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971.
972.
973.
Generation of constitutively active recombinant caspases-3 and -6 by rearrangement of their subunits 总被引:1,自引:0,他引:1
SM Srinivasula M Ahmad M MacFarlane Z Luo Z Huang T Fernandes-Alnemri ES Alnemri 《Canadian Metallurgical Quarterly》1998,273(17):10107-10111
Caspases play a major role in the transduction of the apoptotic signal and execution of apoptosis in mammalian cells. Ectopic overexpression of the short prodomain caspases-3 and -6 precursors in mammalian cells does not induce apoptosis. This is due to their inability to undergo autocatalytic processing/activation and suggests that they depend on the long prodomain caspases for activation. To investigate directly the apoptotic activity of these two caspases in vivo, we engineered constitutively active recombinant caspases-3 and -6 precursors. This was achieved by making contiguous precursor caspases-3 and -6 molecules, which have their small subunits preceding their large subunits. Unlike their wild type counterparts, these recombinant molecules were capable of autocatalytic processing in an in vitro translation reaction, suggesting that they are catalytically active. They were also capable of autoprocessing and inducing apoptosis in vivo independent of the upstream caspases. Furthermore, their autocatalytic and apoptotic activities were inhibited by the pancaspase inhibitor z-VAD-fluoromethylketone, but not by CrmA or Bcl-2, thus directly demonstrating that the targets of inhibition of apoptosis by CrmA and Bcl-2 are upstream of caspases-3 and -6. Since caspases-3 and -6 are the most downstream executioners of apoptosis, the constitutively active versions of these caspases could be used at very low concentrations in gene therapy model systems to induce apoptosis in target tissues or tumors. 相似文献
974.
WH Yu M Kimura A Walczewska JC Porter SM McCann 《Canadian Metallurgical Quarterly》1998,95(13):7795-7798
Adenosine has been identified in the anterior pituitary gland and is secreted from cultured folliculostellate (FS) cells. To determine whether adenosine controls the secretion of anterior pituitary hormones in vitro, adenosine was incubated with anterior pituitaries. It stimulated prolactin (PRL) release at the lowest concentration used (10(-10) M); the stimulation peaked at 10(-8) M with a threefold increase in release and declined to minimal stimulation at 10(-4) and 10(-3) M. Follicle-stimulating hormone release was maximally inhibited at 10(-8) M, whereas luteinizing hormone release was not significantly inhibited. Two selective A1 adenosine receptor antagonists (10(-7) or 10(-5) M) had no effect on basal PRL release, but either antagonist completely blocked the response to the most effective concentration of adenosine (10(-8) M). In contrast, a highly specific A2 receptor antagonist (10(-7) or 10(-5) M) had no effect on basal PRL release or the stimulation of PRL release induced by adenosine (10(-8) M). We conclude that adenosine acts to stimulate PRL release in vitro by activating A1 receptors. Since the A1 receptors decrease intracellular-free calcium, this would decrease the activation of nitric oxide synthase in the FS cells, resulting in decreased release of nitric oxide (NO). NO inhibits PRL release by activating guanylate cyclase that synthesizes cGMP from GTP; cGMP concentrations increase in the lactotrophs leading to inhibition of PRL release. In the case of adenosine, NO release from the FS cells decreases, resulting in decreased concentrations of NO in the lactotrophs, consequent decreased cGMP formation, and resultant increased PRL release. 相似文献
975.
A fetal head and neck malignancy was prenatally diagnosed. The parents allowed the fetus to die during labour, due to the poor prognosis. We discuss the corresponding pathology findings, differential diagnosis, and management of this rare entity. Prenatal diagnosis of fetal neoplasms theoretically improves outcome, although this was not true in our case. 相似文献
976.
977.
A software system for interactive manipulation of three-dimensional data has been developed, based on the Open Inventor tool kit. The primary use of this software system is in the segmentation of tomographic reconstructions of subcellular structures. To this end, the reconstruction is represented by volume rendering and displayed in stereo. A three-dimensional cursor with adjustable shape and size is used to define and isolate regions of interest inside the volume, based on the user's expert knowledge. Once isolated, the region of interest can be conveniently analyzed and displayed. 相似文献
978.
SM Lyons 《Canadian Metallurgical Quarterly》1998,67(1):49-58
Endoscopic evaluation of the patient with lung metastases takes on many forms depending upon the extent of disease and the intent of treatment, be that curative or palliative. Thorascopy, and occasionally mediastinoscopy, may be helpful in assessing operability in patients with extensive disease on a preoperative computed tomography scan. However, when in doubt, exploration is always indicated in the young, good risk patient. Palliative efforts usually concern airway obstruction and malignant effects. A variety of technologies, including laser, brachytherapy, and endoluminal stents, helps manage symptomatic bronchial or tracheal lesions. 相似文献
979.
XS Wu-Peng SC Chua N Okada SM Liu M Nicolson RL Leibel 《Canadian Metallurgical Quarterly》1997,46(3):513-518
The obese phenotypes of the diabetes (db) mouse and fatty fa) rat are due to functional null mutations of the leptin receptor (Lepr). The recessive mutation in the Koletsky (f) obese rat maps to the same genetic intervals as db and fa and fails to complement the fa mutation. Comparison of the sequence of brain Lepr cDNA from +/+ and f/f animals reveals a T2349A transversion resulting in a Tyr763Stop nonsense mutation in the gene just before the transmembrane domain. Virtual absence of Lepr mRNA in whole brain from f/f animals is consistent with the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF) transport of leptin in both f/f and fa/fa mutants is reflected in the approximately 10-fold lower ratio of CSF/plasma leptin concentration in the obese versus lean animals. However, equivalent CSF leptin concentration between lean and obese rats (fa/fa, f/f) indicates that leptin can enter the CSF through a non-Lepr-mediated mechanism, which may be saturated at normal physiological plasma leptin concentration. 相似文献
980.
RA Hahn SM Teutsch AL Franks MH Chang EE Lloyd 《Canadian Metallurgical Quarterly》1998,53(2):96-104, 107
OBJECTIVE: To analyze the prevalence of 11 modifiable behavioral risk factors, including multiple risk factors, among white, black, Asian and Pacific Islander, American Indian, and Hispanic women in the United States. DESIGN: We used Behavioral Risk Factor Surveillance System (BRFSS) data for 1992 to 1994 to examine risk factors (smoking; obesity; diabetes; heavy alcohol consumption; sedentary lifestyle; and inadequate use of seat belts, pap smears, consumption of fruits or vegetables, mammography and colorectal screening, and immunization), among women age 18 to 49, 50 to 64, and 65 and older. We also conducted a multiple regression analysis, comparing the odds of having either 1-2 versus 0 or 3 or more versus 0 risk factors among racial/ethnic groups, controlling for education and family income, to see if racial/ethnic differences can be attributed to socioeconomic differences. RESULTS: US women engage in a variety of behaviors that place them at risk for many causes of morbidity and mortality. Risk profiles vary substantially among racial/ethnic populations: Pacific Islanders have relatively low prevalences of most major risk factors, while blacks and American Indians have relatively high prevalences of many major risk factors. Prevalence differences among racial/ethnic populations are diminished but not eliminated when socioeconomic factors are accounted for. CONCLUSIONS: Appropriately designed programs to help women reduce their behavioral risk factors are needed. Action by health care providers, communities, and policy makers can substantially improve the health of women in the United States. 相似文献