4-Aminopyridine in pediatric traumatic spinal cord injury: A case report.

Spinal cord injury (SCI) presents significant challenges due to its debilitating nature and potential complications. While few medications have shown efficacy in improving neurological recovery, 4-Aminopyridine (4-AP), a voltage-gated potassium channel blocker, has been used clinically off-label to improve neurologic function in adults with spinal cord-related paralysis. However, evidence regarding its safety and effectiveness in the pediatric population remains scarce, as it is approved for use in older patients.

Pediatric Rehabilitation of Acute Hyperextension-Induced Myelopathy After Surfing.

This case is a unique pediatric presentation of a surfer's myelopathy, now referred to as acute hyperextension-induced myelopathy (AHIM), that provides an optimistic rehabilitation outcome. A 13-year-old boy presented to the emergency department with back pain, paraplegia, urinary retention, and dysesthesia following his first surfing lesson while visiting Hawaii. MRI of the thoracic spine without contrast showed a significant T2 hyperintense signal in the T9-T12 distal thoracic cord, consistent with AHIM.

Treatment strategies for genu recurvatum in adult patients with hemiparesis: a case series.

Objective: To report our clinical experience and propose a biomechanical factor-based treatment strategy for improvement of genu recurvatum (GR) to reduce the need for knee-ankle-foot orthosis (KAFO) or surgical treatment.

Design: Case series.

Setting: Outpatient clinic of a Department of Physical Medicine and Rehabilitation in an academic medical center.

The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity.

Mutation of the TRIM (tripartite motif)-NHL family members brat and mei-P26 perturb the differentiation of transit-amplifying progenitor cells resulting in tumour-like phenotypes. The NHL (named after the NCL1, HT2A and LIN41 repeat) domain is essential for their growth suppressive activity, and they can induce cell-cycle exit in a RING-independent manner. TRIM3 is the only bona fide tumour suppressor in the mammalian TRIM-NHL subfamily and similar to the other members of this family, its ability to inhibit cell proliferation depends on the NHL domain.

Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates the development of proneural glioma.

Phosphorylation of Tyr-88/Tyr-89 in the 3(10) helix of p27 reduces its cyclin-dependent kinase (CDK) inhibitory activity. This modification does not affect the interaction of p27 with cyclin-CDK complexes but does interfere with van der Waals and hydrogen bond contacts between p27 and amino acids in the catalytic cleft of the CDK. Thus, it had been suggested that phosphorylation of this site could switch the tumor-suppressive CDK inhibitory activity to an oncogenic activity.

p27kip1 protein levels reflect a nexus of oncogenic signaling during cell transformation.

SV40 small t-antigen (ST) collaborates with SV40 large T-antigen (LT) and activated rasv12 to promote transformation in a variety of immortalized human cells. A number of oncogenes or the disruption of the general serine-threonine phosphatase protein phosphatase 2A (PP2A) can replace ST in this paradigm. However, the relationship between these oncogenes and PP2A activity is not clear.

Interweaving the cell cycle machinery with cell differentiation.

A comprehensive understanding of the mechanisms coupling cell cycle exit and differentiation is important for both cancer biology and tissue development. Cancer cells can arise from either stem/progenitor cells that fail to exit the cell cycle and differentiate, or from de-differentiated cells that have re-entered the cell cycle. Much of our current understanding of this coupling is based on observations made in transformed cell lines.

Somatic cell type specific gene transfer reveals a tumor-promoting function for p21(Waf1/Cip1).

How proteins participate in tumorigenesis can be obscured by their multifunctional nature. For example, depending on the cellular context, the cdk inhibitors can affect cell proliferation, cell motility, apoptosis, receptor tyrosine kinase signaling, and transcription. Thus, to determine how a protein contributes to tumorigenesis, we need to evaluate which functions are required in the developing tumor.

p27kip1 Regulates cdk2 activity in the proliferating zone of the mouse intestinal epithelium: potential role in neoplasia.

Background & Aims: Reduced p27(kip1) expression is a marker of poor prognosis in colorectal neoplasia, and inactivation of p27 in mice (p27(Delta51/Delta51)) causes increased intestinal epithelial cell proliferation and small and large intestinal neoplasia in a diet-dependent manner. Here, we addressed the role of p27 in untransformed intestinal epithelial cells in vivo and the consequence of its targeted inactivation.

Methods: A sequential fractionation procedure was used to isolate murine intestinal epithelial cells relative to their position along the crypt-villus axis, and the levels of cyclins, cyclin-dependent kinases (cdks), and cdk inhibitors and of the complexes formed among them was determined by immunoprecipitation-immunoblotting and kinase assays.

Cooperation between p27 and p107 during endochondral ossification suggests a genetic pathway controlled by p27 and p130.

Pocket proteins and cyclin-dependent kinase (CDK) inhibitors negatively regulate cell proliferation and can promote differentiation. However, which members of these gene families, which cell type they interact in, and what they do to promote differentiation in that cell type during mouse development are largely unknown. To identify the cell types in which p107 and p27 interact, we generated compound mutant mice.

p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow.

Neoangiogenesis involves both bone marrow-derived myelomonocytic and endothelial progenitor cells as well as endothelial cells coopted from surrounding vessels. Cytokines induce these cells to proliferate, migrate, and exit the cell cycle to establish the vasculature; however, which cell cycle regulators play a role in these processes is largely unknown. Here, we report that mice lacking the cell cycle inhibitors p130 and p27 show defects in tumor neoangiogenesis, both in xenografts and spontaneously arising tumors.