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51.
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53.
Tenzer A Zingg D Riesterer O Vuong V Bodis S Pruschy M 《Current Medicinal Chemistry-Anti-Cancer Agents》2002,2(6):727-742
DNA double strand breaks are the pivotal cellular damage induced by ionizing radiation. A plethora of molecular and cellular processes are activated as part of the cellular stress response that result in cell cycle arrest and induction of the DNA-repair machinery to restore the damage of DNA or to activate a cell death program. However ionizing radiation also initiates signal transduction cascades that are generated at cellular sites distant from and independent of DNA-damage. These signaling processes are similar to hormone activated growth factor receptor controlled signal transduction cascades and represent interesting targets for anticancer treatment modalities combining ionizing radiation with molecular defined pharmacological compounds. Activation of these signal transduction cascades upon irradiation or upregulation of growth factor mediated pathways due to oncogene-transformation often contribute to an acquired or inherent treatment resistance in malignant cells. Therefore pharmacological compounds inhibiting specific key-entities of these signal transduction cascades potentially sensitize for radiation induced cell death. Here we describe current preclinical concepts of combined treatment strategies with locoregional-applied ionizing radiation and molecular defined signal transduction inhibitors to overcome a high treatment threshold in tumor cells. 相似文献
54.
The authors compared 130 patients treated for cervical dystonia with original botulinum toxin (BTX) type A (Botox; Allergan, Inc., Irvine, CA), 42 of whom were exposed only to the original BTX type A used before 1998 (25 ng protein/100 units), and 119 treated only with the current BTX type A (5 ng of protein/100 units). Blocking antibodies were detected in 4 of 42 (9.5%) patients treated only with original BTX type A but in none of the 119 patients treated exclusively with current BTX type A (p < 0.004). The current preparation decreased the risk of antibody formation by a factor of six. The authors conclude that the low risk of antibody formation after current BTX type A treatment is related to lower protein load. 相似文献
55.
56.
Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus 总被引:10,自引:0,他引:10
Biofilm formation by Staphylococcus aureus is a serious problem in nosocomial infections. There are great differences in the capacity of S. aureus to express biofilms, but the reasons are unknown. In all, 105 S. aureus strains were tested for a correlation between the agr quorum-sensing system phenotype and the ability of S. aureus to adhere to polystyrene. Some 78% of agr-negative, but only 6% of agr-positive, strains formed a biofilm, demonstrating a profound impact of agr on biofilm formation. This result was confirmed with defined agr mutants and by inhibition of agr with quorum-sensing blockers. The observed effect was not due to differential expression of the autolysin Atl or of the exopolysaccharide polysaccharide intercellular adhesin but seemed to be caused, at least in part, by the surfactant properties of delta-toxin. The detected biofilm-enhancing effect of S. aureus quorum-sensing blockers call into question the proposed therapeutic use of such substances. 相似文献
57.
Dietary zinc deficiency in rats induces hyperplasia in the esophagus and
increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor
incidence. Previous work showed a direct relationship between epithelial
cell proliferation and esophageal tumor incidence in rats given multiple
doses of NMBA. We investigated the effects of single low doses of NMBA in
zinc-deficient rats since a single dose of 5.0 mg/kg was reported to be
non-carcinogenic in rats. Zinc-sufficient and deficient rats received a
single i.g. dose of NMBA at 0.5 or 2.0 mg/kg. At week 14, tumor incidence
was 50% with 0.8 +/- 1.0 tumors/rat, and 80% with 2.2 +/- 1.9 tumors/rat,
in deficient groups, D(0.5) and D(2.0), that received the lower and higher
dose, respectively. In addition, two small papillomas were found in one out
of eight untreated zinc-deficient rats. None of the NMBA-treated or
untreated zinc- sufficient rats had any tumors. Esophageal cell
proliferation, as determined by proliferating cell nuclear antigen (PCNA)
immunohistochemistry, showed that, irrespective of NMBA treatment,
deficient esophagi had significant increases in the number of labeled
cells, the total number of cells, and the labeling index, as compared with
zinc-sufficient ones. Mutations in Ha-ras and p53 genes in esophageal
tumors were detected by single strand conformation polymorphism (SSCP)
analysis. DNA sequencing of variant conformers revealed a point mutation
(GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%) and 5/8 (63%) tumors, from
D(0.5) and D(2.0) rats, respectively. Three out of eight tumors from D(2.0)
rats exhibited SSCP mobility shifts within p53 exons 5 and 7: two tumors
(2/8, 25%) had missense mutations and the third, a silent mutation. Of the
two tumors with p53 mutations, one had a double mutation (transition at
codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and the
other tumor, a transition at codon 172 (AGA-->GGA), with amino acid
changes in all cases. In parallel with PCNA expression, elevated p53
expression was associated with hyperplastic and dysplastic regions, as well
as with tumors, in deficient esophagi. In short, these data indicate that
dietary zinc deficiency, with its associated sustained increased cell
proliferation in the esophagus, can drive an otherwise non-tumorigenic dose
of NMBA into a highly tumorigenic one.
相似文献
58.
A southern Australian Phorbas species has yielded a novel diterpene, phorbasin A (1), possessing an unprecedented carbon skeleton. The structure for phorbasin A was determined by detailed spectroscopic analysis. 相似文献
59.
Introduction
Most cochlear implants are currently compatible with magnetic resonance imaging (MRI) up to 3?T. Nevertheless, this does not completely eliminate the risk of serious accidents. Implant displacements and other adverse events with compatible implants have been reported in the literature.Case reports
Among the six patients who had MRI after receiving implants at our center, we report three cases with adverse events related to the examination. The first case was complicated by magnet displacement with partial demagnetization. The second case showed total demagnetization, which necessitated removal and reimplantation of the implant. The third case involved severe pain sensation which disrupted the MRI scan. The smallest artifact was found with 3D MRI angiography, and largest artifact was found with diffusion and T2 FLASH.Discussion
Moving the patient into the MRI apparatus must be supervised by an otorhinolaryngology specialist or an experienced radiologist. It is important to consider the magnetic field directions, so that angle between the implant magnetic fields and the MRI B0 always remains less than or equal to 90°. In addition, we recommend the use of an “arrow drawing” to facilitate the orientation of the magnetic field directions. Furthermore, to prevent magnet displacement, we recommend systematic use of a protective splint in addition to bandaging. 相似文献60.
Kocianova S Vuong C Yao Y Voyich JM Fischer ER DeLeo FR Otto M 《The Journal of clinical investigation》2005,115(3):688-694
Coagulase-negative staphylococci, with the leading species Staphylococcus epidermidis, are the predominant cause of hospital-acquired infections. Treatment is especially difficult owing to biofilm formation and frequent antibiotic resistance. However, virulence mechanisms of these important opportunistic pathogens have remained poorly characterized. Here we demonstrate that S. epidermidis secretes poly-gamma-DL-glutamic acid (PGA) to facilitate growth and survival in the human host. Importantly, PGA efficiently sheltered S. epidermidis from key components of innate host defense, namely antimicrobial peptides and neutrophil phagocytosis, and was indispensable for persistence during device-related infection. Furthermore, PGA protected S. epidermidis from high salt concentration, a key feature of its natural environment, the human skin. Notably, PGA was synthesized by all tested strains of S. epidermidis and a series of closely related coagulase-negative staphylococci, most of which are opportunistic pathogens. Our study presents important novel biological functions for PGA and indicates that PGA represents an excellent target for therapeutic maneuvers aimed at treating disease caused by S. epidermidis and related staphylococci. 相似文献