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71.
Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.  相似文献   
72.
Thiamine release from nerve membranes by tetrodotoxin   总被引:3,自引:0,他引:3  
Tetrodotoxin (3 x 10(-8) molar) promoted the release of thiamine from perfused rat and frog nerve preparations in a manner similar to other neuroactive drugs. When the rats were injected with thiamine labeled with sulfur-35, analyses of brain, spinal cord, and sciatic nerve homogenates revealed labeled thiamine in membrane, synaptosomes, and mitochondrial subfractions. However, on incubation of these fractions with tetrodotoxin, thiamine was released only from the membrane fragments.  相似文献   
73.
Molecular defect in a gamma-2 heavy chain   总被引:9,自引:0,他引:9  
The first gamma-2 (gamma2) heavy chain disease protein Gif has pyrroli-dinecarboxylic acid as its amino terminal residue, much of the Fd variable region, and an internal deletion of the heavy chain of about 100 residues corresponding to most of the Fd constant region. Normal sequence resumes with a glutamic acid residue at position 216 in the hinge region. This is the third gamma heavy chain disease protein where normal sequence resumes at the same position after the deletion.  相似文献   
74.
Bubble chambers were the dominant technology used for particle detection in accelerator experiments for several decades, eventually falling into disuse with the advent of other techniques. We report here on a new application for these devices. We operated an ultraclean, room-temperature bubble chamber containing 1.5 kilograms of superheated CF3I, a target maximally sensitive to spin-dependent and -independent weakly interacting massive particle (WIMP) couplings. An extreme intrinsic insensitivity to the backgrounds that commonly limit direct searches for dark matter was measured in this device under operating conditions leading to the detection of low-energy nuclear recoils like those expected from WIMPs. Improved limits on the spin-dependent WIMP-proton scattering cross section were extracted during our experiments, excluding this type of coupling as a possible explanation for a recent claim of particle dark-matter detection.  相似文献   
75.
A 4-yr-old male captive hooded seal (Cystophora cristata), previously diagnosed as hypothyroid, died after a 3-wk period of lethargy and inappetance despite treatment that included intramuscular administration of antibiotics and multivitamins. Gross pathologic findings included extensive muscle necrosis over the left flank, an underlying necrotic iliac lymph node, two necrotic pulmonary masses and a necrotic bronchial lymph node. Routine cultures yielded a number of bacterial isolates and a heavy pure fungal growth from the necrotic iliac lymph node; wet preparations of which revealed sporangiophores typical of Mucor sp. Histopathology of necrotic muscle, pulmonary lesions and bronchial and iliac lymph nodes revealed necrosis with a marked pyogranulomatous and eosinophilic inflammatory cell infiltrate and fungal hyphae consistent with a Zygomycete species. This is believed to be the first report of systemic mucormycosis in a pinniped likely to have originated from an injection site reaction.  相似文献   
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Results from the pioneering research on the interactions between pH and denitrification in soil from the 1950s to the present are reviewed, the changing perceptions of this complex relationship are discussed, and the current status of the subject is assessed. Facets of this relationship that are analysed in detail include the direct or indirect influence of pH on overall denitrification rates in soils, changes in the composition of gaseous products that depend on pH, methods for measuring the process, the concept of an optimum pH for denitrification, and the adaptation of microbial denitrifying communities to acidic environments. The main conclusions to be drawn are as follows. Total gaseous emissions to the atmosphere (N2O, NO and N2) have repeatedly been shown to be less in acidic than in neutral or slightly alkaline soils. This may be attributable to smaller amounts of organic carbon and mineral nitrogen available to the denitrifying population under acid conditions rather than a direct effect of low pH on denitrification enzymes. Numerous laboratory and field studies have demonstrated that the ratio N2O:N2 is increased when the pH of soils is reduced. The relation between soil pH and potential denitrification as determined by various incubation methods remains unclear, results being influenced both by original conditions in soil samples and by unknown changes during incubation. The concept of an optimum pH for denitrification has been frequently proposed, but such a term has little or no meaning without reference to specific attributes of the process.  相似文献   
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The study reported here was undertaken to determine the nephrotoxicosis associated with the administration of cisplatin, an antineoplastic agent, to dogs when administered during 6-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface, IV, every 21 days) was given to 61 dogs with malignant neoplasia with a total of 185 doses in 1 (n = 9 dogs), 2 (n = 26 dogs), 3 (n = 4 dogs), 4 (n = 9 dogs), 5 (n = 2 dogs), and 6 (n = 11 dogs) treatments. The cisplatin was given over a 20-minute period after 0.9% NaCl solution (saline solution) was administered IV for 4 hours at a rate of 18.3 ml/kg of body weight/h. After the cisplatin infusion, saline solution diuresis was continued at the same rate for 2 hours. Before each treatment with cisplatin, dogs were evaluated with at least a physical examination, CBC, determination of serum urea nitrogen concentration, and in most cases, determination of serum creatinine concentration and urine specific gravity. Four of the 61 dogs (6.6%) developed clinically evident renal disease after 2 (1 dog), 3 (2 dogs), and 4 (1 dog) doses of cisplatin were administered. Three of the 4 dogs had preexisting disease of the urinary tract prior to the start of treatment. The survival time in dogs that developed renal disease (median, 145 days; range, 15 to 150 days) was similar to that of all dogs in this study (median, 154 days; range, 30 to 500 days), with 13 dogs still alive at the conclusion of the study.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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