Human GPI ELISA Matched Antibody Pair

Background: Excessive neuronal activity in the globus pallidus internus (GPi) is believed to promote parkinsonian akinesia/bradykinesia, but not tremor. Parkinsonian tremor is thought to result from dysfunction in the basal ganglia and cerebello-thalamo-cortical circuits. Whether the GPi is involved in tremorgenesis has not been fully elucidated. This study was designed to quantify the characteristics of oscillatory GPi neurons in patients with Parkinson's disease. Methods: Nine patients undergoing surgery were studied. Microelectrode recordings in the GPi and electromyographic (EMG) activity in the limbs were recorded and the mean spontaneous firing rates (MSFFts) were calculated. Spectral analysis was used to assess neuronal oscillatory patterns. Coherence analysis was applied to explore the relationship between oscillatory neurons and EMG. Results: Of 79 GPi neurons, 50.6% oscillated at the tremor frequency; 25.3% oscillated at beta frequency, and 24.1% did not oscillate. The MSFR of all neurons was 81.5 +/- 7.4 spikes/s. Among neurons oscillating at tremor frequency, 40% were coherent with the tremor. In four neurons, the pattern changed from tremor frequency to beta frequency or vice versa. It appeared that the tremor began before the GPi fired bursts. Conclusion: Some neuronal activity in the GPi correlates with tremor and this correlation might be due to either feedback, maintenance, or initiation. Since there were examples of EMG tremor prior to GPi activity, initiation seems least likely. The data further support the prediction of the classic pathophysiology model of Parkinson's disease.

Management of aggressive malignant musculoskeletal tumors is clinically challenging and awaits the identification of regulator(s) that can be therapeutically used to improve patient outcome. Autocrine motility factor (AMF), a secreted cytokine, is known to alter the bone microenvironment by linking to its receptor AMFR (AMF Receptor), leading to tumor progression. It was noted that both the ligand and its receptor belong to the moonlighting family of proteins, as they contribute to intracellular metabolic function such as glycolysis and gluconeogenesis by expressing glucose-6-phosphate isomerase AMF/GPI and higher protein degradation by expressing AMFR/gp78 functioning as ubiquitin ligase activity. Thus, AMF/GPI and AMFR/gp78 contribute to higher metabolic turnover of protein and glucose. Recently, a large-scale cohort study including 23 different histological types of musculoskeletal tumors revealed that patients with osteosarcoma, multiple myeloma, rhabdomyosarcoma, and angiosarcoma tend to express higher levels of AMF, whereas multiple myeloma patients expressed high levels of AMFR. Consistently, the cellular data showed that a variety of musculoskeletal tumors express AMF and components of bone microenvironment express AMFR. Thus, a novel outlook suggests a cellular link and cross-talk between musculoskeletal tumors and the skeletal milieu are regulated by AMF-AMFR signaling. This review will highlight the pharmacological need for AMF and AMFR inhibitors as unmet medical needs for patients with malignant musculoskeletal tumors.