Hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2) are involved in the down-regulation of CD1a lipid antigen presentation by HIV-1 Nef in dendritic cells

AbstractDendritic cells (DCs) play a major role in in vivo pathogenesis of HIV-1 infection. Therefore, DCs may provide a promising strategy to control and eventually overcome the fatal infection. Especially, immature DCs express all CD1s, the non-MHC lipid antigen -presenting molecules, and HIV-1 Nef down-regulates CD1 expression besides MHC. Moreover, CD1d-restricted CD4+ NKT cells are infected by HIV-1, reducing the number of these cells in HIV-1-infected individuals. To understand the exact role of DCs and CD1-mediated immune response during HIV-1 infection, Nef down-regulation of CD1a-restricted lipid/glycolipid Ag presentation in iDCs was analyzed. We demonstrated the involvement of the association of Nef with hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2), and that Hck, which is expressed strongly in iDCs, augmented this mutual interaction. Hck might be another therapeutic target to preserve the function of HIV-1 infected DCs, which are potential reservoirs of HIV-1 even after antiretroviral therapy

Texture analysis of myopathy

Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects : Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19] ; polymyositis/dermatomyositis (PM-DM) [N=21]. Although three-group analysis achieved up to 58.8% accuracy, two-group analysis of IBM plus PM-DM versus DM1 showed 78.4% accuracy. Despite the small number of subjects, texture analysis of muscle US followed by machine learning might be expected to be useful in identifying myopathic conditions

A Validation Study of the Japanese Version of the Addenbrooke's Cognitive Examination-Revised

The aim of this study was to validate the Japanese version of the Addenbrooke's Cognitive Examination-Revised (ACE-R) [Mori: Japanese Edition of Hodges JR's Cognitive Assessment for Clinicians, 2010] designed to detect dementia, and to compare its diagnostic accuracy with that of the Mini-Mental State Examination. The ACE-R was administered to 85 healthy individuals and 126 patients with dementia. The reliability assessment revealed a strong correlation in both groups. The internal consistency was excellent (α-coefficient = 0.88). Correlation with the Clinical Dementia Rating sum of boxes score was significant (rs = −0.61, p < 0.001). The area under the curve was 0.98 for the ACE-R and 0.96 for the Mini-Mental State Examination. The cut-off score of 80 showed a sensitivity of 94% and a specificity of 94%. Like the original ACE-R and the versions designed for other languages, the Japanese version of the ACE-R is a reliable and valid test for the detection of dementia

Lung metastasis from breast cancer combined with primary lung cancer: Report of a case

We herein report a case of lung metastasis from breast cancer combined with primary lung cancer. A 59-year-old female had received mastectomy 5 years ago, and underwent adjuvant chemotherapy with trastuzumab and anastrozole. Chest computed tomography revealed nodules in right lobe of lung. She underwent partial resection through video-assisted thoracoscopic surgery, and metastatic breast cancer and primary lung cancer were recognized on pathological diagnosis. Two years later after chemotherapy and exemestane with trastuzumab, she was pointed out lung cancer recurrence and has been receiving chemotherapy. When nodules are removed and diagnosed as lung metastasis combined with primary lung cancer, additional treatment should be considered depending on the prognosis of each disease

Texture in aging

Texture analysis characterizes regions in an image by their texture content and has been utilized to infer the underlying structures of medical images such as skeletal muscles. Although potentially useful in tissue diagnosis and assessing disease progression of neuromuscular diseases, the use of texture analysis in such purposes are limited, due to lack of information such as effects of aging. Thus, we performed texture analysis of medial gastrocnemius in healthy individuals form their 20s to late 80s. Among the 283 texture features in 6 classes, the features related to histogram, co-occurrence matrix, absolute gradient, and wavelet were correlated to age in 17-40% of the parameters, while none of the features related to run-length matrix and autoregressive model had significant correlation to age. This study showed that age-dependency in many texture features are present and need to be taken into account in elucidating the clinical significance. By contrast, the features related to run-length matrix and autoregressive model could have clinical utility

Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Base

Association between upper limb movements during drumming and cognition in older adults with cognitive impairment and dementia at a nursing home: a pilot study

BackgroundDespite the association between motor dysfunction and dementia, quantitative assessment of dementia-related specific motor dysfunction in patients with severe dementia is difficult. Thus, this study aimed to develop a new method to measure upper limb motor function in people with dementia.MethodsWe examined the relationship between dementia severity and dementia-related specific motor dysfunction using the Mini-Mental State Examination (MMSE), a dementia screening test. Participants comprised 16 nursing home residents with a mean age of 86 years and MMSE score of 15.75 (range, 1–27) Points. Participants were seated in a circle and instructed to play a drum that was placed in their lap using mallets (drumsticks) in their dominant hand. Acceleration and gyroscopic sensors were attached to their wrists to collect data on arm movements while drumming. Upper limb motor characteristics were confirmed by recording acceleration and arm movement during drumming and analyzing the correlation with handgrip strength.ResultsHandgrip strength was correlated with arm elevation angle during drumming. The arm elevation angle displayed a significant regression equation with the MMSE score and showed the best regression equation along with handgrip strength (adjusted R2 = 0.6035, p = 0.0009).ConclusionWe developed a new method using drums to measure upper limb motor function in people with dementia. We also verified that the average arm elevation angle during drumming could predict cognitive dysfunction. This system may be used to monitor people with dementia in a simple and safe way

Sodium Current by Hindlimb Unloading

This study aimed to characterize the excitability changes in peripheral motor axons caused by hindlimb unloading (HLU), which is a model of disuse neuromuscular atrophy. HLU was performed in normal 8-week-old male mice by fixing the proximal tail by a clip connected to the top of the animal's cage for 3 weeks. Axonal excitability studies were performed by stimulating the sciatic nerve at the ankle and recording the compound muscle action potential (CMAP) from the foot. The amplitudes of the motor responses of the unloading group were 51% of the control amplitudes [2.2 ± 1.3 mV (HLU) vs. 4.3 ± 1.2 mV (Control), P = 0.03]. Multiple axonal excitability analysis showed that the unloading group had a smaller strength-duration time constant (SDTC) and late subexcitability (recovery cycle) than the controls [0.075 ± 0.01 (HLU) vs. 0.12 ± 0.01 (Control), P < 0.01; 5.4 ± 1.0 (HLU) vs. 10.0 ± 1.3 % (Control), P = 0.01, respectively]. Three weeks after releasing from HLU, the SDTC became comparable to the control range. Using a modeling study, the observed differences in the waveforms could be explained by reduced persistent Na+ currents along with parameters related to current leakage. Quantification of RNA of a SCA1A gene coding a voltage-gated Na+ channel tended to be decreased in the sciatic nerve in HLU. The present study suggested that axonal ion currents are altered in vivo by HLU. It is still undetermined whether the dysfunctional axonal ion currents have any pathogenicity on neuromuscular atrophy or are the results of neural plasticity by atrophy