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Objective: This study aimed to determine whether the apparent diffusion coefficients (ADCs) determined by diffusion-weighted imaging (DWI) of magnetic resonance imaging (MRI) could facilitate the malignancy grading of various gliomas. Methods: Sixty patients with a primary cerebral glioma underwent diffusion-weighted and gadolinium-enhanced (Gd) T1-weighted MRI using a 1.5-T MRI scanner. Scoring was performed based on signal intensities on DWI and Gd images. The mean and minimum ADC values were calculated, and Ki-67 staining was performed for each histological sample to evaluate their tumor proliferative potential. Then, the DWI, Gd, and combined scores were analyzed and compared with the Ki-67 staining index and malignant grade. The relationships among the mean and minimum ADC values, Ki-67 staining index, and malignant grade were also evaluated. Results: The minimum ADC was inversely correlated with the Ki-67 staining index, with a low minimum ADC suggestive of tumor malignancy. The qualitative evaluation of the D score of water molecule diffusion on DWI accurately reflected the pathological grades of gliomas, with an effectiveness that was at least as good as the quantitative analysis using the minimum ADC. The diagnostic value of Gd images in determining glioma malignancy grades was inferior to that of DWI. Conclusion: Both DWI and gadolinium-enhanced images of MRI should be considered essential for the diagnosis of tumor malignancy.

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O 6 -methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.

Combined in situ hybridization (ISH) and immunohistochemistry (IHC) under electron microscopy (EM-ISH & IHC) has sufficient ultrastructural resolution to provide two-dimensional images of subcellular localization of pituitary hormone and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals (Quantum dots; Qdots) and confocal laser scanning microscopy (CLSM) enable us to obtain three-dimensional images of the subcellular localization of pituitary hormone and its mRNA. Both EM-ISH & IHC and ISH & IHC using Qdots and CLSM are useful for understanding the relationship between protein and mRNA simultaneously in two or three dimensions. CLSM observation of rab3B and SNARE proteins such as SNAP-25 and syntaxin revealed that both rab3B and SNARE system proteins play an important role and work together as the exocytotic machinery in anterior pituitary cells. Another important issue is the intracellular transport and secretion of pituitary hormone. An experimental pituitary cell line, the GH3 cell, in which growth hormone (GH) is linked to enhanced yellow fluorescein protein (EYFP), has been developed. This stable GH3 cell secretes GH linked to EYFP upon being stimulated by Ca 2+ influx or Ca 2+ release from storage. This GH3 cell is useful for real-time visualization of the intracellular transport and secretion of GH. These three methods enable us to visualize consecutively the processes of transcription, translation, transport, and secretion of pituitary hormone.

Ruptured aneurysms arising from non-branching sites of the internal carotid artery (ICA) are often difficult to treat by neck clipping or endosaccular coiling. We discuss the feasibility of simple endovascular ICA ligation or trapping to treat aneurysms. Data from eleven patients were retrospectively analyzed regarding Hunt and Hess grade on admission, angiographic collateral capacities during digital carotid compression, results of balloon test occlusion of the ipsilateral ICA, type of treatment, and Glasgow outcome scale at discharge. First endovascular treatments were performed by day 5 in four cases. Two patients with good clinical grade and good collateral capacity underwent endovascular ICA trapping in the acute stage and showed good outcomes. Two patients displaying poor clinical grade but good collaterals underwent endosaccular embolization. These aneurysms recurred later and the ICAs were trapped by coils in the chronic stage. Four cases underwent first endovascular treatments in the chronic stage. Three patients with good collaterals underwent endovascular ICA trapping or ligation and showed favorable outcomes. Seven of eleven patients could be treated by endovascular ICA trapping or ligation, which offers a simple, safe method for ruptured ICA trunk aneurysms, if collateral capacity is good and neurological condition is not serious.

In the original manuscript, the word “fluorescein” was erroneously used indistinctly for “fluorescence” and “fluorescent”. Furthermore, “cyan fluorescent protein” was misspelled. These errors have been amended in an amended version of the manuscript, which is available from the Molecules website. The authors and publisher apologize for the inconvenience. [...]

The presence of an intracranial aneurysm together with a pituitary adenoma presents tremendous risk of subarachnoid hemorrhage, during transsphenoidal surgery, particularly when the aneurysm lies near the operative field. A left supraclinoid internal carotid artery aneurysm and a clinically nonfunctioning pituitary adenoma coexisted in a 57-year-old woman. Initially, the aneurysm was treated by endovascular coil placement, and then the patient underwent pseudocapsule-based extracapsular resection of the pituitary tumor via a transnasal transsphenoidal endoscopic approach. Pseudocapsule-based extracapsular total resection was safely performed, because of the extirpated risk of rupture of the coil-treated aneurysm. Recently, transsphenoidal pseudocapsule-based extracapsular resection approach for pituitary adenomas provides a more effective and safe alternative compared to the traditional intracapsular one because of its higher tumor removal and remission rates and lower recurrence rate. Compared with conventional subcapsular removal, pseudocapsule-based extracapsular resection has more risks of aneurysmal rupture that is located adjacent to pituitary adenoma. Thus, in a patient having a cerebral aneurysm with the proximity to the operative field, the cerebral aneurysm should be first treated with endovascular coil placement or direct surgical procedure; subsequently, pseudocapsule-based extracapsular resection of the pituitary tumor via a transnasal transsphenoidal endoscopic approach should be performed.

Cavernous malformations (CVMs) and arteriovenous malformations (AVMs) were immunostained for three smooth muscle cell (SMC)-specific protein markers (smooth muscle alpha-actin, SM1 and SM2). Smooth muscle alpha-actin, a widely used marker of SMCs, is reportedly one of the earliest proteins expressed during differentiation of SMCs and expressed in some kinds of mesoderm-derived cells. In contrast, SM1, an isoform of myosin heavy chain (MHC), is detected only in SMCs. SM2 is another MHC isoform and expressed in the contractile phenotype of SMC. All 14 intraaxial CVMs were positive for smooth muscle alpha-actin, but SM1 was detected in only three of them and SM2 was not found. Their staining pattern resembled that of normal intraparenchymal and pial veins. All 15 cerebral AVMs and 5 out of 6 extraaxial CVMs from the cavernous sinus, orbit and scalp were positive for all three markers, as were the normal cerebral arteries. The venous components of AVMs, as well as the arterial components, expressed SM2, and were different from normal veins in the brain and intraaxial CVMs. This study shows that the histological analysis using the three markers for SMC is useful to differentiate intraaxial CVM from AVM and extraaxial CVMs.

We have characterised the blood vessels found in normal cerebral vasculature and in arteriovenous malformations (AVMs), based on the expression of smooth muscle cell (SMC)-specific proteins. The marker proteins used were smooth muscle alpha-actin and four myosin heavy chain isoforms (SM1, SM2, SMemb and NMHC-A). Specimens of AVM obtained during surgery, and normal cerebral vessels from autopsy cases were studied immunohistochemically and compared. The arterial components of AVM contained an abundance of SMCs of the contractile phenotype, which were positive for alpha-actin, SM1 and SM2, but not for SMemb and NMHC-A. These components showed the same staining pattern as mature normal arteries. Two different types of abnormal veins were found in the AVM specimens: large veins with a thick and fibrous wall (so-called 'arterialised' veins) and intraparenchymal thin-walled sinusoidal veins. The former expressed alpha-actin, SM1, SM2, and SMemb, the latter expressed alpha-actin, SM1, and SM2. These marker expression patterns resembled those of normal cerebral arteries, and the results were compatible with arterialisation of the cerebral veins caused by arteriovenous shunting. However, the expression of SMemb was found only in the arterialised type of veins, not in the sinusoidal type or the arteries that had sustained abnormal blood flow in the AVMs. The thick-walled veins in the AVMs showed the same staining pattern as normal veins of dural plexus origin (large subarachnoid veins and dural sinuses). It is therefore possible to assume that they originated from the dural plexus, and extended into the brain during the formation of AVMs.