: The present study endeavored to differentiate Alzheimer's disease (AD) from vascular dementia (VaD) by comparing the metabolic and hemodynamic parameters. Positron emission tomographic (PET) ...studies were carried out in 13 patients with probable AD and 20 patients with VaD. PET findings were not included in the diagnostic criteria of AD or VaD. Using oxygen‐15 labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), cerebral blood volume, and vascular transit time (VTT) were measured quantitatively during the resting state. To evaluate vascular reactivity (VR), CBF was also measured during 7% CO2 inhalation. Regional CBF from the parietal cortex positively correlated with the neuropsychological scores in both AD and VaD groups. The typical parietotemporal pattern of hypoperfusion and hypometabolism was observed in the AD group, whereas the frontal lobe including the cingulate and superior frontal gyri were predominantly affected in the VaD group. The occipital cortex was preserved in both groups. A significant increase of the OEF was found in the parietotemporal areas in the AD group. No significant prolongation was seen with VTT. There was a marked difference in VR between the two groups: VR was depleted in the VaD group, whereas VR was normal in the AD group. The increased OEF with preserved vascular reserve seen in AD may implicate participation of a vascular factor in the pathogenesis of AD, possibly at the capillary level. Thus, PET provides important functional information in discriminating AD from VaD by comparing the patterns of hypoperfusion and/or hypometabolism, and in the understanding of the underlying hemodynamic pathophysiology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision ...prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Effects of either D1 or D2 agonist on excessive dopamine (DA) release and hyperactivity induced by the microinjection of Bay K 8644 (BAYK), an L-type Ca2+ channel stimulant, into the rat caudate ...putamen were investigated under a novel environmental condition. Hyperactivity and significant increases in extracellular DA levels induced by BAYK were concomitantly observed. D1 agonist, SKF81297, administered into the caudate putamen did not block BAYK-induced hyperactivity measured by monitoring both animal activity and increases in extracellular DA levels. Pretreatment with the D2 agonists, bromocriptine, talipexole and pramipexole, into the caudate putamen significantly blocked BAYK-induced hyperactivity for 45 min after BAYK administration, although the single administration of these agonists significantly potentiated locomotor activity and rearing behavior. Furthermore, these agonists significantly suppressed BAYK-induced extracellular DA levels. Our results indicate that these D2 agonists：1) act on postsynaptic neuronal D2 receptors under conditions of normal or low DA release in the caudate putamen, and 2) act on presynaptic D2 receptors (autoreceptors) when excessive levels of DA are released or hyper DA neuronal activity is induced.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The hematological findings and the complaints of 1, 742 radiation workers in 229 industrial enterprises were investigated by the hematological examination records and the C.M.I. -Health Questionaire. ...As for the blood picture of participants, the mean values for the red blood cell counts (R.B.C.), white blood cell counts (W.B.C.) and hemoglobin contents of both male and female employees were found to be normal. Any particular changes of the elements of W.B.C. of 845 workers were not observed, while a slight decrease in the number of R.B.C. and W.B.C. of male workers could be recognized as their years of experience increased. In the scale of enterprises, R.B.C. and W.B.C. counts of the employees in the enterprises of small scale were significantly lower than those of the middle and the large scale ones. Number of workers who had R.B.C. counts of less than 4 million per mm3 in the group of the exposure dose of under 10 mrem per year was fewer than that of the group of 500 to 1, 000 mrem per year. The R.B.C. counts and hemoglobin contents of workers handling industrial gamma rays were lower than those of workers handling industrial x-rays, radioactive materials or medical x-rays. The W.B.C. counts of the industrial gamma ray and the medical x-ray groups were significantly lower than those of the industrial x-ray and the radioactive material groups. No particular differences in the classification of W.B.C. could be observed by classifying the scale of enterprises, kind of radiation sources, and exposure dose. The number of complaints of each radiation worker by the C.M.I. -Health Questionnaire, distributed as "Polya-Eggenberger" type. Ninety percent of the workers had less than 64 complaints by the C.M.I. -Health Questionnaire. There was no significant correlation between the number of complaints and the exposure dose. It seemed that the radiation workers had many complaints, especially on fatigue and uneasiness, compared with high school students as the control group.
Three hundred and seventy four industrial enterprises listed in the Department of Labor as handling ionizing radiations were investigated by means of questionnaires. Answers were received from 229 ...radiation handling works, involving 1, 742 workers. Number of sources were 824, among which x-ray equipments for nondestructive inspection was ranking at the top and radioactive substances, industrial gamma ray apparata, x-ray diffraction apparata, accelerators, nuclear reactors were following in the given order. According to industrial classification, the order was transportation machine makers (mainly shipbuilding), electric equipment makers, chemical industry, steel and nonsteel metal industry. Characterisitics could be admitted to their radiation sources by the sorts of enterprises. Exposure doses were investigated in those participating in one kind of radiation sources. Calculating for a year, the doses were:below (and including) 10 mrem 53.5%, under 500 mrem 33.9%, under 1000 mrem 8.3%, under 5000 mrem 3.9% and above 5000 mrem 0.4%. The measurement was taken by way of film badge method. It seldom exceeded the exposure doses given by the recommendation of ICRP. Pocket dosimeter showed almost the same, only having a tendency to show a slightly higher amount of dose compared with film badge method. Exposure dose took the order of industrial x-ray, industrial gamma ray, medical x-ray and medical gamma ray. In the scale of enterprises, there was a tendency that the exposure dose was larger in small industries.
Immunoglobulin A (IgA) promotes health by regulating the composition and function of gut microbiota, but the molecular requirements for such homeostatic IgA function remain unknown. We found that a ...heavily glycosylated monoclonal IgA recognizing ovalbumin coats
(
), a prominent gut symbiont of the phylum Bacteroidetes. In vivo, IgA alters the expression of polysaccharide utilization loci (PUL), including a functionally uncharacterized molecular family provisionally named Mucus-Associated Functional Factor (MAFF). In both mice and humans, MAFF is detected predominantly in mucus-resident bacteria, and its expression requires the presence of complex microbiota. Expression of the MAFF system facilitates symbiosis with other members of the phylum Firmicutes and promotes protection from a chemically induced model of colitis. Our data reveal a novel mechanism by which IgA promotes symbiosis and colonic homeostasis.
In the Peyer's patches (PPs), germinal centers (GCs) are chronically induced by bacteria and are the major sites for generation of gut immunoglobulin A (IgA) immune responses. Whether follicular ...dendritic cells (FDCs) within the GCs directly contribute to the IgA production in PPs is unknown. We showed here that direct stimulation of FDCs by bacterial products and retinoic acid synergistically enhanced the expression of the chemokine CXCL13, the survival factor BAFF, and molecules that facilitate the secretion and activation of the cytokine TGF-β1. A reduced production of these molecules by PP FDCs associated with deficiencies in the Toll-like receptor pathway or vitamin A resulted in decreased numbers of GC B cells and defective generation of IgA+ B cells within PP GCs. Our data indicate that PP FDCs are conditioned by environmental stimuli to express key factors for B cell migration, survival, and preferential generation of IgA in gut.
► FDCs from Peyer's patches have unique molecular signatures ► PP FDC transcripts reflect exposure to bacterial components and retinoic acid ► TLR and RAR signaling increases expression of BAFF, CXCL13, and TGF-β1 activators ► FDCs are critical for IgA synthesis in the germinal center of Peyer's patches
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu
. Here we ...identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8
T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
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