Semaphorin 4D/Plexin-B1–mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activity

Plexins are cell surface receptors for semaphorins and regulate cell migration in many cell types. We recently reported that the semaphorin 4D (Sema4D) receptor Plexin-B1 functions as a GTPase-activating protein (GAP) for R-Ras, a member of Ras family GTPases implicated in regulation of integrin activity and cell migration (Oinuma, I., Y. Ishikawa, H. Katoh, and M. Negishi. 2004. Science. 305:862–865). We characterized the role of R-Ras downstream of Sema4D/Plexin-B1 in cell migration. Activation of Plexin-B1 by Sema4D suppressed the ECM-dependent R-Ras activation, R-Ras–mediated phosphatydylinositol 3-kinase activation, and β1 integrin activation through its R-Ras GAP domain, leading to inhibition of cell migration. In addition, inactivation of R-Ras by overexpression of the R-Ras–specific GAP or knockdown of R-Ras by RNA interference was sufficient for suppressing β1 integrin activation and cell migration in response to the ECM stimulation. Thus, we conclude that R-Ras activity is critical for ECM-mediated β1 integrin activation and cell migration and that inactivation of R-Ras by Sema4D/Plexin-B1–mediated R-Ras GAP activity controls cell migration by modulating the activity of β1 integrins

Claw sign predicts first-pass effect in MT

Background: Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the “claw sign,” was examined as candidate preoperative imaging factor for predicting the FPE. Methods: We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE. Results: FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; P = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01–7.06; P = 0.047). Conclusion: The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke

The predictor of LVO with low NIHSS

Background : Intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular treatment have been performed for severe large vessel occlusion (LVO) and the results have been reported at high levels of evidence. However, acute treatment for LVO with mild symptom remains controversial. We retrospectively examined prognostic factors for LVO with mild symptoms. Method : We studied retrospectively the patients within 24 h of onset with large vessel occlusion with NIHSS score ≤ 5. Outcomes were evaluated by modified Rankin Scale (mRS) at 90 days, with 0–2 defined as a good outcome and 3–6 as a poor outcome. Clinical characteristics of each case were examined. Result : Participants comprised 76 patients. Of the 76 patients. ICA occlusion showed good outcome in 17 / 19 cases (90%), whereas MCA occlusion showed good outcome in 36 / 54 cases (67%). Among the 14 cases showing positive results for distal intraarterial signal (d-IAS), outcomes were good in 6 cases (43%). On the other hand, the 32 d-IAS-negative cases showed good outcome in 28 cases (88%). Outcomes were thus significantly poorer for d-IAS-positive cases. Conclusion : MCA occlusion is associated with poor prognosis, even with NIHSS score ≤ 5, and d-IAS may provide a predictor

Takotsubo Cardiomyopathy as a Delayed Complication with a Herbicide Containing Glufosinate Ammonium in a Suicide Attempt: A Case Report

Background. Glufosinate ammonium has a famous delayed complication as respiratory failure, however, delayed cardiogenic complication is not well known. Objectives. The aim of this study is to report a takotsubo cardiomyopathy as a delayed complication of glufosinate ammonium for suicide attempt. Case Report. A 75-year-old woman ingested about 90 mL of Basta, herbicide for suicide attempt at arousal during sleep. She came to our hospital at twelve hours after ingesting. She was admitted to our hospital for fear of delayed respiratory failure. Actually, she felt down to respiratory failure, needing a ventilator with intubation at 20 hours after ingesting. Procedure around respiratory management had smoothly done with no delay. Her vital status had been stable, however, she felt down to circulatory failure and diagnosed as Takotsubo cardiomyopathy at about 41 hours after ingestion. There was no trigger activities or events to evoke mental and physical stresses. Conclusion. We could successfully manage takotsubo cardiomyopathy resulted in circulatory failure in a patient with glufosinate poisoning for suicide attempt. Takotsubo cardiomyopathy should be taken into consideration if circulatory failure is observed for unexplained reasons

INVOLVEMENT OF NETS IN CEREBRAL AVM

BACKGROUND: Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs. METHODS: We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients. RESULTS: Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus. CONCLUSIONS: Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs

Fluorescence-guided bone resection by using Visually Enhanced Lesion Scope in diffuse chronic sclerosingosteomyelitis of the mandible: clinical and pathological evaluation

Diffuse chronic sclerosingosteomyelitis (DCSO) is a refractory disease, becausethe etiology and pathogenesis remain poorly understood and to determine the border betweenunhealthy boneandhealthybone is difficult. However, progressive inflammation, clinical symptoms and a high recurrence rate of DCSO were the reasons for surgical treatment. We report a case of a 66-year old woman with DCSO of the right side of mandible who was treated with hemimandibulectomy and simultaneous reconstruction by vascularized free fibula flap. After preoperative administration of minocycline for 1 month, the bone fluorescence was successfully monitored by using a Visually Enhanced Lesion Scope (VELscope®). Intraoperatively, we could determine the resection boundaries. We investigated the clinical and histopathological findings. The fluorescence findings were well correlated with histopathological findings. Using a VELscope®was handy and useful to determine the border between DCSO lesion andhealthybone. The free fibula flap under the minocycline-derived bone fluorescence by using a VELscope®offered a good quality of mandibular bone and the successful management of an advanced and refractory DCSO

Implementing action for acute stroke based on Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease in Tokushima

Cerebrovascular and cardiovascular disease are the main causes of death in Japan. The leading causes of the need for long-term care in Japan are also cerebrovascular and cardiovascular disease, which together account for more than one-fourth of the total. The Cerebrovascular and Cardiovascular Disease Control Act, of Japanese national law, was promulgated by a legislative act in 2018. On the basis of the Cerebrovascular and Cardiovascular Disease Control Act, the Ministry of Health, Labour and Welfare, Japan, published the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease （Japanese National Plan） in 2020. By the example of the Japanese National Plan, Tokushima prefecture established a cerebrovascular and cardiovascular disease countermeasure promotion plan to progress cerebrovascular and cardiovascular disease measures according to their own circumstances. One of the important measures of the plan is improving emergency transportation systems. Patients with intracranial large vessel occlusion strokes should be served by direct transfer to endovascular capable centers avoiding delays by misguided transfer to primary stroke centers. Considering the limited availability of endovascular capable centers, accurate identification of patients with high probability of having large vessel occlusion strokes in the prehospital setting is importance. To address this problem, we introduced prehospital scale called Field Assessment Stroke Triage for Emergency Destination （FAST-ED） on emergency transportation systems in Tokushima city

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