Background and purpose
Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the ...microtubule‐binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, 18FTHK‐5351, which we have recently developed.
Methods
Paraffin‐embedded brain sections of the patients with PSP were used for autoradiography with 3HTHK‐5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with 18FTHK‐5351. To detect amyloid‐β deposition, PET imaging with Pittsburgh compound B was also performed.
Results
Autoradiography in the brain sections of patients with PSP demonstrated 3HTHK‐5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable 18FTHK‐5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP.
Conclusions
We conclude that 18FTHK‐5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.
Essentials Two groups recently reported GFI1B as a novel causative gene for congenital macrothrombocytopenia. We performed functional analysis of a novel GFI1B mutation and previous mutations. An ...immunofluorescence analysis of the platelet CD34 expression can be useful as a screening test. Mutant-transduced megakaryocytes produced enlarged proplatelet tips which were reduced in number.
Background GFI1B is an essential transcription factor for megakaryocyte and erythrocyte development. Two groups have recently identified GFI1B as a novel causative gene for congenital macrothrombocytopenia associated with α-granule deficiency. Methods We performed whole exome sequencing and identified a novel GFI1B p.G272fsX274 mutation in a family with macrothrombocytopenia, and a decreased number of platelet α-granules and abnormally shaped red blood cells. p.G272fsX274 and the previous two mutations all predicted disruption of an essential DNA-binding domain in GFI1B. We therefore performed functional studies to characterize the biochemical and biological effects of these three patient-derived mutations. Results An immunofluorescence analysis revealed decreased thrombospondin-1 and increased CD34 expression in platelets from our patient. Consistent with the previous studies, the three patient-derived mutants were unable to repress the expression of the reporter gene and had a dominant-negative effect over wild-type GFI1B. In addition, the three mutations abolished recognition of a consensus-binding site in gel shift assays. Furthermore, transduction of mouse fetal liver-derived megakaryocytes with the three GFI1B mutants resulted in the production of abnormally large proplatelet tips, which were reduced in number. Conclusions Our study provides further proof of concept that GFI1B is an essential protein for the normal development of the megakaryocyte lineage.
Background
Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers ...that can predict RPILD development remain unclear.
Objectives
To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM‐ILD.
Methods
In total, 49 patients with PM/DM‐ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti‐MDA5 antibody, compared them between the RPILD (n = 23) and non‐RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL‐15 expression in lung tissues. The IL‐15 production was also investigated using A549 and BEAS‐2B cells.
Results
The RPILD group had significantly higher IL‐15, IL‐1RA, IL‐6, CXCL10, VCAM‐1, anti‐MDA5 antibody and ferritin serum levels than the non‐RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti‐MDA5 antibody, IL‐15, CXCL8, CCL22, IL‐1RA and ferritin were the best combination to distinguish the two groups. IL‐15 and CCL22 were also predictive marker for RPILD development in anti‐MDA5 antibody‐positive patients. Additionally, the RPILD group had significantly high IL‐15 levels in BALF. The lung tissues expressed IL‐15, which increased after cytokine stimulation in the A549 cells.
Conclusion
This study identified a combination of biomarkers predicting PM/DM‐RPILD progression, and IL‐15 is an important cytokine for predicting RPILD development and reflecting ILD severity.
Summary Hip fracture incidence from 2004 to 2006 in the Tottori prefecture of Japan was investigated and compared with previously reported rates. The age- and gender-specific incidence of hip ...fracture in the Tottori prefecture has not plateaued, as has been reported for populations in Northern Europe or North America. Introduction Recent data from Northern Europe and North America indicate that the incidence of hip fracture has plateaued, whereas most reports from Asia indicate that the incidence is increasing. The aims of this study were to investigate the recent incidence of hip fracture in the Tottori prefecture, Japan, and to compare it with previous reports. Methods All hip fractures in patients aged 35 years and older occurring between 2004 and 2006 were surveyed in all of the hospitals from the Tottori prefecture. The age- and gender-specific incidence rates were then calculated. Using these and previously reported data, the estimated number of hip fracture patients was determined using the age- and gender-specific incidence rates in each year from 1986 to 2006. Results The survey identified 851, 906, and 1,059 patients aged 35 years and older, in 2004, 2005, and 2006 respectively. The residual lifetime risk of hip fracture for individuals at 50 years of age was estimated to be 5.6% for men and 20.0% for women. The estimated number of patients from 1986 to 2006 showed a significant increase over time for both genders. Conclusions The age- and gender-specific incidence of hip fracture in the Tottori prefecture, Japan has not plateaued for either gender.
Fine tuning of cell signals by glycosylation Furukawa, Koichi; Ohkawa, Yuki; Yamauchi, Yoshio ...
Journal of biochemistry (Tokyo),
06/2012, Letnik:
151, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Carbohydrates on the glycoproteins and glycosphingolipids expressed on the cell surface membrane play crucial roles in the determination of cell fates by being involved in the fine tuning of cell ...signalling as reaction molecules in the front line to various extrinsic stimulants. In glycoproteins, modification of proteins is performed by substitution of sugar chains to one or multiple sites of individual proteins, leading to quantitative and qualitative changes of receptor functions in the cell membrane. As for glycosphingolipids, majority of them consist of two moieties, i.e. carbohydrates and ceramides, and are localized in the microdomains such as lipid rafts or detergent-resistant microdomains. They generate and/or modulate cell signals to determine the cell fates by interacting with various carbohydrate-recognizing proteins. Modes of glycosylation and mechanisms by which glycosylation is involved in the regulation of cell signals are now hot subjects in glycobiology.
In rhyolite lavas, the high porosity bands are often developed. They potentially act as pathways for gas movement to the lava surface. Since explosive activities of lavas are generally considered to ...be controlled by degassing system, understanding the origin and deformation process of the high porosity bands is important to assessing volcanic hazards. The Takanoobane rhyolite lava in the middle of Kyushu Island in SW Japan is effused at 51±5ka. The volume, flow length, and thickness are 0.14km3, >2km, and about 90m, respectively. The central crystalline part of the lava is characterized by the light-colored bands defined by the high porosity zone (HPZ). On the basis of geological and petrographical studies, we revealed that the HPZ was primary formed by ductile–brittle tearing of the lava (known as cavitation). According to the AMS results, the HPZs were subsequently stretched and flattened laterally during the concentric spreading of the lava. This deformation process could stretch the HPZ not only radially but also laterally. This effective stretching developed the HPZ into pervasive thin bands. Since the HPZs act as degassing pathways to the lava surface, the pervasive HPZ bands may play a role in providing volcanic gasses to void spaces created in surface fold hinges of rhyolite lavas. Thus, this degassing system may promote explosive activity of the lava surface.
A novel decellularization method using sonication treatment is described. Sonication treatment is the combination of physical and chemical agents. These methods will disrupt cell membrane and release ...cell contents to external environments. The cell removal was facilitated by subsequent rinsing of sodium dodecyl sulfate detergents. Sonication treatment is used in the preparation of complete decellularized bioscaffolds. The aim of this study is to confirm the usefulness of sonication treatment for preparation of biological scaffolds. In this study, samples of aortic tissues are decellularized by sonication treatment at frequency of 170 kHz in 0.1% and 2% sodium dodecyl sulfate detergents for 10-h treatment time. The relation between decellularization and sonication parameters such as dissolved oxygen concentration, conductivity, and pH is investigated. Histological analysis and biomechanical testing is performed to evaluate cell removal efficiency as well as changes in biomechanical properties. Minimal inflammation response elicit by bioscaffolds is confirmed by xenogeneic implantation and immunohistochemistry. Sonication treatment is able to produce complete decellularized tissue suggesting that these treatments could be applied widely as one of the decellularization method.
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