For primary bladder tumors, distinguishing urothelial carcinoma (UC) invading the fibromuscular stroma of the prostate (pT4a) from in situ UC involving prostatic ducts can be difficult. Immunohistochemical markers (cytokeratin [CK]5/6, CK5, CK7, CK20, p53, p63, high-molecular-weight keratin [HMWK], androgen receptor, prostate-specific antigen [PSA], prostate specific acid phosphatase [PSAP], laminin, CD44s, CD141) were assessed for their usefulness in determining depth of UC invasion in the prostate. In cystoprostatectomy specimens containing in situ UC in prostatic ducts, both CK5/6 and CK5 clearly differentiated prostatic basal cells from in situ UC. The remaining markers were not effective in determining depth of tumor invasion. Double-stain combinations CK7/CK5 and p53/CK5 were performed and robustly color contrasted in situ tumor from surrounding basal cells. The use of CK5/6, CK5, CK7/CK5, or p53/CK5 is recommended to assist in determining the depth of UC invasion in the prostate when histologic findings are equivocal.
Feline immunodeficiency virus (FIV) is a retrovirus that infects domestic cats, and is an excellent animal model for human immunodeficiency virus type 1 (HIV-1) pathogenesis. The nucleocapsid (NC) protein is critical for replication in both retroviruses. FIV NC has several structural features that differ from HIV-1 NC. While both NC proteins have a single conserved aromatic residue in each of the two zinc fingers, the aromatic residue on the second finger of FIV NC is located on the opposite C-terminal side relative to its location in HIV-1 NC. In addition, whereas HIV-1 NC has a highly charged cationic N-terminal tail and a relatively short C-terminal extension, the opposite is true for FIV NC. To probe the impact of these differences on the nucleic acid (NA) binding and chaperone properties of FIV NC, we carried out ensemble and single-molecule assays with wild-type (WT) and mutant proteins. The ensemble studies show that FIV NC binding to DNA is strongly electrostatic, with a higher effective charge than that observed for HIV-1 NC. The C-terminal basic domain contributes significantly to the NA binding capability of FIV NC. In addition, the non-electrostatic component of DNA binding is much weaker for FIV NC than for HIV-1 NC. Mutation of both aromatic residues in the zinc fingers to Ala (F12A/W44A) further increases the effective charge of FIV NC and reduces its non-electrostatic binding affinity. Interestingly, switching the location of the C-terminal aromatic residue to mimic the HIV-1 NC sequence (N31W/W44A) reduces the effective charge of FIV NC and increases its non-electrostatic binding affinity to values similar to HIV-1 NC. Consistent with the results of these ensemble studies, single-molecule DNA stretching studies show that while WT FIV NC has reduced stacking capability relative to HIV-1 NC, the aromatic switch mutant recovers the ability to intercalate between the DNA bases. Our results demonstrate that altering the position of a single aromatic residue switches the binding mode of FIV NC from primarily electrostatic binding to more non-electrostatic binding, conferring upon it NA interaction properties comparable to that of HIV-1 NC.
Robotic upper urinary tract reconstruction (UUTR) has been widely utilized for surgical management of congenital obstruction. To further reduce morbidity and simplify postoperative care, outpatient robotic pyeloplasty (RP) and robotic ureteroureterostomy (RUU) were performed without ureteral stents, drains, or urethral catheters. The aim of the study was to assess the safety of performing tubeless robotic UUTR as an outpatient procedure. A retrospective review was performed for patients who underwent outpatient tubeless RP and RUU between July 2015 and January 2017. All procedures were primary interventions. No ureteral stents, drains, or urethral catheters were utilized. No regional blocks were utilized. Patients were discharged from the post anesthesia care unit as a scheduled outpatient procedure without an extended stay. Primary outcomes included 30-day complications, emergency room (ER) visits, and readmissions. A total of 19 patients (14 male, 5 female) were identified (RP = 17, RUU = 3), including one patient who underwent staged bilateral RP. Median age was 21.5 months (range 3-220). Median weight was 11.5 kg (range 6-89). Median operative time was 167 min (range 108-249), defined as skin incision to closure. No 30-day complications, ER visits, or readmissions were observed for any patient. The study concludes that pediatric tubeless outpatient robotic UUTR is safe. Further evaluation is needed to assess this approach on a larger scale, as well as assessing the long-term outcomes of tubeless reconstruction.
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