-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats

L-2-Hydroxyglutaric acid (LGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as L-2-hydroxyglutaric aciduria (LHGA). Although this disorder is predominantly characterized by severe neurological findings and pronounced cerebellum atrophy, the neurotoxic mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA, at 0.25-5mM concentrations, on total creatine kinase (tCK) activity from cerebellum, cerebral cortex, cardiac muscle and skeletal muscle homogenates of 30-day-old Wistar rats. CK activity was measured also in the cytosolic (Cy-CK) and mitochondrial (Mi-CK) fractions from cerebellum. We verified that tCK activity was significantly inhibited by LGA in the cerebellum, but not in cerebral cortex, cardiac muscle and skeletal muscle. Furthermore, CK activity from the mitochondrial fraction was inhibited by LGA, whereas that from the cytosolic fraction of cerebellum was not affected by the acid. Kinetic studies revealed that the inhibitory effect of LGA on Mi-CK was non-competitive in relation to phosphocreatine. Finally, we verified that the inhibitory effect of LGA on tCK was fully prevented by pre-incubation of the homogenates with reduced glutathione (GSH), suggesting that this inhibition is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of creatine kinase activity for energy homeostasis, our results suggest that the selective inhibition of this enzyme activity by increased levels of LGA could be possibly related to the cerebellar degeneration characteristically found in patients affected by L-2-hydroxyglutaric aciduria.     

Architectural alterations in rat cerebral microvessels after hypobaric hypoxia

We performed 3-dimensional studies of vascular casts of the microvasculature of the cerebral cortex of rats that were exposed to three weeks of hypobaric hypoxia and of control rats. Scanning electron microscopy of the casts gave the qualitative impression of increased vascularity of the cerebral cortex, particularly the deeper layers, in hypoxic rats. Quantitative analysis of capillary segment lengths revealed a significant shift in the frequency distribution to longer lengths (from 77 ± 8 to 90 ± 14 μm) in the deep, but not in the superficial, layers of the cerebral cortex of hypoxic rats. These findings agree with previous results reporting increased capillary density in the brain after exposure to prolonged hypobaric hypoxia and suggest that capillary segment elongation plays a role in the increased capillary density in the deeper layers of the cerebral cortex.     

Intracerebral vascular occlusion in familial erythrophagocytic lymphohistiocytosis: a case report of two siblings

Neuropathological findings in two siblings with familial erythrophagocytic lymphohistiocytosis (FEL) are reported. Case 1 showed the typical neuropathological findings of FEL with lymphohistiocytic infiltration of the leptomeninges and perivascular spaces. A characteristic erythrophagocytosis was detected in inguinal lymph nodes, lung and bone marrow. Case 2 revealed calcification and necrotic lesions in the brain. In the necrotic areas, parenchymal calcification, vascular medial calcification, and occlusion of many vessels due to subendothelial fibrosis were detected. The areas of necrosis correlated with the distribution of occluded vessels. These changes were most prominent in putamen, internal capsule, thalamus and dentate nucleus. Hypercytokinemia is suspected to be the underlying mechanism for the clinical and laboratory findings in patients with FEL, although the relationship to the vascular pathology is unclear.     

Whistling face syndrome: MR imaging findings in the brain

Whistling face syndrome or cranio-carpotarsal dysplasia is a very rare disorder that consists of a characteristics facies and digital abnormalities. Magnetic resonance imaging investigation of the brain in this syndrome has not been reported previously. This communication describes the brain malformations in an infant with the syndrome, which covered delayed myelination, thickened and infolded cortices (cortical dysplasia), dysplastic corpus callosum, and agenesis of the inferior vermis.     

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 ± 0.38, 2.12 ± 0.37, and 1.38 ± 0.24 (μg/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. Received: 12 August 1996 Accepted: 17 December 1996     

大,巨型垂体腺瘤的手术入路选择

自１９９０年以来收治直径在２－５．６ｃｍ的大、巨型垂体腺瘤３３例。依肿瘤生长形态与扩展范围将其简略分为三种类型。Ａ型：瘤体位于鞍内或侵入蝶窦；Ｂ型；瘤体呈椭圆形或哑铃向鞍上扩展，三脑室明显移位抬高；Ｃ型：瘤体巨大侵入三脑室阻塞室间孔或明显的鞍周扩展。     

Multiple subcortical haemorrhages following lumbar metrizamide myelography

Summary The case is presented of a patient showing multiple subcortical haemorrhages after lumbar metrizamide myelography. This complication after intrathecally administered metrizamide contrast medium appears not to have been reported before. Several different possible explanations are proposed for the phenomena observed in this case.     

Amplification of the c-erbB oncogene is associated with malignancy in primary tumours of neuroepithelial tissue

Summary In various primary brain tumours of neuroepithelial tissue recombinant DNA techniques were used to demonstrate changes of the epidermal growth factor receptor gene, which is homologous to the c-erbB oncogene. Twenty-one of 40 grade III/IV tumours, but only 1 of 16 grade I/II tumours were found to contain amplified and/or rearranged c-erbB sequences. This highly significant difference suggest that c-erbB amplification, rearrangement, or both, are important steps in malignant transformation in a subset of patients with neuroepithelial tumours.     

猪尾导管连接化疗药盒实现肝脏肿瘤多重化疗的可行性研究

目的 探讨使用猪尾造影导管与单一化疗药盒连接实现肝脏肿瘤多重化疗的可行性及初步疗效。资料与方法 对30例晚期肝脏恶性肿瘤患者采用经股动脉穿刺、腹腔动脉内植入猪尾导管与皮下埋置药盒并序贯化疗，统计手术成功率、并发症及临床疗效。结果 30例手术全部成功，发生切口延迟愈合1例。术后随访28例，经影像学复查对比，病变缩小7例，稳定12例，进展9例。随访期间12例患者死亡，术后生存期42d-10个月，中位生存期6个月。另外16例患者至今存活，已达术后2-16个月。结论 采用猪尾造影导管置于腹腔动脉并与化疗药盒相连接，能够对晚期肝脏恶性肿瘤实现多重化疗，技术上简单可行，并发症少，初步疗效令人满意。     

Synopses of Posters Presented at the International Workshop on Brain Uptake and Utilization of Fatty Acids,Lipids, and Lipoproteins: Application to Neurological Disorders

Thirty-five posters were presented at the Workshop on Brain Uptake And Utilization Of Fatty Acids, Lipids, and Lipoproteins. They were grouped into four categories: (1) mechanisms of lipid uptake and transport to the brain, (2) lipoproteins and polyunsaturated fatty acids, (3) eicosanoids in brain function, and (4) fatty acids and lipids in brain disorders. This article summarizes the highlights of the research presented in these posters. The individual abstracts follow these synopses.