31 research outputs found

    Cuf2 Is a Novel Meiosis-Specific Regulatory Factor of Meiosis Maturation

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    Meiosis is the specialized form of the cell cycle by which diploid cells produce the haploid gametes required for sexual reproduction. Initiation and progression through meiosis requires that the expression of the meiotic genes is precisely controlled so as to provide the correct gene products at the correct times. During meiosis, four temporal gene clusters are either induced or repressed by a cascade of transcription factors

    Copper-Dependent Trafficking of the Ctr4-Ctr5 Copper Transporting Complex

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    In Schizosaccharomyces pombe, copper uptake is carried out by a heteromeric complex formed by the Ctr4 and Ctr5 proteins. Copper-induced differential subcellular localization may play a critical role with respect to fine tuning the number of Ctr4 and Ctr5 molecules at the cell surface.We have developed a bimolecular fluorescence complementation (BiFC) assay to analyze protein-protein interactions in vivo in S. pombe. The assay is based on the observation that N- and C-terminal subfragments of the Venus fluorescent protein can reconstitute a functional fluorophore only when they are brought into tight contact. Wild-type copies of the ctr4(+) and ctr5(+) genes were inserted downstream of and in-frame with the nonfluorescent C-terminal (VC) and N-terminal (VN) coding fragments of Venus, respectively. Co-expression of Ctr4-VC and Ctr5-VN fusion proteins allowed their detection at the plasma membrane of copper-limited cells. Similarly, cells co-expressing Ctr4-VN and Ctr4-VC in the presence of Ctr5-Myc(12) displayed a fluorescence signal at the plasma membrane. In contrast, Ctr5-VN and Ctr5-VC co-expressed in the presence of Ctr4-Flag(2) failed to be visualized at the plasma membrane, suggesting a requirement for a combination of two Ctr4 molecules with one Ctr5 molecule. We found that plasma membrane-located Ctr4-VC-Ctr5-VN fluorescent complexes were internalized when the cells were exposed to high levels of copper. The copper-induced internalization of Ctr4-VC-Ctr5-VN complexes was not dependent on de novo protein synthesis. When cells were transferred back from high to low copper levels, there was reappearance of the BiFC fluorescent signal at the plasma membrane.These findings reveal a copper-dependent internalization and recycling of the heteromeric Ctr4-Ctr5 complex as a function of copper availability

    A flow-chart for a critical appraisal of new technology. The experience of near-infrared spectroscopy.

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    Usefulness and limit of NIRS are discusse

    Microvascular decompression in patients with trigeminal neuralgia and multiple sclerosis: results and analysis of possible prognostic factors

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    We evaluated the results of microvascular decompression (MVD) in patients with trigeminal neuralgia (TN) and multiple sclerosis (MS) and we studied the role of several clinical and surgical factors as possible prognosticators of good outcome. To do this we performed, to our knowledge, the first literature review with a pooled analysis of data. A PubMed search of literature was conducted using the following terms: \u201cmicrovascular decompression\u201d, \u201ctrigeminal neuralgia\u201d and \u201cmultiple sclerosis\u201d. We screened 64 articles. Of them, 7 studies were eligible for this review. As outcome indicators we used the acute pain relief (APR) and the recurrence of pain. An APR was obtained in 71.42% and a recurrence of pain was reported in 26.00% of cases, respectively. At univariate analysis, younger age at surgery (p = 0.0419) and performing MVD as the first treatment (p = 0.0384) were associated to a higher probability of APR. The evidence of an MRI brainstem lesion related to the TN (p = 0.0482) was associated to a lower probability to obtain an APR after MVD. None of the evaluated factors affect the probability of recurrence of pain. At multivariate analysis the evidence of a brainstem MRI lesion related to the TN emerged as a negative prognosticator of APR (p = 0.0169). Our literature pooled analysis showed that MVD is effective in treating patients with MS-related TN. The evidence on MRI of a demyelinating plaque related to the TN is associated with a worse response to MVD. These data could suggest that MVD would be indicated mainly in patients without brainstem MRI lesions

    Evidence for induction of hepatic microsomal cytochrome P-450 by cimetidine: binding and kinetic studies

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    The interaction of cimetidine with liver microsomes has been examined by spectral and equilibrium partition studies. First, difference spectroscopy has been used to evaluate the proportion of cytochrome P-450 in rat liver microsomes that exhibits an affinity for cimetidine in the pharmacologically relevant, low micromolar range of drug concentration. The value of 0.45 so obtained has confirmed that a substantial proportion of rat liver cytochrome P-450 has a high binding affinity for this drug. Second, a study of the binding of cimetidine to human liver microsomes by difference spectroscopy and partition equilibrium has detected a similar interaction, thus providing direct support for the postulate that the clinically observed impairment of oxidative drug metabolism may be due in part to inhibition of cytochrome P-450 monooxygenase by cimetidine. Hepatic microsomes from cimetidine-pretreated rats have been shown to exhibit elevated cytochrome P-450 specific content but a decreased proportion of sites with high affinity for the drug; this finding has been shown not to be the consequence of cimetidine-mediated, time-dependent, irreversible monooxygenase inhibition. Although cimetidine pretreatment caused enhanced specific activity of 7-ethoxyresorufin O-dealkylation, the specific activities for O-dealkylation of 7-ethoxycoumarin and 4-nitroanisole were decreased, as were those for the N-dealkylation of morphine, ethylmorphine, aminopyrine, and dimethylnitrosamine. Since cimetidine pretreatment was shown to cause no change in the Michaelis constants for oxidation of morphine or 7-ethoxyresorufin, it is argued that these results provide strong presumptive evidence for changes in the relative abundance of isoenzymes catalyzing these various oxidations. Thus, a dual role of cimetidine, acting both as inhibitor and inducer of the cytochrome P-450 system, is proposed to account for the impaired oxidative metabolism of some drugs that occurs during coadministration with this H2-receptor antagonist

    What Are the Results and the Prognostic Factors of Motor Cortex Stimulation in Patients with Facial Pain? A Systematic Review of the Literature

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    Introduction: Facial pain (FP) is a type of neuropathic pain which recognizes both central and peripheral causes. It can be difficult to treat because it can often become resistant to pharmacological treatments. Motor Cortex Stimulation (MCS) has been used in selected cases, but the correct indications of MCS in FP have not been fully established. Here we systematically reviewed the literature regarding MCS in FP analysing the results of this technique and studying the possible role of different factors in the prognosis of these patients. Methods: A literature search was performed through different databases (PubMed, Scopus, and Embase) according to PRISMA guidelines using the following terms in any possible combination: "facial pain"or "trigeminal"or "anaesthesia dolorosa"and "motor cortex stimulation."Results: 111 articles were reviewed, and 12 studies were included in the present analysis for a total of 108 patients. Overall, at latest follow-up (FU), 70.83% of patients responded to MCS. The preoperative VAS significantly decreased at the latest FU (8.83 ± 1.17 and 4.31 ± 2.05, respectively; p < 0.0001). Younger age (p = 0.0478) and a peripheral FP syndrome (p = 0.0006) positively affected the definitive implantation rate on univariate analysis. Younger age emerged as a factor strongly associated to a higher probability to go to a definitive MCS implant on multivariate analysis (p = 0.0415). Conclusion: Our results evidenced the effectiveness of MCS in treating FP. Moreover, the younger age emerged as a positive prognostic factor for definitive implantation. Further studies with longer FU are needed to better evaluate the long-term results of MCS

    Is There a Place for Spinal Cord Stimulation in the Management of Patients with Multiple Sclerosis? A Systematic Review of the Literature

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    Objective. Spinal cord stimulation (SCS) is a minimally invasive technique mainly used to treat neuropathic pain associated with failed back surgery syndrome. However, this therapy has been utilized to treat other chronic painful conditions, such as pain associated with multiple sclerosis (MS). Nonetheless, the efficacy of SCS in MS patients has not been fully established. In fact, in most of SCS series, MS patients represent only a subset of a bigger cohort which comprises different causes of pain, motor disorder, and other functional limitations. The aim of our study was to systematically review the literature to evaluate the effectiveness of SCS in MS patients. Methods. A literature search was performed through different databases (PubMed, Scopus, and Embase) using the following terms: "multiple sclerosis,""spinal cord stimulation,"and "dorsal column stimulation,"according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Results. A total of 452 articles were reviewed, and 7 studies were included in the present analysis. 373 MS patients were submitted to a stimulation trial, and 82 MS patients underwent a de novo implantation. 285/373 (76.4%) of cases submitted to the SCS trial were enrolled for permanent stimulation. We found a long-lasting improvement in 193/346 (55.8%) MS patients with motor disorders, in 90/134 (67.13%) MS patients with urinary dysfunction, and in 28/34 (82.35%) MS patients with neuropathic pain. The efficacy of SCS was higher for urinary dysfunction (p = 0.0144) and neuropathic pain (p = 0.0030) compared with motor disorders. Conclusions. Our systematic review evidences that SCS is effective in MS patients. Urinary dysfunction and pain symptoms seem to be most responsive to SCS. Further studies are needed to improve the patient selection and clarify the best timing to perform SCS in these patients
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