Objective. Three anti-tumor necrosis factor ␣ (anti-TNF␣) agents have been proved to be effective for rheumatoid arthritis (RA) and other inflammatory disorders. Infliximab and adalimumab have been generated as anti-TNF␣ monoclonal antibodies, while etanercept is engineered from human type II TNF receptors. In spite of all 3 agents' equal efficacy for RA, both infliximab and adalimumab are effective for other diseases such as Crohn's disease and Wegener's granulomatosis, while etanercept is not. We undertook this study to understand the different clinical effects of these anti-TNF␣ agents by analyzing their biologic activities on transmembrane TNF␣.Methods. Jurkat T cells stably expressing an uncleavable form of transmembrane TNF␣ were used for the following studies: 1) flow cytometric analysis of binding activities of anti-TNF agents to cell surface transmembrane TNF␣, 2) complement-dependent cytotoxicity (CDC), 3) antibody-dependent cell-mediated cytotoxicity (ADCC) by using peripheral blood mononuclear cells, and 4) outside-to-inside (reverse) signal transduction through transmembrane TNF␣ estimated by apoptosis and cell cycle analysis using flow cytometry.Results. All of the anti-TNF␣ agents bound to transmembrane TNF␣. Infliximab and adalimumab exerted almost equal CDC activities, while etanercept showed considerably lower activity. ADCC activities were almost equal among these 3 agents. Adalimumab and infliximab induced apoptosis and cell cycle arrest in transmembrane TNF␣-expressing Jurkat T cells, reflecting an outside-to-inside signal transduction through transmembrane TNF␣.Conclusion. Three different anti-TNF agents showed different biologic effects on transmembrane TNF␣. This finding suggests that CDC and outside-toinside signals by anti-TNF␣ antibodies may explain the successful clinical efficacy of adalimumab and infliximab in Crohn's disease and Wegener's granulomatosis.

IntroductionThe transactivation response element DNA-binding protein 43 kDa (TDP-43) is a major component of the ubiquitin-positive and tau-negative inclusions in frontotemporal lobar degeneration and sporadic amyotrophic lateral sclerosis (ALS). TDP-43 may accumulate in cases of Alzheimer’s disease (AD), Lewy body disease (LBD), and argyrophilic grain disease (AGD). However, few studies have focused on the incidence and extent of TDP-43 deposition in aging.ResultsWe analyzed 286 consecutive autopsy brains neuropathologically. Of these, 136 brains with pathologically minimal senile changes were designated as control elderly brains (78.5 ± 9.7 y). For comparison, we selected 29 AD, 11 LBD, and 11 AGD patients from this series of autopsy brains. Sections of the hippocampus, amygdala, medulla oblongata, and lumbar spinal cord were immunostained with anti-phosphorylated TDP-43 antibody (PSer409/410). TDP-43 immunoreactive structures were classified into four types: dystrophic neurites (DNs), neuronal or glial cytoplasmic inclusions, and intranuclear inclusions. TDP-43 immunoreactive structures were observed in 55/136 control elderly (40.0 %), 21/29 AD (72.4 %), 8/11 LBD (72.7 %), and 6/11 AGD (54.5 %) brains. TDP-43 immunoreactive structures in control elderly brains were mostly DNs. These DNs were predominantly present in the uncus of the anterior hippocampus over age 65. The frequency of cases with DNs in the amygdala of control elderly brains was less than that of AD, LBD, and AGD brains. The mean age at death was significantly higher in cases with TDP-43 immunoreactive structures than cases without them.ConclusionsIn conclusion, TDP-43 immunoreactive DNs may develop as a consequence of aging processes in the human brain. In particular, the uncus of the anterior hippocampus is an area highly susceptible to TDP-43 accumulation over age 65.

Background and Purpose-Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. Methods-A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores Ͻ27 or Ͼ1.5 SDs below the age-related mean were regarded as subnormal. Results-MBs were found in 35 subjects (6.8%). MMSE score Ͻ27 was found in 25 subjects (4.8%), with MMSE score Ͼ1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores.

The typical cortical and subcortical PRES lesions showed reversibility, whereas the brain stem and deep white matter lesions showed less reversibility. PRES due to eclampsia showed maximum reversibility compared to hypertension- and drug-related PRES. DWI, even with ADC maps, had limitations in predicting the course of PRES.

BackgroundLewy body–related α-synucleinopathy (LBAS, the abnormal accumulation of pathologic α-synuclein) is found in the central and peripheral nervous systems, including the spinal cord, dorsal root ganglia, and sympathetic ganglia, of Parkinson’s disease patients. However, few studies have focused on the distribution of LBAS in the spinal cord, primary sensory neurons, and preganglionic sympathetic nerves.ResultsWe analyzed 265 consecutive subjects with LBAS who underwent autopsy at a general geriatric hospital. LBAS in the spinal cord was significantly associated with that in the lower brainstem regions that are directly connected to the spinal cord (i.e., the medullary reticular formation and locus ceruleus), but it was not associated with the olfactory bulb–amygdala system, which is not directly connected to the spinal cord, suggesting that the lower brainstem is a key structure regarding the spread of LBAS to the spinal cord. In the primary sensory neurons, most subjects with LBAS in the dorsal root ganglia had LBAS in the dorsal root, and all subjects with LBAS in the dorsal root also had LBAS in the dorsal horn, suggesting that LBAS spreads retrogradely from the axonal terminals of the dorsal horn to the somata of the dorsal root ganglia via the dorsal root. In the preganglionic sympathetic nerves, the LBAS in the sympathetic ganglia preceded that in the nucleus of the intermediolateral column of the thoracic cord, suggesting that LBAS spreads retrogradely through the preganglionic sympathetic nerves.ConclusionsLBAS in the spinal cord was associated with the lower regions of the brainstem, but not with the olfactory bulb or amygdala. LBAS may spread centrifugally along the primary sensory neurons, whereas it may spread centripetally along the preganglionic sympathetic nerves.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0236-9) contains supplementary material, which is available to authorized users.

BAE can yield long-term benefit in patients with hemoptysis due to benign diseases. Technical problems in the procedure had an impact on the short-term effect. The degree of hemorrhage or the severity of angiographical findings were not significant factors affecting the outcome. The most significant factor affecting long-term results was whether the inflammation caused by the underlying disease was medically well controlled.

In patients with head and neck cancer, posttreatment imaging can be complicated and difficult to interpret because of the complexity of the surgical procedures performed and the postirradiation changes, but such imaging is critical for the evaluation of (a) the response to therapy and (b) tumor control. Posttreatment changes are affected by the type of surgery performed, reconstruction, neck dissection, and radiation therapy. Three types of flaps are used for reconstruction in the head and neck region: (a) the local flap, with geometric repositioning of adjacent tissue; (b) the pedicle flap, with rotation of donor tissue and preservation of the original vascular system; and (c) the free flap, with transfer of tissue that is revascularized by using microvascular surgical techniques. The posttreatment imaging findings in patients with head and neck cancer can be divided into four groups: altered anatomy secondary to surgical reconstruction, tumor recurrence, potential postsurgical complications, and possible postirradiation changes. Potential postsurgical complications are wound infection, abscess, fistula, flap necrosis, hematoma, chylous fistula, and serous retention. Possible postirradiation changes include mucosal necrosis, osteoradionecrosis, radiation-induced vasculopathy, radiation pneumonitis, radiation lung fibrosis, radiation-induced brain necrosis, and radiation-induced secondary malignancies. A familiarity with the imaging characteristics of posttreatment changes and of the potential complications caused by surgery and irradiation and an ability to differentiate these findings from tumor recurrence are essential for posttreatment surveillance and follow-up management of patients with head and neck cancer.

The presence of cerebral white matter lesions (WMLs) on MRI is suggested to be a predictive factor for vascular dementia and stroke. To investigate the relationship between arterial stiffness and WMLs, we performed brain MRI to evaluate the presence of two subtypes of WML-periventricular hyperintensities (PVH) and deep white matter lesions (DWML)-and furthermore, determined the brachial-ankle pulse wave velocity (ba-PWV) as a marker of arterial stiffness in 132 elderly asymptomatic subjects (49 men and 83 women, 70.3+/-9.0 years). PVH and DWML were observed in 41 (31.0%) and 53 (40.2%) subjects, respectively. The ba-PWV values were significantly greater in subjects with PVH than in those without. DWML also tended to be associated with ba-PWV, but the correlation was not statistically significant. In multiple logistic regression analysis, age and decreased DBP were independently associated with PVH. ba-PWV was also detected as an independent factor for the appearance of PVH (adjusted odds ratio: 2.84, p=0.015) but not DWML. These results indicate that the increase in arterial stiffness contributes to the pathogenesis of PVH rather than DWML. Although further study is needed to clarify the difference between WML subtypes, our study suggests that the measurement of ba-PWV is a simple and useful tool for detecting cerebral arterial dysfunction.