Impaired astrocytes and diffuse activation of microglia in the cerebral cortex in simian immunodeficiency virus-infected Macaques without simian immunodeficiency virus encephalitis

Various types of neuronal damage have been reported in acquired immunodeficiency syndrome (AIDS) dementia. We previously demonstrated that inflammation and cortical damage occur independently according to viral tropism in a simian immunodeficiency virus (SIV)-infected macaque model of AIDS dementia. To elucidate the pathogenesis of cortical degeneration, we examined the frontal cortex of SIV-infected macaques and found apoptosis and decreased expression of the excitatory amino acid transporter 2 in astrocytes and diffuse activation of microglia in association with limited neuronal damage. Some activated microglia also expressed excitatory amino acid transporter 2 but not proinflammatory cytokines. No inflammatory changes were seen in the cortex or the white matter, and SIV-infected cells were not detected in or around cortical lesions either by immunohistochemistry or by the polymerase chain reaction detection of SIV genomes of extracted DNA from microdissected tissue samples. These results indicate that an astrocytic abnormality and a compensatory activation of microglia might provide a protective effect against neuronal degeneration in the frontal cortex of SIV-infected macaques without SIV encephalitis.     

Increased frequency of CD4+T cells expressing fractalkine receptor CX3CR1 in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its AIDS susceptible polymorphisms are not associated with the disease

To investigate whether fractalkine receptor CX3CR1 polymorphisms that have been associated with rapid progression to AIDS among HIV-1 positive individuals also affects the risk of human T cell lymphotropic virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP), we compared the allele frequencies of V249I and T280M between 233 HAM/TSP patients and 213 HTLV-1 seropositive asymptomatic carriers (HCs). Although the frequency and absolute number of peripheral blood CX3CR1+CD4+T cells were significantly increased in HAM/TSP patients compared to HCs and uninfected controls independent of HTLV-1 trans-activator protein Tax, we could not observe any association between the two polymorphisms and the risk of HAM/TSP in our cohort.     

Severe Subarachnoid Hemorrhage Associated with Cerebral Venous Thrombosis in Early Pregnancy: A Case Report

Background

Cerebral venous thrombosis (CVT) rarely induces subarachnoid hemorrhage (SAH). During late pregnancy and puerperium, CVT is an uncommon but important cause of stroke. However, severe SAH resulting from CVT is extremely rare during early pregnancy.

Objective

We report on a rare case of severe SAH due to CVT, and discuss the potential pitfalls of CVT diagnosis in early pregnancy.

Case Report

A 32-year-old pregnant woman (9th week of pregnancy) presented with slight head dullness. Initial magnetic resonance imaging (MRI) revealed focal, abnormal signal intensity in the left thalamus. Nine days later, the patient developed a generalized seizure and severe SAH was detected with computed tomography (CT) scan. MRI and cerebral angiography revealed a completely thrombosed superior sagittal sinus, vein of Galen, straight sinus, and right transverse sinus. Transvaginal sonography indicated a missed abortion. The day after admission, the patient presented again with a progressive loss of consciousness and signs of herniation. The patient underwent emergency decompressive craniotomy, followed by intrauterine curettage. Two months later, she made an excellent recovery except for a slight visual field defect.

Conclusions

A rare case of severe SAH due to CVT is reported, with emphasis on the potential pitfalls of CVT diagnosis in early pregnancy.     

Axonal damage revealed by accumulation of beta-amyloid precursor protein in HTLV-I-associated myelopathy

We investigated the localization and extent of beta-amyloid precursor protein (APP) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The results from this study show that APP, used as a marker of early axonal damage in HAM/TSP lesions, is more intensively expressed in areas of active-inflammatory lesions than those of inactive-chronic lesions. The close localization to the areas containing inflammation (activation of macrophage/microglia) is striking and suggests that axonal damage is closely associated with inflammation in active-chronic lesions. Although inflammatory cell infiltration in the central nervous system (CNS) is rarely found in inactive-chronic lesions, a few clusters of APP+ axons are found in the spinal cord white matter in some cases. The presence of APP+ axons without relation to inflammatory cells in inactive-chronic lesions, suggest that soluble neurotoxic factors might induce axonal changes in the CNS of HAM/TSP. The occasional myelinated fibers in the anterior and posterior spinal roots in lower thoracic to lumbar levels had APP+ axons, suggesting that spinal nerve roots can be affected in HAM/TSP, especially in lower thoracic to lumbar levels. Impairment of fast axonal transport may contribute to the development of disability in patients with HAM/TSP.     

CD70 antibody-drug conjugate: A potential novel therapeutic agent for ovarian cancer

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC₅₀ values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm³, P < .01; SKOV3cisR: 232.2 vs 584.9 mm³, P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.     

Germanium myopathy: clinical and experimental pathological studies

Summary Pathological examinations were carried out on the skeletal muscle of a patient with germanium intoxication. The prominent histochemical finding was vacuolar myopathy with lipid excess, increased acid phosphatase activity and decreased cytochrome c oxidase activity. Ultrastructural lesions revealed a mitochondrial abnormality, autophagic vacuoles and accumulation of high electron-dense materials in deformed mitochondria and at the periphery of lipid droplets. Furthermore, the toxic effect of germanium on skeletal muscle was confirmed by the experimentally induced germanium myopathy, which showed autophagic degeneration, decreased cytochrome c oxidase activity and a mitochondrial abnormality with high electron-dense materials.     

Impact of diabetes and Krebs von den Lungen‐6 on coronavirus disease 2019 severity: A single‐center study from Japan

Aims/IntroductionDiabetes mellitus is reported as a risk factor for increased coronavirus disease 2019 (COVID‐19) severity and mortality, but there have been few reports from Japan. Associations between diabetes mellitus and COVID‐19 severity and mortality were investigated in a single Japanese hospital.Materials and MethodsPatients aged ≥20 years admitted to Osaka City General Hospital for COVID‐19 treatment between April 2020 and March 2021 were included in this retrospective, observational study. Multivariable logistic regression analysis was carried out to examine whether diabetes mellitus contributes to COVID‐19‐related death and severity.ResultsOf the 262 patients included, 108 (41.2%) required invasive ventilation, and 34 (13.0%) died in hospital. The diabetes group (n = 92) was significantly older, more obese, had longer hospital stays, more severe illness and higher mortality than the non‐diabetes group (n = 170). On multivariable logistic regression analysis, age (odds ratio [OR] 1.054, 95% confidence interval [CI] 1.023–1.086), body mass index (OR 1.111, 95% CI 1.028–1.201), history of diabetes mellitus (OR 2.429, 95% CI 1.152–5.123), neutrophil count (OR 1.222, 95% CI 1.077–1.385), C‐reactive protein (OR 1.096, 95% CI 1.030–1.166) and Krebs von den Lungen‐6 (OR 1.002, 95% CI 1.000–1.003) were predictors for COVID‐19 severity (R ²= 0.468). Meanwhile, age (OR 1.104, 95% CI 1.037–1.175) and Krebs von den Lungen‐6 (OR 1.003, 95% CI 1.001–1.005) were predictors for COVID‐19‐related death (R ²= 0.475).ConclusionsDiabetes mellitus was a definite risk factor for COVID‐19 severity in a single Japanese hospital treating moderately‐to‐severely ill patients.     

An autopsied case of the Crow-Fukase syndrome: a neuropathological study with emphasis on spinal roots

Summary An autopsied case of the Crow-Fukase syndrome is reported. Neuropathological findings were as follows: (1) in the sural nerve, there was marked decrease of large and small myelinated fibers. Myelinated fibers showing axonal degeneration and segmental demyelination and remyelination were moderately increased. (2) In the lumbar spinal roots, myelinated fibers showing segmental demyelination and remyelination were frequently observed. The density of myelinated fibers of the ventral root was less at the dural site than the spinal site, while that of the dorsal roots was less at the spinal site than the dural site. (3) In the dorsal root ganglion, there were Nageotte's residual nodules and satellitosis; (4) in the lumbar and thoracic spinal cord, there was pallor of the dorsal column; and (5) nerve cells showing central chromatolysis were frequently observed in the spinal anterior horn cells. Segmental demyelination and remyelination in the spinal roots and loss of myelinated fibers with axonal degeneration in the sural nerve are fibers with axonal degeneration in the sural nerve are main neuropathological features of this syndrome.     

Negative prognostic outcomes of percutaneous transhepatic biliary drainage in distal cholangiocarcinoma: a retrospective analysis using propensity score matching

International Journal of Clinical Oncology - The efficacy of different types of preoperative biliary drainage for cholangiocarcinoma has been debated over the past two decades. Controversy...