Analysis of Global Sumoylation Changes Occurring during Keratinocyte Differentiation

Sumoylation is a highly dynamic process that plays a role in a multitude of processes ranging from cell cycle progression to mRNA processing and cancer. A previous study from our lab demonstrated that SUMO plays an important role in keratinocyte differentiation. Here we present a new method of tracking the sumoylation state of proteins by creating a stably transfected HaCaT keratinocyte cell line expressing an inducible SNAP-SUMO3 protein. The SNAP-tag allows covalent fluorescent labeling that is denaturation resistant. When combined with two-dimensional gel electrophoresis, the SNAP-tag technology provides direct visualization of sumoylated targets and can be used to follow temporal changes in the global cohort of sumoylated proteins during dynamic processes such as differentiation. HaCaT keratinocyte cells expressing SNAP-SUMO3 displayed normal morphological and biochemical features that are consistent with typical keratinocyte differentiation. SNAP-SUMO3 also localized normally in these cells with a predominantly nuclear signal and some minor cytoplasmic staining, consistent with previous reports for untagged SUMO2/3. During keratinocyte differentiation the total number of proteins modified by SNAP-SUMO3 was highest in basal cells, decreased abruptly after induction of differentiation, and slowly rebounded beginning between 48 and 72 hours as differentiation progressed. However, within this overall trend the pattern of change for individual sumoylated proteins was highly variable with both increases and decreases in amount over time. From these results we conclude that sumoylation of proteins during keratinocyte differentiation is a complex process which likely reflects and contributes to the biochemical changes that drive differentiation

Rupture of the ilio-psoas tendon after a total hip arthroplasty: an unusual cause of radio-lucency of the lesser trochanter simulating a malignancy

Avulsion fracture or progressive radiolucency of lesser trochanter is considered a pathognomic finding in patients with malignancies. Although surgical release of the iliopsoas tendon may be required during a total hip arthroplasty (THA), there is no literature on spontaneous rupture of the ilio-psoas tendon after a THA causing significant functional impairment. We report here such a case, which developed progressive radiolucency of the lesser trochanter over six years after a THA, simulating a malignancy. The diagnosis was confirmed by MRI. Because of the chronic nature of the lesion, gross retraction of the tendon into the pelvis, and low demand of our patient, he was treated by physiotherapy and gait training. Injury to the ilio-psoas tendon can occur in various steps of the THA and extreme care should be taken to avoid this injury. Prevention during surgery is better, although there are no reports of repair in the THA setting. This condition should be considered in patients who present with progressive radioluceny of the lesser trochanter, especially in the setting of a hip/pelvic surgery. Awareness and earlier recognition of the signs and symptoms of this condition will aid in diagnosis and will direct appropriate management

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Safety and Effectiveness of Central Venous Catheterization in Patients with Cancer: Prospective Observational Study

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catherization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catherization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC

Patients with schizophrenia show deficits of working memory maintenance components in circuit-specific tasks

Working memory (WM) deficits are a neuropsychological core finding in patients with schizophrenia and also supposed to be a potential endophenotype of schizophrenia. Yet, there is a large heterogeneity between different WM tasks which is partly due to the lack of process specificity of the tasks applied. Therefore, we investigated WM functioning in patients with schizophrenia using process- and circuit-specific tasks. Thirty-one patients with schizophrenia and 47 controls were tested with respect to different aspects of verbal and visuospatial working memory using modified Sternberg paradigms in a computer-based behavioural experiment. Total group analysis revealed significant impairment of patients with schizophrenia in each of the tested WM components. Furthermore, we were able to identify subgroups of patients showing different patterns of selective deficits. Patients with schizophrenia exhibit specific and, in part, selective WM deficits with indirect but conclusive evidence of dysfunctions of the underlying neural networks. These deficits are present in tasks requiring only maintenance of verbal or visuospatial information. In contrast to a seemingly global working memory deficit, individual analysis revealed differential patterns of working memory impairments in patients with schizophrenia

Functions of the multi-interacting protein KIDINS220/ARMS in cancer and other pathologies

Development of an organ and subsequently the whole system from an embryo is a highly integrated process. Although there is evidence that different systems are interconnected during developmental stages, the molecular understanding of this relationship is either not known or only to a limited extent. Nervous system development, amongst all, is maybe the most crucial and complex process. It relies on the correct distribution of specific neuronal growth factors and hormones to the specific receptors. Among the plethora of proteins that are involved in downstream signalling of neuronal growth factors, we find the kinase-D interacting substrate of 220 kDa (KIDINS220), also known as ankyrin-rich repeat membrane spanning (ARMS) protein. KIDINS220 has been shown to play a substantial role in the nervous system and vascular system development as well as in neuronal survival and differentiation. It serves as a downstream regulator for many important neuronal and vascular growth factors such as vascular endothelial growth factor (VEGF), the neurotrophin family, glutamate receptors and ephrin receptors. Moreover, activation and differentiation of B- and T-cells, as well as tumour cell proliferation has also shown to be related to KIDINS220. This review comprehensively summarises the existing research data on this protein, with a particular interest in its role in cancer and in other pathologies

Set-shifting as a component process of goal-directed problem-solving

In two experiments, we compared secondary task interference on Tower of London performance resulting from three different secondary tasks. The secondary tasks were designed to tap three different executive functions, namely set-shifting, memory monitoring and updating, and response inhibition. Previous work using individual differences methodology suggests that, all other things being equal, the response inhibition or memory tasks should result in the greatest interference. However, this was not found to be the case. Rather, in both experiments the set-shifting task resulted in significantly more interference on Tower of London performance than either of the other secondary tasks. Subsequent analyses suggest that the degree of interference could not be attributed to differences in secondary task difficulty. Results are interpreted in the light of related work which suggests that solving problems with non-transparent goal/subgoal structure requires flexible shifting between subgoals – a process that is held to be impaired by concurrent performance of a set-shifting task

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

BackgroundTo better characterize short- term and long- term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD).MethodsPatients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long- term pancreatic function, recurrence, and survival) were collected.ResultsSixty- five patients from 18 institutions with a median age of 13 years (4 months- 22 years) and a median (IQR) follow- up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30- day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non- SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival.ConclusionThis is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/2/pbc28425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/1/pbc28425_am.pd