ObjectivesTo prevent the onset of lifestyle-related diseases associated with metabolic syndrome (MetS) in Japan, research into the development of a useful screening method is strongly desired. We developed a new screening questionnaire (JAMRISC) utilizing a logistic regression model and evaluated its ability to predict the development of MetS, type 2 diabetes and other lifestyle-related diseases in Japanese populace.MethodsJAMRISC questionnaire was sent to 1,850 individuals in Rumoi, a small city in Hokkaido. We received a total of 1,054 valid responses. To maximize the target individuals accurately diagnosed with MetS, logistic regression analysis was used to generate a unique metabolic syndrome score calculation formula as taking into consideration the clinical relevance of each question item as individual coefficients.ResultsThe results of our comparative research utilizing both JAMRISC and Finnish Diabetes Risk Score (FINDRISC) questionnaires revealed the usefulness of JAMRISC for its ability to detect risks for MetS, pre-MetS, diabetes, and pre-diabetes. Study of disease risk detection via JAMRISC questionnaire targeting the 4283 residents of Rumoi indicated a high detection rate for pre-MetS (98.8 %), MetS (94.2 %), pre-diabetes (85.1 %) and type 2 diabetes (94.9 %). In addition, JAMRISC was useful not only as a MetS risk score test, but also as a screening tool for diagnosing insulin resistance.ConclusionsJAMRISC questionnaire is a useful instrument for the detection of early risk of not only MetS and type 2 diabetes but also insulin resistance.

Ultrasonication is considered one of the most effective agitations for inducing the spontaneous formation of amyloid fibrils. When we induced the ultrasonication-dependent fibrillation of β2-microglobulin and insulin monitored by amyloid-specific thioflavin T (ThT) fluorescence, both proteins showed a significant decrease in ThT fluorescence after the burst-phase increase. The decrease in ThT fluorescence was accelerated when the ultrasonic power was stronger, suggesting that this decrease was caused by the partial denaturation of preformed fibrils. The possible intermediates of denaturation retained amyloid-like morphologies, secondary structures, and seeding potentials. Similar denaturation intermediates were also observed when fibrils were denatured by guanidine hydrochloride or sodium dodecyl sulfate. The presence of these denaturation intermediates is consistent with the main-chain-dominated architecture of amyloid fibrils. Moreover, in the three types of denaturation experiments conducted, insulin fibrils were more stable than β2-microglobulin fibrils, suggesting that the relative stability of various fibrils is independent of the method of denaturation.

We report a case of gastric invasive micropapillary carcinoma (IMPC) in an 86-year-old female patient. She was admitted to our hospital with a chief complaint of bloody emesis. Upper gastrointestinal endoscopy found a gastric adenocarcinoma at the antrum. The biopsy specimens showed moderately differentiated adenocarcinoma with invasive small tumor nests. Distal gastrectomy with systematic lymph node dissection demonstrated that the tumor had IMPC through a pathological examination. Despite the depth of tumor invasion (the submucosa), extensive lymph node metastases were observed. Anti-D2-40 immunostaining revealed numerous infiltrating tumor cell nests in the lymphatic vessels, which could explain subsequent multiple lymph node metastases. The adenocarcinoma showed intestinal phenotypes by several immunohistochemical studies. One of these antibodies (CD10) clearly demonstrated the inverted apical-basal (inside-out) pattern of IMPC, whereas it showed an ordinary pattern in intestinal metaplasia adjacent to the tumor. Furthermore, genetic analysis by direct sequencing revealed a point mutation in the exon 5 of TP53 in the tumor. The mutation presumably harbors a missense mutation from Arg to His at the codon 175 (R175H). R175H has been previously described as a ‘gain-of-function' mutation with a high invasive or metastatic potential in several types of cancers. In summary, this is one of the first reported cases of gastric IMPC with intestinal phenotypes harboring a TP53 R175H mutation in the literature.

We report the properties of CsCaCl 3 , storage phosphors doped with Eu, Ce, or Cu. Both doped and undoped CsCaCl 3 samples were synthesized as ceramics. For undoped CsCaCl 3 , thermally stimulated luminescence (TSL) spectrum showed a broad band around 360390 nm, and optically stimulated luminescence (OSL) spectrum exhibited the same band with a shoulder near 320 nm. These bands were attributed to different kinds of defects or impurities. The OSL and TSL spectra of Eu-doped CsCaCl 3 showed a band around 440 nm arising from the 5d4f transition of Eu 2+. The Ce-doped CsCaCl 3 showed the OSL and TSL bands originating from the 5d4f transition of Ce 3+ . An intense band at 345 nm appeared in the OSL spectrum of Cu-doped CsCaCl 3 due to Cu + , and an additional peak at 430 nm was ascribed to Cu + ion perturbed by OH ¹ ion. On the other hand, the TSL spectrum of Cu-doped CsCaCl 3 had a peak around 470 nm and it was assigned to Cu 2+ . The TSL glow curves of the undoped, Eudoped, Ce-doped, and Cu-doped CsCaCl 3 were different from each other. This suggested that the dopant ions influenced the trapping process of electronhole pairs, which were formed upon irradiation.

Bovine β-lactoglobulin (βLG) has a folding intermediate with a non-native α-helical structure. Our previous study indicated that the moderate α-helical propensity of the wild-type sequence likely contributes to circumventing non-productive intermediates. In the present study, we analyzed the dynamics of the denatured βLG and performed high-pressure NMR measurements and H/D exchange pulse labeling experiments to obtain structural information of the intermediates. The results suggested that the three portions of the sequence, the C-terminal, the middle, and the N-terminal regions, sequentially attain individual native structures. Probably, the order of folding of these regions is programed in the βLG sequence to avoid non-native aggregations. Recent experiments showed that myoglobin can form a domain-swapped dimer in a certain solvent condition. Here, using a coarse-grained symmetrized Go model, we performed a series of folding simulations of two apo-myoglobin molecules restrained in a high density condition, addressing competition of formation of a domain-swapped dimer with folding to two monomer structures. In addition to the domain-swapped dimer found in the X-ray crystallography, we also found some other forms of domain swapping. Folding pathway analysis clarified that separation between monomer folding and domain-swapping arose at a relatively early state, where inter-chain contacts between helices AB of one chain and helices GH of another chain tend to result in the domain swapping. 3P062 アポミオグロビンのドメインスワッピングとフォールディン グの競合:分子シミュレーション解析 3P063 超音波によるアミロイド線維形成と分解 Ultrasonication dependent induction and degradation of amyloid fibrilsSayaka Noda, Masatomo So, Masayuki Adachi, Yuji Goto (Inst. Protein Res., Osaka Univ.)Amyloid fibrils, associated with more than 20 degenerative diseases including Alzheimer's disease, has been thought to be highly stable aggregates consisting of cross β structure. Recently, our group reported that ultrasonication is one of the powerful methods of agitation for accelerating spontaneous fibrillation. More recently, it has been found that high amplitude of ultrasonication also induces the decrease of Thioflavin T fluorescence intensity, suggesting that fibrils convert to amorphous aggregates. Here, we compared the effects of ultrasonication on the fibrils and native monomers using human insulin and β 2 -microglobulin. We discuss the stability of fibrils and monomers against surface denaturation at the cavitation bubbles induced by ultrasonication. 3P064 中性子散乱によるヒト α-シヌクレインのダイナミクス変化 の検出Changes in the dynamics of human α-synuclein detected by neutron scattering