65 research outputs found

    A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status

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    <p>Abstract</p> <p>Background</p> <p>To investigate non-patient irritable bowel syndrome (IBS) change to IBS and to determine factors predictive of the onset of IBS, individual biological factors, psychological factors, behavioral factors, and environmental factors were examined.</p> <p>Methods</p> <p>The subjects were 105 non-patient IBS (male = 59, female = 46, average age:21.49 ± 2.37), including 68 of the diarrhea-predominant type and 37 of the constipation-predominant type selected from 1,409 university and technical college students by use of a questionnaire based on the Rome II diagnostic criteria. The subjects were followed for three years, and various characteristics and IBS symptoms were serially observed (12 times). The IBS incidence rate was calculated.</p> <p>Results</p> <p>During the three years, 37 non-patient IBS (35.24%) changed to IBS: 28 diarrhea-predominant type and 9 constipation-predominant type. All IBS symptoms disappeared in 26 non-patient IBS subjects (24.76%). According to quantification method II (discriminant analysis), seven factors (stressor, two kinds of stress coping styles, cognitive appraisal, eating habits, sleeping time, and psychologically abuse) were adopted as a predictive model for IBS incidence and were confirmed as predictive of IBS.</p> <p>Conclusion</p> <p>The results of this research show that non-patient IBS is a changeable state that can change into IBS or persons without symptoms. Most of the non-patient IBS subjects who became asymptomatic had had symptoms for six months or less. Furthermore, the longer a non-patient IBS subject had symptoms, the higher the risk of a change to IBS became. The findings suggest the usefulness of identifying and approaching non-patient IBS as early as possible to prevent the onset of IBS. It must be noted that the persons surveyed in the present study had only the diarrhea-predominant and constipation-predominant types. Therefore, the findings of the present study are limited only these two types. Further study including the mixed type is needed.</p

    An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer\u27s disease

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    The β-site amyloid precursor protein cleaving enzyme-1 (BACE1), an essential protease for the generation of amyloid-β (Aβ) peptide, is a major drug target for Alzheimer\u27s disease (AD). However, there is a concern that inhibiting BACE1 could also affect several physiological functions. Here, we show that BACE1 is modified with bisecting N-acetylglucosamine (GlcNAc), a sugar modification highly expressed in brain, and demonstrate that AD patients have higher levels of bisecting GlcNAc on BACE1. Analysis of knockout mice lacking the biosynthetic enzyme for bisecting GlcNAc, GnT-III (Mgat3), revealed that cleavage of Aβ-precursor protein (APP) by BACE1 is reduced in these mice, resulting in a decrease in Aβ plaques and improved cognitive function. The lack of this modification directs BACE1 to late endosomes/lysosomes where it is less colocalized with APP, leading to accelerated lysosomal degradation. Notably, other BACE1 substrates, CHL1 and contactin-2, are normally cleaved in GnT-III-deficient mice, suggesting that the effect of bisecting GlcNAc on BACE1 is selective to APP. Considering that GnT-III-deficient mice remain healthy, GnT-III may be a novel and promising drug target for AD therapeutics
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