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"Hashimoto, H"
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Recent structural studies of carbohydrate-binding modules
2006
Carbohydrate-binding modules (CBMs) are found in many carbohydrate-active enzymes. CBMs bind to a range of polysaccharides, their primary function being to increase the catalytic efficiency of the carbohydrate-active enzymes against soluble and/or insoluble substrates. CBMs bind to their target ligands with high specificities and affinities. Thus, CBM systems are excellent models to study the mechanism of protein-carbohydrate interaction. To date, CBMs have been classified into 45 different families and many structural and functional studies have been reported. At present, three-dimensional structures of CBMs from 31 different families have been determined. These structures demonstrate that the fold most commonly found in CBMs is the β-sandwich. In the past few years, about 10 new structures from different families have been reported. These enable detailed classification of CBM structures. This article reviews recent structural and functional studies of CBMs and discusses the sub-classification of β-sandwich CBMs.
Journal Article
Clinical characteristics and outcome of human herpesvirus-6 encephalitis after allogeneic hematopoietic stem cell transplantation
2017
In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11.09,
P
<0.001; relative risk in transplantation from HLA-mismatched unrelated donor, 9.48,
P
<0.001; vs transplantation from HLA-matched related donor) and GvHD prophylaxis by calcineurin inhibitor alone. At 100 days after transplantation, the overall survival rate was 58.3% and 80.5% among patients with and without HHV-6 encephalitis, respectively (
P
<0.001). Neuropsychological sequelae remained in 57% of 121 evaluated patients. With both foscarnet and ganciclovir, full-dose therapy (foscarnet ⩾180 mg/kg, ganciclovir ⩾10 mg/kg) was associated with better response rate (foscarnet, 93% vs 74%,
P
=0.044; ganciclovir, 84% vs 58%,
P
=0.047). HHV-6 encephalitis is not rare not only in cord blood transplant recipients but also in recipients of HLA-mismatched unrelated donors. In this study, development of HHV-6 encephalitis was associated with a poor survival rate, and neurological sequelae remained in many patients.
Journal Article
Methodology for pediatric head computed tomography image segmentation and volumetric calculation using a tablet computer and stylus pen
2024
Purpose
This study presents a MATrix LABoratory (MATLAB)-based methodology for calculating intracranial volumes from head computed tomography (CT) data and compares it with established methods.
Methods
Regions of interest (ROI) were manually segmented on CT images using a stylus pen, facilitated by mirroring a computer desktop onto a tablet. The volumetric process involved three main steps: (1) calculating the volume of a single voxel, (2) counting the total number of voxels within the segmented ROI, and (3) multiplying this voxel count by the single-voxel volume. This method was applied to 83 pediatric head CT scans from patients with minor head trauma, and the volumetric results were compared with those obtained from OsiriX.
Results
A paired t-test revealed a statistically significant difference (
p
< 0.001) between volumes obtained with our MATLAB-based method and those from OsiriX, with our method measuring 0.32% higher. However, an unpaired t-test found no statistically significant differences between the volumetric population groups (
p
= 0.84).
Conclusion
The significant difference identified by the paired t-test likely reflects statistical distinctions arising from differences in the calculation methods of the two approaches. Conversely, the unpaired t-test suggests no statistically detectable differences between the volumetric populations. Although this does not imply that the two methods produce identical results, the volumetric populations derived from our method may originate from the same underlying population as those obtained using OsiriX. By taking these points into account, our method has the potential to serve as a valuable tool for volumetric measurements.
Journal Article
Effects of dance on motor functions, cognitive functions, and mental symptoms of Parkinson's disease: A quasi-randomized pilot trial
2015
•Dance was effective in improving motor functions of walking and balance of Parkinson's disease (PD).•Dance also improved cognitive function (frontal lobe function, motor imagery) of PD.•Dance was effective in improving symptoms of depression and apathy of PD.•Compared to standard PD exercise, dance improved mental and general symptoms of PD.
To examine the effectiveness of dance on motor functions, cognitive functions, and mental symptoms of Parkinson's disease (PD).
This study employed a quasi-randomised, between-group design.
Dance, PD exercise, and all assessments were performed in community halls in different regions of Japan.
Forty-six mild-moderate PD patients participated.
Six PD patient associations that agreed to participate in the study were randomly assigned to a dance group, PD exercise group, or non-intervention group. The dance and PD exercise groups performed one 60-min session per week for 12 weeks. Control group patients continued with their normal lives. All groups were assessed before and after the intervention.
We used the Timed Up-and-Go Test (TUG) and Berg Balance Scale (BBS) to assess motor function, the Frontal Assessment Battery at bedside (FAB) and Mental Rotation Task (MRT) to assess cognitive function, and the Apathy Scale (AS) and Self-rating Depression Scale (SDS) to assess mental symptoms of PD. The Unified Parkinson's Disease Rating Scale (UPDRS) was used for general assessment of PD.
When comparing results before and after intervention, the dance group showed a large effect in TUG time (ES=0.65, p=0.006), TUG step number (ES=0.66, p=0.005), BBS (ES=0.75, p=0.001), FAB (ES=0.77, p=0.001), MRT response time (ES=0.79, p<0.001), AS (ES=0.78, p<0.001), SDS (ES=0.66, p=0.006) and UPDRS (ES=0.88, p<0.001).
Dance was effective in improving motor function, cognitive function, and mental symptoms in PD patients. General symptoms in PD also improved. Dance is an effective method for rehabilitation in PD patients.
Journal Article
Exploring rare cellular activity in more than one million cells by a transscale scope
2021
In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in
Dictyostelium discoideum
, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.
Journal Article
Ultrafast electronic state conversion at room temperature utilizing hidden state in cuprate ladder system
2015
Photo-control of material properties on femto- (10
−15
) and pico- (10
−12
) second timescales at room temperature has been a long-sought goal of materials science. Here we demonstrate a unique ultrafast conversion between the metallic and insulating state and the emergence of a hidden insulating state by tuning the carrier coherence in a wide temperature range in the two-leg ladder superconductor Sr
14-x
Ca
x
Cu
24
O
41
through femtosecond time-resolved reflection spectroscopy. We also propose a theoretical scenario that can explain the experimental results. The calculations indicate that the holes injected by the ultrashort light reduce the coherence among the inherent hole pairs and result in suppression of conductivity, which is opposite to the conventional photocarrier-doping mechanism. By using trains of ultrashort laser pulses, we successively tune the carrier coherence to within 1 picosecond. Control of hole-pair coherence is shown to be a realistic strategy for tuning the electronic state on ultrafast timescales at room temperature.
Controlling material properties on sub-picosecond scales using photons could allow for ultrafast optoelectronic devices. Here, the authors propose an ultrafast photoinduced metal-to-insulator transition in a two-leg ladder cuprate superconductor based on time-resolved reflection spectroscopy.
Journal Article
Impact of the presence of HLA 1-locus mismatch and the use of low-dose antithymocyte globulin in unrelated bone marrow transplantation
2017
HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (
n
=2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+);
n
=109) with those of 1MMUD without ATG (1MM-ATG(−);
n
=1115). The median total dose of ATG (thymoglobulin) was 2.5 mg/kg (range 1.0–11.0 mg/kg) in the 1MM-ATG(+) group. The rates of grade III–IV acute GvHD, non-relapse mortality (NRM) and overall mortality were significantly lower in the MUD group than in the 1MM-ATG(−) group (hazard ratio (HR) 0.77,
P
=0.016; HR 0.74;
P
<0.001; and HR 0.87,
P
=0.020, respectively). Likewise, the rates of grade III–IV acute GVHD, NRM and overall mortality were significantly lower in the 1MM-ATG(+) group than in the 1MM-ATG(−) group (HR 0.42,
P
=0.035; HR 0.35,
P
<0.001; and HR 0.71,
P
=0.042, respectively). The outcome of allo-HCT from 1MM-ATG(−) was inferior to that of allo-HCT from MUD even in the recent cohort. However, the negative impact of 1MMUD disappeared with the use of low-dose ATG without increasing the risk of relapse.
Journal Article
PACAP is an Endogenous Protective Factor—Insights from PACAP-Deficient Mice
by
Brubel, R.
,
Szabadfi, K.
,
Lakatos, A.
in
Animals
,
Autoimmune Diseases - physiopathology
,
Biomedical and Life Sciences
2012
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.
Journal Article
Elevated bone marrow eosinophil count is associated with high incidence of severe acute GvHD after allogeneic hematopoietic stem cell transplantation
2017
Predicting severe acute GvHD (aGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging but critical. Mild aGvHD may have a favorable impact on relapse, whereas severe aGvHD is associated with poor outcomes. The aim of this study was to evaluate whether elevated eosinophil count in the bone marrow (BM) at 1 month after HSCT is associated with a high incidence of new and severe aGvHD. We enrolled 101 consecutive patients; median age was 50 years, and 50.5% patients were male. The median eosinophil concentration in BM at 1 month after HSCT was 1.1% (quartile 0.4–2.2%). The adjusted hazards ratio at 95% confidence interval for severe aGvHD was 1.26 (1.12–1.42,
P
<0.001), per 1% increase in eosinophil concentration, and 3.76 (1.41–10.05,
P
=0.008) for the high-risk group at a cutoff value of 4.0%. In addition, the predictive accuracy described by area under the curve of receiver operating characteristics, increased from 0.784 to 0.866 (
P
=0.033) with the increasing concentration of eosinophils. In conclusion, elevated concentration of eosinophils in BM was associated with high incidence and predictive accuracy of severe aGvHD. BM eosinophil concentration can be one of the key markers to predict aGvHD.
Journal Article
Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse
2016
JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development.
Journal Article