A rare case of nivolumab-related myasthenia gravis and myocarditis in a patient with metastatic gastric cancer.

BACKGROUND: Although rare, several immune-related adverse effects can be life-threatening. Here, we describe a metastatic gastric cancer patient presenting with nivolumab-related myasthenia gravis and myocarditis, a previously unreported adverse effect of gastric cancer treatment. CASE PRESENTATION: A 66-year-old man with metastatic gastric cancer visited the emergency department because of dizziness after the first dose of nivolumab. Diagnoses of nivolumab-related myasthenia gravis and myocarditis were established. Myocardial biopsy results and anti-acetylcholine receptor antibody positivity confirmed the diagnoses. Despite plasma exchange and intravenous methylprednisolone and immunoglobulin administration, the patient's general condition gradually worsened, and he died. CONCLUSIONS: Strict monitoring for cardiac and neuromuscular symptoms after nivolumab administration is necessary to rapidly treat these adverse effects.

[Repeated Bow hunter's stroke by artery-to-artery embolism from the vertebral artery dissecting aneurysm formed by head rotation: A case report].

A 55-year-old woman suffered from diplopia and occipital pain after shoveling snow. She was diagnosed with the right vertebral artery dissecting aneurysm at the level of the axial vertebra and repeatedly had cerebral infarctions in the posterior circulation. She had subluxation of the atlantoaxial vertebra as an underlying disease. Right vertebral angiogram with the head rotated to the left showed the right vertebral artery occlusion and left vertebral angiogram with the head rotated to the right showed stenosis at the C1-C2 level, leading to the diagnosis of Bow hunter's stroke. After wearing a cervical collar and taking 100 |mg of aspirin, she had no recurrence of cerebral infarction and later underwent C1-C2 posterior fusion to prevent the recurrence of cerebral infarction. She finished taking aspirin 6 months after the surgery, and there has been no recurrence of cerebral infarction. We report here a case of Bow hunter's stroke, a rare disease, with good clinical outcomes after C1-C2 posterior fusion.

Heterogenous Genetic, Clinical, and Imaging Features in Patients with Neuronal Intranuclear Inclusion Disease Carrying NOTCH2NLC Repeat Expansion.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder that is caused by the abnormal expansion of non-coding trinucleotide GGC repeats in NOTCH2NLC. NIID is clinically characterized by a broad spectrum of clinical presentations. To date, the relationship between expanded repeat lengths and clinical phenotype in patients with NIID remains unclear. Thus, we aimed to clarify the genetic and clinical spectrum and their association in patients with NIID. For this purpose, we genetically analyzed Japanese patients with adult-onset NIID with characteristic clinical and neuroimaging findings. Trinucleotide repeat expansions of NOTCH2NLC were examined by repeat-primed and amplicon-length PCR. In addition, long-read sequencing was performed to determine repeat size and sequence. The expanded GGC repeats ranging from 94 to 361 in NOTCH2NLC were found in all 15 patients. Two patients carried biallelic repeat expansions. There were marked heterogenous clinical and imaging features in NIID patients. Patients presenting with cerebellar ataxia or urinary dysfunction had a significantly larger GGC repeat size than those without. This significant association disappeared when these parameters were compared with the total trinucleotide repeat number. ARWMC score was significantly higher in patients who had a non-glycine-type trinucleotide interruption within expanded poly-glycine motifs than in those with a pure poly-glycine expansion. These results suggested that the repeat length and sequence in NOTCH2NLC may partly modify some clinical and imaging features of NIID.

Possible role of inter-domain salt bridges in oligopeptidase B from Trypanosoma brucei: critical role of Glu172 of non-catalytic ß-propeller domain in catalytic activity and Glu490 of catalytic domain in stability of OPB.

Oligopeptidase B (OPB) is a member of the prolyl oligopeptidase (POP) family of serine proteases. OPB in trypanosomes is an important virulence factor and potential pharmaceutical target. Characteristic structural features of POP family members include lack of a propeptide and presence of a ß-propeller domain (PD), although the role of the ß-PD has yet to be fully understood. In this work, residues Glu(172), Glu(490), Glu(524) and Arg(689) in Trypanosoma brucei OPB (Tb OPB), which are predicted to form inter-domain salt bridges, were substituted for Gln and Ala, respectively. These mutants were evaluated in terms of catalytic properties and stability. A negative effect on kcat/Km was obtained following mutation of Glu(172) or Arg(689). In contrast, the E490Q mutant exhibited markedly decreased thermal stability, although this mutation had less effect on catalytic properties compared to the E172Q and R689A mutants. Trypsin digestion showed that the boundary regions between the ß-PD and catalytic domains (CDs) of the E490Q mutant are unfolded with heat treatment. These results indicated that Glu(490) in the CD plays a role in stabilization of Tb OPB, whereas Glu(172) in the ß-PD is critical for the catalytic activity of Tb OPB.