Symptomatic hypersomnia due to orexin deficiency in hypothalamic lesions

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and other abnormal manifestations of REM sleep. Recently, it was discovered that the pathophysiology of idiopathic narcolepsy-cataplexy is linked to orexin ligand deficiency in the brain and cerebrospinal fluid. Orexin neurons localize in the posterior hypothalamic area, which was previously described as "waking center" by von Economo in 1920s. Hypersomnia due to orexin ligand deficiency can also occur during the course of other neurological conditions, such as hypothalamic tumor, encephalopathy and demyelinating disorder (i.e. symptomatic hypersomnia). We experienced 8 pediatric cases with symptomatic hypersomnia. These cases were diagnosed as brain tumor (n = 2), head trauma (n = 1), encephalopathy (n = 1), demyelinating disorder (n = 3) and infarction (n = 1). Six pediatric cases with orexin measurements from the literatures were additionally included and total 14 cases were studied. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, a review of the case histories reveals numerous unquestionable cases of symptomatic hypersomnia. In these cases, the occurrences of the hypersomnia run parallel with the rise and fall of the causative diseases. Most of symptomatic hypersomnia cases show both extended nocturnal sleep time and EDS consisting of prolonged sleep episodes of NREM sleep. The features of nocturnal sleep and EDS in symptomatic hypersomnia are more similar to idiopathic hypersomnia than to narcolepsy.     

Interleukin-13 induces goblet cell differentiation in primary cell culture from Guinea pig tracheal epithelium

The Th2 cytokines, interleukin (IL)-4 and IL-13, bind to IL-4Ralpha, and cause goblet cell metaplasia/hyperplasia with increased mucin expression in vivo. However, there is not enough evidence that these cytokines directly induce mucin production in vitro. In this study, primary epithelial cells from guinea pig trachea were cultured at an air-liquid interface, and immediately after achieving confluence at Day 7 they were treated with human recombinant IL-4 or IL-13 for 14 d. IL-13-treated cells consisted of a large number of fully mature goblet cells with a smaller number of ciliated cells. Secretory granules of the goblet cells were positive for both periodic acid-Schiff and toluidine blue, and showed exocytosis. By contrast, IL-4 failed to induce goblet cell differentiation. The electric resistances of IL-13-treated cells were lower than those of IL-4-treated cells and nontreated cells, suggesting leaky epithelia. MUC5AC protein level in cell lysates measured by ELISA was several-fold higher in IL-13-treated cells than in nontreated cells, whereas the level in IL-4-treated cells was not changed. These data suggest that human recombinant IL-13, but not IL-4, can induce differentiation into mature goblet cells that produce MUC5AC protein in guinea pig tracheal epithelial cells in vitro.     

Phosphorylation of three regulatory serines of Tob by Erk1 and Erk2 is required for Ras-mediated cell proliferation and transformation

tob is a member of an emerging family of genes with antiproliferative function. Tob is rapidly phosphorylated at Ser 152, Ser 154, and Ser 164 by Erk1 and Erk2 upon growth-factor stimulation. Oncogenic Ras-induced transformation and growth-factor-induced cell proliferation are efficiently suppressed by mutant Tob that carries alanines but not glutamates, mimicking phosphoserines, at these sites. Wild-type Tob inhibits cell growth when the three serine residues are not phosphorylated but is less inhibitory when the serines are phosphorylated. Because growth of Rb-deficient cells was not affected by Tob, Tob appears to function upstream of Rb. Intriguingly, cyclin D1 expression is elevated in serum-starved tob(-/-) cells. Reintroduction of wild-type Tob and mutant Tob with serine-to-alanine but not to glutamate mutations on the Erk phosphorylation sites in these cells restores the suppression of cyclin D1 expression. Finally, the S-phase population was significantly increased in serum-starved tob(-/-) cells as compared with that in wild-type cells. Thus, Tob inhibits cell growth by suppressing cyclin D1 expression, which is canceled by Erk1- and Erk2-mediated Tob phosphorylation. We propose that Tob is critically involved in the control of early G(1) progression.     

Development of a food-frequency questionnaire to measure the dietary calcium intake of adult Japanese women

Assessing calcium intake is necessary for epidemiological studies on osteoporosis. This study was aimed at developing a valid food frequency questionnaire (FFQ) to estimate the dietary calcium intake of Japanese people. The FFQ contains 26 items, representing common sources of calcium. The respondents, 74 women aged 15 - 79 years living in Fukui city, whose dietary calcium intake was estimated at 638 +/- 306 (S.D.) mg based on a one-day weighted food record kept during the National Nutrition Survey of 1996, were asked to indicate their consumption frequency and usual portion size (large, medium, small) for each food item. Trained dieticians interviewed the subjects to confirm their answers to the FFQs. The mean calcium intake per day according to the FFQ (655 +/- 222 mg) did not differ significantly from that according to the one-day food record. The coefficient of correlation between these methods was 0.512, a statistically significant value. The calcium intake from dairy products showed a good correlation, r = 0.717. The coefficient of correlation between the values estimated based on two FFQ filled out three days apart was 0.900, showing good test-retest reliability. Therefore, this FFQ is valid and reliable in estimating dietary calcium intake for epidemiological studies.     

Effect of orthography on the usage of recognition heuristic

This study examined the effect of orthography (kanji, kana, and alphabet) on the usage of recognition heuristic, in the context of ecological rationality research. Forty-five students participated and performed the task consisted of randomly drawn two-alternative questions about population sizes of the 20 largest Chinese cities, except Beijing and Shanghai. It was found that kanji and kana tasks led to the usage of recognition heuristic more than alphabet task. Furthermore, judgments in kanji and kana tasks were more accurate than in alphabet task. These results suggested that the usage of recognition heuristic was facilitated when it increased judgment accuracy, and that recognition heuristic had ecological rationality.     

Histochemical demonstration of a Na(+)-coupled transporter for short-chain fatty acids (slc5a8) in the intestine and kidney of the mouse

Short-chain fatty acids in the intestinal lumen affect colonic cell proliferation as well as function as an energy source for intestinal epithelial cells. A novel transporter of monocarboxylates, Slc5a8, is expressed abundantly in the colon, where it may participate in the Na(+)-coupled absorption of short-chain fatty acids produced by bacterial fermentation of dietary fiber. The present study examined the cellular localization of Slc5a8 in the murine gastrointestinal tract and kidney by in situ hybridization and immunohistochemistry. The hybridization signals were recognized in the terminal ileum and whole length of the large intestine, and were especially intense in the distal colon and rectum. The immunoreactivity of Slc5a8 was restricted to the striated border (the brush border) of enterocytes, and was not present in goblet cells, Paneth cells, or lamina propria cells. In the kidney, proximal tubules of both the cortex and the outer stripe of the outer medulla intensely expressed Slc5a8 mRNA, while the distal portions, including the loop of Henle, lacked the signals. The renal Slc5a8 immunoreactivity was localized only in the brush border of proximal tubules, not along the basolateral membrane. Thyroid follicular cells were immunoreactive for Slc5a8, with predominant labeling on the apical membrane. No other organs, including the esophagus, stomach, liver, pancreas, and salivary glands contained any notable signals of Slc5a8. These findings on the cellular and subcellular localization of Slc5a8 under normal conditions are helpful for understanding the physiological and pathological roles of Slc5a8.     

RNA expression analysis of a congenital intracranial teratoma

Congenital intracranial tumors are extremely rare and account only for 0.5%-1.5% of brain tumors in children. We report a large intrauterine congenital teratoma in a female fetus at gestation weeks 37, which was diagnosed by detecting the tumor and associated craniomegaly with ultrasonography (US) and magnetic resonance (MR) imaging. The tumor had replaced the cerebral hemispheres and produced prenatal manifestations. Pathologic examination showed an immature teratoma, which was differentiated from all three germ layers. Microarray analysis revealed upregulation of ten genes and downregulation of three genes, as well as upregulation of 41 genes of ribosomal proteins in teratoma cells, compared to normal brain tissue of the patient. The data from the microarray analysis offer not only the potential to help define disease pathogenesis but may also provide clues to identify potential molecular therapeutic targets.     

Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate

PURPOSE: To evaluate the feasibility of using a biodegradable intrascleral implant for intraocular sustained delivery of betamethasone phosphate (BP). METHODS: The intrascleral implant (0.5 mm thick and 4 mm in diameter) was made of poly(DL-lactide) containing 25% betamethasone phosphate. The in vitro release of BP from the implant was evaluated by high-performance liquid chromatography (HPLC). The implants were placed into a scleral pocket in the rabbit's eye. The concentrations of BP in the aqueous humor, vitreous, and retina-choroid were measured by HPLC. The toxicity and biocompatibility of the implant were evaluated by slit lamp examination, electroretinography, and light microscopy. RESULTS: In vitro studies demonstrated that the implants released BP in a biphasic pattern for at least 8 weeks. The BP concentrations in the vitreous and the retina-choroid remained within the concentration range capable of suppressing inflammatory responses for more than 8 weeks. The BP concentration was greater in the retina-choroid than in the vitreous. In the aqueous humor, BP was below the detection limit during the observation period. No significant toxicity to the retina was observed. Also, the implant showed good biocompatibility in the eye. CONCLUSIONS: These results suggest that the intrascleral implant would be a promising system for delivery of steroid to the posterior segment of the eye.     

Demographics,lifestyles, health characteristics,and dietary intake among dietary supplement users in Japan

BACKGROUND: The associations between supplement use and certain demographics, lifestyles, health characteristics, and dietary intakes have not been studied in a large population in non-Western societies. The objective of our study was to investigate the association between supplement use and demographics, lifestyles, health characteristics, and dietary intake in a population-based cohort study in Japan. METHODS: Subjects were the 78 531 participants (45-74 years) who completed a self-administered questionnaire in 1995 or 1998 in a 5-year follow-up survey by the Japan Public Health Center-based prospective Study on cancer and cardiovascular disease. The questionnaire included enquiries about supplement use, occupation, height, weight, smoking, alcohol, physical activity, dietary behaviours, working hours, subjective stress, as well as intakes for 138 foods. RESULTS: The supplement users were likely to have formerly smoked or never smoked. Female supplement users were likely to consume alcohol moderately. The prevalence of users was higher in the elderly, the self-employed, those with lower body mass index, greater physical activity, lower frequency of eating prepared food, higher frequency of eating out, and higher stress level in both sexes after mutual adjustment. Mean intakes of energy and nutrients were lower for users than for non-users. CONCLUSION: The demographics, lifestyles, health characteristics, and dietary intakes may need to be adjusted when evaluating the effect of dietary supplements on disease because they can become potential confounding factors.     

7-hydroperoxycholesterol and oxysterols as indices of oxidative stress: chronic ethanol feeding and rat skeletal muscle

The present study is undertaken to determine if ethanol affects 7-hydroperoxycholesterol or oxysterols in rat skeletal muscle after chronic ethanol feeding. Wistar rats were fed a liquid diet containing ethanol as 35% of total calories. After 6 weeks, soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) skeletal muscles were dissected out. We measured 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH) and 3beta-hydroxycholest-5-en-7-one (7-keto). We found that in response to chronic alcohol feeding, there were significant increases in soleus 7alpha-OH (P=0.0005), 7beta-OH (P=0.0005) and 7-keto (P=0.0007), but in the plantaris, 7beta-OH increased (P=0.0418). Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.