1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuroblastic apoptosis in the subventricular zone is caused by 1-methy-4-phenylpiridinium (MPP+) converted from MPTP through MAO-B

Intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration induces apoptosis of subventricular zone (SVZ) doublecortin (Dcx)-positive neural progenitor cells (migrating neuroblasts, A cells). Actually, a metabolite of MPTP, 1-methy-4-phenylpiridinium (MPP⁺), is responsible for neural progenitor cell toxicity. In the present study, to examine whether the MPTP-induced SVZ cell apoptosis is caused directly by MPP⁺ metabolized through monoamine oxidase B (MAO-B), MPTP or MPP⁺ was intracerebroventricularly (icv) injected into C57BL/6 mice. At Day 1 postinjection, many terminal deoxynucleotidyl transferase-mediated dUTP endlabeling (TUNEL)-positive cells were observed in the SVZ of both low (36 μg) and high (162 μg) dose MPTP- and MPP⁺-injected mice. The number of Dcx-positive A cells showed a significant decrease following high dose of MPTP- or MPP⁺-injection on Days 1 and 3, respectively, whereas that of EGFR-positive C cells showed no change in mice with any treatment. In addition, prior icv injection of a MAO-B inhibitor, R(?)-deprenyl (deprenyl), inhibited MPTP-induced apoptosis, but not MPP⁺-induced apoptosis. MAO-B- and GFAP-double positive cells were detected in the ependyma and SVZ in all mice. It is revealed from these results that icv injection of MPTP induces apoptosis of neural progenitor cells (A cells) in the SVZ via MPP⁺ toxicity. In addition, it is suggested that the conversion from MPTP to MPP⁺ is caused mainly by MAO-B located in ependymal cells and GFAP-positive cells in the SVZ.     

Phagocytized corpora amylacea as a histological hallmark of astrocytic injury in neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating and necrotizing disorder of the CNS that mainly affects the optic nerve and spinal cord. The etiology is still uncertain; however, the discovery of serum anti‐aquaporin‐4 (AQP4) autoantibody is becoming the center of attention, and a new hypothesis is emerging that NMO is essentially astrocytopathy provoked by this autoantibody. In this study, we focused on corpora amylacea (CA), glycoproteinaceous inclusions in astrocytic processes. We examined 57 lesions in nine cases of NMO spectrum disorder, and demonstrated that CA were phagocytized by macrophages in 42 lesions (74%) of eight cases, while phagocytized figures were not seen in unaffected areas. Phagocytized CA were frequently encountered in early‐phase lesions still retaining myelin structures, while fewer or none were found in chronic destructive lesions. Moreover, phagocytized CA were significantly smaller in diameter than intact ones, and CA were decreased or absent in most lesions assessed. These findings suggest the following pathophysiological process: the astrocytes are affected at an early phase in NMO, CA are expelled from the astrocytes and phagocytized by macrophages finally leading to clearance. A phagocytized figure and subsequent loss of CA can be a histological hallmark of astrocytic injury of NMO.     

Periodontal disease and pneumonia mortality in haemodialysis patients: A 7‐year cohort study

Aim

To evaluate the association between periodontal disease and pneumonia mortality in haemodialysis patients.

Materials and Methods

This prospective cohort study included 211 patients (mean age, 64.4 years) undergoing haemodialysis at a single medical centre. The patients underwent a baseline clinical dental examination in 2008 and were then followed up until July 2015. Periodontal disease was defined as the presence of clinical attachment loss of ≥4 mm in ≥30% of the probed sites. The primary endpoint, that is death from pneumonia, was determined by reviewing death certificates and was analysed using the competing‐risks regression model.

Results

At baseline, 92 patients (43.6%) had periodontal disease. The median follow‐up period was 84 months (interquartile range, 36–86 months). Of the 68 deaths that occurred, 21 were from pneumonia. The multivariable competing‐risks regression model showed that periodontal disease was significantly associated with death from pneumonia (adjusted subhazard ratio, 3.49; 95% confidence interval, 1.14–10.64), after adjusting for other baseline health characteristics.

Conclusions

The results of this study suggest that periodontal disease is independently associated with pneumonia mortality in haemodialysis patients. Future studies evaluating the potential effect of oral interventions for periodontal health improvement on pneumonia in haemodialysis patients would be of great interest.     

Loss of ATE1-mediated arginylation leads to impaired platelet myosin phosphorylation,clot retraction,and in vivo thrombosis formation

Protein arginylation by arginyl–transfer RNA protein transferase (ATE1) is emerging as a regulator protein function that is reminiscent of phosphorylation. For example, arginylation of β-actin has been found to regulate lamellipodial formation at the leading edge in fibroblasts. This finding suggests that similar functions of β-actin in other cell types may also require arginylation. Here, we have tested the hypothesis that ATE1 regulates the cytoskeletal dynamics essential for in vivo platelet adhesion and thrombus formation. To test this hypothesis, we generated conditional knockout mice specifically lacking ATE1 in their platelets and in their megakaryocytes and analyzed the role of arginylation during platelet activation. Surprisingly, rather than finding an impairment of the actin cytoskeleton structure and its rearrangement during platelet activation, we observed that the platelet-specific ATE1 knockout led to enhanced clot retraction and in vivo thrombus formation. This effect might be regulated by myosin II contractility since it was accompanied by enhanced phosphorylation of the myosin regulatory light chain on Ser19, which is an event that activates myosin in vivo. Furthermore, ATE1 and myosin co-immunoprecipitate from platelet lysates. This finding suggests that these proteins directly interact within platelets. These results provide the first evidence that arginylation is involved in phosphorylation-dependent protein regulation, and that arginylation affects myosin function in platelets during clot retraction.     

Distinctive features of degenerating Purkinje cells in spinocerebellar ataxia type 31

Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant form of pure cerebellar ataxia that is caused by a disease‐specific insertion containing penta‐nucleotide repeats (TGGAA)_n. Neuropathologically, cerebellar Purkinje cells are preferentially affected and reduced in number in SCA31, and they are often surrounded by halo‐like amorphous materials. In the present study, we performed neuropathological analyses on two SCA31 brains, and discussed the serial morphological changes of Purkinje cells in SCA31.We found that bent, elongated, often folded nuclei were observed frequently in degenerating Purkinje cells with the halo‐like structure. Conversely, Purkinje cells without this structure developed marked atrophy with severely slender and condensed nuclei. On the basis of these pathological findings, we propose two different processes for Purkinje cell degeneration in SCA31, namely, shrinkage of Purkinje cells with or without the halo‐like amorphous materials. The former, but not the latter, was considered to be specific to SCA31. Correspondingly, fragmentation of the Golgi apparatus was observed more frequently in Purkinje cells with the halo‐like structure than in those without this structure. We consider that the profound nuclear deformity and fragmentation of the Golgi apparatus are closely linked with the formation of the halo‐like structure in SCA31.     

Clinical application of stress-breaking ball attachment for implant overdenture

PatientThe patient was a 62-year-old partially edentulous woman with missing bilateral premolars and molars in the mandibular jaw. The patient selected implant supported-removable partial denture rehabilitation. Implants were placed bilaterally at the distal extension of the denture base in order to minimize denture displacement. The stress-breaking ball (SBB) attachment consists of a flat-top ball head male and O-ring rubber female. The female was covered by a silicone housing with three amounts of space to allow three kinds of settlement (0.3 mm, 0.5 mm, and 0.7 mm); they were selected by thickness or pressure displacement of the mucosa and occlusal force. After the healing period, the SBB attachments (0.3 mm) were placed on the implants, and the implant-supported removable partial denture was then conventionally fabricated. The delivered denture had sufficient retention and appropriate stress breaking.DiscussionThe advantages of SBB attachments over conventional attachments are as follows: (1) they prevent the implant from excessive occlusal force, (2) they are ready-made, (3) they show appropriate retention, and (4) they can be easily mounted on the denture base. The disadvantages of these attachments are as follows: (1) they are approximately 1 mm higher than conventional ball attachments and (2) the retentive force cannot be adjusted.ConclusionThe use of a stress-breaking attachment for implant overdenture rehabilitation should be considered so that the occlusal force is equally distributed between the alveolar ridge and the implants.