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31.
32.
DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein 总被引:7,自引:0,他引:7
Fanconi anemia (FA) is a cancer-predisposition syndrome characterized by hypersensitivity to interstrand-cross-link (ICL) inducers. FA hypersensitivity to ICL has been correlated with alterations in homologous recombination, non-homologous end-joining, telomere maintenance, DNA-damage assessment and checkpoint regulation, processes in which the components of the RAD50/MRE11/NBS1 (RMN) complex are involved. To better characterize the mechanisms by which ICL are processed in human cells and to gain insight into their toxicity in FA, we examined (i). the RMN complex assembling in response to the ICL inducers mitomycin C (MMC) and photoactivated 8-methoxypsoralen and (ii). the proficiency of FA cells to perform RMN activation in response to ICL inducers. We show here that ICL activates the assembly of the RMN proteins into subnuclear foci, and that their formation proceeds independently of ICL incision, a step mainly dependent on XP-F/ERCC1 heterodimer activity. Interestingly, FA cells were unable to form RMN foci in response to either ICL inducer. Analysis by pulsed-field gel electrophoresis and single-cell gel electrophoresis of MMC-treated cells showed that FA cells from complementation group C (FA-C cells, defective in the FANCC gene) form double-strand breaks and unhook MMC-induced ICL similarly to FANCC wild-type cells. These observations imply that the absence of RMN assembly in FA-C cells is not simply due to the absence of DNA ends produced as intermediates of ICL processing, and indicates a direct role for FANCC in RMN focus assembly in response to ICL inducers. Moreover, we show that the formation of foci, including BRCA1 and/or RAD51 proteins, is significantly delayed in FA cells. These alterations in the assembly of DNA-repair proteins in FA provide an interpretation for the DNA-damage processing anomalies observed in FA cells and for the genetic instability and the cancer predisposition of the syndrome. 相似文献
33.
Mireille Baltzinger Michela Ori Massimo Pasqualetti Irma Nardi Filippo M Rijli 《Developmental dynamics》2005,234(4):858-867
The skeletal structures of the face and throat are derived from cranial neural crest cells (NCCs) that migrate from the embryonic neural tube into a series of branchial arches (BAs). The first arch (BA1) gives rise to the upper and lower jaw cartilages, whereas hyoid structures are generated from the second arch (BA2). The Hox paralogue group 2 (PG2) genes, Hoxa2 and Hoxb2, show distinct roles for hyoid patterning in tetrapods and fishes. In the mouse, Hoxa2 acts as a selector of hyoid identity, while its paralogue Hoxb2 is not required. On the contrary, in zebrafish Hoxa2 and Hoxb2 are functionally redundant for hyoid arch patterning. Here, we show that in Xenopus embryos morpholino-induced functional knockdown of Hoxa2 is sufficient to induce homeotic changes of the second arch cartilage. Moreover, Hoxb2 is downregulated in the BA2 of Xenopus embryos, even though initially expressed in second arch NCCs, similar to mouse and unlike in zebrafish. Finally, Xbap, a gene involved in jaw joint formation, is selectively upregulated in the BA2 of Hoxa2 knocked-down frog embryos, supporting a hyoid to mandibular change of NCC identity. Thus, in Xenopus Hoxa2 does not act redundantly with Hoxb2 for BA2 patterning, similar to mouse and unlike in fish. These data bring novel insights into the regulation of Hox PG2 genes and hyoid patterning in vertebrate evolution and suggest that Hoxa2 function is required at late stages of BA2 development. 相似文献
34.
Vincenzo Di Stefano Raffaele Ornello Andrea Gagliardo Angelo Torrente Elisa Illuminato Valeria Caponnetto Ilaria Frattale Raffaella Golini Chiara Di Felice Fabiola Graziano Maria Caccamo Davide Ventimiglia Salvatore Iacono Gabriella Matarazzo Francesco Armetta Giuseppe Battaglia Alberto Firenze Simona Sacco Filippo Brighina 《Nutrients》2021,13(4)
Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life. 相似文献
35.
Andrea Calcagno Valeria Ghisetti Teresa Emanuele Mattia Trunfio Silvia Faraoni Lucio Boglione Elisa Burdino Sabrina Audagnotto Filippo Lipani Marco Nigra Antonio DAvolio Stefano Bonora Giovanni Di Perri 《Emerging infectious diseases》2021,27(1):303
We measured severe acute respiratory syndrome coronavirus 2 spike protein subunits S1/S2 antibodies by using capillary electrophoresis and a chemiluminescence immunoassay for 5,444 active healthcare workers in Italy. Seroprevalence was 6.9% and higher among participants having contact with patients. Seroconversion was not observed in 37/213 previously infected participants. 相似文献
36.
Luca Boeri Federico Belladelli Paolo Capogrosso Walter Cazzaniga Luigi Candela Edoardo Pozzi Luca Valsecchi Enrico Papaleo Paola Viganò Costantino Abbate Filippo Pederzoli Massimo Alfano Francesco Montorsi Andrea Salonia 《Andrologia》2021,53(1):e13861
A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting. 相似文献
37.
Filippo Montali Alessandra Panarese Barbara Binda Laura Lancione Francesco Pisani 《Transplantation proceedings》2021,53(4):1272-1274
Transplant renal artery stenosis (TRAS) is a common vascular complication after kidney transplantation, leading to worsening or refractory hypertension, deterioration in renal function, and possible cause of graft loss. Early diagnosis and an appropriate treatment are crucial for organ preservation. Endovascular treatment, including percutaneous transluminal angioplasty and stent implantation, is considered the first-line therapy for TRAS. Here we report the case of a 69-year-old woman with end-stage renal disease for chronic kidney disease not biopsy proven, who underwent a kidney transplant from expanded criteria donors on December 2018. Postoperative course was characterized by delayed graft function. Doppler ultrasonography (US) showed an increase of peak systolic velocity at the origin of the renal artery, and parvus-tardus waveform in periferic graft arteries and an abdominal computed tomography scan confirmed a stenosis at the origin of the main renal artery (TRAS). The patient underwent a percutaneous transluminal angioplasty. It was not possible to place a stent at the particular location of the stenosis at the anastomosis. Despite the improvement of the graft's perfusion, monitored with Doppler US, the patient showed a very poor improvement in renal function and remained on hemodialysis for months. A percutaneous needle biopsy reported a normal renal parenchyma and excluded acute rejection. During this period, the patient received immunosuppressive therapy. About 6 months after the transplant, the patient had an unexpected and slow renal function recovery until she was weaned completely from hemodialysis. 相似文献
38.
39.
Gianfranco Donatelli Andrea Spota Fabrizio Cereatti Stefano Granieri Ibrahim Dagher Renaud Chiche Jean-Marc Catheline Guillaume Pourcher Lionel Rebibo Daniela Calabrese Simon Msika Carmelisa Dammaro Hadrien Tranchart Panagiotis Lainas Thierry Tuszynski Filippo Pacini Roberto Arienzo Jean-Marc Chevallier Jean-Loup Dumont 《Surgery for obesity and related diseases》2021,17(8):1432-1439
BackgroundEndoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.ObjectivesTo evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.SettingRetrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.MethodsEID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents.ResultsA total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).ConclusionEarly EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results. 相似文献
40.
Ester Illiano Francesco Trama Vito Mancini Antonio Ruffo Giuseppe Romeo Filippo Riccardo Consuelo Fabi Giuseppe Carrieri Felice Crocetto Fabrizio Iacono Elisabetta Costantini 《Translational andrology and urology》2021,10(2):555
BackgroundPeyonie’s disease (PD) mostly affects males in the fifth decade of life, with a prevalence in the general population ranging between 0.5% and 20.3%. The pathology of PD is characterized by fibrosis of the tunic albuginea of the cavernous bodies of the penis, with the presence of pain in the erection and penile deformity. This is associated with decreased sexual function for both participants. The objective of the study was to investigate the influence of PD pathology on both male patients’ and their female partners’ sexual spheres, and analyze changes in sexual function and perception following penile correction surgery.MethodsProspective study, we included male patients with PD and their female partner sexually active. Patients underwent corporoplasty with multiple plications. The male and female sexuality was evaluated before surgery and three months after male treatment by the Female sexual Function Index (FSFI); International Index of Erectile Function (IIEF); Visual Analogical Scale (VAS).ResultsFrom January 2018 to November 2019 we included 35 couple. The female subjects before partner’s surgery presented dyspareunia, loss of sexual desire, inability to achieve orgasm, and sexual dissatisfaction. At three months after surgical treatment there was an improvement of sexual function in both male patients and female partners (desire P<0.0001, arousal P<0.0001, lubrification P<0.0001, orgasm P<0.0001, satisfaction P<0.0001, pain P<0.0001). As regarding male patients the pain decreased significantly (VAS score from 6 to 2.5), while there was no statistically significant improvement in erectile function (P=0.05).ConclusionsOur findings suggest that a viable approach to treatment of PD patients that involves their partners could lead to better functional and psychological results. 相似文献