Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan.

BACKGROUND: The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. METHODS: We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. RESULTS: The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99-2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84-4.86), while that of those with other cancers was 1.93 (95% CI: 1.57-2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46-2.93). CONCLUSIONS: Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Long-Term Implantable, Flexible, and Transparent Neural Interface Based on Ag/Au Core-Shell Nanowires.

Neural interfaces enabling light transmittance rely on optogenetics to control and monitor specific neural activity, thereby facilitating deeper understanding of intractable diseases. This study reports the material strategy underlying an optogenetic neural interface comprising stretchable and transparent conductive tracks and capable of demonstrating high biocompatibility after long-term (5-month) implantation. Ag/Au core-shell nanowires contribute toward improving track performance in terms of stretchability (<60% strain), transparency (<83%), and electrical resistance (15 Ω sq-1 ). The neural interface integrated with gel-coated exterior microelectrodes preserves low impedance (1.1-3.2 Ω cm2 ) in a saline solution over the evaluated 5-month period. Besides the use of efficient conductive materials, surface treatment using antithrombogenic polymer tends to prevent the growth of granulation tissue, thereby facilitating clear monitoring of electrocorticograms (ECoG) in a rodent during chronic implantation. The flexible and transparent neural interface pathologically exhibits noncytotoxicity and low inflammatory response while efficiently recording evoked ECoG in a nonhuman primate via optogenetic stimulation. The proposed highly reliable interface can be employed in multifaceted approaches for translational research based on chronic implants.

The localization of α-synuclein in the process of differentiation of human erythroid cells.

Although the neuronal protein α-synuclein (α-syn) is thought to play a central role in the pathogenesis of Parkinson's disease (PD), its physiological function remains unknown. It is known that α-syn is also abundantly expressed in erythrocytes. However, its role in erythrocytes is also unknown. In the present study, we investigated the localization of α-syn in human erythroblasts and erythrocytes. Protein expression of α-syn increased during terminal differentiation of erythroblasts (from day 7 to day 13), whereas its mRNA level peaked at day 11. α-syn was detected in the nucleus, and was also seen in the cytoplasm and at the plasma membrane after day 11. In erythroblasts undergoing nucleus extrusion (day 13), α-syn was detected at the periphery of the nucleus. Interestingly, we found that recombinant α-syn binds to trypsinized inside-out vesicles of erythrocytes and phosphatidylserine (PS) liposomes. The dissociation constants for binding to PS/phosphatidylcholine (PC) liposomes of N-terminally acetylated (NAc) α-syn was lower than that of non NAc α-syn. This suggests that N-terminal acetylation plays a significant functional role. The results of the present study collectively suggest that α-syn is involved in the enucleation of erythroblasts and the stabilization of erythroid membranes.

[A case of Möbius syndrome with congenital facial palsy and supranuclear oculomotor palsy].

An 18-year-old man with congenital weakness in the facial and mastication muscles was referred to us. His facial senses were intact; however, the bilateral massetter and facial muscles were extremely weak and atrophic. He presented lagophthalmos and had difficulty in closing his mouth. The voluntary movements of his left eye, such as abduction, adduction, and elevation, were partially impaired, without the impairment of the Bell phenomenon. Nerve conduction studies of the facial nerves revealed normal distal latencies for bilateral orbicularis oculi. Blink reflexes were not evoked on both sides. Needle electromyography showed a chronic neurogenic change in the tongue. A biopsy of the biceps brachii and skin did not show abnormality. We diagnosed his condition as Möbius syndrome with congenital facial palsy and supranuclear oculomotor palsy. Möbius syndrome, which manifests itself as congenital and non-progressing facial and abducens palsy, is associated with many clinical symptoms and is probably heterogenous nosological entity. Although several cases of Möbius syndrome with supranuclear binocular elevation palsy were previously known, this is the first case of Möbius syndrome presenting supranuclear monocular elevation palsy.

Complications of a trophic xenotransplant approach in parkinsonian monkeys.

Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.

Mutant protein kinase Cgamma found in spinocerebellar ataxia type 14 is susceptible to aggregation and causes cell death.

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disease characterized by various symptoms including cerebellar ataxia. Recently, several missense mutations in the protein kinase Cgamma (gammaPKC) gene have been found in different SCA14 families. To elucidate how the mutant gammaPKC causes SCA14, we examined the molecular properties of seven mutant (H101Y, G118D, S119P, S119F, Q127R, G128D, and F643L) gammaPKCs fused with green fluorescent protein (gammaPKC-GFP). Wild-type gammaPKC-GFP was expressed ubiquitously in the cytoplasm of CHO cells, whereas mutant gammaPKC-GFP tended to aggregate in the cytoplasm. The insolubility of mutant gammaPKC-GFP to Triton X-100 was increased and correlated with the extent of aggregation. gammaPKC-GFP in the Triton-insoluble fraction was rarely phosphorylated at Thr(514), whereas gammaPKC-GFP in the Triton-soluble fraction was phosphorylated. Furthermore, the stimulation of the P2Y receptor triggered the rapid aggregation of mutant gammaPKC-GFP within 10 min after transient translocation to the plasma membrane. Overexpression of the mutant gammaPKC-GFP caused cell death that was more prominent than wild type. The cytotoxicity was exacerbated in parallel with the expression level of the mutant. These results indicate that SCA14 mutations make gammaPKC form cytoplasmic aggregates, suggesting the involvement of this property in the etiology of SCA14.