Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system

Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 microM. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders.     

Short echo time MR spectroscopy of brain tumors: Grading of cerebral gliomas by correlation analysis of normalized spectral amplitudes

Purpose:

To process single voxel spectra of low‐ and high‐grade gliomas. To propose correlation analysis of the scatter plots of normalized spectral amplitudes as a pattern recognition tool for the classification (grading) of brain tumors. To propose a spectrum processing approach that improves the differentiation of proton spectra with dominating macromolecule and lipid peaks.

Materials and Methods:

LCModel was used to process spectra. Mean metabolite concentrations and mean normalized spectra were obtained for normal white matter and for gliomas. The mean spectra of macromolecules and lipids (ML) in the range 1.4–0.9 ppm, and mean difference spectra (DS) without ML and lactate were computed. Correlation analysis of the scatter plot of the patient and mean normalized spectral amplitudes and dispersion of the scatter plot points were used for classification and grading of tumors.

Results:

It was found advantageous to perform the classifications using DS spectra. The shape of ML spectrum and concentration of tCr seem to be a good markers for glioma grade.

Conclusion:

Combining a qualitative comparison of the patient and mean DS spectra of the tumors using correlation analysis of normalized spectra amplitudes with a quantitative comparison of metabolite concentrations is a powerful tool in studying brain lesions. J. Magn. Reson. Imaging 2010;31:39–45. © 2009 Wiley‐Liss, Inc.     

Morphological heterogeneity of oral salivary gland carcinomas: a clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

We analyzed 41 oral salivary gland carcinomas from consecutive 290 salivary gland carcinoma database (14%) with emphasis on the histological spectrum and clinical outcome of adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA). The cohort included 14 ACCs, 14 mucoepidermoid carcinomas (MECs), 8 PLGAs, 3 adenocarcinomas, not otherwise specified and 2 acinic cell carcinomas. Mean age was 48, 58 and 61 yrs for ACC, MEC and PLGA, respectively. Eight patients (19.5%) died of tumor at a mean interval of 66.5 months. ACC and PLGA showed similar mean age, gender distribution, predominant palatal localization, nodal metastasis, perineural invasion and MIB-1 index. However, ACC tended to show higher tumor stage and residual tumor (R1/R2) more frequently than PLGA, but this was statistically not significant. ACC and PLGA showed overlapping architectural patterns. However, ACCs displayed well organized basal-luminal differentiation, highlighted by CK5/CK7 immunostaining. In contrast, PLGA showed a disorganized histological and immunohistological pattern. C-Kit expression (CD117) was common in ACC, generally mirroring that of CK7 and virtually lacking in PLGA. Kaplan-Meier analysis demonstrated a similar clinical course for ACC and PLGA with 5 years survivals of 87% and 80%, respectively. Fluorescence in situ hybridization (FISH) performed on all 290 salivary carcinomas confirmed the specificity of the translocation t (11; 19) for MEC and its absence in all other carcinomas including ACC and PLGA. Our results emphasize the diversity of oral salivary gland carcinomas and the overlapping clinicopathological features of ACC and PLGA.     

Readers' Forum Smooth-Muscle-Type Myofilaments and Actin in Reactive and Neoplastic Nonmuscle Cells

The authors report a case of low-grade retroperitoneal malignant peripheral nerve sheath tumor (MPNST) showing Schwannian and fibroblastic differentiation in individual tumor cells. The tumor was detected in a 29-year-old male and posed diagnostic difficulty because of the unusual morphologic and immunophenotypic features. Morphologic examination of the H&;E sections revealed a rather circumscribed, highly vascular, moderately cellular spindle cell tumor. The neoplastic cells were arranged in vague, short fascicles, distributed haphazardly amid hemangiopericytoma-like vascular channels, and showed occasional whorls. Myxoid stroma and keloid-like collagen bundles were frequently seen. There were satellite nodules outside the main tumor mass and low mitotic activity but no necrosis. The tumor cells stained strongly and diffusely for both S-100 protein and CD34. Electron microscopy revealed cells with processes and focal lamina, and prominent rough endoplasmic reticulum. Although the capacity of MPNST to exhibit divergent differentiation is well known, fibroblastic differentiation is generally poorly and inconsistently documented. The present case represents an unambiguous demonstration of the co-expression within individual tumor cells of Schwannian and fibroblastic differentiation in a low-grade MPNST. The literature on this subject is reviewed.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.     

颅内多发性胶质瘤的CT与MRI特征

目的 分析颅内多发性胶质瘤（MCG）CT与MBI特征,探讨其在诊断与鉴别诊断中的价值。资料与方法 搜集经手术病理证实的MCG15例,其中CT检查4例,MRI检查7例,CT＋MRI检查4例。对其临床及CT、MRI资料进行回顾性分析。结果 15例共检出病灶34个,病灶主要分布于额叶、颞叶、顶叶。CT平扫病灶大多呈低密度或等密度,MR T1WI大多表现为低或等信号（96．1％）,T2WI均表现为高信号（100％）;瘤周多为轻度或中度水肿及占位效应;增强扫描病灶大多表现为明显不均匀或花环样强化。结论 MCG具有一定的CT与MRI特征,具有一定的诊断意义,但其在影像学诊断上仍需与转移瘤、多发性硬化、多发性淋巴瘤鉴别。     

光动力学疗法辅助显微技术治疗脑胶质瘤

目的 观察血卟啉单甲醚光动力学疗法辅助手术治疗脑胶质瘤的近期疗效和随访效果。方法 1999～2001年，应用光动力学疗法辅助手术治疗脑胶质瘤34例。术中暴露肿瘤前，静脉推注血卟啉单甲醚5mg／kg。显微镜下切除肿瘤后，以能量密度200J／cm^2 He-Ne激光照射肿瘤残腔。术后避光3d，观察近期临床表现，出院后定期随访2.4年。结果 大部分患者术后临床症状缓解或消失；出院时Karnofsky记分升高者28例，无变化者6例，改善率82.4％(28／34)；全部病例无皮肤光敏反应；术后1年生存率为76.5％(26／34)；术后2年生存率为52.9％。结论 激光光动力学疗法是一种有效的脑胶质瘤辅助治疗方法，近期临床效果满意，有利于提高生存率和生存质量，延长患者生命。     

Low-grade thermal injury

It is very popular to use hot-water bottles or some electric heaters to keep one warm when sleeping or sitting in cold days in China.l Unfortunately, people might be burned as a result of prolonged contact with the heaters because of senseless due to falling asleep, drunk or some diseases just like diabetes. This special case we reported here may help us to improve the diagnosis and treatment of low-grade thermal injury.     

Diffuse Astrocytoma Initially Presenting as a Massive Intracerebral Hemorrhage: Case Report

We report the case of a 58-year-old woman with low-grade astrocytoma, who developed massive intracranial hemorrhage as the first presentation of this disease, and become comatose and subsequently underwent an emergency craniotomy. A small amount of tumor-like tissue was observed on the wall of the hematoma cavity. Histological analysis of the resected specimen indicated diffuse astrocytoma [World Health Organization (WHO) grade II]. The patient was discharged without neurological deficits 2 weeks after the operation. A non-enhanced tumor-like nodule was observed on magnetic resonance imaging 3 months after the operation, which was monitored carefully but was not treated by adjuvant therapy. The tumor grew gradually, and a second operation was performed 3 years after the first, in which the tumor was completely resected. Histological analysis of the resected specimen again indicated diffuse astrocytoma (WHO grade II). Although rare, brain tumors, including low-grade astrocytoma, should be considered a possible cause of subcortical hemorrhage in patients without risk factors for intracranial hemorrhage.     

MR perfusion-weighted imaging may help in differentiating between nonenhancing gliomas and nonneoplastic lesions in the cervicomedullary junction

Purpose:

To evaluate the ability of dynamic susceptibility‐weighted contrast‐enhanced magnetic resonance (MR) perfusion imaging (DSC‐PWI) in distinguishing between nonenhancing gliomas and nonenhancing, nonneoplastic lesions in the cervicomedullary junction region.

Materials and Methods:

This retrospective study involved eight patients with nonenhancing gliomas in the medulla oblongata and eight patients with nonenhancing nonneoplastic lesions. The relative cerebral blood volume (rCBV) ratios, peak heights, and percentage of signal intensity recovery derived from time‐signal intensity curves of these nonenhancing lesions were compared.

Results:

The mean peak height of nonenhancing gliomas was significantly higher than the value of their reference regions of interest (ROIs). In contrast, mean peak height of nonneoplastic lesions was significantly lower than their reference ROIs. The mean peak height and mean maximal rCBV ratio of nonenhancing gliomas were significantly higher than those of nonenhancing, nonneoplastic lesions (P<0.05). There was no significant difference with regard to percentage of signal intensity recovery between the two groups.

Conclusion:

DSC‐PWI could be a useful adjuvant tool to differentiate between nonenhancing gliomas and nonenhancing, nonneoplastic lesions in the cervicomedullary junction region. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.