CLN7 is a polytopic lysosomal membrane protein deficient in variant late infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. In this study fluorescence protease protection assays and mutational analyses revealed the N-and C-terminal tails of CLN7 in the cytosol and two N-glycosylation sites at N371 and N376. Both partially and non-glycosylated CLN7 were correctly transported to lysosomes. To identify lysosomal targeting motifs, we generated CD4-chimera fused to the N-and C-terminal domains of CLN7. Lysosomal localization of the chimeric proteins requires a consensus acidic dileucine-based motif in the N-terminus and two tandem tyrosine-based signals in the C-terminus. Mutation of these sorting motifs resulted in cell surface redistribution of CD4 chimeras. However, the dileucine-based motif is of critical importance for lysosomal localization of the full-length CLN7 in different cell lines. Cell surface biotinylation revealed that at equilibrium 22% of total CLN7 is localized at the plasma membrane. Mutation of the dileucine motif or the co-expression of dominantnegative mutant dynamin K44A led to a further increase of CLN7 at the plasma membrane. Our data demonstrate that CLN7 contains several cytoplasmic lysosomal targeting signals of which the N-terminal dileucine-based motif is required for the predominant lysosomal targeting along the indirect pathway and clathrin-mediated endocytosis of CLN7.
The ganglioglioma, a mixed tumor with neuronal and glial elements, occurs occasionally in children and young adults. Its incidence, clinical presentation, radiological features, and natural history have not been clearly defined. A review of 111 primary brain tumors treated at our institution shows that 9.0% were gangliogliomas. The temporal lobe was the most common site involved. All patients presented with seizures but were neurologically intact. The CT scan showed a partially calcified mass, frequently isodense or nearly so, with minimal enhancement. Complete removal produced dramatic improvement in seizure control. Radiotherapy and/or chemotherapy are reserved for tumors showing malignant changes in the astrocytic component. Patients with chronic epilepsy, or whose seizures escape control despite anticonvulsants, should be examined with this tumor in mind. Following removal of these low-grade temporal lobe tumors, fewer seizures are seen, and the long-term prognosis is very good.
Objective: This study examined a set of patients who were symptomatic for low back pain and who had significant lumbar hypolordosis as assessed by visual evaluation of magnetic resonance images to investigate the frequency of comorbid paraspinal muscle spasms as determined via history or physical examination. Methods: A retrospective chart review was performed on 50 patients who had significant hypolordosis on magnetic resonance imaging (MRI) (Cobb angle b20°) to determine whether they were positive for paraspinal muscle spasms by either history or physical examination. Results: Of the 50 patients with significant hypolordosis on MRI, 66% (33) had a history of paraspinal muscle spasms, 76% (38) had a positive physical examination for palpation of paraspinal muscle spasms, and 48% (24) were positive for both history and physical examination. Conclusions: This retrospective study suggests that most symptomatic patients with significant hypolordosis on lumbar MRI have a positive history or physical examination for paraspinal muscle spasm. Thus, MRI finding of significant hypolordosis (Cobb angle b20°) could potentially be a valuable tool in addition to medical history and physical examination in aiding clinicians in diagnosing paraspinal muscle spasms in symptomatic patients and in helping them to formulate appropriate and effective treatments.
A survey of 23 children treated for arteriovenous malformations of the brain is presented. Venous angiomas and aneurysms of the vein of Galen were excluded. Spontaneous hemorrhage was the first symptom in 83%. Angiographically occult arteriovenous malformations were found in 22% of cases. Contrast-enhanced CT failed to opacify abnormal vessels in most of these occult lesions. Fourteen patients underwent complete excision of their malformation with only 1 death (7.1% surgical mortality). Overall mortality for the group was 21.7%. Outcome was related to treatment modality and clinical condition on presentation. Four of 8 patients presenting in deep coma died, but 3 are normal and one slightly disabled. A spontaneous cerebral hemorrhage in a child is probably due to a vascular malformation, even when angiography and enhanced CT are negative. Optimal management consists of complete removal of the malformation; residual lesions tend to rebleed with fatal outcome. With aggressive treatment, complete recovery is possible even for children who present in coma.
The authors report the successful total excision of an intracranial teratoma in a neonate. The pathology of this rare tumor and its prognosis in relation to the maturity of individual cell lines is discussed. A review of the previous operation experience in the neonatal age group shows that radical surgical excision of the tumor has seldom been attempted. There are no reported survivors with normal neurological development. The clinical presentation, preoperative evaluation, and operative management are discussed. Emphasis is laid on intensive supportive care in the perioperative period. The difficulty in predicting a benign or malignant course in these tumors justifies extreme caution in making a prognosis and demands careful follow-up supervision. Reoperation is indicated for recurrent benign tumors; malignant germ-cell tumors may respond to combined irradiation and chemotherapy.
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