Prevention of Pulmonary Cement Embolism by Inferior Vena Cava Filter following Vertebroplasty-related Cement Intravasation.

A 77 year old woman with recent history of vertebroplasty for treatment of multiple osteoporotic lumbar vertebral body compression fractures presented for post-procedure care. A series of radiographs and cross-sectional imaging of the lumbar spine revealed an unexpected finding of cured bone cement within a small lumbar vertebral vein, the inferior vena cava and within the spokes of an inferior vena cava filter which had originally been placed two years earlier. Inferior vena cava filters have become the standard of care to prevent pulmonary embolism in the setting of deep venous thrombosis. However, cases of foreign materials becoming entrapped in filters are uncommon despite the documented frequency of intravasation of bone cement into the circulatory system following vertebroplasty procedures. This case is significant because it illustrates the rare occurrence of an inferior vena cava filter capturing intravasated bone cement and preventing its migration to the pulmonary circulation.

An Incidental Discovery Following Hypertension and Headaches: A Pheochromocytoma Case Report.

Pheochromocytomas (PCC) are rare neuroendocrine tumors of the adrenal medulla that arise from chromaffin cells. These cells are neural crest derivatives and are innervated by the splanchnic nerve of the sympathetic nervous system which releases acetylcholine that in turn binds to nicotinic acetylcholine receptors of the adrenal medulla causing the release of catecholamines. The dopamine, norepinephrine, and epinephrine released from these tumors are responsible for the episodic hyperadrenergic symptoms seen in these cases such as hypertension, palpitations, and headaches. This case report discusses the incidental finding of a unilateral PCC in a 58-year-old woman who initially presented to our emergency department complaining of intermittent chest pain and headaches for two days.

Inoperable Left Renal Vein Leiomyosarcoma Refractory to Chemotherapy Invades Inferior Vena Cava and Right Atrium: A Case Report.

Mesenchymal stem cells differentiate into a plethora of cell types. These differentiated cell types include osteoblasts, chondrocytes, myocytes, and adipocytes. Sarcomas occur secondary to malignant transformation of these mesenchymal, pluripotent stem cells. Involuntary smooth muscle is responsible for the make up of hollow organs and vasculature in our body and is regulated by our autonomic nervous system, hormones, as well as chemical and local mediators. Cancer involving smooth muscle cells is designated as leiomyosarcoma (LMS). LMS can arise from any location in the body where smooth muscle is present and is frequently reported in the abdomen and pelvis, as well as the trunk, extremities, and throughout the retroperitoneum.

Crossed Aphasia in a Patient with Anaplastic Astrocytoma of the Non-Dominant Hemisphere.

Aphasia describes a spectrum of speech impairments due to damage in the language centers of the brain. Insult to the inferior frontal gyrus of the dominant cerebral hemisphere results in Broca's aphasia - the inability to produce fluent speech. The left cerebral hemisphere has historically been considered the dominant side, a characteristic long presumed to be related to a person's "handedness". However, recent studies utilizing fMRI have shown that right hemispheric dominance occurs more frequently than previously proposed and despite a person's handedness. Here we present a case of a right-handed patient with Broca's aphasia caused by a right-sided brain tumor. This is significant not only because the occurrence of aphasia in right-handed-individuals with right hemispheric brain damage (so-called "crossed aphasia") is unusual but also because such findings support dissociation between hemispheric linguistic dominance and handedness.

Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy.

Autophagy, the primary recycling pathway of cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the response to cellular stress. The Hsp90-Cdc37 chaperone complex coordinately regulates the activity of select kinases to orchestrate many facets of the stress response. Although both maintain mitochondrial integrity, the relationship between Hsp90-Cdc37 and autophagy has not been well characterized. Ulk1, one of the mammalian homologs of yeast Atg1, is a serine-threonine kinase required for mitophagy. Here we show that the interaction between Ulk1 and Hsp90-Cdc37 stabilizes and activates Ulk1, which in turn is required for the phosphorylation and release of Atg13 from Ulk1, and for the recruitment of Atg13 to damaged mitochondria. Hsp90-Cdc37, Ulk1, and Atg13 phosphorylation are all required for efficient mitochondrial clearance. These findings establish a direct pathway that integrates Ulk1- and Atg13-directed mitophagy with the stress response coordinated by Hsp90 and Cdc37.

Mapping the phosphorylation sites of Ulk1.

Ulk1 is a serine/threonine kinase that controls macroautophagy, an essential homeostatic recycling pathway that degrades bulk cytoplasmic material and directs the turnover of organelles such as peroxisomes and mitochondria. Further, macroautophagy is potently induced by signals that trigger metabolic stress, such as hypoxia and amino acid starvation, where its recycling functions provide macromolecules necessary to maintain catabolic metabolism and cell survival. Substrates for Ulk1 have not been identified, and little is known regarding post-translational control of Ulk1 kinase activity and function. To gain insights into the regulatory mechanisms of Ulk1, we developed a robust purification protocol for Ulk1 and demonstrated that Ulk1 is highly phosphorylated and requires autophosphorylation for stability. Importantly, high-resolution, tandem mass spectrometry identified multiple sites of phosphorylation on Ulk1, including several within domains known to regulate macroautophagy. Differential phosphorylation analyses also identified sites of phosphorylation in the C-terminal domain that depend upon or require Ulk1 autophosphorylation.

Monitoring the autophagy pathway in cancer.

Autophagy is an ancient cell survival pathway that is induced by metabolic stress and that helps prevent bioenergetic failure. This pathway has emerged as a promising new target in cancer treatment, where agents that inhibit autophagic degradation have efficacy in preventing cancer and in treating resistant disease when combined with conventional chemotherapeutics, which generally activate the pathway. However, agents that specifically target the autophagy pathway are currently lacking, and monitoring the effects of therapeutics on the autophagy pathway raises several challenges. Here we review the potential roles of the autophagy pathway in tumor progression and in maintenance of the malignant state, and introduce novel methods that we have developed that allow one to monitor autophagic activity ex vivo and in vivo.