Oculomotor fascicular syndrome involving the right superior rectus and the inferior oblique muscles

We report a case of partial oculomotor palsy due to a brainstem infarction. A 70-year-old female noted a sudden onset of double vision. Visual acuity was normal in both eyes. Pupils were round and isocoric. The right eye was hypotropic and showed an elevation deficit. Bell’s phenomenon was not evident in the right eye. MRI showed a low intensity on the T1-weighted image and a high intensity on the T2-weighted image in the right ventrolateral portion of the mesencephalon. The partial oculomotor paresis of this case reflects damage of the oculomotor nerve fascicles that supply the inferior oblique and superior rectus muscles. We diagnosed the case as right oculomotor fascicular syndrome. This case report also suggests that acquired monocular elevation paresis can be caused by a lesion in the midbrain.     

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB

Mucopolysaccharidosis III (MPS III) has four forms (A-D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal alpha-N-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of CpGH89 from Clostridium perfringens, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for >20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of CpGH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB.     

小肠移植后排异反应的监测

检测猪同种异体小肠移植后的受者血浆N-乙酰氨基己糖酶、外周血单个核细胞前凝血质活性、血清肿瘤坏死因子、血清白细胞介素2和6,并与同期的粘膜活检结果作对照,发现它们在排异早期即有显著升高,其中单个核细胞前凝血质活性和白细胞介素2的变化早于排异反应的病理变化,提示术后检测这些指标将有助于排异反应的早期诊断。     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Hepatotoxic effects of repeated administration of oriental hornet (Vespa orientalis) venom

Venom sac extract (VSE) of the Oriental hornet (Vespa orientalis) has been shown to exert a toxic effect on hepatic cells. The present work set out to examine its effect on liver cells using serum levels of a lysosomal hydrolase as a marker of injury in rats. Serum activities of beta-N-acetyl hexosaminidase (BNAH; EC 3.2.1.30) were found to be positively correlated with the number of treatments received by the rats. The maximal elevation occurred from the third to the sixth day and comprised a 2-3-fold increase over the control mean level. This enhancement effect was reversible. The rat envenomend for 2 wk showed 3.5 times as much BNAH activity as in control rats. Biochemical analysis revealed increased specific activity of the lysosomal enzyme in rats treated repeatedly with VSE.     

Atypical presentation of late‐onset Tay‐sachs disease

Introduction: Late‐onset Tay‐Sachs disease (LOTS) is a lysosomal storage disease caused by deficient Beta‐hexosaminidase A activity. Methods: We describe a 53‐year‐old woman who presented with adult‐onset leg weakness, and whose initial diagnosis was progressive muscular atrophy without identifiable etiology. Development of cerebellar ataxia in mid‐life prompted reassessment. Results: Beta‐hexosaminidase A quantification assay demonstrated absence of the isozyme. Genetic testing identified compound heterozygous mutations in the HEXA gene, confirming the diagnosis of LOTS. Conclusions: The phenotypic spectrum of LOTS includes motor neuronopathy, ataxia, choreoathetosis, neuropathy, and psychiatric symptoms in various combinations. This patient highlights the emergence of different clinical features over many years and emphasizes the need to consider LOTS in the differential diagnosis of progressive muscular atrophy. Muscle Nerve 49 : 768–771, 2014