Isolated Paralysis of the Adductor Pollicis: A Case Report

We report a case of isolated paralysis of the right adductor pollicis in a 30-year-old woman. Electromyographic study showed involvement of the deep motor branch of the ulnar nerve. A ganglion and an anomalous muscle were both ruled out clinically and by MRI as a possible cause of the paralysis. At surgical exploration, we found a fibrous band joining the pisiform and the hook of the hamate bone that compressed the deep motor branch of the ulnar nerve. The fibrous band was excised, and a neurolysis of the motor branch of the ulnar nerve was performed. At followup, eight months later, the patient had fully recovered strength of the adductor muscle

Simultaneous Bilateral Flexion-Type Salter-Harris II Fractures of the Proximal Tibia: A Case Report and Review of the Literature

A rare case is reported of bilateral physeal lesions of the proximal tibia classified as Salter-Harris type II, which occurred simultaneously after a “flexion type” injury in a 14-year-old boy. Treatment was conservative on the nondisplaced side and surgical, by closed reduction and internal fixation, on the displaced side. There was no previous diagnosis of Osgood-Schlatter disease. After reviewing all the cases described previously, which occurred either consecutively or simultaneously, we conclude that less resistance of the growth plate, typical of late adolescence, likely represents the cause of this type of lesion

An MRI volumetric study for leg muscles in congenital clubfoot

PURPOSE: To investigate both volume and length of the three muscle compartments of the normal and the affected leg in unilateral congenital clubfoot. METHODS: Volumetric magnetic resonance imaging (VMRI) of the anterior, lateral and postero-medial muscular compartments of both the normal and the clubfoot leg was obtained in three groups of seven patients each, whose mean age was, respectively, 4.8 months, 11.1 months and 4.7 years. At diagnosis, all the unilateral congenital clubfeet had a Pirani score ranging from 4.5 to 5.5 points, and all of them had been treated according to a strict Ponseti protocol. All the feet had percutaneous lengthening of the Achilles tendon. RESULTS: A mean difference in both volume and length was found between the three muscular compartments of the leg, with the muscles of the clubfoot side being thinner and shorter than those of the normal side. The distal tendon of the tibialis anterior, peroneus longus and triceps surae (Achilles tendon) were longer than normal on the clubfoot side. CONCLUSIONS: Our study shows that the three muscle compartments of the clubfoot leg are thinner and shorter than normal in the patients of the three groups. The difference in the musculature volume of the postero-medial compartment between the normal and the affected side increased nine-fold from age group 2 to 3, while the difference in length increased by 20 %, thus, showing that the muscles of the postero-medial compartment tend to grow in both thickness and length much less than the muscles of the other leg compartments

Myc and Omomyc functionally associate with the Protein Arginine Methyltransferase 5 (PRMT5) in glioblastoma cells

The c-Myc protein is dysregulated in many human cancers and its function has not been fully elucitated yet. The c-Myc inhibitor Omomyc displays potent anticancer properties in animal models. It perturbs the c-Myc protein network, impairs c-Myc binding to the E-boxes, retaining transrepressive properties and inducing histone deacetylation. Here we have employed Omomyc to further analyse c-Myc activity at the epigenetic level. We show that both Myc and Omomyc stimulate histone H4 symmetric dimethylation of arginine (R) 3 (H4R3me2s), in human glioblastoma and HEK293T cells. Consistently, both associated with protein Arginine Methyltransferase 5 (PRMT5)-the catalyst of the reaction-and its co-factor Methylosome Protein 50 (MEP50). Confocal experiments showed that Omomyc co-localized with c-Myc, PRMT5 and H4R3me2s-enriched chromatin domains. Finally, interfering with PRMT5 activity impaired target gene activation by Myc whereas it restrained Omomyc-dependent repression. The identification of a histone-modifying complex associated with Omomyc represents the first demonstration of an active role of this miniprotein in modifying chromatin structure and adds new information regarding its action on c-Myc targets. More importantly, the observation that c-Myc may recruit PRMT5-MEP50, inducing H4R3 symmetric di-methylation, suggests previously unpredictable roles for c-Myc in gene expression regulation and new potential targets for therapy

Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer

In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa

Nucleoporin 153 regulates estrogen-dependent nuclear translocation of endothelial nitric oxide synthase and estrogen receptor beta in prostate cancer.

Nucleoporin 153 (Nup153), key regulator of nuclear import/export, has been recently associated to oncogenic properties in pancreatic and breast tumour cells modulating either cell motility and migration or gene expression by chromatin association. In the present work, we have characterized the role of Nup153 in a cellular model of prostate cancer (PCa). The analysis of several immortalized cell lines derived from freshly explants of prostate cancer specimens showed that Nup153 protein was higher and present in multimeric complexes with eNOS and ER f as compared to normal/hyperplastic prostate epithelial cells. This phenomenon was enhanced in the presence of 17 f-estradiol (E2, 10-7M). Further experiments revealed that eNOS and ER f were present in a DNA binding complexes associated with Nup153 promoter as demonstrated by ChIPs. Notably, after Nup153 depletion (siNup153), a reduction of migration capacity and colony formation in primary tumor-derived and metastatic PCa cells was observed. In addition, eNOS and ER f nuclear localization was lost upon siNup153 regardless of E2 treatment, suggesting that Nup153 is a key regulator of prostate cancer cell function and of the nuclear translocation of these proteins in response to hormone stimulus. Taken altogether our findings indicate that in PCa cells: i. the expression and function of Nup153 is modulated by estrogen signaling; ii. Nup153 contributes to cell migration and proliferation; iii. Nup153 regulates the nuclear translocation of eNOS and ER f by forming a multimeric complex. Our findings unveil Nup153 as a novel component of the estrogen-dependent multimeric complex, thus representing a potential therapeutic candidate in prostate cancer