Neighbourhood relationships moderate the positive association between family caregiver burden and psychological distress in Japanese adults: a cross-sectional study.

OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

Enhancement of intestinal immune function in mice by ß-D-glucan from aureobasidium pullulans ADK-34.

ß-Glucans, glucose polymers that are the main constituents of the outer cell walls of micro-organisms such as fungi and yeast, are known to play an immunostimulatory role. We prepared ß-glucan (ß-(1-3),(1-6)-D-glucan) from an edible cultured fungus through fermentation techniques using a strain of Aureobasidium pullulans ADK-34. The purity of this ß-glucan preparation (AP-FBG) was demonstrated to be high through various instrumental analyses. We then examined the effects of AP-FBG on intestinal immune systems. We prepared Peyer's patch (PP) cells and measured interleukin (IL)-5, IL-6, and IgA production in culture media with AP-FBG. We found that both cytokines and IgA increased; furthermore, IL-6 secreted by PP dendritic cells (PPDCs) cultured in the presence of AP-FBG significantly increased. We tested IgA production after oral administration of AP-FBG for 2 weeks and found that AP-FBG tended to promote the production of IgA in the small intestine. Interestingly, we observed a significant increase in IgA production in the small intestines of mice treated with cyclophosphamide (CY; an immunosuppressant) after oral administration of AP-FBG diet compared with CY-treated and control diet mice. Production of IL-6 and IgA by PP cells and IL-6 production by PPDCs in AP-FBG-fed and CY-treated mice also increased. These results demonstrate that AP-FBG has the ability to activate PPDC and induce IL-6 production and IgA secretion in PP cells. These abilities were more clearly expressed when AP-FBG was orally administered in a CY-induced immunosuppressed condition. Therefore, AP-FBG may be a useful ingredient for preparing functional foods with immunomodulatory activities.

Identification of lactose ureide, a urea derivative of lactose, in milk and milk products.

With the widespread consumption of milk, the complete characterization of the constituents of milk and milk products is important in terms of functionality and safety. In this study, a novel nonreducing carbohydrate was separated from powdered skim milk and was identified using electron spray ionization-mass spectrometry (m/z 385.1[M + H(+)]), ¹H, ¹³C, ¹H¹H-correlation spectroscopy, and heteronuclear single quantum-nuclear magnetic resonance spectra. The carbohydrate was identified as a lactose derivative of urea, N-carbamoyl-o-ß-D-galactopyranosyl-(1-4)-D-glucopyranosylamine (lactose ureide, LU). For the HPLC analysis of LU in milk and milk products, benzoylated LU, hepta-o-benzoyl lactose ureide (melting point 137-139°C; m/z 1,113 [M + H⁺]; wavelength of maximum absorption, λ(max), 229 nm; molar extinction coefficient, ε, 8.1037 × 107), was used as a standard. The crude nonreducing carbohydrate fraction from raw milk, thermally processed milk, and milk products such as powdered milks were directly benzoylated and subjected to HPLC analysis using an octadecylsilyl column to determine the quantity of LU. The content of LU in 10% solutions of powdered skim milk and powdered infant formula (5.0±1.1 and 4.9±1.5 mg/L, respectively) were almost 3-fold higher than that of UHT milk (1.6±0.5 mg/L) and higher than that of low-temperature, long-time-processed (pasteurized at 65°C for 30 min) milk (1.2±0.3 mg/L) and the fresh raw milk sample (0.3±0.1 mg/L). A time-course of the LU content in raw milk during heating at 110°C revealed that LU increased with time. From these results, it is likely that LU is formed by the Maillard-type reaction between the lactose and urea in milk and milk products. Because the concentration of LU in milk increased with the degree of processing heat treatment, it could serve as an indicator of the thermal deterioration of milk. Although it is known that the human intestine is unable to digest LU, the gastrointestinal bacteria in human subjects are able to digest and utilize urea nitrogen in formation of essential amino acids that are available to the host human. These findings suggest that LU in milk might have a functional role in human health.

Accuracy of self-reported height, weight and waist circumference in a Japanese sample.

Objective: Inconsistent results have been found in prior studies investigating the accuracy of self-reported waist circumference, and no study has investigated the validity of self-reported waist circumference among Japanese individuals. This study used the diagnostic standard of metabolic syndrome to assess the accuracy of individual's self-reported height, weight and waist circumference in a Japanese sample. Methods: Study participants included 7,443 Japanese men and women aged 35-79 years. They participated in a cohort study's baseline survey between 2007 and 2011. Participants' height, weight and waist circumference were measured, and their body mass index was calculated. Self-reported values were collected through a questionnaire before the examination. Results: Strong correlations between measured and self-reported values for height, weight and body mass index were detected. The correlation was lowest for waist circumference (men, 0.87; women, 0.73). Men significantly overestimated their waist circumference (mean difference, 0.8 cm), whereas women significantly underestimated theirs (mean difference, 5.1 cm). The sensitivity of self-reported waist circumference using the cut-off value of metabolic syndrome was 0.83 for men and 0.57 for women. Conclusions: Due to systematic and random errors, the accuracy of self-reported waist circumference was low. Therefore, waist circumference should be measured without relying on self-reported values, particularly in the case of women.

Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials.

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5-9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.

A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement.

The prognosis of patients with metastatic retinoblastoma is poor with conventional chemotherapy and radiation. Since retinoblastoma is highly chemosensitive, dose-escalation of chemotherapeutic agents with stem cell support should be promising. We report our experience with high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) in patients with metastatic retinoblastoma. Five patients with metastatic retinoblastoma underwent HDC with autologous SCT following conventional chemotherapy and local radiation therapy. Stem cells (bone marrow in four and peripheral blood stem cells in one) were collected after marrow involvement was cleared. Melphalan was a key drug in all patients, and was administered in combination with other agents such as cisplatin, cyclophosphamide, carboplatin or thiotepa. Three patients are currently alive disease-free at 113, 107 and 38 months, respectively, from the time of SCT. They had no central nervous system (CNS) involvement. The two patients who died of disease had CNS involvement. No long-term sequelae of HDC have been noted. Our treatment strategy using HDC appears to be effective for treating metastatic retinoblastoma without CNS involvement.

High-dose chemotherapy for high-risk retinoblastoma: clinical course and outcome of 14 cases in the National Cancer Center, Japan.

The prognosis of high-risk retinoblastoma (RB) with extraocular disease, relapse, or invasion of the cut end of the optic nerve is extremely poor. Following the discontinuation of thiotepa production in Japan, BU- and melphalan (Mel)-based regimens have been used, followed by the standard treatment for neuroblastoma. This study retrospectively analyzed 14 high-risk RB patients who underwent high-dose chemotherapy (HDC) and hematopoietic SCT; 8 received a BU/Mel conditioning regimen and 6 received other regimens. The disease status at HDC was relapse in 8 patients and extraocular involvement in 5. All patients received peripheral blood stem cell infusion >1.5 × 10(6)/kg. Engraftment occurred within a median of 11 days (BU/Mel: 10-13, others: 9-13). Primary toxicities included mucositis (⩾grade 3) in 9 patients (4 with BU/Mel, 5 with others). Veno-occlusive disease (VOD) occurred in two 1-year-old patients in the BU/Mel group. There were no treatment-related deaths. Of 4 (2 with BU/Mel, 2 with others) patients with central nervous system (CNS) relapse after HDC, 3 died. In conclusion, the BU/Mel regimen may be feasible for high-risk RB under careful monitoring for VOD, particularly in younger patients. CNS relapse associated with a lethal prognosis occurred after all regimens; therefore, further evaluation of HDC efficacy for high-risk RB is required.

Biochemical characteristics of Enterobacter agglomerans and related strains found in buckwheat seeds.

Thirty strains of bacteria were randomly isolated and identified from buckwheat seeds. The phenotypic characteristics of these strains agree well with those of the Enterobacter agglomerans-Erwinia herbicola complex. On the basis of the difference in indole production and gas production from D-glucose, the isolates were divided into 3 phenotypic groups, viz. I, II and III. Twenty two strains were in phenotypic group 1, which is negative for indole production and gas production from D-glucose, and resembles Pantoea agglomerans. All six strains in phenotypic group II, which is positive for indole production and negative for gas production from D-glucose, were identified as Erwinia ananas. Two strains in phenotypic group III, which is negative for indole production and positive for gas production from D-glucose, were identified as Rahnella aquatilis.

Bacterial mutagenicity of terasi and antimutagenicity of Indonesian jasmine tea against terasi.

Terasi, a traditional fermented product of Indonesia was evaluated by Salmonella mutagenesis assay. The higher the heating temperature and the longer the heating time, the more mutagenicity observed in both terasi and its starter, and the highest mutagenic activity was shown by heating each of them at 100 degrees C for 60 min. Terasi starter has stronger mutagenic properties as compared to terasi. Indonesian jasmine tea, which is a yellow tea, was examined for its antimutagenic properties against mutagenic terasi. Tea component presented in fraction C (water soluble, chloroform and ethyl acetate insoluble fraction) as well as in fraction D (water soluble, chloroform, ethyl acetate and n-butanol insoluble fraction) were found to suppress the mutagenicities exerted by heated terasi and heated terasi starter. Yet, the tea components presented in fraction E (chloroform soluble fraction) were found to enhance the mutagenicity of terasi.

The heterocyclic amine binding receptors of Lactobacillus gasseri cells.

Lactobacillus gasseri is a common inhabitant of human intestine. The L. gasseri strains SBT10239 and SBT10241 have shown high antimutagenicity and binding properties with different heterocyclic amines. In order to identify the cell wall components involved in binding with the heterocyclic amines, the cells and cell walls of L. gasseri strains were subjected to different chemical and enzymatical treatments, prior to the binding experiments. The results indicated that the binding receptors for heterocyclic amines are the carbohydrate moieties of the cell wall. Binding of the heterocyclic amines with L. gasseri cell walls and the carbohydrate content showed high correlation coefficient, whereas it was insignificant or negative with protein content. The lectin binding studies revealed that the glucose molecules of the cell wall has a significant role in binding the heterocyclic amines. The inhibition caused by the lectin Concanavalin A was reversed when treated with methyl glucoside, a competitive inhibitor of Concanavalin A and restored the binding of heterocyclic amine with the cells.

Effects of strong pulsed magnetic fields on the cardiac activity of an open chest dog.

The heart of an open chest dog was stimulated by strong magnetic fields which were damped sinusoidal pulses with the one-cycle period of 1.47 ms. Stimulation effects were detected by electrocardiograph (ECG) and arterial blood pressure as a function of the strength of the field, the triggering point in the cardiac cycle, and the position of a stimulating coil. The threshold for arrhythmias was a minimum for the stimuli triggered at the apex of the T wave and on the P wave in the ECG. Premature ventricular and premature atrial contractions occurred according to whether the coil was placed over the ventricles or the atria. Ventricular defibrillation can not be attained by the magnetic stimulus with the flux density of 9.2 T which was the maximum field used.

Desmutagenicity of milk cultured with Lactobacillus acidophilus strains against mutagenic heated tauco.

Desmutagenicity of milk cultured with Lactobacillus acidophilus strains on the mutagenicity of heated salty and sweet tauco were examined using streptomycin dependent (SD) 510 strain of Salmonella typhimurium TA98 as tester culture. Cultured milk samples widely exhibited desmutagenic effects against mutagenic heated salty and sweet tauco. Mutagenicity of heated salty tauco was inhibited by acidophilus cultured milks stronger than that of heated sweet tauco. Milk cultured with strains SBT2054, SBT0299, SBT0274, SBT10238. SBT1702, SBT10240, SBT10241 and SBT10239 showed high inhibition against the mutagenicity of both heated salty and sweet taucos. Maximum inhibition was reached after 24 hr of incubation which corresponded to stationary growth phase. Desmutagenic activities of the acidophilus cultured milks against mutagenic heated tauco were mainly attributed to the bacterial cells and also to casein of milk.

Binding properties of lactic acid bacteria from 'Idly' towards food-borne mutagens.

Lactic acid bacteria from the fermented non-dairy food 'Idly' were examined in vitro for their ability to bind food-borne mutagens. They were subjected to high pressures and temperatures to investigate alterations in their binding potential. All the isolates tested exhibited good binding activity towards the amino acid pyrolysates 3-amino-1-4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-d]indole and a moderate level of binding of 2-amino-6-methyl-dipyrido[1,2-3',2'-d]imidazole. No significant binding activity was observed with other mutagens, such as aflatoxins. High-pressure and heat treatment did not substantially alter the binding activity of the bacteria.

Effects of intraperitoneally administered dietary fibers on superoxide generation from peritoneal exudate macrophages in mice.

To clarify whether edible polysaccharides (dietary fibers) have a host defense stimulating activity, the effects of intraperitoneally administered dietary fiber on the generation of microbicidal superoxide anion (O2-) in mouse peritoneal exudate macrophages (MP) were investigated. MP obtained from mice injected cellulose or pectin generated larger amount of O2- when stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA) or during phagocytosis of opsonized zymosan than those from mice injected proteose peptone, a widely used elicitor for MP. Especially, generated O2- from cellulose-elicited MP was as strikingly large as that from MP elicited by lentinan, a strong antitumor polysaccharide, when stimulated by TPA. Yeast mannan had no effect on O2(-)-generation. These results suggest the possibility that cellulose and pectin may act as host defense stimulators. The augmentation by cellulose or pectin of O2(-)-generation during phagocytosis was not inhibited by the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). However, the augmentation was completely disappeared when the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) was added. These results strongly suggest that the augmentation of O2(-)-generation in phagocytosing MP by cellulose or pectin might be due to the increased activity of PKC in the MP, and that CaM may not be involved in the augmentation.

Dietary restriction augments superoxide generation in mouse peritoneal macrophages: an investigation using a chemiluminescence probe specific for superoxide anion.

It has not been clarified whether dietary restriction alters macrophage functions, although the augmentation of T cell functions by dietary restriction is well known. Forty percent dietary restriction on 9-week-old male C3H/He mice caused a decrease of body weight. However, one of the major macrophage functions, the generation of superoxide anion (O2), was augmented in proteose peptone-elicited peritoneal macrophages (MPs) from diet-restricted mice. This increase was more striking when the cells were stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA), which directly activated protein kinase C, than by opsonized zymosan which binded to receptors on the cells. These results strongly suggest that the augmentation of O2- generation in MPs by dietary restriction is due to the increased activity of protein kinase C which phosphorylate and activate O2-generating enzyme system NADPH oxidase. It is thought that one of the major factors for the reduced incidence of tumor and infection in diet-restricted animals is the augmentation of O2-generation in MPs.

Augmentation of superoxide generation in phagocytosing murine peritoneal macrophages by dietary restriction.

The effects of dietary restriction on the generation of superoxide anion (O2-) in phagocytosing mouse peritoneal macrophages (MPs) were investigated. MPs obtained from diet-restricted mice generated larger amount of O2- during phagocytosis of opsonized zymosan than those from unrestricted mice. This augmentation of the O2- generation was not inhibited by the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). However, the augmentation was clearly disappeared when the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was added. These results strongly suggest that the augmentation of O2- generation in phagocytosing MPs by dietary restriction is due to the increased activity of CaM in the MPs, and that PKC is not involved in the augmentation. It is thought that one of the major factors for the reduced incidence of tumor and infection in diet-restricted animals is the augmentation of O2- generation in MPs.

[Case of hepatocellular carcinoma with a marked reduction in the tumor size induced by PSK administration alone].

A 56-year-old man was admitted to our hospital because of right abdominal pain. The edge of the liver was felt 4.5 fingers breadth below the xiphoid process. AFP was 20100 ng/ml and CEA was 5.6 ng/ml. The chest X-ray indicated existence of lymphangitis and some nodular density suggesting lung metastasis in the both lower-lung fields. 99mTc-phytate liver scan showed a large defect along the antero-inferior margin of the right hepatic lobe, which revealed an abnormal uptake of 67Ga-citrate. Ultrasonograms demonstrated a solid mass, 8 X 9 cm, in the right lobe of the liver. A CT-scan of the abdomen also showed a large, rounded, low attenuation mass with central necrosis in the right hepatic lobe: the pancreas and the remaining retroperitoneal structures appeared normal. Following the administration of PSK alone, 3 g daily, for three months, a remarkable regression of both hepatomegaly and lung metastasis was observed. Liver scan, ultrasonograms and CT-scan showed a striking resolution of the intrahepatic mass except central necrosis. AFP decreased to 33.7 ng/ml and CEA was 8.2 ng/ml. After about one year, however, ultrasonogramms showed a newly growing solid mass, 3.5 X 3.5 cm, in the left lobe of the liver. A needle biopsy specimen was taken from the intrahepatic mass, and it was interpreted as hepatoma. He is now healthy.

Changes in microtubule-related proteins and autophagy in long-term vitamin E-deficient mice.

Vitamin E deficiency induces neuronal dysfunction and while oxidative stress is likely to be involved in mediating this process, the detailed mechanisms remain to be elucidated. Previously, we found axonal degeneration in the hippocampal CA1 region in vitamin E-deficient mice of 6 months of age (long-term). However, 3 month-old (short-term) vitamin E-deficient mice did not exhibit axonal degeneration in same region. In order to characterize the mechanisms involved in axonal degeneration in long-term vitamin E-deficient mice, we examined changes in microtubule-related proteins. Long-term vitamin E-deficiency led to significantly increased expression of the phosphorylated form of collapsin response mediator protein (CRMP)-2 compared to short-term deficiency. It is well known that CRMP-2 plays a crucial role in the maintenance of neurite function. Similarly, long-term vitamin E-deficiency significantly decreased the expression of silent mating type information regulation (SIRT)-2 mRNA compared to short-term deficiency. SIRT-2 belongs to a family of class III histone deacetylases (HDACs) and functions in the deacetylation of tubulins. Furthermore, the expression of microtubule-associated protein light chain (MAP-LC)3-2, which is a key autophagy protein was significantly higher in the short-term vitamin E-deficiency than the long-term deficiency. These results indicate that the mechanisms of axonal injury in long-term vitamin E-deficient mice are related to dysfunction in microtubules assembly via alterations in microtubule-related proteins and autophagy.