Cross-tolerance of recipient-derived transforming growth factor-beta dendritic cells

Administration of donor-derived immature dendritic cells (DC) treated with transforming growth factor-beta (TGF-beta) to prevent allograft rejection is not applicable for clinical use. We therefore attempted to explore the use of recipient-derived DC pulsed with donor antigens via the indirect pathway (cross-priming). DC were propagated from C3H (H2(k)) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). TGF-beta (0.2 ng/mL) was added at the initiation of culture. The resultant TGF-beta DC were pulsed with B10 (H2(b)) splenocyte lysate. Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-beta. C3H DC pulsed with B10 antigens stimulated a proliferative response in C3H T cells which was inhibited when DC were treated with TGF-beta, and the cytotoxic T-lymphocyte (CTL) activity was also inhibited. This observation correlated with reduced interferon-gamma (IFN-gamma) and increased IL-10 production. A single injection of TGF-beta DC prolonged allograft survival (median survival time [MST] 18 days vs 10 days in no-DC treatment control; P < .05). These data indicated that an approach utilizing recipient DC as a "vaccine" strategy is possible.     

Vasectomy in men with primary progressive aphasia.

OBJECTIVE: To study the frequency of vasectomy in men with primary progressive aphasia (PPA). BACKGROUND: PPA is a dementia syndrome in which aphasia emerges in relative isolation during the initial stages of illness. On the basis of a clinical observation in a patient who dated the onset of symptoms to the period after a vasectomy, and because of the curious sharing of the tau protein exclusively by brain and sperm, vasectomy rates were examined in men with PPA. METHOD: This study used a case control design. Forty-seven men with PPA and 57 men with no cognitive impairment (NC) between 55 and 80 years of age were surveyed about a history of vasectomy. RESULTS: The age-adjusted rate of vasectomy in PPA patients (40%) was higher than in NC (16%, P=0.02). There was a younger age at onset for the patients with vasectomy (58.8 vs. 62.9 y, P=0.03). CONCLUSIONS: Vasectomy may constitute one risk factor for PPA in men. Potential mechanisms mediating risk include vasectomy-induced immune responses to sperm, which shares antigenic epitopes with brain. Antisperm antibodies can also develop in women and become risk factors for PPA.     

Is there predictive criteria for transfer of patients to a rehabilitation ward after hip and knee total arthroplasty? Elaboration of French clinical practice guidelines.

OBJECTIVE: To develop clinical practice guidelines concerning predictive criteria for transfer of patients to a rehabilitation ward after hip and knee total arthroplasty. METHOD: The SOFMER (French Physical Medicine and Rehabilitation Society) methodology, associating a systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, was used. RESULTS: From systematic literature review and collection of French professional practice, we cannot distinguish the patients undergoing THA and TKA who can transfer to a rehabilitation ward. For both types of patients, the main criteria determining transfer are demographic criteria such as older age or female sex; psychosocial and environmental criteria such as living alone, feeling unable to return home directly (pre-operative education could modify this criterion); and surgeon advice based on the pre and post-operative clinical and functional status. CONCLUSION: Studies with good methodological quality are urgently needed to evaluate the use of predictive tools such as the RAPT, separating THA and TKA, and using as parameters of assessment functional status and handicap reduction.     

Reversible go-no go deficits in a case of frontal lobe tumor

A 50-year-old woman had been treated for a psychiatric disorder for three years. Findings during the elementary neurological examination were essentially normal. However, a computed tomographic scan revealed a large meningioma in the falx involving the medial aspects of the frontal lobes bilaterally. Neuropsychological examination demonstrated deficits in complex attentional tasks and also many errors of commission in the go-no go test. Following surgical excision of the tumor, her go-no go performance became normal. This patient shows that damage to the medial frontal lobe can cause deficits in go-no go performance, and that these deficits can be reversible following resolution of the lesion.     

Brain-behavior correlation in children depends on the neurocognitive network

We examined brain-behavior correlations in 12 children (age range 9.3 to 11.7 years) during a selective attention task that required the visual search of a conjunction of features and during a response inhibition task that required the inhibition of a pre-potent response during "no-go" blocks. We found that the association between performance in these tasks and brain activation as measured by functional magnetic resonance imaging (fMRI) depended on the neurocognitive network. Specifically, better performance during the no-go task was associated with greater activation in the response inhibition network including the prefrontal cortex and basal ganglia. In contrast, better performance during the visual search task was associated with less activation in the selective attention network including superior parietal lobule and lateral premotor cortex. These results show that the relation of performance to the magnitude of neural activation is complex and may display differential relationships based on the cognitive domain, anatomical region, and perhaps also developmental stage.     

Neurofibrillary tangles,amyloid, and memory in aging and mild cognitive impairment

BACKGROUND: Large numbers of neurofibrillary tangles (NFTs) and amyloid plaques are diagnostic markers for Alzheimer disease (AD), but lesser numbers of these lesions are also seen in nondemented elderly individuals. Much of the existing literature suggests that the NFTs of AD have a closer correlation with cognitive function than do amyloid plaques. Whether a similar relationship exists in normal aging and mild cognitive impairment (MCI), a condition that frequently reflects a preclinical stage of AD, remains unknown. OBJECTIVE: To determine the distribution patterns of beta-amyloid plaques and NFTs and the association of these lesions with memory performance in nondemented individuals. METHODS: We investigated regional distributions and neuropsychological correlates of NFTs and amyloid plaques in cognitively normal elderly persons and subjects with MCI who received neuropsychological testing before death.Subjects Eight nondemented subjects who volunteered to receive annual neuropsychological testing and agreed to brain donation were studied. Five subjects showed no cognitive impairment, and 3 were diagnosed with MCI. RESULTS: Distribution of NFTs followed a rigorous and hierarchical pattern, but distribution of amyloid plaques varied among individuals. Subjects with MCI displayed higher NFT densities than did nonimpaired subjects. In addition, NFT density in the temporal lobe correlated with memory scores, whereas density of amyloid plaques did not. CONCLUSIONS: Neurofibrillary tangles are more numerous in medial temporal lobe regions associated with memory function and show a relationship to performance on memory tests in nondemented individuals. These results suggest that NFTs may constitute a pathological substrate for memory loss not only in AD but also in normal aging and MCI.     

Radiographic anomalies and obstructive sleep apnea syndrome

BACKGROUND: The purpose of this study was to identify the particular cranio-facial pattern observed in patients with obstructive sleep apnea syndrome and to search for possible correlations between morphological anomalies and disease severity. MATERIAL AND METHODS: The study group included 49 dentate patients, mean age 47.7 years suffering from obstructive sleep apnea syndrome. Most of the patients were overweight. RESULTS: Typical features observed in these patients were a short craniospinal field, a retro-maxillary, a retro-mandibula, antero-inferior vertical excess of the face, and class II malocclusion. No correlation between severity of obstructive sleep apnea syndrome and craniofacial morphology could be identified. DISCUSSION: These results are in agreement with data in the literature. The absence of a morphological correlation appears to be related to the type of patients studied (overweight). Indeed, two categories of sleep apnea patients have been identified: obese patients who have few or no anomalies of the facial skeleton and thin patients with characteristic open bite class II malocclusion.     

Tumour necrosis and microvascular proliferation are associated with 9p deletion and CDKN2A alterations in 1p/19q-deleted oligodendrogliomas

A subset of oligodendrogliomas and oligoastrocytomas has been associated with 1p/19q deletion. Subsequently, this genetic alteration was linked to chemosensitivity and classic histology of oligodendrogliomas. Tumoural progression includes deletions of 9p, 10q and alterations of CDKN2A. However, these (epi)genetic changes have not been associated with specific histological features. In a series of 45 gliomas including oligodendrogliomas, oligoastrocytomas and astrocytomas, deletions of chromosomal regions implied in these tumours (1p, 9p, 10, 17p13, 19q and 22) were looked for by microsatellite analysis. Tumours that were deleted for 1p and 19q were selected. Subsequently, presence of deletions in the other studied regions, (epi)genetic changes in p14ARF, CDKN2A and CDKN2B, as well as histological features, were associated to these tumours. 1p/19q deletion was observed in 22 tumours. Twenty-one of them presented regions of classic histology of oligodendroglioma. A deletion of 9p was found in eight of them, always in association with tumour necrosis and/or microvascular proliferation. In addition, (epi)genetic alterations of CDKN2A were observed in 71% of these tumours. Presence of regions of classic histology of oligodendroglioma in a tumour sample is predictive of 1p/19q deletions. Necrosis and/or microvascular proliferation are signs of an additional 9p deletion. Finally, as CDKN2A (epi)genetic alterations were found in 71% of the 1p/19q/9p-deleted oligodendrogliomas, CDKN2A may have a role in oligodendroglioma-associated microvascular proliferation.