Decreased Striatal Dopa Uptake Correlated with Fronto-Temporal Glucose Utilization in Alzheimer\u27s Disease

開始ページ、終了ページ: 冊子体のページ付

A PET Study of Memory for Future Plan

開始ページ、終了ページ: 冊子体のページ付

CD(8+ )T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

BACKGROUND: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD(8+ )TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD(3+), CD(4+ )and CD(8+)) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. METHODS: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD(68 )for macrophages, anti-elastase for neutrophils, and anti-CD(3), anti-CD(4), anti-CD(8 )for CD(3+)TLs, CD(4+)TLs, and CD(8+)TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV(1), FVC, TLC, DLCO, PaO(2), PaCO(2 )and P(A-a)O(2))] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. RESULTS: Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD(68+ )cells for the 16.6% ± 2, CD(3+ )TLs for the 28.8% ± 7, CD(4+ )TLs for the 14.5 ± 4 and CD(8+ )TLs for the 13.8 ± 4. CD(8+)TLs correlated inversely with FVC % predicted (r(s )= -0.67, p = 0.01), TLC % predicted (r(s )= -0.68, p = 0.01), DLCO % predicted (r(s )= -0.61, p = 0.04), and PaO(2 )(r(s )= -0.60, p = 0.04). Positive correlations were found between CD(8+)TLs and P(A-a)O(2 )(r(s )= 0.65, p = 0.02) and CD(8+)TLs and MRC score (r(s )= 0.63, p = 0.02). Additionally, CD(68+ )cells presented negative correlations with both FVC % predicted (r(s )= -0.80, p = 0.002) and FEV(1 )% predicted (r(s )= -0.68, p = 0.01). CONCLUSION: In UIP/IPF tissue infiltrating mononuclear cells and especially CD(8+ )TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis

Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2

© 2017 The Authors. Published by Nature Publishing Group. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/cddis.2017.176Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs. Here, we report the in vitro and in vivo activity of DS in combination with copper (Cu) against CD34(+)/CD38(+) leukemia stem-like cells sorted from KG1α and Kasumi-1 AML cell lines, as well as primary CD34(+) AML samples. DS plus Cu (DS/Cu) displayed marked inhibition of proliferation, induction of apoptosis, and suppression of colony formation in cultured AML cells while sparing the normal counterparts. DS/Cu also significantly inhibited the growth of human CD34(+)/CD38(+) leukemic cell-derived xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was closely associated with activation of the stress-related ROS-JNK pathway as well as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-κB pathways. In summary, our findings indicate that DS/Cu selectively targets leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising LSC-targeted activity of this repurposed agent for treatment of relapsed and refractory AML

Acquired and congenital disorders of sung performance: A review.

Many believe that the majority of people are unable to carry a tune. Yet, this widespread idea underestimates the singing abilities of the layman. Most occasional singers can sing in tune and in time, provided that they perform at a slow tempo. Here we characterize proficient singing in the general population and identify its neuronal underpinnings by reviewing behavioral and neuroimaging studies. In addition, poor singing resulting from a brain injury or neurogenetic disorder (i.e., tone deafness or congenital amusia) is examined. Different lines of evidence converge in indicating that poor singing is not a monolithic deficit. A variety of poor-singing "phenotypes" are described, with or without concurrent perceptual deficits. In addition, particular attention is paid to the dissociations between specific abilities in poor singers (e.g., production of absolute vs. relative pitch, pitch vs. time accuracy). Such diversity of impairments in poor singers can be traced to different faulty mechanisms within the vocal sensorimotor loop, such as pitch perception and sensorimotor integration

Intact verbal description of letters with diminished awareness of their forms

Visual processing and its conscious awareness can be dissociated. To examine the extent of dissociation between ability to read characters or words and to be consciously aware of their forms, reading ability and conscious awareness for characters were examined using a tachistoscope in an alexic patient. A right handed woman with 14 years of education presented with incomplete right hemianopia, alexia with kanji (ideogram) agraphia, anomia, and amnesia. Brain MRI disclosed cerebral infarction limited to the left lower bank of the calcarine fissure, lingual and parahippocampal gyri, and an old infarction in the right medial frontal lobe. Tachistoscopic examination disclosed that she could read characters aloud in the right lower hemifield when she was not clearly aware of their forms and only noted their presence vaguely. Although her performance in reading kanji was better in the left than the right field, she could read kana (phonogram) characters and Arabic numerals equally well in both fields. By contrast, she claimed that she saw only a flash of light in 61% of trials and noticed vague forms of stimuli in 36% of trials. She never recognised a form of a letter in the right lower field precisely. She performed judgment tasks better in the left than right lower hemifield where she had to judge whether two kana characters were the same or different. Although dissociation between performance of visual recognition tasks and conscious awareness of the visual experience was found in patients with blindsight or residual vision, reading (verbal identification) of characters without clear awareness of their forms has not been reported in clinical cases. Diminished awareness of forms in our patient may reflect incomplete input to the extrastriate cortex.