Dificultad diagnóstica en masa retroperitoneal. Reporte de un caso / Diagnostic difficulty in retroperitoneal mass: A case report

El Schwannoma se origina de la vaina perineural de Schwannoma, se detecta con frecuencia incidentalmente en estudios imagenológicos siendo el principal método diagnóstico la Tomografía Computada. El tratamiento es la resección quirúrgica con márgenes libres. Se presenta una paciente femenina de 49 años, en control por oncología por enfermedad de base, cáncer de mama izquierda, se identifica por TAC y PECT/TC imagen voluminosa en retroperitoneo situación lateroaórtica izquierda de configuración no quística e hipermetabólica, solicita biopsia percutánea, ante la falta de ventana, se decide exeresis completa de masa. Diagnóstico definitivo patológico Schwannoma. Sin indicación de tratamiento adyuvante, cursa buena evolución postoperatoria sin recidiva.

Schwannoma, a benign tumor that arises from Schwann cells of the perineural nerve sheath, is often incidentally detected in imaging tests and mainly diagnosed by CT scan. Treatment consists of surgical resection with clear margins. We present the case of a 49-year-old female patient subject to Oncology Department follow-up due to an underlying disease, left breast cancer. A large, hypermetabolic, noncystic mass in the retroperitoneal region is identified by CT and PECT/CT scan in the left lateral aortic area. A percutaneous biopsy is requested. Due to the limited acoustic window, complete resection of the mass is decided. Final histopathology diagnosis of Schwannoma. No adjuvant treatment indication; undergoing favorable postoperative progress, without recurrence

Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates.

Degradation rates of most proteins in eukaryotic cells are determined by their rates of ubiquitination. However, possible regulation of the proteasome's capacity to degrade ubiquitinated proteins has received little attention, although proteasome inhibitors are widely used in research and cancer treatment. We show here that mammalian 26S proteasomes have five associated ubiquitin ligases and that multiple proteasome subunits are ubiquitinated in cells, especially the ubiquitin receptor subunit, Rpn13. When proteolysis is even partially inhibited in cells or purified 26S proteasomes with various inhibitors, Rpn13 becomes extensively and selectively poly-ubiquitinated by the proteasome-associated ubiquitin ligase, Ube3c/Hul5. This modification also occurs in cells during heat-shock or arsenite treatment, when poly-ubiquitinated proteins accumulate. Rpn13 ubiquitination strongly decreases the proteasome's ability to bind and degrade ubiquitin-conjugated proteins, but not its activity against peptide substrates. This autoinhibitory mechanism presumably evolved to prevent binding of ubiquitin conjugates to defective or stalled proteasomes, but this modification may also be useful as a biomarker indicating the presence of proteotoxic stress and reduced proteasomal capacity in cells or patients.

The JAMM motif of human deubiquitinase Poh1 is essential for cell viability.

Poh1 deubiquitinase activity is required for proteolytic processing of polyubiquitinated substrates by the 26S proteasome, linking deubiquitination to complete substrate degradation. Poh1 RNA interference (RNAi) in HeLa cells resulted in a reduction in cell viability and an increase in polyubiquitinated protein levels, supporting the link between Poh1 and the ubiquitin proteasome pathway. To more specifically test for any requirement of the zinc metalloproteinase motif of Poh1 to support cell viability and proteasome function, we developed a RNAi complementation strategy. Effects on cell viability and proteasome activity were assessed in cells with RNAi of endogenous Poh1 and induced expression of wild-type Poh1 or a mutant form of Poh1, in which two conserved histidines of the proposed catalytic site were replaced with alanines. We show that an intact zinc metalloproteinase motif is essential for cell viability and 26S proteasome function. As a required enzymatic component of the proteasome, Poh1 is an intriguing therapeutic drug target for cancer.

Femoral central venous catheter-associated deep venous thrombosis in children with diabetic ketoacidosis.

OBJECTIVE: To describe the incidence of clinical deep venous thrombosis associated with femoral central venous catheters (CVC-DVT) in children with diabetic ketoacidosis (DKA). DESIGN: Retrospective case-matched control series. SETTING: Pediatric intensive care units of two university-affiliated hospitals. PATIENTS: All eight pediatric DKA patients with femoral central venous catheters between 1998 and 2001, and 16 age-matched control patients with femoral central venous catheters and circulatory shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The records of all children with DKA and the control patients were reviewed. CVC-DVT was defined as persistent ipsilateral leg swelling after removal of a femoral central venous catheter. Control patients with coagulopathies, thrombocytopenia, cancer, and hyperglycemia were excluded. Four of eight patients with DKA developed CVC-DVT compared with none of the 16 control patients (p = .007, Fisher's exact test). All four patients with DKA and CVC-DVT were <3 yrs old. Doppler ultrasound examination was performed on three of the four patients with clinical CVC-DVT, confirming the diagnosis in each case. CONCLUSIONS: This study suggests that young children with DKA have an increased incidence of clinical DVT associated with the placement of femoral central venous catheters.

Streptococcus mutans ffh, a gene encoding a homologue of the 54 kDa subunit of the signal recognition particle, is involved in resistance to acid stress.

The ability of Streptococcus mutans, a bacterial pathogen associated with dental caries, to tolerate rapid drops in plaque pH (acidurance), is considered an important virulence factor. To study this trait, Tn917 mutants of S. mutans strain JH1005 which display acid sensitivity have been isolated and partially characterized. In this paper, the characterization of one of these mutants, AS17, is reported. Preliminary sequence analysis revealed that the transposon insertion in AS17 occurred in the intergenic region of a two-gene locus which has been named sat for secretion and acid tolerance. This locus displays a high degree of homology to the ylxM-ffh operon of Bacillus subtilis. The sat+ locus was cloned by complementation of a conditional Escherichia coli ffh mutant with an S. mutans genomic library. Sequencing of the complementing clone identified the intact ylxM and ffh genes as well as a partial ORF with homology to the proUlopuAC gene of B. subtilis which encodes the binding protein of the ProU/OpuA osmoregulated glycine betaine transport system. RNA dot blot experiments indicated steady-state levels of ffh mRNA in the mutant that were approximately eightfold lower compared to parental levels. This suggests a partial polar effect of the sat-1::Tn917 mutation on ffh expression. Upon acid shock (pH 5), wild-type ffh mRNA levels were found to increase approximately four- to eightfold compared to unstressed (pH 7.5) levels. Mutant levels remained unaltered under the same conditions. Experiments designed to investigate the origins of the acid-sensitivity of the mutant revealed a lack of an acid-adaptive/tolerance response. Assays of proton-extruding ATPase (H+/ATPase) specific activity measured with purified membranes derived from acid-shocked AS17 showed twofold lower levels compared to the parent strain. Also, AS17 was found to be unable to ferment sorbitol although it was able to grow in glucose and a variety of other sugar substrates. These findings suggest that Ffh may be involved in the maintenance of a functional membrane protein composition during adaptation of S. mutans to changing environmental conditions.