Egg white hydrolysate inhibits oxidation in mayonnaise and a model system.

The flavor deterioration of mayonnaise is induced by iron, which is released from egg yolk phosvitin under acidic conditions and promotes lipid oxidation. To prevent oxidative deterioration, natural components, rather than synthetic chemicals such as ethylenediaminetetraacetic acid have been required by consumers. In the present study, we evaluated the inhibitory effects of three egg white components with the same amino acid composition, namely egg white protein, hydrolysate, and the amino acid mixture, on lipid oxidation in mayonnaise and an acidic egg yolk solution as a model system. We found that the hydrolysate had the strongest inhibitory effect on lipid oxidation among the three components. The mechanism underlying the antioxidant effect was associated with Fe2+-chelating activity. Thus, egg white hydrolysate may have the potential as natural inhibitors of lipid oxidation in mayonnaise.

Construction of an expressible BAC library of the unculturable insect microorganism, stink bug Plautia stali symbiont, for the search of biologically active and useful symbiont products.

While gene products and metabolites of insect symbiotic bacteria may act as useful resources for insect-microbe studies and medicinal use, it is usually difficult to obtain the insect symbionts to some extent in quantity because most of them are unculturable. In this study, the possibility of using bacterial artificial chromosome (BAC) libraries as a heterologous gene expression tool for the discovery of novel symbiont metabolites was evaluated. A BAC library was constructed from the symbiont purified from the posterior midgut cecum of the stink bug Plautia stali. The BAC library, which consisted of 513 clones with an average insert size of 41 kb, represented greater than five-fold coverage of the genome. The ability of the BAC clones to express plural genes from large-sized insert DNA in Escherichia coli was examined by the growth of BAC-transformed leu operon-deficient DH10B cells on M9 minimal medium supplemented with glucose. Two BAC clones complemented leucine deficiency in DH10B cells; the clones contained the leu operon of the symbiont chromosome. The P. stali symbiont genes introduced into the BAC vector are functional in E. coli, and these genes are expressed in an operon unit. BAC libraries can be used to generate gene product- and metabolite-libraries, facilitating to characterize potential metabolites of the P. stali symbiont.

[Marginal zone lymphoma of mucosa-associated lymphoid tissue of the parietal pleura; report of a case].

An 76-year-old man was referred to our hospital due to right hydrothorax. The diffuse thickening of parietal pleura with increased fluoro-2-deoxy-D-glucose (FDG) uptake was noted by computed tomography (CT) and positron emission tomography (PET). Surgical biopsy was performed and the tumor was diagnosed as mucosal associated lymphoid tissue (MALT) lymphomas of parietal pleura origin by pathology. Complete remission was achieved by postoperative chemotherapy (R-CHOP), and the patient is now alive without recurrence.

Assessing the Postprandial Glycemic Response to Japonica Rice (Oryza sativa L. cv. Koshihikari) with a Small Amount of Lysolecithin and Canola Oil in Japanese Adult Men: a Double-blind, Placebo-controlled, Crossover Study.

A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after consuming japonica rice. Overall, 17 Japanese adult men were assigned to consume 150 g of normally cooked japonica rice (placebo group) and 150 g of japonica rice cooked with 18 mg of lysolecithin and 1.8 g of canola oil (treatment group); these lipids were added as emulsified formulation (EMF) for stability and uniformity. Subsequently, blood samples were collected before and 30, 45, 60, 90, and 120 min after consuming test foods. There was no significant difference in blood glucose, insulin, and triglyceride levels between the groups. However, a stratified analysis of 11 subjects with body mass index (BMI) ≥ 22 revealed that blood glucose levels were significantly lower after 30 min in the treatment group than in the placebo group (p = 0.041). Through in vitro digestibility test, the rice sample of the treatment group was observed to release significantly less glucose within 20 min than that in the placebo group rice. These results suggest that the combination of a small amount of lysolecithin and canola oil modulated the increase in postprandial blood glucose levels induced by the intake of cooked japonica rice in adult men with BMI ≥ 22. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center, (UMIN000045744; registered on 15/10/2021).

Impact of Rice Bran Oil Emulsified Formulation on Digestion and Glycemic Response to Japonica Rice: An In Vitro Test and a Clinical Trial in Adult Men.

To assess the effect of rice bran oil emulsified formulation (EMF) on cooked rice, a single-arm open clinical trial and in vitro testing for digestion and glycemic response were performed. Fifteen Japanese men consumed 200 g of packed rice, cooked with or without EMF. Blood samples were collected 0, 30, 60, and 120 min post-consumption and analyzed for glucose, insulin, and triglyceride levels. Continuous glucose monitoring (CGM) and sensory evaluation were also performed. A two-step in vitro digestion test, simulating gastric and small intestinal digestion was conducted. EMF-added rice group showed higher insulin response levels at 60 min than the placebo group. Stratification of participants with HbA1c ≥ 5.6 or an insulinogenic index ≤ 0.4 revealed a significant reduction in Cmax glucose levels. A significant correlation was observed between venous and CGM blood glucose levels and no significant sensory differences were observed. The in vitro test revealed significantly lower C∞, equilibrium starch concentrations, with EMF. Clinical trial suggests that EMF may stimulate insulin secretion and reduce blood glucose levels in participants with lower insulin responses. In vitro tests suggest that EMF inhibits glycemic digestion. This trial was registered at the UMIN Center (UMIN000053495; registered 31 January 2024).

Exclusive expression of VMAT2 in noradrenergic neurons increases viability of homozygous VMAT2 knockout mice.

The vesicular monoamine transporter 2 (VMAT2) translocates monoamine neurotransmitters from the neuronal cytoplasm into synaptic vesicles. Since VMAT2-/- mice die within a few days of birth, it is difficult to analyze the detailed VMAT2 functions using these mice. In this study, we generated human VMAT2 transgenic mice that expressed VMAT2 in noradrenergic neurons with the aim to rescue the lethality of VMAT2 deletion. The expression of human VMAT2 in noradrenergic neurons extended the life of VMAT2-/- mice for up to three weeks, and these mice showed severe growth deficiency compared with VMAT2+/+ mice. These results may indicate that VMAT2 expressed in noradrenergic neurons has crucial roles in survival during the first several weeks after birth, and VMAT2 functions in other monoaminergic systems could be required for further extended survival. Although VMAT2 rescue in noradrenergic neurons did not eliminate the increased morbidity and lethality associated with VMAT2 deletion, the extension of the lifespan in VMAT2 transgenic mice will enable behavioral, pharmacological and pathophysiological studies of VMAT2 function.

[Sarcoidosis with right middle lobe atelectasis initially suspected of malignant lymphoma; report of a case].

60-year-old woman was admitted with an abnormal shadow on the chest roentgenogram. Computed tomography showed atelectasis of the right middle lobe and hilar and mediastinal lymphadenopathy. Bronchoscopic examination revealed an obstruction at the orifice of the right middle lobe bronchus and biopsy was performed. The biopsy suggested malignant lymphoma. A diagnosis of methotrexate-associated lymphoproliferative disorders was suspected because the patient was administered methotrexate to treat the rheumatoid arthritis. The video-assisted thoracoscopic surgery was performed. Histological examination showed no malignancy and sarcoidosis in the peribronchial lymph nodes. The compressed middle lobe bronchus by enlarged lymph nodes was consider to be the cause of the middle lobe atelectasis.

[Lymphoepithelioma-like carcinoma（ LELC） of the lung].

A 77-year-old woman was admitted to our hospital with abnormal chest shadow detected on a medical checkup. Chest computed tomography(CT)showed a well-defined tumor in the upper lobe of the right lung. On positron emission tomography by fluorodeoxyglucose(FDG),the tumor revealed to be positive. We performed right upper lobectomy with hilar and mediastinal lymph node dissection. The histopathological diagnosis was lymphoepithelioma-like carcinoma (LELC). In the past 25-years, 41 cases have been reported in Japan. The average age is 64 years old, including 25 male cases and 16 female cases. Among these cases, more than half were in the early resectable stage.

High resolution imaging of ultrafine bubbles in water by Atmospheric SEM-CL.

Various analytical methods such as high-resolution observation of ultrafine bubbles in water are required to clarify the mechanisms and interrelationships of various effects brought about by ultrafine bubbles. In this study, we used atmospheric scanning electron microscopy-cathodoluminescence (ASEM-CL) method for observing ultrafine bubbles in water. ASEM can observe samples in water, and the fine electron beam provides high spatial resolution. Furthermore, the gas in the bubble can be estimated from the CL emission spectrum. We have measured characteristics such as bubble size and particle number density. Also, the CL spectra has shown that the ultrafine bubbles contained nitrogen.

Effect of an Emulsified Formulation on Vegetable Carotenoid Bioaccessibility.

We investigated the effect of neutral lipids, polar lipids, and an emulsified formulation (EMF) on carotenoid bioaccessibility in an in vitro digestion assay of vegetables. These reagents enhanced carotenoid bioaccessibility. Contrary to our previous report, they also exhibited effects on lutein. Bile extracts/pancreatin concentrations also participated in the bioaccessibility. The EMF, which consisted of lower amounts of oil, had the same effect on lutein as rapeseed oil. These reagents also showed effects in the aging model, with more reduced bile extract/pancreatin concentrations, suggesting that lipids and EMF contributed to carotenoid bioaccessibility in bile/pancreatic juice secretions due to aging and disease.

[Adult Bochdalek hernia combined with pneumothorax].

A 71-year-old man, who had been given a diagnosis of Bochdalek hernia in infancy, was referred to our hospital for dyspnea The chest X-ray and computed tomography (CT) showed left pneumothorax with bullas and intestines in his left thoracic cavity. He was admitted to our hospital and a chest tube was inserted into the left pleural cavity. The left lung expanded immediately and air leakage was stopped. He became asymptomatic and he was discharged from the hospital on the 8th day. Most Bochdalek hernias are observed in infancy, and adult cases combined with pneumothorax and bullas are very rare.

[Human pulmonary dirofilariasis].

The patient was a 60's-year-old man, who was incidentally pointed out a coin lesion in the right lung by chest radiogram. Chest computed tomography showed a round-shaped, well defined nodule of 2.5 cm in size in the right S1. Positron emission tomography did not show the accumulation of fluorodeoxyglucose in the nodule. We considered the tumor to be benign, but the patient chose surgical treatment. Partial resection of the lung was performed by thoracoscopic surgery. Histopathological diagnosis was human pulmonary dirofilariasis.

The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population.

BACKGROUND: Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors. We therefore hypothesized that variations in the A2A adenosine receptor (ADORA2A) gene modify genetic susceptibility to METH dependence/psychosis. METHODS: We first analyzed variations in the exons and exon-intron boundaries of the ADORA2A gene in METH dependent/psychotic patients. Then an association analysis between these single nucleotide polymorphisms and METH dependence/psychosis was performed using a total of 171 METH dependent/psychotic patients and 229 controls. RESULTS: We found 6 variations, of which one single nucleotide polymorphism (SNP) was novel. Significant associations were observed between the allelic and genotypic frequencies of the Exon2+751 (rs5751876) SNP and METH dependence/psychosis. These associations were observed especially in females. In the clinical feature analyses, significant associations were observed between the SNP and the patient subgroup using METH alone (i.e., without concomitant use of other substances of abuse). CONCLUSIONS: These results suggest that the ADORA2A gene could be a vulnerability factor for METH dependence/psychosis, especially in females and/or in patients using only METH.

Gene amplification of ERBB2 and EGFR in adenocarcinoma in situ and intramucosal adenocarcinoma of Barrett's esophagus.

We examined 11 cases of carcinoma arising from Barrett's esophagus consisting of two adenocarcinomas in situ (ACIS), two intramucosal adenocarcinomas, and seven overt invasive adenocarcinomas. Overexpression of p53 (implying a mutation of the p53 gene), ERBB2, and EGFR was measured by immunohistochemistry, and gene amplification of ERBB2 and EGFR was measured by fluorescence in situ hybridization (FISH). In all cases of ACIS and the intramucosal adenocarcinomas, almost all cancer cells overexpressed p53, however the populations overexpressing ERBB2 and EGFR varied in different cases: in one ACIS, ERBB2 was coexpressed in all the cancer cells, in the other ACIS and one intramucosal adenocarcinoma, ERBB2 was overexpressed in about 50% and only 10% of the p53-positive cells respectively. EGFR was co-expressed in 20% in the other intramucosal adenocarcinoma. Protein overexpression of ERBB2 or EGFR corresponded to the amplification of their respective genes on a cell by cell basis. These gene amplifications, however, were not found in the seven invasive adenocarcinomas. Thus we speculate that the gene amplification occurred late in the dysplasia-carcinoma sequence probably after the mutation of p53. Furthermore, new clonal expansion accompanied by tumor invasion might have extinguished the originally amplified genes in these tumors.

C9orf10 protein, a novel protein component of Puralpha-containing mRNA-protein particles (Puralpha-mRNPs): characterization of developmental and regional expressions in the mouse brain.

Puralpha has been implicated in mRNA transport and translation in neurons. We previously reported that Puralpha is a component of mRNA/protein complexes (Puralpha-mRNPs) with several other proteins. Among them, we found the C9orf10 (Homo sapiens chromosome 9 open reading frame 10) protein, which was recently characterized as a component of RNA-containing structures. However, C9orf10 itself remains poorly understood. To characterize C9orf10 expression at the protein level, we raised an antibody against C9orf10 and compared the spatial and developmental expressions of this protein and Puralpha in the mouse brain. C9orf10 was expressed as early as embryo stage 12, whereas Puralpha was expressed from 5 days after birth. In adults, C9orf10 expression was most prominent in the hippocampus, caudate putamen, cerebral cortex, and cerebellum, unlike the uniform distribution of Puralpha. C9orf10-positive cells also showed immunoreactivity to Puralpha. C9orf10 expression was restricted to neurons, judging by the immunoreactivity to neuron-specific nuclear protein or CaM kinase II. These observations suggest an accessory role of C9orf10 for Puralpha in a limited brain region in addition to other possible functions that have not yet been determined.

Methamphetamine-induced locomotor activity and sensitization in dopamine transporter and vesicular monoamine transporter 2 double mutant mice.

RATIONALE: The dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2) play pivotal roles in the action of methamphetamine (MAP), including acute locomotor effects and behavioral sensitization. However, the relative impact of heterozygous DAT and VMAT2 knockouts (KOs) on the behavioral effects of MAP remains unknown. OBJECTIVES: To evaluate the roles of DAT and VMAT2 in MAP-induced locomotor behavior, we examined locomotor activity and sensitization in heterozygous DAT KO (DAT+/-), heterozygous VMAT2 KO (VMAT2+/-), double heterozygous DAT/VMAT2 KO (DAT+/-VMAT2+/-), and wild-type (WT) mice. RESULTS: Acute 1 mg/kg MAP injection induced significant locomotor increases in WT and VMAT2+/- mice but not in DAT+/- and DAT+/-VMAT2+/- mice. Acute 2 mg/kg MAP significantly increased locomotor activity in all genotypes. Repeated 1 mg/kg MAP injections revealed a delayed and attenuated development of sensitization in DAT+/- and DAT+/-VMAT2+/- mice compared to WT mice and delayed development in VMAT2+/- mice. In repeated 2 mg/kg MAP injections, DAT+/- and DAT+/-VMAT2+/- mice showed delayed but not attenuated development of sensitization, while there was no difference in the onset of sensitization between VMAT2+/- and WT mice. In DAT+/-VMAT2+/- mice, all of MAP-induced behavioral responses were similar to those in DAT+/- but not VMAT2+/- mice. CONCLUSIONS: Heterozygous deletion of DAT attenuates the locomotor effects of MAP and may play larger role in behavioral responses to MAP compared to heterozygous deletion of VMAT2.

Methamphetamine-induced hyperthermia and lethal toxicity: role of the dopamine and serotonin transporters.

We examined the hyperthermic and lethal toxic effects of methamphetamine in dopamine transporter (DAT) and/or serotonin transporter (SERT) knockout (KO) mice. Methamphetamine (45 mg/kg) caused significant hyperthermia even in the mice with a single DAT gene copy and no SERT copies (DAT+/- SERT-/- mice). Mice with no DAT copies and a single SERT gene copy (DAT-/- SERT+/- mice) showed significant but reduced hyperthermia when compared to wild-type mice after methamphetamine. Surprisingly, DAT/SERT double KO mice exhibited a paradoxical hypothermia after methamphetamine. These results demonstrate that methamphetamine exerts a hyperthermic effect via DAT, or via SERT, in the absence of DAT. The selective norepinephrine transporter blocker (20 mg/kg nisoxetine) caused hyperthermia in DAT/SERT double KO mice, suggesting that the norepinephrine system is not responsible for methamphetamine-induced paradoxical hypothermia in the double KO mice. DAT gene deletion in mice strikingly increased LD50 of methamphetamine by 1.7-1.8 times that of wild-type mice, suggesting that the lethal toxic effect of methamphetamine is mainly dependent on DAT. Moreover, dissociation between hyperthermic and lethal toxic effects of methamphetamine in DAT single KO mice and DAT/SERT double KO mice suggest that hyperthermia is not a prerequisite for methamphetamine-induced lethality. Methamphetamine (45 mg/kg) significantly increased mRNA of interleukin-1beta, which is the major endogenous pyrogen, in the hypothalamus of wild-type mice but not in DAT/SERT double KO mice, which provides a partial mechanism of methamphetamine-induced paradoxical hypothermia. These results suggest that DAT and SERT are key molecules for hyperthermic and lethal toxic effects of methamphetamine.

Norepinephrine transporter blockade can normalize the prepulse inhibition deficits found in dopamine transporter knockout mice.

Dopamine transporter knockout (DAT KO) mice display deficits in sensorimotor gating that are manifested by reduced prepulse inhibition (PPI) of the acoustic startle reflex. Since PPI deficits may model some of the cognitive dysfunctions identified in certain neuropsychiatric patients, we have studied the effects of transporter blockers on PPI in wild-type and DAT KO mice. Treatments with High dose psychostimulants that block DAT as well as the norepinephrine (NET) and serotonin (SERT) transporters (60 mg/kg cocaine or methylphenidate) significantly impaired PPI in wild-type mice. By contrast, these treatments significantly ameliorated the PPI deficits observed in untreated DAT KO mice. In studies with more selective transport inhibitors, the selective NET inhibitor nisoxetine (10 or 30 mg/kg) also significantly reversed PPI deficits in DAT KO mice. By contrast, while the SERT inhibitor fluoxetine (30 mg/kg) normalized these PPI deficits in DAT KO mice, citalopram (30 or 100 mg/kg) failed to do so. The 'paradoxical' effects of cocaine and methylphenidate in DAT KO mice are thus likely to be mediated, at least in part by the ability of these drugs to block NET, although serotonin systems may also have some role. Together with recent microdialysis data, these results support the hypothesis that prefrontal cortical NET blockade and consequent enhancement of prefrontal cortical extracellular dopamine mediates the reversal of PPI deficits in DAT KO mice.

Correlation of tau gene polymorphism with age at onset of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease and its prevalence increases with age. The microtubule-associated protein tau (MAPT) is thought to be implicated in the pathogenesis of PD. Association of the MAPT H1 haplotype with PD in Caucasians has been extensively studied, however, the results were inconsistent. In this study, we investigated whether MAPT gene variants contribute to the pathogenesis process including the age at onset in Japanese PD. Promoter region of MAPT gene was analyzed to find polymorphisms in Japanese population. Two single nucleotide polymorphisms (SNPs), C-639T and Del-568TIns, in promoter region were found. C-639T was novel. Unlike Caucasians, the -226C and -45A alleles consisting of the H1 haplotype were monomorphic in Japanese population. Association analysis was performed using 240 PD and 191 controls in these SNPs. No significant association was observed between these SNPs and PD. Haplotype analysis also showed no significant association (P=0.72). However, the age at onset showed significant correlation with the genotypes of Del-568TIns in PD samples when analyzed by Kendall rank correlation test (Kendall tau=-0.098, P=0.0243). These results suggested that MAPT gene variants may modify the pathogenesis process of PD.