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排序方式: 共有635条查询结果,搜索用时 8 毫秒
1.
Mark A. Trifiro Parsa Kazemi-Esfarjani Leonard Pinsky 《Trends in Endocrinology and Metabolism》1994,5(10):416-421
X-linked muscular atrophy is a form of adult-onset, usually slowly progressive spinal and bulbar motor neuron degenerative disease that is uniquely associated with male hypogonadism. The mutation responsible for this syndrome is expansion of the trinucleotide repeat—cytosine (C), adenine (A), guanine (G)—in a 5′-translated portion of the androgen receptor (AR) gene from a normal, polymorphic length of n = 11–31 to n ≥ 40. The resulting androgen receptor (AR) protein has an expanded polyglutamine tract in its NH2-terminal modulatory domain, and is postulated to lose a basic, intrinsic function that causes a mild form of androgen insensitivity; however, almost certainly, it also gains a novel, extrinsic function that is selectively neuronotoxic. The unexplained mechanism that culminates in this form of neuronspecific death is the prototype for three different adult-onset neuronopathies that are caused by (CAG)n expansions in other genes. 相似文献
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Christina D Cota Pooneh Bagher Piotr Pelc C Owen Smith Christina R Bodner Teresa M Gunn 《Developmental dynamics》2006,235(12):3438-3447
Mahogunin Ring Finger 1 (Mgrn1) encodes a RING-containing protein with ubiquitin ligase activity that has been implicated in pigment-type switching. In addition to having dark fur, mice lacking MGRN1 develop adult-onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation of complete situs inversus in a small proportion of adult Mgrn1 mutant mice suggested that embryonic lethality resulted from congenital heart defects due to defective establishment and/or maintenance of the left-right (LR) axis. Here we report that Mgrn1 is expressed in a pattern consistent with a role in LR patterning during early development and that many Mgrn1 mutant embryos show abnormal expression of asymmetrically expressed genes involved in LR patterning. A range of complex heart defects was observed in 20-25% of mid-to-late gestation Mgrn1 mutant embryos and another 20% were dead. This finding was consistent with 46-60% mortality of mutants by weaning age. Our results indicate that Mgrn1 acts early in the LR signaling cascade and is likely to provide new insight into this developmental process as Nodal expression was uncoupled from expression of other Nodal-responsive genes in Mgrn1 mutant embryos. Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis. 相似文献
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Effect of filter vent blocking on carbon monoxide exposure from selected lower tar cigarette brands.
Two studies were conducted to determine the effect of blocking filter vents on carbon monoxide (CO) exposure under ad lib smoking conditions. In Study 1, 12 daily cigarette smokers smoked cigarettes from the brands Now (1 mg tar by the FTC Method) and Marlboro Lights (10 mg tar) under each of two vent-blocking conditions (unblocked and finger blocked). Blocking filter vents with fingers led to an 85% increase in CO for the brand Now, but had no added effect on CO exposure from the Marlboro Lights. In Study 2, another 12 daily cigarette smokers smoked cigarettes from each of four additional brands: Carlton (1 mg tar), Now (2 mg tar), Virginia Slims Ultra-lights (5 mg tar), and Virginia Slims Lights (8 mg tar). Blocking filter vents with the lips caused all four brands to produce equal CO exposures. Blocking vents increased smokers' exposure to CO by 239% when smoking Carltons and by 44% when smoking Nows. No significant increases in CO with blocking were found for either of the Virginia Slims brands. These results suggest that the degree to which a brand is ventilated determines whether that brand is susceptible to increased CO yields as a result of vent blocking. 相似文献
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Intracerebral clysis in a rat glioma model 总被引:4,自引:0,他引:4
Bruce JN Falavigna A Johnson JP Hall JS Birch BD Yoon JT Wu EX Fine RL Parsa AT 《Neurosurgery》2000,46(3):683-691
OBJECTIVE: Intracerebral clysis (ICC) is a new term we use to describe convection-enhanced microinfusion into the brain. This study establishes baseline parameters for preclinical, in vivo, drug investigations using ICC in a rat glioma model. METHODS: Intracranial pressure was measured, with an intraparenchymal fiber-optic catheter, in male Fischer rats 10, 15, 20, and 25 days after implantation of C6 glioma cells in the right frontal lobe (n = 80) and in control rats without tumor (n = 20), before and during ICC. A 25% albumin solution (100 microl) was infused through an intratumoral catheter at 0.5, 1.0, 2.0, 3.0, and 4.0 microl/min. Infusate distribution was assessed by infusion of fluorescein isothiocyanate-dextran (Mr 20,000), using the aforementioned parameters (n = 36). Brains were sectioned and photographed under ultraviolet light, and distribution was calculated by computer analysis (NIH Image for Macintosh). Safe effective drug distribution was demonstrated by measuring tumor sizes and apoptosis in animals treated with N,N'-bis(2-chloroethyl)-N-nitrosourea via ICC, compared with untreated controls. Magnetic resonance imaging noninvasively confirmed tumor growth before treatment. RESULTS: Intracranial pressure increased with tumor progression, from 5.5 mm Hg at baseline to 12.95 mm Hg on Day 25 after tumor cell implantation. Intracranial pressure during ICC ranged from 5 to 21 mm Hg and was correlated with increasing infusion volumes and increasing rates of infusion. No toxicity was observed, except at the higher ends of the tumor size and volume ranges. Fluorescein isothiocyanate-dextran distribution was greater with larger infusion volumes (30 microl versus 10 microl, n = 8, P < 0.05). No significant differences in distribution were observed when different infusion rates were compared while the volume was kept constant. At tolerated flow rates, the volumes of distribution were sufficient to promote adequate drug delivery to tumors. N,N'-Bis(2-chloroethyl)-N-nitrosourea treatment resulted in significant decreases in tumor size, compared with untreated controls. CONCLUSION: The C6 glioma model can be easily modified to study aspects of interstitial delivery via ICC and the application of ICC to the screening of potential antitumor agents for safety and efficacy. 相似文献
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Parsa CJ Organ CH Barkan H 《Archives of surgery (Chicago, Ill. : 1960)》2000,135(5):570-3; discussion 573-5
10.
Gurvinder Kaur Eli T. Sayegh Andrew Larson Orin Bloch Michelle Madden Matthew Z. Sun Igor J. Barani C. David James Andrew T. Parsa 《Neuro-oncology》2014,16(5):628-636
Atypical meningiomas (AMs) and malignant meningiomas (MMs) are tumors with a lower incidence and poorer prognosis than benign meningiomas. The role of radiotherapy as an adjuvant to surgical resection, especially for AMs, is incompletely defined. In this study, the English-language literature was systematically reviewed for studies that reported tumor characteristics, treatment parameters, and clinical outcomes after adjuvant radiotherapy for AM and MM, including overall survival, progression-free survival, and/or time to recurrence or mortality. Clinical outcomes were further assessed in the context of resection status, timing of administration, and radiation dose. Outcomes after stereotactic radiosurgery were also examined. Treatment toxicity and other potential prognostic or confounding factors were appraised. Ten and 11 studies for AM and MM, respectively, met the inclusion criteria. The median 5-year progression-free survival and overall survival after adjuvant radiotherapy were 54.2% and 67.5%, respectively, for AM and 48% and 55.6% for MM. The complication rates were 11.1% for AM and 5.1% for MM. Incomplete resection and radiation dose <50 Gy conferred significantly poorer 5-year progression-free survival. Most studies were unable to demonstrate a statistically significant prognostic benefit for adjuvant radiotherapy in AM. In conclusion, adjuvant radiotherapy significantly improved local control of AMs and MMs, especially after subtotal resection. Study limitations, including inadequate statistical power, may underlie the studies'' inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors. 相似文献