Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.     

Expression-dependent perturbation of nucleosomal phases at HS2 of the human beta-LCR: possible correlation with periodic bent DNA

DNA bend sites appear periodically at average intervals of 680 bp, corresponding to a length of four nucleosomes, in the human epsilon-, beta- and Ggamma-Agamma-psibeta-globin gene regions. We found that the HS2 region flanked by two DNA bend sites accommodated five nucleosomes and they were regularly phased throughout the region with the exception of that located in the middle, which corresponded to the precise location of HS2 and included the binding site for NF-E2. There appeared to be several phases in this region in the reconstituted chromatin and in erythroid K562 cells where the globin genes are expressed, whereas only one phase was adopted in non-erythroid HeLa cells. Meanwhile, almost unique phases were adopted at the flanking bend sites in vitro as well as in vivo. Sequences of 30 bp containing the bend centers cloned into the vector alone showed identical nucleosomal phases to those observed with the in vitro and in vivo experiments and removing the bend sites caused disruption of the phases at the bend sites as well as those in their direct vicinity. Finally, the nucleosome in this HS2 region had an inhibitory effect on NF-E2 binding, although remodeling occurred with the nuclear extract from K562 cells in the presence of ATP. This suggests that HS2 is placed at a region of weak nucleosome phasing activity along with factor binding sites.     

Significance of arterial ketone body ratio as a parameter of oxygen metabolism in cardiac surgery]

Postoperative course after cardiac surgery is characterized by a progressive increased cellular oxygen demand and limited oxygen supply. It is mandatory to assess the adequacy of tissue oxygenation and to correct inadequate oxygenation rapidly in cardiac surgery. The present study was designed to evaluate the relationship between the arterial ketone body ratio (AKBR) and the status of oxygen demand and supply relationship in cardiac surgery. We measured oxygen consumption, oxygen delivery, oxygen extraction, mixed venous oxygen saturation, lactate, lactate/pyruvate (L/P) and AKBR in 43 patients undergoing open heart surgery at selected 10 periods before, during and after cardiopulmonary bypass (CPB). AKBR significantly decreased immediately after the beginning of CPB and returned to pre-CPB level more quickly than lactate and L/P did. AKBR at several periods a significant correlation with lactate and L/P at delayed periods. There was a significant correlation between AKBR and L/P during and after CPB. Furthermore, oxygen consumption, oxygen extraction, mixed venous oxygen saturation, and lactate were correlated with AKBR significantly. But there was no correlation between the parameter of oxygen metabolism and both lactate and L/P. In conclusion, it appears from these data that AKBR in cardiac surgery may be helpful as a rapid guide for estimating the degree of anaerobiosis.     

Removal of dissolved estrogen in sewage effluents by β-cyclodextrin polymer

Substances with estrogenic activity are found in effluents of municipal sewage plants and dairy farms. These effluents have the potential to induce feminization in male fish. In this study, cyclodextrin polymers (CDPs) that are insoluble in both polar and non-polar solvents were selected for the removal of dissolved estrogens in the effluent of a municipal sewage plant. The removal capacity of CDPs was high in the order of β-CDP ≥ γ-CDP ? α-CDP. The mechanism for adsorption of estrogens to β-CDP was not only due to a host-guest interaction as molecular recognition by β-cyclodextrin (β-CD), but also due to adsorption by the polymer matrix. β-CDP of 0.2% (w/v) removed 17β-estradiol (E2) of about 70% from 10⁻¹¹ mol/L, and more than 90% from ≥ 10⁻¹⁰ mol/L. The removal ratios of E2 in the presence of cholesterols, which are contained at higher concentrations than estrogens in sewage effluents and are adsorptive competitor for β-CDP, were about 85% at a cholesterol/E2 molar ratio of 100 and > 90% at molar ratios of 0.1, 1, and 10. The effluent from a municipal sewage plant had estrogenic activity corresponding to 5.5 × 10⁻¹¹ molE2/L by yeast two-hybrid assay. The estrogens in the effluent were also removed > 90% by the β-CDP treatment. Therefore, β-CDP is able to remove dissolved estrogens over a wide range of concentrations in the presence of various contaminants such as wastewaters.     

Cytokine-induced neutrophil chemoattractant gene expression in the rat hypothalamus by osmotic stimulation

Cytokine-induced neutrophil chemoattractant (CINC) is one of the chemokines and has chemotaxity for neutrophils. Recently, we found the presence of stress-sensitive CINC expression in the hypothalamic nuclei such as the paraventricular nucleus. Since CINC was predominantly co-localized with vasopressin in the supraoptic nucleus (SON), we investigated the effect of hyperosmotic challenge on CINC mRNA in the hypothalamus. We found that CINC mRNA expression in the hypothalamus was augmented within 30 min following osmotic stimulation and immediately returned to the basal level. The suckling, which is a stimulation to oxytocin neurons in the SON, has no effect on CINC mRNA expression in the hypothalamus. This is the first evidence that the chemokine in the brain is activated by osmotic stimulation.     

Advanced fabrication technologies of integrated-type structure for a-Si solar cells

This paper proposes a new advanced fabrication technology for a low-cost integrated-type a-Si solar cell. Integrated-type cells provide many advantages and have been industrialized with a laser patterning method. However, a higher throughput and more efficient patterning method was required for applying a-Si solar cells to a power generating system. Plasma CVM (Chemical Vaporization Machining) was first applied to advanced patterning because of its advantages of high speed and selectivity. In this method, a plasma generated under high pressure localizes near the wire electrode and concentrates reactive radicals. As a result, we achieved an etching rate of more than 1 μm/s and selective patterning of a 200 μm-wide a-Si layer in 1 s multiline patterning was also developed for large-area modules.     

Survival and disability in stroke by stroke subtype based on computed tomographic findings in three rural Japanese communities

PURPOSE: We conducted an epidemiological study of survival and disability in stroke in three Japanese communities to seek community strategies for improvement in survival and disability. METHODS: A total of 297 first-ever strokes were identified between 1988 and 1992 in three rural communities (total population = 47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of daily living by sex, age-group and stroke subtypes. Successful review of computed tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and the data were used for subtype analyses. RESULTS: For all strokes (n = 297) survival rates were 85% for 30 day, 70% for one year, 62% for three year. The rates tended to be lower in women than in men. The rates were lowest in ages less than 60 at thirty day, and in ages 80 and older at the end of the first and third year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage and cortical cerebral infarction had lower survival rates than intracerebral hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80 in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar infarction. The proportion of stroke survivors who need assistance from others in the first and third years tended to be higher in women than in men. The proportion was higher in older patients than in the younger, and higher for intracerebral hemorrhage with ventricular rupture and cortical cerebral infarction than in other subtypes of stroke. From logistic regression analysis, the odds ratio for disability in the first year was 6.55 for ages 80 and older compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage with ventricular rupture, 4.53 for cortical cerebral infarction compared with lacunar infarction. In the third year the odds ratio was significant for ages 70-79, and decreased for intracerebral hemorrhage with ventricular rupture (odds ratio = 2.98), and increased for cortical cerebral infarction (odds ratio = 6.06). CONCLUSIONS: Survival and disability in stroke depended on age and stroke subtypes. Even after age adjustment, stroke subtypes with large cerebral involvement had worse prognosis than stroke subtypes. Community-based hypertension control programs are important to prevent any subtypes of stroke. Stroke subtypes as well as age should be taken into account to develop effective care and medical treatments for strokes.     

Thoracoabdominal aortic repair without using assisted bypass

A 41-year-old man, who had undergone descending aortic repair following rupture of the DeBakey type III aortic dissection, underwent thoracoabdominal aneurysm repair 1 year after the first surgery. The operation was performed by partial-clamping and single crossclamping without using assisted bypass or shunt, in order to minimize bleeding ensuing the re-thoracotomy and dissection between lung and the graft.