No abstract

The nucleostemin (NS) gene encodes a nucleolar protein found at high levels in several types of stem cells and tumor cell lines. The function of NS is unclear but it may play a critical role in S-phase entry by stem/progenitor cells. Here we characterize NS expression in murine male germ cells. Although NS protein was highly expressed in the nucleoli of all primordial germ cells, only a limited number of gonocytes showed NS expression in neonatal testes. In adult testes, NS protein was expressed at high levels in the nucleoli of spermatogonia and primary spermatocytes but at only low levels in round spermatids. To evaluate the properties of cells expressing high levels of NS, we generated transgenic reporter mice expressing green fluorescent protein (GFP) under the control of the NS promoter (NS-GFP Tg mice). In adult NS-GFP Tg testes, GFP and endogenous NS protein expression were correlated in spermatogonia and spermatocytes but GFP was also ectopically expressed in elongated spermatids and sperm. In testes of NS-GFP Tg embryos, neonates, and 10-day-old pups, however, GFP expression closely coincided with endogenous NS expression in developing germ cells. In contrast to a previous report, our results support the existence in neonatal testes of spermatogonial stem cells with long-term repopulating capacity. Furthermore, our data show that NS expression does not correlate with cell-cycle status during prepuberty, and that strong NS expression is essential for the maintenance of germline stem cell proliferation capacity. We conclude that NS is a marker of undifferentiated status in the germ cell lineage during prepubertal spermatogenesis. STEM CELLS 2008; 26:3237-3246 Disclosure of potential conflicts of interest is found at the end of this article.

Background: The internal carotid artery (ICA) usually runs posterolaterally to the external carotid artery (ECA), but occasionally we encounter the twisted carotid bifurcation, a variant in which the ICA courses medially to the ECA during carotid endarterectomy (CEA). Prediction of this anomaly in the preoperative evaluation is mandatory, although descriptions in the literature are limited. We reviewed the clinical features of patients underwent CEA and analyzed preoperative cerebral angiography, especially anteroposterior (AP) view to determine whether it could be a predictive modality. Methods:In 58 consecutive CEA cases, we simply classified them into 3 groups; type 1 (the ICA runs laterally and the ECA runs medially), type 2 (the ICA and ECA run to overlap each other) and type 3 (the ICA runs medially and the ECA runs laterally), based on the findings of AP view of cerebral angiography. We compared the clinical features and intraoperative findings of those groups.Results: Of 58 cases, type 1-3 were 24, 30 and 4 cases, respectively. Twisted carotid bifurcations were recognized in 7 cases (12.4%), including 3 cases in type 2 and 4 in type 3, and all twisted cases were found on the right side. Twisted carotids and right-sided lesion were significantly frequent in type 3, but no statistical differences of coexisting diseases were recognized among 3 groups. CEA of twisted carotid bifurcations were performed successfully with correction of the carotid position in 3 and as it was in 4 cases. Conclusions:Twisted carotid bifurcations were observed during operation in 10% in type 2 and 100% in type 3. CEA of twisted carotid bifurcations can be performed safely with or without correction of the carotid position. AP view of cerebral angiography could be useful for preoperative evaluation.

Background Intracranial pseudoaneurysm formation due to a ruptured non-traumatic aneurysm is extremely rare. We describe the radiological findings and management of pseudoaneurysms due to ruptured cerebral aneurysms in our case series and previously reported cases. Patients and methods Four additional and 20 reported patients presenting with subarachnoid hemorrhage (SAH) are included. Radiological findings and clinical features of these patients were reviewed. Results In our series, three-dimensional computed tomographic angiography (3D-CTA) and/or angiography showed an irregular- or snowman-shaped cavity extending from the parent artery. The radiological examination additionally revealed delayed filling and retention of contrast medium. These findings were the same as previously reported cases. One patient underwent direct clipping of the true aneurysm. For the other three patients with aneurysms at the basilar and anterior communicating arteries, the true portion of the aneurysm was embolized with platinum coils. During the procedures, care was taken not to insert the coils into the distal pseudoaneurysm portion to prevent rupture. The review of 24 cases revealed that the location of the aneurysms was most frequent in the anterior communicating artery (41.7%), and 86.7% of patients were in a severe stage of SAH (>Grade 3 in WFNS or Hunt & Kosnik grading) implying abundant SAH. Conclusions Pseudoaneurysm formation in SAH after non-traumatic aneurysm rupture is rare. However, in cases with an irregular-shaped aneurysm cavity, pseudoaneurysm formation should be taken into consideration.

ASL was able to reveal hyperperfusion and was of great diagnostic value in the peri-ictal phase of late seizure after stroke.

BackgroundHypertension is the prime risk factor for stroke, and primary aldosteronism (PA) is the most common cause of secondary hypertension. The prevalence of PA in stroke patients has never been reported. The aim of this study was to elucidate the prevalence of PA.MethodsA total of 427 consecutive patients with acute stroke were prospectively enrolled for this study. The screening tests were performed at the initial visit and a week after admission by measuring plasma aldosterone concentration and plasma renin activity. The rapid adrenocorticotropic hormone (ACTH) test was performed as the confirmatory test when both screening tests were positive. The primary endpoint was a final diagnosis of PA.ResultsThe sensitivity of the dual screening system for the diagnosis of PA was 88.2 %, and PA was finally diagnosed in 4.0 % of acute stroke patients and in 4.9 % of stroke patients with a history of hypertension. Patients with PA were less likely to be male and have diabetes, and they had higher blood pressure at the initial visit, lower potassium concentration, and more intracerebral hemorrhage. The rapid ACTH test was performed safely even in acute stroke patients.ConclusionsThe prevalence of PA is not low among acute stroke patients. Efficient screening of PA should be performed particularly for patients with risk factors.Trial registrationUMIN-CTR; UMIN000011021. Trial registration date: June 23, 2013 (retrospectively registered).

Glioblastoma (GBM) is the most aggressive and destructive form of brain cancer. Animal models that can unravel the mechanisms underlying its progression are needed to develop rational and effective molecular therapeutic approaches. In this study, we report the development of mouse models for spontaneous gliomas representing distinct progressive stages of disease that are governed by defined genetic alterations. Neural stem/ progenitor cell (NPC)-specific constitutive Ras activation in vivo plus p53 deficiency led to development of primarily anaplastic astrocytoma (grade III), whereas combined loss of p53 plus p16 Ink4a /p19Arf led to development of GBM (grade IV) at 100% penetrance within 6 weeks. These glioma models showed enhanced stem cell properties (stemness) accompanied by malignant progression. Notably, we determined that, in our models and in human specimens, downregulation of the homeodomain transcription factor NKX2.2, which is essential for oligodendroglial differentiation, was correlated with increased tumor malignancy. NKX2.2 overexpression by GBM-derived glioma-initiating cells (GIC) induced oligodendroglial differentiation and suppressed self-renewal capacity. By contrast, Nkx2.2 downregulation in mouse NPCs accelerated GBM formation. Importantly, the inhibitory effects of NXK2.2 on GIC self-renewal were conserved in human cells. Thus, our mouse models offer pathobiologically significant advantages to investigate the nature of brain tumors, with improved opportunities to develop novel mechanism-based therapeutic approaches. Cancer Res; 71(3); 1135-45. Ó2010 AACR.

IntroductionIntracranial branch atheromatous disease is a type of ischemic stroke that is caused by narrowing or occlusion of the orifice of the penetrating artery by atheromatous plaque. Pontine branch atheromatous disease is usually diagnosed using indirect findings such as the extension of a lesion to the basal surface of the pons because of the difficulty of demonstrating plaque in the basilar artery.Case presentationA 72-year-old Japanese man developed sudden dysarthria and left hemiparesis, and his symptoms deteriorated thereafter. Brain magnetic resonance imaging revealed an acute infarction in the territory of the right paramedian pontine artery extending to the basal surface. Non-contrast-enhanced three-dimensional fast spin-echo T1 imaging with variable flip angles and three-dimensional fast imaging with steady-state acquisition revealed a plaque in the dorsal wall of the basilar artery that spread to the origin of the paramedian pontine artery that branched toward the infarction. Although antithrombotic agents were started, the left hemiparesis got worse and became flaccid on the following day.ConclusionsThis is the first report to confirm the pathological basis of branch atheromatous disease by three-dimensional images using the new modalities of 3-Tesla magnetic resonance imaging. The use of these techniques will foster better understanding of the clinicopathological mechanisms of branch atheromatous disease.