Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter

Major depression is conditionally linked to a polymorphism of the human serotonin transporter gene (SLC6A4). During the presentation of aversive, but not pleasant, pictures, healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging. s carriers also showed greater coupling between the amygdala and the ventromedial prefrontal cortex, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression.     

Messungen zum Aggregationsverhalten perfluorierter Alkansäuren

With the use of various techniques an attempt was made to characterize the aggregates that exist in micellar surfactant solutions of salts of the perfluornonanoic acid. The cmc values of the investigated systems were determined by conductivity and surface tension measurements. Conclusions about the shape of the micellar aggregates were drawn from rheologic and electric birefringence measurements. For the lithium, the ammonium and the tetramethylammonium surfactants the existence of normal micelles with spherical shape and with all surfactant ions lying at the micellar surface was found. The perfluornonanoate surfactants with the ammonium counterions that are partially substituted by alkyl groups showed in all investigations a behaviour that was different from the normal case. It was postulated that these solutions contain emulsion-droplet-like giant micelles with the surfactant ions and counterions solubilized as ion pairs in the interior of the micelles. Some of these giant micelles do not have spherical shape; these solutions showed electric birefringence. In most cases the giant micelles disappeared at higher temperatures. Only normal small micelles with spherical symmetry could then be detected and the measured values were again in the range for values of normal C₈-perfluordetergents. On the basis of the investigated systems reasons and models for the formation of giant micelles are discussed.     

Verfahren zur automatischen Messung von Enzymkinetiken

Zusammenfassung Es wird ein neues Verfahren zur automatischen Untersuchung von Enzymkinetiken angegeben. Die Umsatzgeschwindigkeit einer Enzymreaktion in Abhängigkeit von jeweils einer veränderlichen Größe wird hierbei am durchlaufenden Reaktionsgemisch kontinuierlich gemessen und registriert. Unabhängige Veränderliche kann eine Konzentration (z. B. Substrat-, Coenzym-, Wasserstoffionenkonzentration) oder die Temperatur sein. Am Beispiel der Ermittlung einer Aktivitäts-pS-Kurve (Koordinaten:v=Umsatzgeschwindigkeit;pS=negativer Logarithmus der Substratkonzentration) wird das Verfahren im Einzelnen beschrieben. Unsere Methode eignet sich bisher zur Untersuchung von Enzymen, deren Umsatz durch Messung der Lichtabsorption erfaßbar ist. Als Beispiel werden Aktivitäts-pS-Kurven von Lactatdehydrogenase aus menschlichem Herzmuskel- und Leberhomogenisat sowie von Kaninchenmuskel-LDH gezeigt und die ermittelten Michaeliskonstanten angegeben.     

The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.     

Quantitative comparison between two phase contrast techniques: diffraction enhanced imaging and phase propagation imaging

Two x-ray phase contrast imaging techniques are compared in a quantitative way for future mammographic applications: diffraction enhanced imaging (DEI) and phase propagation imaging (PPI). DEI involves, downstream of the sample, an analyser crystal acting as an angular filter for x-rays refracted by the sample. PPI simply uses the propagation (Fresnel diffraction) of the monochromatic and partially coherent x-ray beam over large distances. The information given by the two techniques is assessed by theoretical simulations and compared at the level of the experimental results for different kinds of samples (phantoms and real tissues). The imaging parameters such as the energy, the angular position of the analyser crystal in the DEI case or the sample to detector distance in the PPI case were varied in order to optimize the image quality in terms of contrast, visibility and figure of merit.     

Expression of IL-18 in patients with head and neck squamous cell carcinoma

Interleukin-18 (IL-18), a recently described cytokine secreted mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. The purpose of this study was to determine tissue expression and serum levels of IL-18 in head and neck squamous cell carcinoma (HNSCC) and to evaluate ethanol and endotoxin-driven cytokine secretion. In 24 patients with primary HNSCC and 28 healthy controls, PBMC were isolated and incubated with 50 mM ethanol, LPS (doses 25 ng/ml, 250 ng/ml, 2500 ng/ml) and both agents for 24 h. Levels of IL-18 in serum, and cell supernatants were analysed by capture ELISA, IL-18 tissue level by immunoblotting. Serum levels of IL-8, IL-10 and IL-12, IFN-gamma, and endotoxin plasma levels were also determined. Statistical analysis involved Welch t-test and Page's test for trend. The majority of patients with HNSCC had high concentrations of serum IL-18. The level of IL-18 in the sera of these patients had a mean level of 271.7 pg/ml, while the mean IL-18 serum level in healthy controls was 174,0 pg/ml (p<0.001). Levels of IL-10 and IL-12, IFN-gamma were not increased in patients. Endotoxin was not detectable in either group. LPS stimulated dose-dependently IL-18 secretion from PBMC of patients and controls in vitro (p<0.05). Incubation with ethanol alone did not affect basal IL-18 secretion, but ethanol reduced LPS-stimulated IL-18 secretion compared to LPS stimulation alone. The mRNA expression of IL-18 in unstimulated PBMC and the response of PBMC to ethanol and LPS was similar in patients and controls. Our data on elevated serum levels of IL-18 in the majority of HNSCC cancer patients, irrespective of its biological activity, suggest that serum IL-18 might be a candidate for a new marker for HNSCC. The pathways for IL-18 production and its mechanisms of action in patients with HNSCC remain to be determined. Understanding of the immunological pathways might offer new therapeutic options in head and neck cancer in the future.     

Quantitation of cytomegalovirus (hCMV) DNA and β-actin DNA by duplex real-time fluorescence PCR in solid organ (liver) transplant recipients

Even now rare human cytomegalovirus (hCMV) reactivation is still a life-threatening complication after solid organ transplantation. Although PCR techniques are regarded as the most sensitive detection methods for hCMV, their accuracy and reproducibility are limited. This is a major disadvantage with quantitative PCR assays, which are thought to provide valuable information about hCMV latency or active viral replication in transplant patients. To enhance the diagnostic safety of quantitative hCMV PCR, we developed a duplex real-time fluorescence PCR that is capable of quantifying hCMV DNA and beta-actin DNA as internal control simultaneously within one reaction. By the use of 6-carboxyfluorescein and hexa-chloro-6-carboxyfluorescein as reporter fluorophores and 4-(4'-dimethylamino-phenylazo) benzoic acid as dark quencher dye, hCMV DNA and beta-actin DNA could be quantified in parallel in a wide linear range from 10(1) to 10(7) copies, each. To test the clinical applicability of this approach, we investigated hCMV DNA kinetics in peripheral leukocytes of three hCMV antigen-positive and four antigen-negative patients after liver transplantation, as assessed by intracellular hCMV pp65 alkaline phosphate-anti-alkaline phosphate (APAAP) complex. While all APAAP-negative individuals remained PCR negative, kinetics of HCMV DNA in leukocyte DNA samples of APAAP-positive patients correlated closely with hCMV antigen tests. Here, comparison of separate and simultaneous target quantitation revealed identical results. It is of interest that, while single hCMV antigen positivity is commonly not regarded as a reliable parameter of viral reactivation, in our study a viral load greater than 10(4) copies/2x10(5) beta-actin DNA copies clearly indicated a subsequent increase in APAAP-positive leukocytes. We conclude that with the presented method the reliability of hCMV quantitation via real-time PCR can be substantially increased and may be used to monitor hCMV kinetics in vivo.     

A LISREL 8 model with constrained parameters for twin and adoptive families

Constrained optimization recently has been implemented in the LISREL software package, allowing formulation of parent-offspring transmission models in a simple and efficient manner. A reverse path model of parental transmission is described within the LISREL framework for application to twin and/or adoptive family data. The model incorporates genetic and environmental parameter constraints arising from assortative mating and cultural transmission. An illustration of the LISREL model is given using measures obtained from twins and parents involving fear of social criticism.