Cerebral space-occupying cysts following radiation and chemotherapy of malignant gliomas

Summary Eight cases of cerebral cyst formation among 50 patients (= 16%) with malignant supratentorial gliomas treated by surgery, megavoltage radiation, and multiple-agent chemotherapy are reported. Five of them developed signs of intracranial hypertension or progressive neurological deficit, while in three patients cerebral cysts were detected by CT without clinical deterioration. At operation or autopsy, or both, the large fluid-filled, smooth-walled cysts were lined by glio-mesenchymal scar tissue with no or little tumour recurrence in five, while three patients showed large recurrent tumour masses associated with necrosis and cyst formation. Clinical signs or CT evidence, or both, of cerebral cysts developed 4 to 12 months (average 10 months) after the first craniotomy, and 3 to 9 months after termination of radiotherapy, usually after the second to fourth course of polychemotherapy. The cystic cavities which are attributed to increased necrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these patients occurred 3 weeks to 6 months after surgical treatment of cyst formation, their life span ranging from 9 to 22 months. The pathogenesis and clinical problems related to cerebral cysts arising following multimodality treatment of malignant brain tumours are discussed.     

Discrimination of face identities and expressions in children with autism: Same or different?

Abstract. Autism is a pervasive developmental disorder (PDD) characterized by the association of communication and socialization impairments, and by repetitive stereotyped behaviours. The Minnesota Test of Affective Processing (MNTAP) was used to investigate the discrimination of face identities and face expressions by autistic children. Young children in the 6- to 10-year-old age range suffering from PDD were compared to paired normal children. When the expressions on faces remained neutral, autistic patients had more difficulty in distinguishing different faces than in matching the same facial identities in face pairs: they perceived different faces as being identical. However, recognition errors disappeared when expressions were changed together with face identity. When autistic children were asked to distinguish expressions, they discriminated better identity than difference, just as normal children do. Analysis of face and expression discrimination in terms of identity and difference is a novel approach for the understanding of the clinical features of autism. Autistic children seek sameness and use an atypical strategy to analyse human faces and expressions.     

Exosomes and anti-tumour immunotherapy

Exosomes are 60 to 90 nm membrane vesicles originating from late endosomes and secreted from most hematopoietic and epithelial cells in vitro. B cell derived-exosome antigenicity was first reported in 1996 in MHC class II restricted CD4+ T lymphocytes. In 1998, we reported that dendritic cell derived-exosomes are immunogenic in mice leading to tumor rejection. These findings have renewed the interest in exosomes. The current challenge consists in understanding the mechanisms and the physiological relevance of exosomes that could contribute to the design of the optimal exosome based-vaccination. Here, we will focus on the biological features pertaining to dendritic cell- and tumor cell derived-exosomes and will discuss their potential clinical implementation.     

Neurofibrillary degeneration of the Alzheimer-type: an alternate pathway to neuronal apoptosis?

Neuronal death is a process which may be either physiological or pathological. Apoptosis and necrosis are two of these processes which are particularly studied. However, in neurodegenerative disorders, some neurons escape to these types of death and "agonize" in a process referred to as neurofibrillary degeneration. Neurofibrillary degeneration is characterized by the intraneuronal aggregation of abnormally phosphorylated microtubule-associated Tau proteins. A number of studies have reported a reactivation of the cell cycle in the neurofibrillary degeneration process. This reactivation of the cell cycle is reminiscent of the initiation of apoptosis in post-mitotic cells where G1/S markers including cyclin D1 and cdk4/6, are commonly found. However, in neurons exhibiting neurofibrillary degeneration, both G1/S and G2/M markers are found suggesting that they do not follow the classical apoptosis and an aberrant cell cycle occurs. This aberrant response leading to neurofibrillary degeneration may be triggered by the sequential combination of three partners: the complex Cdk5/p25 induces both apoptosis and the "abnormal mitotic Tau phosphorylation". These mitotic epitopes may allow for the nuclear depletion of Pin1. This latter may be responsible for escaping classical apoptosis in a subset of neurons. Since neurofibrillary degeneration is likely to be a third way to die, molecular mechanisms leading to changes in Tau phosphorylation including activation of kinases such as cdk5 or other regulators such as Pin1 could be important drug targets as they are possibly involved in early stages of neurodegeneration.     

Innervation of supporting cells in the apical turns of the guinea pig cochlea is from type II afferent fibers

The outer supporting cells in the apical turns of the guinea pig cochlea receive a dense innervation. Our previous study (Fechner et al. [1998] J. Comp. Neurol. 400:299-300) suggested that this innervation of the Deiters' and Hensen's supporting cells was not derived from efferent fibers of the olivocochlear bundle, but its origin has not been further specified. To test the hypothesis that the innervation was afferent in origin, we traced apical afferent fibers that were retrogradely labeled by extracellular injections of horseradish peroxidase. Labeled afferent fibers were of two types: type I fibers contacted inner hair cells, whereas type II fibers crossed the tunnel and contacted outer hair cells. Significantly, most of the type II fibers also formed branches to the outer supporting cells. Although a few olivocochlear efferent fibers formed such branches, counts indicated that the overwhelming majority of the branches were produced by type II afferent fibers. These branches were not produced by basal type II fibers. Apical type II fibers also differed from basal fibers by having shorter lengths, spiraling both apically and basally, and contacting all three rows of outer hair cells. These innervation differences suggest differences in the ways that information from outer hair cells is processed in the apex versus the base of the cochlea.