum. However, all models require parameters as inputs. Unfortunately, most of the parameters needed for modeling the TM are not well known. In this work, several approaches for inferring the material properties of the TM are explored. First, constitutive modeling is used to estimate an elastic modulus based on the elastic modulus of collagen and experimentally observed fiber densities. Second, experimental tension and bending test results from the literature are re-interpreted using composite laminate theory. Lastly, dynamic measurements of the cat TM are used in conjunction with a composite shell model to bound the material parameters. Values from the literature, both measurement and modeling efforts, and from the present analysis are brought together to form a coherent picture of the TM's material properties. In the human, the data bound the elastic modulus between 0.1 and 0.3 GPa. In the cat, the data suggest a range of 0.1-0.4 GPa. These values are significantly higher than previous estimates. 相似文献