The Growth Factor Midkine Antagonizes VEGF Signaling In Vitro and In Vivo

Midkine (MDK) is a heparin-binding growth factor involved in growth, survival, migration, and differentiation of various target cells and dysregulation of MDK signaling is implicated in a variety of inflammatory diseases and cancers. Although MDK has been reported to act on endothelial cells and to have proangiogenic effects, the exact role of MDK in angiogenesis is poorly defined. Here, we report that MDK is actually a modulator of angiogenesis and that it can abrogate the vascular endothelial growth factor A (VEGF-A)-induced proliferation of human microvascular endothelial cells in vitro through the downregulation of proangiogenic cytokines and through the upregulation of the antiangiogenic factor, tissue inhibitor of metalloproteinase 2. Phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2) and of downstream signaling molecules, such as phosphatidylinositol-3-kinase and mitogen-activated protein kinases, is also impaired. Moreover, MDK downregulates VEGF-A-induced neovascularization and vascular permeability in vivo. We propose a model in which MDK is a new modulator of the VEGF-A-VEGFR-2 axis.     

Assessment of cellular expression of parathyroid hormone-related protein mRNA and protein in multiple myeloma

The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.     

Effect of local heat versus ice on blepharoptosis resulting from ocular myasthenia

OBJECTIVE: To determine the effect of heat versus ice application to a ptotic eyelid in patients with ocular or systemic myasthenia. DESIGN: Observational case series. PARTICIPANTS: Three consecutive patients and one subsequent patient with ptosis and clinical or laboratory signs of myasthenia were initially evaluated. METHODS: In all four patients, the heat test and the ice test were performed. In three patients, the modified sleep test was also performed. In the heat or ice test, the patient was asked to hold a heat or ice pack, respectively, over the closed ptotic eye for 10 to 15 minutes. The modified sleep test was performed by having the patient close both eyes for a 10- to 15-minute period. Photographs were taken before and immediately after each test. MAIN OUTCOME MEASURE: The effect of heat or ice on ptosis. RESULTS: Transient complete improvement of ptosis in three patients and marked improvement in one patient was noted after each test. The results of the heat, ice, and modified sleep tests were identical. CONCLUSIONS: Marked improvement of myasthenic ptosis in all four patients occurred regardless of local warming or cooling. The common denominator of all these tests, rest, seems to be the relevant factor in the study as designed.     

Eagle syndrome: entrapment of the glossopharyngeal nerve? Case report and review of the literature

Eagle syndrome is characterized by unilateral pain in the oropharynx, the side of the face, and the earlobe. It is caused by an elongated styloid process; resection of the elongated process eliminates the pain. Although quite rare, this syndrome is well represented in the oral, ear, nose, and throat surgery literature. In the neurosurgical literature, on the other hand, there is little if any mention of Eagle syndrome. The author presents a case of a woman who suffered from severe pain in the throat, the side of the face, and the ear. After the diagnosis of Eagle syndrome was made based on radiographic findings and was confirmed using a local anesthetic block, resection of the elongated styloid process was performed, resulting in complete and lasting pain relief. Eagle syndrome, which is caused by compression of the glossopharyngeal nerve as it passes the elongated styloid process, may be classified as an entrapment syndrome deserving of neurosurgical attention. The goal of this report is to familiarize neurosurgeons with Eagle syndrome and its diagnostic work up and treatment.     

Successful allogeneic stem cell transplant after invasive pulmonary zygomycosis

We report the successful outcome of allogeneic stem cell transplant (SCT) in a patient with acute lymphoblastic leukaemia (ALL) and pulmonary zygomycosis diagnosed prior to transplant. The lesion was surgically excised and SCT proceeded with antifungal therapy, granulocyte transfusions and G-CSF support during the period of neutropenia.     

Local-global processing in Alzheimer's disease: an examination of interference, inhibition and priming

Impairments of memory, praxis, gnosis, language and executive functioning are well documented in Alzheimer's disease (AD). Functions, such as attention, however, have only recently been systematically investigated. We used Navon-type stimuli (large "global" digits composed of smaller "local" digits) to assess 12 AD participants' plus age-matched controls' ability to focus and alter the scale of their spatial attention. In the first experiment, participants responded to either the global or local characters within a block, ignoring characters at the other spatial scale. Healthy young adults (n=12) demonstrated the normal 'global precedence' effect on this task. In contrast, participants with AD and their age-matched controls were significantly faster on the local task than on the global task, suggesting in these groups a 'local precedence' effect. This consisted of both a local advantage and a local-on-global interference effect. In a second experiment, participants searched for designated targets which occurred unpredictably at either the local or global spatial scale. Participants with AD were significantly slower and more error-prone than older controls. In addition, participants with AD showed a greater cost in reaction time (RT) when required to switch spatial scales on consecutive trials, compared to no switch responses at the same spatial scale on consecutive trials. Thus, AD may impair the ability to process global figures, due perhaps to involvement of posterior parietal areas. Further, participants with AD were poor at inhibiting irrelevant stimuli and at inhibiting attentional allocation to an irrelevant spatial scale, which may relate to prefrontal pathology.