Palliative Gamma Knife Radiosurgery for a Small Part of a Large Vestibular Schwannoma in an Elderly Patient

We report a case of a large vestibular schwannoma in an 80-year-old female patient that shrank after palliative Gamma Knife radiosurgery (GKS). Neurological symptoms included hearing deterioration and facial palsy. The tumor volume was 21.9 mL. Craniotomy was considered high-risk, and conventional GKS was risky, owing to the risk of transient enlargement. Therefore, GKS was performed on only a portion of the tumor. The marginal dose (12 Gy) volume was 3.8 mL (17.4%). The tumor began to shrink after transient enlargement. Sixty months later, the tumor volume was only 3.1 mL, and the patient was able to maintain independent activities of daily living without salvage treatment

Normothermic treatment in acute clinical encephalitis: a case report

Abstract Introduction Encephalitis is a common infection of the brain, associated with a high risk of mortality and morbidity despite intensive supportive therapy. This report describes a patient with acute clinical meningoencephalitis who responded dramatically when her body temperature was decreased to normothermia (36 to 37°C) in combination with barbiturate therapy. Case presentation A 15-year-old, previously healthy girl presented with a 2-day history of headache and meningeal stiffness and pyrexia. Cranial magnetic resonance imaging showed high-intensity signals in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. On day 4 of admission, the level of consciousness decreased and ataxic respiration and apnea appeared. After that, fever (body temperature >40°C) developed with remarkable tachycardia. The body temperature was decreased with the use of a forced-air-cooling blanket and head cooling. The core temperature, measured in the bladder, was maintained at between 36 and 37°C for 5 days. During the period of normothermia, thiopental sodium was given continuously for 3 days. After normothermia, the level of consciousness increased without the development of fever, and ventilatory support was withdrawn. Conclusion Our experience suggests that normothermic treatment in combination with barbiturate therapy may be an effective option for the management of brain swelling associated with acute meningoencephalitis, particularly when accompanied by a persistent high fever.</p

Protein C activity as a potential prognostic factor for nursing home-acquired pneumonia

[Introduction] Despite the poor prognosis for nursing home acquired pneumonia (NHAP), a useful prognostic factor is lacking. We evaluated protein C (PC) activity as a predictor of in-hospital death in patients with NHAP and community-acquired pneumonia (CAP). [Methods] This prospective, observational study included all patients hospitalized with pneumonia between July 2007 and December 2012 in a single hospital. We measured PC activity at admission and investigated whether it was different between survivors and non-survivors. We also examined whether PC activity 20 mg/dL, respiratory rate >30/min, and blood pressure 65). When it was a useful prognostic factor for pneumonia, we combined PC activity with the existing prognostic scores, the pneumonia severity index (PSI) and CURB-65, and analyzed its additional effect by comparing the areas under the receiver operating characteristic curves (AUCs) of the modified and original scores. [Results] Participants comprised 75 NHAP and 315 CAP patients. PC activity was lower among non-survivors than among survivors in NHAP and all-pneumonia (CAP+NHAP). PC activity <55% was a useful prognostic predictor for NHAP (Odds ratio 7.39 (95% CI; 1.59–34.38), and when PSI or CURB-65 was combined with PC activity, the AUC improved (from 0.712 to 0.820 for PSI, and 0.657 to 0.734 for CURB-65). [Conclusions] PC activity was useful for predicting in-hospital death of pneumonia, especially in NHAP, and became more useful when combined with the PSI or CURB-65

Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition

iPS細胞を用いて肺胞上皮細胞の分化評価に成功 --肺の障害研究への足がかりに--. 京都大学プレスリリース. 2020-12-14.Alveologenesis is a developmental step involving the expansion of the lung surface area which is essential for gas exchange. The gas exchange process is mediated by alveolar type I (AT1) cells, which are known to be differentiated from alveolar type II (AT2) or bipotent cells. Due to the difficulty of isolating and culturing primary AT1 cells, the mechanism underlying their differentiation is not completely understood. We performed single‐cell RNA sequencing (scRNA‐seq) of fibroblast‐dependent alveolar organoids (FD‐AOs), including human induced pluripotent stem cell (hiPSC)‐derived epithelial cells and fetal lung fibroblasts, and identified hiPSC‐derived AT1 (iAT1) cells. A comparison of the FD‐AOs and fibroblast‐free alveolar organoids showed that iAT1 cells were mainly present in the FD‐AOs. Importantly, the transcriptomes of iAT1 cells were remarkably similar to those of primary AT1 cells. Additionally, XAV‐939, a tankyrase inhibitor, increased iAT1 cells in passaged FD‐AOs, suggesting that these cells were differentiated from hiPSC‐derived AT2 (iAT2) cells through the inhibition of canonical Wnt signaling. Consequently, our scRNA‐seq data allowed us to define iAT1 cells and identify FD‐AOs as a useful model for investigating the mechanism underlying human AT1 cell differentiation from AT2 cells in vitro

p38 mitogen-activated protein kinase determines the susceptibility to cigarette smoke-induced emphysema in mice

BACKGROUND: There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown. This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure. METHODS: In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant). The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury. RESULTS: Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice. SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2, protein levels of KC, MIP-1α, IL-1β, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure. CONCLUSIONS: Cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema. Its selective inhibition ameliorated lung inflammation and injury in a murine model of cigarette smoke exposure. p38 MAPK pathways are a possible molecular target for the treatment of chronic obstructive pulmonary disease

Multiple phosphorus chemical sites in heavily phosphorus-doped diamond

We have performed high-resolution core level photoemission spectroscopy on a heavily phosphorus (P)-doped diamond film in order to elucidate the chemical sites of doped-phosphorus atoms in diamond. P 2p core level study shows two bulk components, providing spectroscopic evidence for multiple chemical sites of doped-phosphorus atoms. This indicates that only a part of doped-phosphorus atoms contribute to the formation of carriers. From a comparison with band calculations, possible origins for the chemical sites are discussed

Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo

ヒトiPS細胞由来肺前駆細胞の拡大培養とマウス肺への移植・生着に成功 --肺再生医療の実現へ大きな一歩--. 京都大学プレスリリース. 2021-07-30.Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported. Herein, we established an expansion system of hLPs based on their three-dimensional culture in core-shell hydrogel microfibers, that ensures the maintenance of their bipotency for differentiation into alveolar and airway epithelial cells including alveolar type II (AT2) cells. Further, we developed an efficient in vivo transplantation method using an endoscope-assisted transtracheal administration system; the successful engraftment and in vivo differentiation of hLPs into alveolar epithelial cells (incorporated into the alveoli) was observed. Importantly, expanded hLPs in the context of microfibers were successfully transplanted into the murine lungs, opening avenues for cell-based therapies of lung diseases. Therefore, our novel method has potential regenerative medicine applications; additionally, the high-quality hLPs and AT2 cells generated via the microfiber-based technology are valuable for drug discovery purposes