Prostaglandin D synthase (beta-trace) in healthy human sleep

STUDY OBJECTIVES: The prostaglandin D system plays an important role in animal sleep. In humans, alterations in the prostaglandin D system have been found in diseases exhibiting sleep disturbances as a prominent symptom, such as trypanosoma infection, systemic mastocytosis, bacterial meningitis, major depression, or obstructive sleep apnea. Assessment of this system's activity in relation to human physiologic sleep was the target of the present study. DESIGN: Serum concentrations of lipocalin-type prostaglandin D synthase (L-PGDS, former beta-trace), and plasma levels of the pineal hormone melatonin were measured in 20 healthy humans (10 women, 10 men; aged: 23.3 +/- 2.39 years) at 4-hour intervals over a period of 5 days and nights, which included physiologic sleep, rapid eye movement sleep deprivation, and total sleep deprivation. In addition, the serum L-PGDS and plasma melatonin levels of 6 subjects were determined under conditions of bright white (10,000 lux) or dark red light (< 50 lux) in a crossover design during total sleep deprivation. Nocturnal blood sampling was performed by a through-the-wall tube system. L-PGDS was measured by an automated immunonephelometric assay, and melatonin was analyzed by direct radioimmunoassay. RESULTS: Serum L-PGDS concentrations showed marked time-dependent changes with evening increases and the highest values at night (P < .0005). This nocturnal increase was suppressed during total sleep deprivation (P < .05), independent of external light conditions and melatonin secretion. Rapid eye movement sleep deprivation had no impact on circulating L-PGDS levels. CONCLUSIONS: The circadian L-PGDS pattern and its suppression by total sleep deprivation indicate an interaction of the prostaglandin D system and human sleep regulation. L-PGDS measurements may well provide new insights into physiologic and pathologic sleep regulation in humans.     

A set of specific miRNAs is connected with murine and human gastric cancer

MircoRNAs as a new class of regulatory molecules have been investigated in many specific cells and organs in healthy and diseased conditions. Although miRNA signatures can be directly assessed in patients' affected tissues such as tumor sections, recent studies revealed that miRNA profiles can also be obtained indirectly, that is, from the patients' peripheral blood. For better understanding of miRNA's contribution to gastric carcinoma (one of the leading causes of cancer‐related mortality worldwide), we screened for deregulated miRNAs in blood collected from human cancer patients and compared the expression patterns with a gastric carcinoma mouse model (Tff1 knock‐out). The profiles were assessed using species‐specific miRNA microarrays. Among many dozens of deregulated miRNAs (219 in H. sapiens; 75 in M. musculus), a subset of eight miRNAs comparable in sequence from both species was noted. By in silico analysis, their involvement in targeting neoplastic and MAPkinase pathways was demonstrated. We found a high probability of linkage of all noted miRNAs to pathways in cancer with P‐values of 0.013 and 0.018 in mice and humans, respectively. Linkage to the MAPK‐signaling pathway in mice was observed with a P‐value of 0.01. Moreover, when comparing the 219 deregulated miRNAs obtained from blood with deregulated miRNAs derived from gastric cancer (GC) tissues, as published previously, 24 miRNAs were identical. If confirmed in a larger patient pool, these miRNAs could constitute appropriate blood‐born biomarkers for GC. © 2012 Wiley Periodicals, Inc.     

Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level

Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3′-fluorothymidine triphosphate (IC₅₀ 0.63 μM), 2′,3′-dideoxy-3′-fluoroguanosine triphosphate (IC₅₀ 0.71 μM) and 2′,3′-dideoxy-3′-fluorouridine triphosphate (IC₅₀ 2.96 μM). The most efficient 2′,3′-dideoxynucleoside triphosphates were 2′,3′-dideoxycytidine triphosphate (ddCTP; IC₅₀ 1.0 μM), 2′,3′-dideoxyadenosine triphosphate (IC₅₀ 1.6 μM) and 2′,3′-dideoxythymidine triphosphate (IC₅₀ 1.82 μM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3′-fluorothymidine and 2′,3′-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity. Received: 5 April 2000     

Pattern of serum autoantibodies allows accurate distinction between a tumor and pathologies of the same organ

PURPOSE: Recent studies impressively showed the diagnostic potential of seroreactivity patterns for different tumor types, offering the prospect for low-cost screening of numerous tumor types simultaneously. One of the major challenges toward this goal is to prove that seroreactivity profiles do not only allow for identifying a tumor but also allow for distinguishing tumors from other pathologies of the same organ. EXPERIMENTAL DESIGN: We chose glioma as a model system and tested 325 sera (88 glioma, 95 intracranial tumors, 60 other brain pathologies, and 82 healthy controls) for seroreactivity on a panel of 35 antigens. RESULTS: We were able to discriminate between glioma and all other sera with cross-validated specificity of 86.1%, sensitivity of 85.2%, and accuracy of 85.8%. We obtained comparably good results for the separation of glioma versus nontumor brain pathologies and glioma versus other intracranial tumors. CONCLUSION: Our study provides first evidence that seroreactivity patterns allow for an accurate discrimination between a tumor and pathologies of the same organ even between different tumor types of the same organ.     

Innominate artery enlargement in congenital arteriovenous fistula with subsequent tracheal compression and stridor

To demonstrate that airway obstruction may be the first manifestation of a congenital fistula, a female newborn is reported who presented with increasing stridor during her first 23 months of life. Magnetic resonance imaging and Doppler echocardiography revealed an enlarged innominate artery with turbulent flow. Angiography demonstrated an arteriovenous fistula between the right subclavian artery and right subclavian vein and an abnormal origin of the right internal thoracic artery. Bronchoscopy showed a pulsating compression of the middle section of the trachea. Closure and division of the fistula and aortotruncopexy were performed. The stridor disappeared, and there was marked relief of the tracheal obstruction, confirmed by bronchoscopy. It is concluded that, a search for enlarged vessels is necessary in cases of airway obstruction.     

Experiences with the first 100 consecutive pregnancies achieved after in vitro fertilization and embryo transfer at the University Women's Hospital in Erlangen

As of March 31, 1985, 100 clinical pregnancies have been achieved since the program for extracorporeal fertilization was started in Erlangen. 531 (71%) of 768 follicular punctures resulted in an embryo transfer. The overall pregnancy rate is 13% with regard to the total number of laparoscopies and 19% with regard to the number of embryo transfer. The most effective stimulation proved to be the pure hMG regimen. Employing this protocol, we have achieved a clinical pregnancy rate after IVF and ET of 32% during the last 6 months. Oocyte recovery related to the number of patients is 97%, with laparoscopy being superior to ultrasonically guided puncture. The success rate is appreciably affected by both the number of transferred embryos and the atraumatic transfer technique. We question the rationale of supporting the luteal phase.     

Empiric immunization versus serologic screening: developing a cost-effective strategy for the use of hepatitis A immunization in travelers

BACKGROUND: Older individuals and those born overseas are thought at increased risk of prior exposure and thus have naturally acquired immunity to hepatitis A. Whether these individuals or other groups of international travelers should be screened for acquired immunity or empirically immunized is not clear. Hepatitis A serology and risk factor data was obtained prospectively in patients presenting for hepatitis A immunization and used to develop a cost-effective strategy for the use of serologic screening and empiric immunization in our traveler population. METHOD: Candidates for hepatitis A immunization were routinely screened for total hepatitis A serum antibody. Risk factor data including country of birth, travel history, and history of jaundice was collected. Cost-effectiveness was assessed by comparing the cost of serology to screen all patients plus cost to immunize those found to be seronegative with, the cost of empirically immunizing all patients. RESULTS: Analyses were conducted comparing age, travel history, country of birth, and history of jaundice for significance in predicting seropositivity in a group of 115 subjects. Country of birth was statistically a significant predictor of positive results with 80.0% of foreign-born patients positive for total antibody against hepatitis A compared with 35.6% of patients born in the United States. Living outside of the United States (defined as greater than 30 days) was also correlated with a higher prevalence of hepatitis A positive serology. Age was not predictive for the group as a whole. A lower prevalence (24.3%) was noted in the group of US born individuals aged 30 to 60. Travel and prior history of jaundice failed to demonstrate significance. CONCLUSIONS: Employing a simple cost-effectiveness equation using cost of serological testing, cost of vaccine, and prevalence of acquired immunity in the community, a strategy was developed. In our population it was cost-effective to screen all foreign-born individuals and those who had lived outside the United States.     

Disturbed sleep in children with Tourette syndrome: a polysomnographic study

OBJECTIVE: To evaluate objective data on sleep quantity/quality and motor activity during night sleep in children with Tourette syndrome (TS). METHOD: Polysomnography of 17 unmedicated TS children (ages: 7;11-15;5, mean: 11;10 years) without comorbid attention-deficit hyperactivity disorder (ADHD) was compared with 16 age-, sex- and IQ-matched healthy controls. Sleep analyses according to the procedure of Rechtschaffen and Kales were supplemented by counting epochs with short arousal-related movements (相似文献   

Percutaneous coronary intervention in the elderly: procedural success and 1-year outcomes

Clinical trials have found increased morbidity in elderly persons presenting for percutaneous coronary intervention for chronic stable angina. Long-term follow-up is limited for the elderly following percutaneous coronary intervention. The authors reviewed all coronary interventions performed from January 1998 to August 2001. One year following the procedure, subjects were screened for death, need for revascularization, and myocardial infarction. There were 401 subjects aged ≥65years (mean 73.4±6.0years) and 479 subjects aged <65years (mean 55.6±6.7 years). Although there was no difference in 1-year rate of subsequent myocardial infarction or in revascularization, the elderly were more likely to die during hospitalization (4.7% vs. 1.0%, p<0.01), and at 1 year (10.2% vs. 4.0%, p<0.01). When controlled for ejection fraction, age was no longer significant in either predischarge mortality or in 1-year mortality. Excess postpercutaneous coronary intervention mortality in the elderly may be due to underlying comorbidities and not due to subsequent myocardial infarction or revascularization.