Bowel movement frequency, stool consistency, and risk of disabling dementia: a population-based cohort study in Japan.

OBJECTIVES: This population-based study aimed to evaluate the association between bowel habits from midlife and dementia. STUDY DESIGN: This was a cohort study using certification records for national long-term care insurance in Japan. METHODS: Participants aged 50 to 79 years who reported bowel habits from eight districts within the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from 2006 to 2016 for incident dementia. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for men and women separately using Cox proportional hazards models accounting for various lifestyle factors and medical histories. RESULTS: Among 19,396 men and 22,859 women, 1889 men and 2685 women were diagnosed with dementia. In men, the multivariable-adjusted HRs compared with bowel movement frequency (BMF) of once/day were 1.00 (95% CI: 0.87-1.14) for twice/day or more, 1.38 (1.16-1.65) for 5-6 times/week, 1.46 (1.18-1.80) for 3-4 times/week, and 1.79 (1.34-2.39) for <3 times/week (P for trend <0.001). In women, the corresponding HRs were 1.14 (0.998-1.31), 1.03 (0.91-1.17), 1.16 (1.01-1.33), and 1.29 (1.08-1.55) (P for trend = 0.043). Harder stool was associated with higher risk (P for trend: 0.0030 for men and 0.024 for women), with adjusted HRs compared to normal stool of 1.30 (1.08-1.57) for hard stool and 2.18 (1.23-3.85) for very hard stool in men, and 1.15 (1.002-1.32) and 1.84 (1.29-2.63) in women. CONCLUSIONS: Lower BMF and harder stool were each associated with higher risk of dementia.

Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation.

BACKGROUND: MicroRNAs (miRNAs) may facilitate cell-to-cell communication via extracellular vesicles (EVs). The biological roles of miRNAs in EVs on allergic airway inflammation are unclear. METHODS: Airway-secreted EVs (AEVs) were isolated from bronchoalveolar lavage fluid (BALF) of control and house-dust mite (HDM) allergen-exposed HDM-sensitized mice. The expression of miRNAs in AEVs or miRNAs and mRNAs in lung tissue was analysed using miRNA microarray. RESULTS: The amount of AEV increased 8.9-fold in BALF from HDM-exposed mice compared with that from sham-control mice. HDM exposure resulted in significant changes in the expression of 139 miRNAs in EVs and 175 miRNAs in lung tissues, with 54 miRNAs being common in both samples. Expression changes of these 54 miRNAs between miRNAs in AEVs and lung tissues after HDM exposure were inversely correlated. Computational analysis revealed that 31 genes, including IL-13 and IL-5Ra, are putative targets of the miRNAs up-regulated in AEVs but down-regulated in lung tissues after HDM exposure. The amount of AEV in BALF after HDM exposure was diminished by treatment with the sphingomyelinase inhibitor GW4869. The treatment with GW4869 also decreased Th2 cytokines and eosinophil counts in BALFs and reduced eosinophil accumulation in airway walls and mucosa. CONCLUSION: These results indicate that selective sorting of miRNA including Th2 inhibitory miRNAs into AEVs and increase release to the airway after HDM exposure would be involved in the pathogenesis of allergic airway inflammation.

Expression of Periostin in Normal, Atopic, and Nonatopic Chronically Inflamed Canine Skin.

In humans, periostin plays a critical role in the enhancement and chronicity of allergic skin inflammation; however, whether it is involved in the pathogenesis of canine dermatitis remains unknown. The aim of this study was to examine the expression patterns of periostin in healthy, atopic, and nonatopic chronically inflamed canine skin. Biopsy specimens from 47 dogs with skin disease and normal skin tissue from 5 adult beagles were examined by light microscopy, immunohistochemistry, and in situ hybridization. In normal skin, periostin was localized just beneath the epidermis and around the hair follicles. In chronically inflamed skin, periostin expression was most intense in the dermis with inflammatory cell infiltrates. In contrast, low levels of periostin were detected in acutely inflamed and noninflamed skin. Conversely, all canine atopic dermatitis tissues characteristically showed the most intense expression of periostin in the superficial dermis, particularly at the epidermal-dermal junction. In situ hybridization showed that periostin mRNA was broadly expressed in the basal epidermal keratinocytes, outer root sheath cells, and dermal fibroblasts in normal dog skin. High expression of periostin mRNA was observed in fibroblasts in dog skin with chronically inflamed dermatitis. Moreover, in some chronically inflamed skin specimens, periostin mRNA expression was increased in basal keratinocytes. The severity score of chronic pathologic changes and CD3+ cell number in the dermis were correlated with distribution pattern of periostin in the atopic skin. These data suggest that periostin could play a role in the pathophysiology of chronic dermatitis, including atopic dermatitis, in dogs.

Modification of the excess risk of coronary heart disease due to smoking by seafood/fish intake.

Seafood/fish intake has been regarded as a protective factor for coronary heart disease (CHD), while smoking is a strong risk factor. To examine whether associations between smoking and risk of CHD are modified by seafood/fish intake, we studied 72,012 Japanese men and women aged 45-74 years who completed 2 food frequency questionnaires, 5 years apart, during the period 1995-2009. After 878,163 person-years of follow-up, 584 incident cases of CHD (101 fatal and 483 nonfatal), including 516 myocardial infarctions, were documented. There was a clear dose-response association between smoking and CHD risk among subjects with a low seafood/fish intake (<86 g/day) but not among those with a high seafood/fish intake (≥86 g/day). Compared with never smokers, the multivariable hazard ratios in light (1-19 cigarettes/day), moderate (20-29 cigarettes/day), and heavy (≥30 cigarettes/day) smokers were 2.39 (95% confidence interval (CI): 1.60, 3.56), 2.74 (95% CI: 1.90, 3.95), and 3.24 (95% CI: 2.12, 4.95), respectively, among low seafood/fish eaters and 1.13 (95% CI: 0.64, 1.99), 1.29 (95% CI: 0.95, 2.04), and 2.00 (95% CI: 1.18, 3.51), respectively, among high seafood/fish eaters. Compared with heavy smokers with a low seafood/fish intake, light smokers with a high seafood/fish intake had substantially reduced risk of CHD (hazard ratio = 0.57, 95% CI: 0.32, 0.98). High seafood/fish intake attenuated the positive association between smoking and risk of CHD.

Nocturnal intermittent hypoxia and the development of type 2 diabetes: the Circulatory Risk in Communities Study (CIRCS).

AIMS/HYPOTHESIS: Although the associations between obstructive sleep apnoea and type 2 diabetes mellitus have been reported in cross-sectional design studies, findings on the prospective association between the two conditions are limited. We examined prospectively the association between nocturnal intermittent hypoxia as a surrogate marker of obstructive sleep apnoea and risk of type 2 diabetes. METHODS: A total of 4,398 community residents aged 40 to 69 years who had participated in sleep investigation studies between 2001 and 2005 were enrolled. Nocturnal intermittent hypoxia was assessed by pulse-oximetry and defined by the number of oxygen desaturation measurements < or =3% per h, with five to <15 per h corresponding to mild and 15 events or more per h corresponding to moderate-to-severe nocturnal intermittent hypoxia, respectively. The development of type 2 diabetes was defined by: (1) fasting serum glucose > or =7.00 mmol/l (126 mg/dl); (2) non-fasting serum glucose > or =11.1 mmol/l (200 mg/dl); and/or (3) initiation of glucose-lowering medication or insulin therapy. Multivariable model accounted for age, sex, BMI, smoking status, current alcohol intake, community, borderline type 2 diabetes, habitual snoring, excessive daytime sleepiness, sleep duration and (for women) menopausal status. RESULTS: By the end of 2007, 92.2% of participants had been followed up (median follow-up duration [interquartile range] 3.0 [2.9-4.0] years) and 210 persons identified as having developed diabetes. The multivariable-adjusted hazard ratio (95% CI) for developing type 2 diabetes was 1.26 (0.91-1.76) among those with mild nocturnal intermittent hypoxia and 1.69 (1.04-2.76) among those with moderate-to-severe nocturnal intermittent hypoxia (p = 0.03 for trend). CONCLUSIONS/INTERPRETATION: Nocturnal intermittent hypoxia was associated with increased risk of developing type 2 diabetes among middle-aged Japanese.

Cross-cultural comparison of the sleep-disordered breathing prevalence among Americans and Japanese.

The aim of the present study was to compare the prevalence of sleep-disordered breathing among Hispanic and white Americans and Japanese. A 1-night sleep study using a single-channel airflow monitor was performed on 211 Hispanics and 246 Whites from the Minnesota field centre (St Paul, MN, USA) of the Multi-Ethnic Study of Atherosclerosis (MESA), and 978 Japanese from three community-based cohorts of the Circulatory Risk in Communities Study (CIRCS) in Japan. The respiratory disturbance index and sleep-disordered breathing, defined as a respiratory disturbance index of > or =15 events x h(-1), were estimated. The prevalence of sleep-disordered breathing was higher in males (34.2%) than females (14.7%), and among Hispanics (36.5%) and Whites (33.3%) than among Japanese (18.4%), corresponding to differences in body mass index. Within body mass index strata, the race difference in sleep-disordered breathing was attenuated. This was also true when body mass index was adjusted for instead of stratification. The strong association between body mass index and sleep-disordered breathing was similar in Japanese and Americans. The prevalence of sleep-disordered breathing was lower among Japanese than among Americans. However, the association of body mass index with sleep-disordered breathing was strong, and similar among the race/ethnic groups studied. The majority of the race/ethnic difference in sleep-disordered breathing prevalence was explained by a difference in body mass index distribution.

Associations between weight change since 20 years of age and sleep-disordered breathing among male truck drivers.

BACKGROUND: Limited evidence for association of weight gain with sleep-disordered breathing (SDB) has been produced for Asian populations whose body mass index (BMI) levels are lower than in western countries. OBJECTIVE: The aim of this study was to examine weight change since 20 years of age and risk of SDB among Japanese. DESIGN: Retrospective cohort study. SUBJECTS: This study includes a large sample of 5320 male Japanese truck drivers aged 30-69 years. MEASUREMENTS: The respiratory disturbance index (RDI) was selected as an indicator of SDB, and it was estimated with a one-night sleep test using an airflow monitor, and the Epworth Sleepiness Scale (ESS) was used to estimate excessive daytime sleepiness. RESULTS: Respiratory disturbance and sleepiness were more prevalent among men with BMI of 25.0-29.9 and > or =30.0 kg/m(2) than among those with BMI of 18.5-24.9; multivariable odds ratios (ORs) were 1.8(1.5-2.0), P<0.001 and 4.4(3.5-5.5), P<0.001 for RDI > or =10, and 1.2(0.9-1.4), P=0.18 and 1.5(1.1-2.1), P=0.02 for ESS > or =11, respectively. Compared with men showing BMI changes within +/-1.0, the respective multivariable ORs for those with BMI changes of 3.0-4.9 and > or =5.0 were 1.4(1.2-1.6), P<0.001 and 2.4(2.0-2.9), P<0.001 for RDI > or =10, and 1.2(0.9-1.6), P=0.22 and 2.0(1.5-2.6), P<0.001 for ESS > or =11. The corresponding ORs for weight gain of > or =10.0 kg compared with weight change less than +/-5.0 kg were 2.0(1.7-2.4), P<0.001 for RDI > or =10 and 1.5(1.2-2.0), P=0.002 for ESS > or =11. Similar trends were observed for RDI > or =20. CONCLUSION: Our results suggest that an increase in BMI of > or =5 kg/m(2) or weight gain of > or =10 kg is a risk factor for SDB and excessive daytime sleepiness among Japanese truck drivers.

Body mass index and weight change since 20 years of age and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based Study.

BACKGROUND: Obesity and weight gain are associated with increased risk of coronary heart disease in Western countries. However, their impact is not well elucidated in Asia, where body mass index (BMI) levels are generally lower than in Western countries. We examined associations of BMI (kg/m(2)) and weight change with risk of coronary heart disease in Japanese people. METHODS AND RESULTS: A total of 43 235 men and 47 444 women aged 40-69 years living in communities were followed up from 1990 to 2001 in the Japan Public Health Center-based (JPHC) prospective study . During 879 619 person-years of follow-up, we documented 399 cases of coronary heart disease (334 myocardial infarction and 65 sudden cardiac death) for men and 119 (95 myocardial infarction and 24 sudden cardiac death) for women. Compared with persons with BMI 23.0-24.9, men, but not women, with BMI >/=30.0 had higher risk of coronary heart disease and myocardial infarction; the multivariable relative risks for men were 1.8 (1.1-3.0) and 1.9 (1.1-3.2), respectively. When weight change was examined according to BMI at age 20 years, men with initial BMI <21.7 who gained more than 10 kg compared with men of no weight change had a twofold higher risk of coronary heart disease. Both men and women with initial BMI >/=21.7 showed no association between weight loss and the risk. CONCLUSIONS: High BMI was associated with increased risk of coronary heart disease among men. Also, weight gain was associated with increased risk among lean men.

Molecular architecture of the mouse DNA polymerase alpha-primase complex.

The DNA polymerase alpha-primase complex is the only enzyme that provides RNA-DNA primers for chromosomal DNA replication in eukaryotes. Mouse DNA polymerase alpha has been shown to consist of four subunits, p180, p68, p54, and p46. To characterize the domain structures and subunit requirements for the assembly of the complex, we constructed eukaryotic polycistronic cDNA expression plasmids expressing pairwise the four subunits of DNA polymerase alpha. In addition, the constructs contained an internal ribosome entry site derived from poliovirus. The constructs were transfected in different combinations with vectors expressing single subunits to allow the simultaneous expression of three or four of the subunits in cultured mammalian cells. We demonstrate that the carboxyl-terminal region of p180 (residues 1235 to 1465) is essential for its interaction with both p68 and p54-p46 by immunohistochemical analysis and coprecipitation studies with antibodies. Mutations in the putative zinc fingers present in the carboxyl terminus of p180 abolished the interaction with p68 completely, although the mutants were still capable of interacting with p54-p46. Furthermore, the amino-terminal region (residues 1 to 329) and the carboxyl-terminal region (residues 1280 to 1465) were revealed to be dispensable for DNA polymerase activity. Thus, we can divide the p180 subunit into three domains. The first is the amino-terminal domain (residues 1 to 329), which is dispensable for both polymerase activity and subunit assembly. The second is the minimal core domain (residues 330 to 1279), required for polymerase activity. The third is the carboxyl-terminal domain (residues 1280 to 1465), which is dispensable for polymerase activity but required for the interaction with the other three subunits. Taken together, these results allow us to propose the first structural model for the DNA polymerase alpha-primase complex in terms of subunit assembly, domain structure, and stepwise formation at the cellular level.

Activation of the cellular src gene by transducing retrovirus.

Newly isolated strains of avian sarcoma virus, S1 and S2, were shown to have the transduced cellular src gene as their viral transforming gene (Yamagishi et al., Virology 137:266-275, 1984). In this work, the S1 and S2 genomes were molecularly cloned, and the junction sequences between the viral genomes and the c-src genes and the complete nucleotide sequences of the v-src genes transduced in these viruses were determined. Data on the junction sequences suggested that 5' recombination had occurred between the 5'-noncoding region of c-src and the 5' region of the gag sequence encoding p19 in both viruses and that 3' recombination had occurred in the last coding exon of c-src with either the middle portion of the env sequence encoding gp85 for S1 or the 3' portion of pol coding for reverse transcriptase for S2. Comparison of the amino acid sequences of the S1 and S2 src products deduced from the nucleotide sequences (pp62S1-src and pp62S2-src with that of c-src protein (pp60c-src) indicated that in pp62S1-src the 8 carboxy-terminal amino acid residues of the total of 533 in pp60c-src are replaced by 43 residues translated from the env sequence at the wrong frame. In pp62S2-src, on the other hand, the 14 carboxy-terminal amino acids of pp60c-src are replaced by the 38 carboxy-terminal residues of reverse transcriptase. The mechanism of c-src transduction and the structural changes necessary for pp60c-src activation are discussed.

Purification of enzymatically active poliovirus proteinase 3C produced in Escherichia coli.

A viral protein 3C of the poliovirus (PV) Sabin 2 strain, a possible core region of the viral proteinase, was expressed in Escherichia coli using a recombinant DNA technology. The protein was recovered as a soluble protein from the insoluble protein fraction of the bacterial lysate, and was purified by a simple procedure with column chromatography. The viral capsid precursor P1 (1ABCD) of the PV Sabin 3 strain, which had been similarly produced in E. coli, was mixed with the purified or crude recombinant 3C. Immunoblotting assay with monoclonal antibodies specific to capsid proteins 1C (VP3) and 1D (VP1) of the PV Sabin 3 strain revealed that the in vitro reaction products contained 1C (VP3), 1D (VP1) and 1ABC (VP0-VP3). The data indicated that processing of the polyprotein P1 by the recombinant 3C proceeded properly in vitro, although an undigested product, 1ABC, is always detected in the reaction mixture. The results strongly suggest that, in addition to a protein 3CD, the 3C protein itself is also catalytically active in the processing of the viral capsid precursor polyprotein P1.

Prognostic significance of pleural lavage cytology immediately after thoracotomy in patients with lung cancer.

Pleural lavage cytology immediately after thoracotomy was performed in 467 patients with lung cancer who had little or no pleural effusion. Forty-two patients (9.0%) had positive results. The positivity of pleural lavage cytology was significantly related to the degree of pleural extension of the tumor, microscopic pleural dissemination, cytologic results of minimal pleural effusion, pathologic stage, presence of lymphatic permeation or vascular invasion, and cell type (adenocarcinoma was predominant). The 3-year survival of the patients having negative and positive results of cytology were 68.7% and 22.9%, respectively. The prognosis of the group with positive results was as poor as that of patients with stage IIIB or IV disease. Pleural lavage cytology is an important prognostic factor that indicates microscopic exfoliation of cancer cells into the pleural cavity, that is, subclinical malignant pleural effusion.

Development of a new inhibitor of glucosylceramide synthase.

Analogs of the potent inhibitor of glucosylceramide (GlcCer) synthase, D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4), based on substitutions in the palmitoyl group were made by means of a stereo-selective synthetic method in order to elucidate the role of the hydrophobic portion in both the inhibitory action toward the enzyme and the biological effects. While P4 strongly inhibited GlcCer synthase with an IC(50) of 0.5 microM in vitro, it also inhibited cell growth by 50% at the concentration of 7 microM. The shorter N-acyl chain analogs including decanoyl, octanoyl, and hexanoyl groups showed similar IC(50) values for GlcCer synthase (around 2 microM) but the hexanoyl analog exhibited only a slight inhibitory effect on cell growth, showing the dissociation between GlcCer depletion and cell growth. Several compounds which exhibit similar hydrophobicity to the hexanoyl analog of P4 were subsequently designed. We found that D-threo-1-phenyl-2-benzyloxycarbonylamino-3-pyrrolidino-1-pr opanol (PBPP) was a most potent inhibitor, showing an IC50 of 0.3 microM. In cultured cells, PBPP was able to deplete glycosphingolipids without affecting cell growth or the ceramide level.

The mouse putative pheromone receptor was specifically activated by stimulation with male mouse urine.

To detect the biological activity of mammalian putative pheromone receptors (V1Rs and V2Rs), the mouse V1R gene was introduced into a primary culture of vomeronasal cells using the adenovirus expression system, and the response of these cells to mouse urine was analyzed by calcium imaging. These cells specifically responded to male but not female mouse urine. This response was attenuated by pertussis toxin, a specific inhibitor of G-protein G(ialpha)/G(oalpha) coupling from receptors. Our findings indicate that a putative pheromone receptor was specifically activated by mouse urine, a major source of mouse pheromones, and suggest that G(i)/G(o) are functionally coupled with the receptor.

A synthetic ceramide analog (L-PDMP) up-regulates neuronal function.

To address the role of brain gangliosides in synaptic activity, the ceramide analogs, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) and its enantiomer, L-PDMP, were used to inhibit and stimulate ganglioside biosynthesis in cultured cortical neurons. Prolonged treatment with both PDMP isomers exhibited opposite effects on functional synapse formation measured by spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons: suppression by D-PDMP and facilitation by L-PDMP. Up-regulation of synaptic activity by L-PDMP could be correlated with the slow but robust activation of p42 mitogen-activated protein kinase. Treatment with L-PDMP after transient forebrain ischemia in rats ameliorated the deficit of a well-learned spatial memory by an 8-arm maze task, suggesting a new potential therapeutic approach for neurodegenerative disorders.

Predominant expression of Brn-2 in the postmitotic neurons of the developing mouse neocortex.

The expression of Brn-2, a central nervous systems (CNS)-specific POU domain transcription factor, in the developing mouse neocortex was examined with an anti-Brn-2 antibody. Brn-2 protein was first detected in CNS on embryonic day (E) 11.5, and remained strong until E15.5. From E11.5 to postnatal day (P) 0, a high level of Brn-2 expression was observed in the subventricular zone, the intermediate zone, and the outer layer of the neocortex, but not in the ventricular zone. In the double-staining experiments, most of the Brn-2 positive cells were also positive for NCAM-H, an adhesion molecule specific to post-mitotic neurons. Furthermore, BrdU-labeling experiments demonstrated the presence of Brn-2 protein exclusively in postmitotic cells. These results indicated that, in the developing neocortex, Brn-2 expression is up-regulated after the final cell division. Therefore, this transcription factor may be involved in the migration and/or maturation process of the immature neuronal cells.

Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas.

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.

Transcriptional regulatory region of Brn-2 required for its expression in developing olfactory epithelial cells.

Brain-2 is a class III POU transcription factor expressed in developing nervous system. In this study, we have examined the transcriptional regulatory region of Brn-2. Expression of Brn-2 is activated when P19 embryonal carcinoma cells are induced to differentiate into neural cells with retinoic acid (RA). In P19 cells, the 0.5 kb upstream region of Brn-2 was sufficient for the transcriptional activation during RA-induced differentiation. Deletion analysis of the 0.5 kb region located a proximal enhancer (between -422 and -379 with respect to the translational initiation codon), which was essential for the activation. By gel shift assay and methylation interference assay, a specific binding factor was detected that recognized a core sequence GAGCCAAT found within the proximal enhancer. To examine whether the 0.5 kb upstream region can function in embryos, transgenic mice were generated that contained LacZ gene driven by the 0.5 kb upstream region. In these transgenic mice, LacZ was expressed in developing olfactory epithelial cells between embryonic day 12.5 and 14.5. Immunostaining with an anti-Brain-2 antibody demonstrated the expression of Brain-2 in the olfactory epithelium (most likely olfactory receptor neurons) at similar developmental stages. These results suggest that the 0.5 kb upstream region of Brn-2 is sufficient for the expression in the developing olfactory cells and that the DNA binding factor recognizing the proximal enhancer may be involved in the olfactory cell specific expression.

Expression of brain-2 in the developing olfactory bulb.

The expression of Brain-2, a POU domain transcription factor, was examined in the developing olfactory bulb. Brain-2 was expressed mainly in the output neurons, mitral cell and tufted cells in the main olfactory bulb (MOB), and mitral/tufted cells (MT cells) in the accessory olfactory bulb (AOB). It was not expressed in granular cells in either the MOB or the AOB. Our results suggest that Brain-2 was specifically expressed in output neurons but not in interneurons in the developing olfactory bulb. Brain-2 may play a role in the development of these output neurons.

Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding.

Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% Oenothera biennis Linn oil (OBLO, linoleic acid + gamma-linolenic acid) from a wild plant, evening primrose oil (EPO, linoleic acid + gamma-linolenic acid) from a cultivated plant, bio-gamma-linolenic acid oil from mold (BIO, palmitic acid + oleic acid + linoleic acid + gamma-linolenic acid), safflower oil (linoleic acid), palm oil (PLO, palmitic acid + oleic acid + linoleic acid), or soybean oil (linoleic acid + alpha-linolenic acid) with 0.5% cholesterol for 13 wk. Though there were no significant differences in the food intake among the groups, the body weight gain of the OBLO group was significantly lower than that of the other groups except for the BIO and PLO groups, and that of the EPO and SBO groups were the highest among the groups. The liver weight of the OBLO group was significantly lower than that of other groups, and that of the PLO group was the highest among the groups. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL) cholesterol concentrations of the OBLO and EPO groups were consistently lower than those in the other groups. However, those of the BIO group were higher than those in the OBLO and EPO groups. The liver cholesterol concentration of the PLO group was the highest among all groups except for the EPO group. The fecal neutral sterol and bile acid extraction of the BIO group tended to increase compared to the other groups. The results of this study demonstrate that OBLO and EPO inhibit the increasing of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations in the presence of excess cholesterol in the diet compared with the other dietary oils.