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Narcolepsy is a lifelong, crippling sleep disorder. Although the discovery of the hypocretin system has been a breakthough in genetics, the epidemiological aspects of narcolepsy remain elusive. Ethnic predisposition was suggested to partially account for the 2,500-fold difference in the reported prevalence rates of narcolepsy between Japanese (0.59%) and Israeli Jews (0.00023%). We carried out a general population study, conducting a random telephone survey with a structured questionnaire, which included a validated screening instrument (a Chinese version of the Ullanlinna Narcolepsy Scale). It was followed by clinical-polysomnographic-HLA confirmation of the subjects determined to be positive for narcolepsy based on the questionnaire. Of 9,851 subjects interviewed, 28 subjects (0.28%, 58% female) were screened positive. Ninety percent had a second detailed interview, 64% had HLA typing, and over half of them had a sleep assessment. Only three subjects were found to have genuine narcolepsy. The most common nonnarcolepsy diagnoses were sleep apnea syndrome and sleep-wake schedule disorder. The prevalence rate of narcolepsy in Southern (Hong Kong) Chinese was found to be 0.034% (95% confidence interval = 0.010-0.117%). All available narcoleptic subjects were HLA DRB1-1501 positive and 50% were DQB1-0602 positive. The prevalence rate of narcolepsy among Chinese is comparable to the rates for other populations in studies with stringent epidemiological designs, suggesting that major cross-ethnic differences in the prevalence rates of narcolepsy previously reported likely resulted from methodological limitations.

A primary culture of mouse endometrial epithelium grown on permeable supports was established and the electrogenic ion transport across the endometrial epithelium was studied using the short-circuit current (I(SC)) technique. Enzymatically isolated mouse endometrial cells were immunostained with epithelial cells markers, cytokeratins, indicating an epithelial origin of the culture. Mouse endometrial epithelial cells grown on Millipore filters formed polarized monolayers with junctional complexes as revealed by light and electron microscopy. The cultured monolayers exhibited an average basal I(SC) of 4.6 +/- 0.3 microA/cm2, transepithelial voltage of 2.7 +/- 0.2 mV and transepithelial resistance of 599 +/- 30 omega cm2. The basal current was reduced by 85% in Na+-free solution and 13% in Cl(-)-free solution. The basal current could also be substantially (57.7%) blocked by an apical Na+ channel blocker, amiloride (10 microM), suggesting that Na+ absorption largely contributed to the basal current. Apical addition of Cl- channel blocker, DPC (2 mM), also exhibited an inhibitory effect, 19.4%, on the basal I(SC), indicating minor involvement of Cl- secretion as compared to that of Na+ absorption. The cultured endometrial epithelium also responded to a number of secretagogues including adrenaline and forskolin with increases in the I(SC), which could involve substantial Cl- secretion. The present study has established a culture of mouse endometrial epithelium exhibiting predominantly Na+ absorption under unstimulated condition, and Cl- secretion in response to various secretagogues. This culture may be useful for studying various regulatory mechanisms of electrogenic ion transport across the endometrial epithelium.

Regulation of anion secretion by adrenoceptors in primary culture of mouse endometrial epithelium was investigated using the short circuit current (ISC) technique. Adrenaline stimulated a sustained increase in the ISC in a concentration‐dependent manner. The adrenaline‐induced ISC could be inhibited by pretreatment with diphenylamine 2,2'‐dicarboxylic acid (DPC) or replacement of external Cl− and HCO3−, but not by amiloride or replacement of Na+ in apical solution. The concentration‐dependent responses of the adrenaline‐induced ISC to the CF channel blockers glibenclamide and DPC were examined and exhibited IC50 values of 380 and 960 μm, respectively. The effect of various adrenoceptor agonists on the ISC was examined. The order of potency appeared to be isoprenaline > adrenaline > noradrenaline, while no response was elicited by the α‐adrenoceptor agonist methoxamine, indicating a predominant involvement of β‐adrenoceptors. The β‐adrenoceptor antagonist propranolol was found to be much more effective than the α‐adrenoceptor antagonist phentolamine in inhibiting the ISC responses induced by all adrenoceptor agonists examined. The effect of adrenaline on the ISC was mimicked by an adenylate cyclase activator, forskolin, but suppressed by the adenylate cyclase inhibitor MDL 12,330A, indicating the involvement of cAMP. Our results demonstrate that anion secretion by the mouse endometrial epithelium is regulated by β‐adrenoceptors and involves a cAMP‐dependent mechanism.

In our Southern Chinese narcolepsy series, bi-modal peak pattern of age of onset, excess winter birth and tight association of HLA DQB1*0602 with cataplectic narcolepsy were found.

The uterine fluid composition is largely determined by the absorptive and secretory activities of the endometrial epithelium. The present study explored the cellular mechanisms involved in adrenaline-stimulated anion secretion across the cultured mouse endometrial epithelium using the short-circuit current (ISC) technique in conjunction with transporter inhibitors and channel blockers. Cultured endometrial epithelial monolayers responded to basolateral application of adrenaline with an increase in ISC, which was attributable to both Cl- and HCO3- secretion. When extracellular Cl- or HCO3- was removed, the adrenaline-induced response, as measured by the total charge transfer per unit area, was reduced to 53% and 46%, respectively. When both Cl- and HCO3- were absent from the bathing solutions, the adrenaline-induced response was reduced to only 2% of the response when both ions were present, indicating substantial contribution of Cl- and HCO3- secretion to the adrenaline-stimulated response. Cellular mechanisms, e.g., transporters and ion channels, involved in Cl- or HCO3- secretion were investigated separately. Cl- secretion was found to depend on the activities of basolaterally located Na+-K+-ATPase, Na+-K+-2Cl- cotransporter, and K+ channels, while evidence suggested that HCO3- secretion depends substantially on basolaterally situated Na+-HCO3- cotransporter and Na+-H+ exchanger. Similar to what was seen for Cl- exit, a large portion of HCO3- appeared to exit apically through anion channels. The results indicate that the uterine fluid composition in the mouse may be regulated by adrenaline through stimulation of both Cl- and HCO3- secretion and may be fine-tuned through an elaborate operation of different cellular mechanisms.