Deactivation of Macrophages with Interleukin-4 Is the Key to the Isolation of Tropheryma whippelii

Whipple's disease is a systemic illness caused by a specific agent. Despite recognition of bacteria in lesions, efforts to isolate the causative agent remained futile. A novel strategy was devised to culture Whipple bacilli in deactivated mononuclear phagocytes. Infected tissue was inoculated into human phagocytes deactivated with interleukin (IL)-4, IL-10, and dexamethasone. Within 8-10 days, diastase-resistant periodic acid-Schiff-positive inclusions appeared, corresponding to intact and degenerating bacteria shown to be Tropheryma whippelii by electron microscopy and molecular analyses. T. whippelii was passaged several times in deactivated monocytes and a monoblastic cell line. Time-kinetics growth studies and comparative polymerase chain reaction analysis documented multiplication of T. whippelii in deactivated macrophages. Complementary studies showed that IL-4 rendered phagocytes permissive for T. whippelii, a strong indication that host factors contribute to the pathogenesis of Whipple's disease. The propagation of T. whippelii will permit microbiologic, immunologic, seroepidemiologic, and therapeutic studies of this pathoge

RealExperienceInsight: A smartphone app to conduct survey and experimental research

We introduce RealExperienceInsight (REI), an ambulatory assessment smartphone app platform that will enable behavioral and social scientists to remotely administer experiments and surveys in the field. REI will allow researchers to integrate surveys created in third-party software (e.g., Qualtrics, Unipark) and to collect data from smartphone built-in sensors. It will be possible to schedule surveys and reminders, based on dates/times as well as on events (e.g., after 10,000 steps). REI will be able to collect data from other smartphone apps. REI will be available for Android/iOS and works with an easy-to-use interface and requires no programming from researchers. REI is developed in three stages. First, the outlined app is programmed. Second, external researchers are called in for trial runs (beta stage) to improve REI. Third, we will launch an open call to participate in a project that aims to evaluate and compare REI with conventional methods (e.g., paper-pencil diaries). REI is expected to advance behavioral and social sciences by facilitating the collection of ecologically valid data. REI’s user-friendliness helps to tackle some of the digital and computational challenges currently facing researchers interested in society and human behavior and enables these researchers to engage with computationally demanding methods. While the technical specification with professional app developers has been completed, we are currently raising additional money for the comprehensive app programming. Crowdfunding within the scientific community is scheduled

Influence of the cholinergic agonist RS 86 on normal sleep: sex and age effects

In 36 healthy control subjects (21 females, 15 males; age range 18-65 years; mean age 41.8 years, SD 15.6 years), a bedtime dose of 1.5 mg RS 86, an orally acting cholinergic agonist, shortened rapid eye movement (REM) latency, increased REM sleep, and decreased slow-wave sleep. Six of the subjects (greater than 40 years old) even displayed sleep-onset REM periods after the drug. Results of the present study agree well with those of studies using other cholinomimetics (i.e., physostigmine, arecholine) and confirm the importance of the cholinergic system for REM sleep regulation. Since RS 86 mimicked some of the REM sleep abnormalities specific for patients with depressive disorders, the cholinergic system may play a role in the pathogenesis and pathophysiology of depressive diseases

Small hepatocytes in culture develop polarized transporter expression and differentiation

Rat small hepatocytes have been shown to proliferate in culture and to form organoids with differentiated hepatocytes in vitro. To evaluate the degree of polarized transporter differentiation of rat small hepatocytes during 9 weeks of culturing, we studied the time-dependent expression and subcellular localization of the major bile salt and organic anion transport systems of hepatocytes [i.e. the basolateral sodium-taurocholate co-transporting protein (Ntcp), organic-anion-transporting polypeptide 1b2 (Oatp1b2), the canalicular bile-salt export pump (Bsep) and multidrug-resistance-associated protein 2 (Mrp2)]. Small hepatocytes proliferated and differentiated in culture and formed sharply demarcated colonies as assessed by morphology, alpha-fetoprotein, albumin and Mrp1 expression. Polarized surface transporter expression was evident after 5 weeks of culturing for Ntcp, Oatp1b2 and Mrp2, and after 7 weeks for Bsep. After 9 weeks in culture, the vast majority of matured hepatocytes expressed Ntcp/Oatp1b2 at the basolateral and Bsep/Mrp2 at the canalicular plasma-membrane domains. This polarized transporter expression was accompanied by canalicular secretion of fluorescein-diacetate and cholylglycyl-fluorescein. Furthermore, an anastomizing three-dimensional network of bile canaliculi developed within piling-up colonies. These data demonstrate that cultured rat small hepatocytes acquire a fully differentiated transporter expression phenotype during their development into hepatic 'organoid-like' clusters of mature hepatocytes. Thereby, the time-dependent sequence of transporter expression mirrored the ontogenesis of transporter expression in developing rat liver, supporting the concept that small hepatocytes correspond to the hepatocyte lineage derived from embryonic hepatoblasts and/or from a different pool of 'committed hepatocyte progenitor cells'

Initial REM sleep suppression by clomipramine: a prognostic tool for treatment response in patients with a major depressive disorder

sample of 82 depressed patients, that the amount of rapid eye movement (REM) sleep suppres-sion during the initial 2 nights of treatment with amitriptyline correlated positively with clinical response. Gillin et al. (1978) were able to rep-licate this finding in six depressed patients. From these results, it may be speculated that poly-somnographic measurement of REM sleep in patients during the initial nights of treatment with ~tidepressive drugs may offer the possi-bility of improving drug therapy. Whereas in clinical practice the response to antidepressive medication can only be evaluated after at least 10-14 days of medication (Woggon 1983), the predictive value of REM sleep changes may al-low us to avoid unsuccessful treatment early in the course of therapy. The above-cited studies raise the question of whether or not it is possible to establish the threshold of initial REM sleep suppression ecessary for successful drug ther-apy, thereby providing a substantial differen-tiai-therapeutic tool that could influence the choice of drug or dosage. The aim of the presen

Deactivation of macrophages with interleukin‐4 is the key to the isolation of Tropheryma whippelii

Whipple's disease is a systemic illness caused by a specific agent. Despite recognition of bacteria in lesions, efforts to isolate the causative agent remained futile. A novel strategy was devised to culture Whipple bacilli in deactivated mononuclear phagocytes. Infected tissue was inoculated into human phagocytes deactivated with interleukin (IL)-4, IL-10, and dexamethasone. Within 8-10 days, diastase-resistant periodic acid-Schiff-positive inclusions appeared, corresponding to intact and degenerating bacteria shown to be Tropheryma whippelii by electron microscopy and molecular analyses. T. whippelii was passaged several times in deactivated monocytes and a monoblastic cell line. Time-kinetics growth studies and comparative polymerase chain reaction analysis documented multiplication of T. whippelii in deactivated macrophages. Complementary studies showed that IL-4 rendered phagocytes permissive for T. whippelii, a strong indication that host factors contribute to the pathogenesis of Whipple's disease. The propagation of T. whippelii will permit microbiologic, immunologic, seroepidemiologic, and therapeutic studies of this pathoge