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The ankyrin repeat domain-55 ( ANKRD55 ) gene contains intronic single nucleotide polymorphisms (SNPs) associated with risk to contract multiple sclerosis, rheumatoid arthritis or other autoimmune disorders. Risk alleles of these SNPs are associated with higher levels of ANKRD55 in CD4 + T cells. The biological function of ANKRD55 is unknown, but given that ankyrin repeat domains constitute one of the most common protein-protein interaction platforms in nature, it is likely to function in complex with other proteins. Thus, identification of its protein interactomes may provide clues. We identified ANKRD55 interactomes via recombinant overexpression in HEK293 or HeLa cells and mass spectrometry. One hundred forty-eight specifically interacting proteins were found in total protein extracts and 22 in extracts of sucrose gradient-purified nuclei. Bioinformatic analysis suggested that the ANKRD55-protein partners from total protein extracts were related to nucleotide and ATP binding, enriched in nuclear transport terms and associated with cell cycle and RNA, lipid and amino acid metabolism. The enrichment analysis of the ANKRD55-protein partners from nuclear extracts is related to sumoylation, RNA binding, processes associated with cell cycle, RNA transport, nucleotide and ATP binding. The interaction between overexpressed ANKRD55 isoform 001 and endogenous RPS3, the cohesins SMC1A and SMC3, CLTC, PRKDC, VIM, β-tubulin isoforms, and 14-3-3 isoforms were validated by western blot, reverse immunoprecipitaton and/or confocal microscopy. We also identified three phosphorylation sites in ANKRD55, with S436 exhibiting the highest score as likely 14-3-3 binding phosphosite. Our study suggests that ANKRD55 may exert function(s) in the formation or architecture of multiple protein complexes, and is regulated by (de)phosphorylation reactions. Based on interactome and subcellular localization analysis, ANKRD55 is likely transported into the nucleus by the classical nuclear import pathway and is involved in mitosis, probably via effects associated with mitotic spindle dynamics., (Copyright © 2019 Ugidos, Mena, Baquero, Alloza, Azkargorta, Elortza and Vandenbroeck.)

An intronic variant in ANKRD55, rs6859219, is a genetic risk factor for multiple sclerosis, but the biological reasons underlying this association are unknown. We characterized the expression of ANKRD55 in human PBMCs and cell lines. Three ANKRD55 transcript variants (Ensembl isoforms 001, 005, and 007) could be detected in PBMCs and CD4(+) T cells but were virtually absent in CD8(+), CD14(+), CD19(+), and CD56(+) cells. Rs6859219 was significantly associated with ANKRD55 transcript levels in PBMCs and CD4(+) T cells and, thus, coincides with a cis-expression quantitative trait locus. The processed noncoding transcript 007 was the most highly expressed variant in CD4(+) T cells, followed by 001 and 005, respectively, but it was not detected in Jurkat, U937, and SH-SY5Y cell lines. Homozygotes for the risk allele produced more than four times more transcript copies than did those for the protective allele. ANKRD55 protein isoforms 005 and 001 were predominantly located in the nucleus of CD4(+) T cells and Jurkat and U937 cells. ANKRD55 was produced by primary cultures of murine hippocampal neurons and microglia, as well as by the murine microglial cell line BV2, and it was induced by inflammatory stimuli. ANKRD55 protein was increased in the murine mouse model of experimental autoimmune encephalomyelitis. Flow cytometric analysis of CNS-infiltrating mononuclear cells showed that CD4(+) T cells and monocytes expressed ANKRD55 in experimental autoimmune encephalomyelitis mice, with the higher fluorescence intensity found in CD4(+) cells. A low percentage of microglia also expressed ANKRD55. Together, these data support an important role for ANKRD55 in multiple sclerosis and neuroinflammation., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors., Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis., Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10(-8)) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10(-12)), CD28 (rs6435203, p=1.35×10(-9)), LPP (rs4686953, p=3.35×10(-8)), ETS1 (rs3809006, p=7.74×10(-9)), DLEU1 (rs806349, p=8.14×10(-12)), LPIN3 (rs6072343, p=7.16×10(-12)) and IFNGR2 (rs9808753, p=4.40×10(-10)). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus., Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Cytogenetic and gene expression analyses in head and neck squamous cell carcinomas (HNSCC) have allowed identification of genomic aberrations that may contribute to cancer pathophysiology. Nevertheless, the molecular consequences of numerous genetic alterations still remain unclear., Methods: To identify novel genes implicated in HNSCC pathogenesis, we analyzed the genomic alterations present in five HNSCC-derived cell lines by array CGH, and compared high level focal gene amplifications with gene expression levels to identify genes whose expression is directly impacted by these genetic events. Next, we knocked down TRPC6, one of the most highly amplified and over-expressed genes, to characterize the biological roles of TRPC6 in carcinogenesis. Finally, real time PCR was performed to determine TRPC6 gene dosage and mRNA levels in normal mucosa and human HNSCC tissues., Results: The data showed that the HNSCC-derived cell lines carry most of the recurrent genomic abnormalities previously described in primary tumors. High-level genomic amplifications were found at four chromosomal sites (11q21-q22.2, 18p11.31-p11.21, 19p13.2-p13.13, and 21q11) with associated gene expression changes in selective candidate genes suggesting that they may play an important role in the malignant behavior of HNSCC. One of the most dramatic alterations of gene transcription involved the TRPC6 gene (located at 11q21-q22.2) which has been recently implicated in tumour invasiveness. siRNA-induced knockdown of TRPC6 expression in HNSCC-derived cells dramatically inhibited HNSCC-cell invasion but did not significantly alter cell proliferation. Importantly, amplification and concomitant overexpression of TRPC6 was also found in HNSCC tumour samples., Conclusions: Altogether, these data show that TRPC6 is likely to be a target for 11q21-22.2 amplification that confers enhanced invasive behavior to HNSCC cells. Therefore, TRPC6 may be a promising therapeutic target in the treatment of HNSCC.

Objectives: To share our experience performing laparoscopic pyeloplasty and our contributions to this surgery., Methods: Between March 2004 and January 2006 we have performed 12 laparoscopic pyeloplasties in 12 patients. We modified our technique as we found difficulties during operations. By the only modification of patient position we have achieved a significant improve in our technique., Results: We describe how we performed the operation in the first cases and how we do it today, with the new position. We also describe the advantages observed., Conclusions: With our technique we achieve an important surgical time reduction, improvements in safety and reduction of surgical complications.

Von Hippel Lindau disease is a highly uncommon autosomic dominant condition characterised by the presence of cerebellar hemangioblastomas, retina angioma, pancreas, kidney and epididymal cysts, and renal cells carcinoma. This article describes the case report of a male patient with Von Hippel Lindau disease which presented as a jaundice secondary to biliary obstruction due to pancreatic cystic mass. After urological examination, bilateral cystic lesions and right renal solid lesion were detected requiring surgical treatment. A review is made of the diagnostic and therapeutic aspects, highlighting the significance of early diagnosis and treatment.

Objective: Genitourinary tract involvement arising from non-Hodgkin lymphoma occurs in 10% of patients; prostatic infiltration is uncommon and accounts for less than 0.1%. The uncommon clinical onset of this infrequent condition prompted us to report on the present case., Methods/results: A 41-year-old male patient with lower urinary tract outflow obstruction arising from prostatic enlargement secondary to non-Hodgkin lymphoma (Burkitt's lymphoma) is described. Treatment with chemotherapy achieved good results. The clinical features, diagnostic and therapeutic aspects are discussed and the literature briefly reviewed., Conclusion: The present case emphasizes the need to include non-Hodgkin lymphoma in the differential diagnosis of lower urinary tract outflow obstructive symptoms in young men with prostatic enlargement.

Objective: The genitourinary tract is one of the most common sites of extrapulmonary tuberculosis (30%-33%), followed by the lymphatic tissue, skeletal system and gut. Due to the diagnostic methods and therapeutic modalities currently available, it is infrequent to find advanced tuberculosis with extensive genitourinary involvement., Methods/results: Herein we describe a patient with advanced genitourinary tuberculosis characterized by loss of right renal unit, left hydronephrosis due to ureterovesical junction stricture, contracted bladder, prostatic caseation and urethral stricture. Right nephrectomy and bladder substitution ileocystoplasty were performed. The clinical features, diagnostic and therapeutic aspects are discussed and the literature briefly reviewed., Conclusion: Extensive genitourinary tuberculosis is uncommon. The importance of early diagnosis and treatment is emphasized in order to avoid the irreversible sequelae.

Inflammatory iliac aneurysms are uncommon and account for 1-2% of total abdominal aneurysms. These aneurysms are more susceptible to present urological symptoms and are difficult to diagnose because of their uncommon incidence and location in the deep pelvis which makes them little accessible to physical examination. This case report presents one patient with right obstructive uropathy secondary to extrinsic ureteral trapping due to inflammatory iliac aneurysm which evolved favourably after ureterolysis, endoaneurysmectomy and interposition of aortoiliac graft. A brief review of diagnostic and therapeutic aspects in the literature is included. The relevance of a high degree of suspicion to diagnose this entity in patients with otherwise explainable vesical irritative symptoms, haematuria or renal failure is highlighted.

Objectives: Ureteral calculi are usually small and arise from the kidney. The term 'giant' has been applied to ureteral stones that are more than 5 cms in length and/or 50 gms or more in weight. The low incidence of this condition prompted us to report this case., Methods/results: Herein we describe a patient with multiple giant ureteral calculi with no evidence of underlying ureteral lesion, who required nephroureterectomy due to the damage caused to the renal unit by the obstructive uropathy. The literature is briefly reviewed, with special reference to the diagnostic and therapeutic aspects., Conclusions: Giant ureteral calculi are uncommon. They may cause scanty urological symptoms and might therefore be missed. If undiagnosed, renal function may be compromised by the obstructive uropathy.

Objective: Prostatic cancer can produce signs and symptoms by local growth, direct invasion or distant metastases. In rare occasions, these tumors can show a clinical variance due to trophic factors, biologically active, secreted in neoplastic environment but with systemic relevance. These syndromes are called paraneoplastic syndromes. This uncommon condition is described herein., Method/results: We report a case of inappropriate antidiuretic hormone secretion as the presenting feature of advanced prostatic carcinoma. The pathogenic features, diagnostic and therapeutic aspects are reviewed., Conclusions: Although its frequency is low, we must consider prostatic carcinoma in patients with inappropriate antidiuretic hormone secretion syndrome. When the acute situation is resolved, hormonal treatment in disseminated carcinomas will return to normal the clinical and analytical parameters derived from this syndrome.

Objective: Ectopic ureter is a congenital anomaly more frequent in the female, in the pediatric age and is commonly left-sided. The present article reports an uncommon case without the common features of this anomaly., Methods/results: We report on a 67-year-old man with complete duplex system and ectopic obstructive megaureter in the prostatic urethra with a silent onset. The diagnostic and therapeutic aspects in the literature are briefly discussed., Conclusion: Because this anomaly is asymptomatic and incidentally discovered because of contralateral disease, the approach is conservative.

Objectives: Although uncommon, prostatic surgical bed lithiasis may present among post-TURP complications. The present study underscores the importance of diagnosis and treatment., Methods/results: We report on a patient with magnesium ammonium phosphate hourglass lithiasis in the prostatic surgical bed one year and a half following transurethral resection due to adenomyomatous prostatic hyperplasia that was successfully treated by intracorporeal lithotripsy with the Lithoclast. The physiopathological, clinical, diagnostic and therapeutic aspects are discussed., Conclusions: This condition should be suspected in patients with dysuric syndrome post-TURP. The importance of simple complementary diagnostic procedures as DRE and plain abdominal films in discarding lithiasis in underscored. We consider retrograde endoscopic manipulation and ultrasonic lithotripsy or penumatic lithotripsy with the Lithoclast to be the safest procedures for this type of lithiasis.

Objectives: Ureteral metastasis from renal adenocarcinoma is uncommon. The rarity of this disease prompted us to report on the present case, with special reference to diagnosis., Methods/results: A patient with metachronous metastasis in the ureteral stump from clear cell renal adenocarcinoma resected three years earlier is described. The etiopathogenic, clinical, diagnostic and therapeutic aspects are briefly reviewed., Conclusions: Ureteral metastases, although uncommon, are generally ipsilateral to the renal tumor and arise from aggressive renal carcinomas that are locally advanced with vascular and/or lymphatic spread. We underscore the importance of retrograde pyelography and ureterorenoscopy in the diagnostic workup of all patients with gross hematuria following nephrectomy due to hypernephroma.

Renal carcinoma natural history is unpredictable. Spontaneous metastases regression after nephrectomy, as well as late recurrence are suggestive of this peculiar human neoplasm. tumor metastases localized to thyroid gland are uncommon in clinical practice; and carcinoma of the kidney, breast, lung, melanoma and gastrointestinal tract tumors are responsible for the majority of them. This paper reports on a patient with metachronous thyroid gland metastases after fourteen years of renal carcinoma nephrectomy, with one year after hemithyroidectomy recurrence on cervical striated muscle followed by surgical excision. Therapeutical aspects are briefly reviewed in literature, emphasizing surgical treatment and the need of all-life follow-up, with more alert attitude toward thyroid gland after renal cell carcinoma nephrectomy.

Objectives: Ureteral involvement due to endometriosis is uncommon. Its silent onset and the progression of ureteral obstruction, if undiagnosed, can lead to the loss of the renal unit. The present case is described to underscore the importance of early diagnosis., Methods/results: We report on a patient with obstructive uropathy secondary to intrinsic ureteric endometriosis that had undergone nephrectomy due to parenchymal destruction. One year following resection of the endovesical portion, recurrence in the ureteral stump was observed. The clinical features, the diagnostic and clinical aspects are briefly discussed., Conclusions: Although ureteric involvement is uncommon, renal function of patients with pelvic endometriosis must be followed closely by analyses, ultrasound and/or intravenous urography for early detection of this condition.

Calculi in the male urethra are rare and are generally associated with urethral disorder (diverticuli, stricture, complication posturethroplasty, etc.). Treatment is generally by excision and resolution of the underlying cause. We report a case of urethral calculus, of apparently idiopathic etiology, that had treated by endoscopic ultrasonic disruption. The importance of preoperative etiologic diagnosis is underscored.

We report a case of paratesticular rhabdomyosarcoma in a 5-year-old boy who was submitted to radical orchidectomy via the inguinal approach and high ligation of the spermatic cord. Clinical and retroperitoneal staging classify this case under group I of the Intergroup Rhabdomyoma Study. Adjuvan chemotherapy with 12 courses of VAC have achieved a good clinical course to date (14 months after surgery) and a good outcome is predicted. We review the literature and discuss the features of this mesenchymal tumor.

We report a case of vesicovaginal fistula in an 8-year-old girl caused by a foreign body in the vagina. The foregoing condition was associated with vesical lithiasis. Correction of the fistula was performed during the same surgical procedure for stone removal, without waiting for 3-6 months to elapse as advocated by most of the authors. A review of the literature revealed only one such case has been reported earlier.