Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra.

Marinesco bodies (MBs) are spherical nuclear inclusions found in pigmented neurons of the substantia nigra. Although MBs are abundant in senescent brains, how they are related to aging processes remains unclear. Here, we performed a morphometric analysis of midbrain pigmented neurons to identify the possible influence of MBs on nuclear size. The transected area of the nucleus (nuclear area) was larger in the presence of MBs and was correlated with the area of MB (MB area) in all tested brains. The MB-associated nuclear enlargement was significant even after MB areas were subtracted from nuclear areas. Moreover, higher MB immunoreactivity of p62 was detected in the nucleoplasm of the enlarged MB-associated nuclei. This study on human brains is the first quantitative approach demonstrating MB-associated nuclear enlargement and progressive accumulation of small nucleoplasmic materials. Although cellular hypertrophy is usually considered to be an indication of the upregulation of cellular function, this might not always be the case. These findings suggest that an age-related decline of ubiquitin-proteasome and autophagy system activity and stagnation of undegradable materials are one of the candidate mechanisms to explain the age-related decline of neural activity in the substantia nigra.

Early-onset herpes simplex encephalitis type 1 triggered by COVID-19 disease: A case report.

Coronavirus disease 2019 (COVID-19) causes a systemic inflammatory response and a temporary immunosuppression of hosts. Several reports have showed that reactivation of herpes simplex virus type 1 (HSV-1) is strongly associated with COVID-19. We present a case of a 66-year-old female, who developed HSV-1 encephalitis, showing impaired consciousness and typical MRI findings such as hyperintense lesions in the temporal lobe, insular cortices, bilateral medial frontal lobe on diffusion-weighted imaging, 7 days after the onset of COVID-19 symptoms. The number of cases of encephalitis in patients with COVID-19 is increasing. However, there has been limited reports of HSV-1 encephalitis following COVID-19, especially for cases with an interval of 7 days or less from the onset of COVID-19 symptoms to the onset of HSV-1 encephalitis. Our case highlights the importance of considering HSV-1 encephalitis in the differential when managing a patient with COVID-19-associated neurologic complications, even if it is in the early stages of COVID-19.

Leukemic mature B-cell neoplasm observed during the treatment with romiplostim in patient with thrombocytopenia and liver cirrhosis.

We report here a new adverse event of romiplostim which is a protein analog of thrombopoietin. Leukemic mature B-cell neoplasm was observed during the treatment of thrombocytopenia in a patient with liver cirrhosis. Their relationship was suggested clinically but the mechanism of leukemic expansion of lymphoma cells was not clarified.

Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C.

It is unknown whether diabetes mellitus is a risk factor of the hepatocarcinogenesis in patients with chronic hepatitis C. Three hundred eleven anti-hepatitis C virus (HCV) -positive patients who had undergone liver biopsies were studied. Patients with histologically proven cirrhosis or withdrawing within 12 months were excluded. Thus, the remaining 279 patients were followed-up for 65.9 +/- 29.4 months until the occurrence of hepatocellular carcinoma (HCC). During the observation period, HCC developed in 13 patients. Diabetes, age, sex, habitual alcohol intake, history of blood transfusion, serum alpha-fetoprotein level, histological findings, HCV genotype, viral load, and interferon therapy were assessed as potential risk factors. The Cox proportional hazard model identified that diabetes mellitus, histological staging, and age were independently associated with the occurrence of HCC. With multivariate analysis, only diabetes mellitus and age were associated with the occurrence of HCC. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C.