Adiponectin--its potential to predict and prevent coronary artery disease.

BACKGROUND: Recent evidence suggests that epicardial adipose tissue may contribute locally to the pathogenesis of coronary artery disease (CAD). We investigated how local and systemic adiponectin, an adipokine with anti-inflammatory and insulin sensitizing properties, is related to the presence of CAD and cardiovascular risk factors. METHODS: Serum and adipose tissue samples from subcutaneous and pericoronary depots were collected from sixty consecutive patients with CAD who required coronary artery bypass grafting or patients without CAD who underwent cardiac surgery for aortic valve replacement. Western blot, ELISA and PCR were used to detect and determine the adiponectin concentrations and expression in the samples. RESULTS: Adiponectin concentrations in the serum and pericoronary fat of patients without CAD were significantly higher than in patients with CAD ( P < 0.01). However, the expression of adiponectin mRNA did not differ in any instances. Male gender, BMI > 30 and type 2 diabetes were significantly correlated to decreased serum adiponectin ( P < 0.03). CONCLUSION: Pericoronary fat specifically secretes metabolically active adiponectin. Its local and systemic concentrations are inversely correlated to the presence of coronary artery disease, indicating its anti-atherogenic effects. As for patients with CAD, adiponectin might be a promising marker for intra-individual monitoring of cardiovascular risk factors and thus a course of secondary prevention. Further evaluation is necessary to elucidate whether a novel therapeutic option could be derived against the onset and progression of CAD.

Emission spectroscopy of negative hydrogen ion sources: From VUV to IR.

The target parameters of negative ion sources regarding the current of extracted negative ions, the current of co-extracted electrons, the pulse duration, the duty cycle, and the availability of the system can be rather strict. Knowledge of plasma parameters such as the electron temperature and the electron density and also properties of molecules or photon fluxes can provide essential insights into the ion source physics needed for reaching the target parameters. Emission spectroscopy is a non-invasive tool enabling access to line-of-sight averaged values of plasma parameters. This paper gives an overview of the application of emission spectroscopy in the visible range, extended for long wavelengths to the near-IR and for short wavelengths to the vacuum ultraviolet (VUV)/UV range. The amount of information to be gained from measured emission spectra is directly correlated with the effort invested for calibrating the system. Examples are given, ranging from simple monitoring to the complex evaluation of molecular spectra and the determination of highly energetic photon fluxes in the VUV/UV range. Additional emphasis is laid on the population models needed for the interpretation of measured spectra.

Three-dimensional flow-through protein platform.

We have developed a new protein microarray (ImmunoFlow Protein Platform, IFPP) that utilizes a porous nitrocellulose (NC) membrane with printed spots of capture probes. The sample is pumped actively through the NC membrane, to enhance binding efficiency and introduce stringency. Compared to protein microarrays assayed with the conventional incubation-shaking method the rate of binding is enhanced on the IFPP by at least a factor of 10, so that the total assay time can be reduced drastically without compromising sensitivity. Similarly, the sensitivity can be improved. We demonstrate the detection of 1 pM of C-reactive protein (CRP) in 70 microL of plasma within a total assay time of 7 min. The small sample and reagent volumes, combined with the speed of the assay, make our IFPP also well-suited for a point-of-care/near-patient setting. The potential clinical application of the IFPP is demonstrated by validating CRP detection both in human plasma and serum samples against standard clinical laboratory methods.

Rate of formation of the ClO dimer in the polar stratosphere: implications for ozone loss.

The gas-phase recombination of chlorine monoxide (ClO) has been investigated under the conditions of pressure and temperature that prevail in the Antarctic stratosphere during the period of maximum ozone (O3) disappearance. Measured rate constants are less than one-half as great as the previously accepted values. One-dimensional model calculations based on the new rate data indicate that currently accepted chemical mechanisms can quantitatively account for the observed O3 losses in late spring (17 September to 7 October). A qualitative assessment indicates that the existing mechanisms can only account for at most one-half of the measured O3 depletion in the early spring (28 August to 17 September), indicating that there may be additional catalytic cycles, besides those currently recognized, that destroy O3.

Chronic atrial fibrillation: decreased actin expression in patients with chronic atrial fibrillation.

AIM: Chronic atrial fibrillation (AF) is characterized by a severe contractile dysfunction and myolysis, which develops progressively. Myolysis and the remodelling of the cellular ultrastructure is associated with the replacement of sarcomeres by glycogen. The aim of our study was to determine if myolysis is characterized by a reduction in actin concentration. METHODS: Right atrial samples from 18 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen. Eight patients had chronic AF (>3 months) and 10 patients were in sinus rhythm (SR). Actin concentration was determined by sodium dodecyl sulfate-polycrylamide gel electrophoresis (SDS-PAGE), Western blot and quantified by optical densitometry. RESULTS: Immunoblot analysis demonstrated actin expression in all hearts. In myocardial samples from patients with chronic AF we found a 2.1 fold reduction in actin expression. (P<0.001) CONCLUSION: The decrease in actin concentration via myolysis, might decrease energy consumption and be an additional mechanism for contractile dysfunction in chronic AF.

Disruption of the FA/BRCA pathway in bladder cancer.

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression.

Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene.

Primary fibroblasts from patients with the genetic disease Fanconi anemia, which are hypersensitive to cross-linking agents, were used to screen a cDNA library for sequences involved in their abnormal cellular response to a cross-linking challenge. By using library partition and microinjection of in vitro-transcribed RNA, a cDNA clone, pSPHAR (S-phase response), which is able to correct the permanent repression of semiconservative DNA synthesis rates characteristic of these cells, was isolated. Wild-type SPHAR mRNA is expressed in all fibroblasts so far analyzed, including those of Fanconi anemia patients. Correction of the abnormal response in these cells appears therefore to be due to overexpression after cDNA transfer rather than to genetic complementation. The cDNA contains an open reading frame coding for a polypeptide of 7.5 kDa. Rabbit antiserum directed against a SPHAR peptide detects a protein of 7.9 kDa in Western blots (immunoblots) of whole-cell extracts from proliferating, but not resting, fibroblasts. The deduced amino acid sequence of SPHAR contains a motif found in the cyclins, and it is proposed that SPHAR acts within the injected cell by interfering with the cyclin-controlled maintenance of S phase. In agreement with this proposal, normal cells transfected with an antisense SPHAR expression vector have a significantly reduced rate of DNA synthesis during S phase and a prolonged G2 phase, reflecting the need for postreplicative DNA processing before entry into mitosis.

Enhancing the accuracy of the Fowler method for monitoring non-constant work functions.

The Fowler method is a prominent non-invasive technique to determine the absolute work function of a surface based on the photoelectric effect. The evaluation procedure relies on the correlation of the photocurrent with the incident photon energy hν which is mainly dependent on the surface work function χ. Applying Fowler's theory of the photocurrent, the measurements can be fitted by the theoretical curve near the threshold hν⪆χ yielding the work function χ and a parameter A. The straightforward experimental implementation of the Fowler method is to use several particular photon energies, e.g. via interference filters. However, with a realization like that the restriction hν ≈ χ can easily be violated, especially when the work function of the material is decreasing during the measurements as, for instance, with coating or adsorption processes. This can lead to an overestimation of the evaluated work function value of typically some 0.1 eV, reaching up to more than 0.5 eV in an unfavorable case. A detailed analysis of the Fowler theory now reveals the background of that effect and shows that the fit-parameter A can be used to assess the accuracy of the determined value of χ conveniently during the measurements. Moreover, a scheme is introduced to quantify a potential overestimation and to perform a correction to χ to a certain extent. The issues are demonstrated exemplarily at the monitoring of the work function reduction of a stainless steel sample surface due to caesiation.

Inhibition of inducible nitric oxide synthesis by oxidized lipoprotein(a) in a murine macrophage cell line.

Increased plasma levels of human lipoprotein(a) (Lp(a)) are highly correlated with the development of atherosclerotic lesions. During our study, we investigated the effects of native and hypochlorite oxidized lipoprotein(a) (ox-Lp(a)) on nitric oxide production by the inducible nitric oxide synthase (iNOS) in lipopolysaccharide/interferon stimulated mouse macrophages (J774A.1). Ox-Lp(a) (0-2 microg/ml) induces a dose dependent inhibition of inducible nitric oxide synthesis. iNOS protein expression showed a dose dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of ox-Lp(a). Ox-Lp(a) decreases iNOS mRNA synthesis as shown by reverse transcription-polymerase chain reaction. Ox-Lp(a) induced iNOS inhibition might contribute to the development of atherosclerotic lesions by reducing the anti-atherogenic effects of nitric oxide.

Stimulation of nitric oxide synthesis by the aqueous extract of Panax ginseng root in RAW 264.7 cells.

1. In this study, we investigated the effect of Panax ginseng root aqueous extracts upon inducible nitric oxide synthesis in RAW 264.7 cells. Panax ginseng root extract has been used in the Asian world for centuries as a traditional herb to enhance physical strength and resistance and is becoming more and more popular in Europe and North America. 2. Incubation of murine macrophages (RAW 264.7 cells) with increasing amounts of aqueous extracts of Panax ginseng (0.05 - 0.8 microg microl(-1)) showed a dose dependent stimulation of inducible nitric oxide synthesis. 3. Polysaccharides isolated from Panax ginseng showed strong stimulation of inducible nitric oxide synthesis, whereas a triterpene-enriched fraction from an aqueous extract of Panax ginseng did not show any stimulation. 4. Inducible nitric oxide synthase protein expression was enhanced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of Panax ginseng extract. This was associated with an incline in inducible nitric oxide synthase mRNA-levels as determined by semiquantitative polymerase chain reaction and electromobility shift assay studies indicated enhanced nuclear factor-kappaB DNA binding activity. 5. As nitric oxide plays an important role in immune function, Panax ginseng treatment could modulate several aspects of host defense mechanisms due to stimulation of the inducible nitric oxide synthase.

Endocarditis after nipple piercing in a patient with a bicuspid aortic valve.

Piercing the skin for cosmetic reasons can be dangerous in young adults who have previously undergone surgery for congenital defects of the heart. We report the case of a 24-year-old man in whom coarctation of the aorta had been corrected 15 years earlier. Two months after piercing his left nipple without antibiotic prophylaxis, he developed a local mastitis, followed by bacterial endocarditits that required replacement of the aortic valve.

Testosterone inhibits expression of inducible nitric oxide synthase in murine macrophages.

We investigated the effect of testosterone, the main sexual steroid hormone in men, upon inducible nitric oxide synthesis in murine macrophages. Incubation of murine macrophages (RAW 264.7 cells) stimulated by bacterial lipopolysaccharide (2 microg/ml) with increasing amounts of testosterone (0.1-40 microM) showed a dose dependent inhibition of inducible nitric oxide synthesis. Inducible nitric oxide synthase protein expression was reduced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of testosterone. This was associated with a decline in iNOS mRNA-levels as determined by competitive semiquantitative PCR. As nitric oxide plays an important role in immune defense and atherosclerosis prevention, testosterone-induced iNOS inhibition could lead to an elevated risk of infection as well as to the development of atherosclerotic lesions.

Modulation of the spontaneous G2 phase blockage in Fanconi anemia cells by caffeine: differences from cells arrested by X-irradiation.

The effect of caffeine on the endogenous G2 phase cell cycle blockage of Fanconi anemia (FA) cells was compared with the effect of caffeine on the G2 phase blockage induced in control cells by X-irradiation. The G2 phase accumulations in FA cells could be completely resolved by exposure to 1.5 mM caffeine. This was also observed in three brothers with endogenous G2 phase blockage due to unusual BrdU sensitivity. In contrast, G2 phase blockage induced by X-irradiation was only partially resolved by exposure to caffeine. The rescued G2 phase cells from FA patients were arrested within the following G1 phase compartments. This was not seen in X-irradiated cells from control donors. These results point towards a different nature and/or repair mechanism of the endogenous G2 phase lesion in FA cells compared to that induced by X-irradiation in control cells.

The CardioOP-Data Clas (CDC). Development and application of a thesaurus for content management and multi-user teleteaching in cardiac surgery.

OBJECTIVES: Self-directed and customized medical education programs are gaining importance in health care instruction. We prototypically implemented a repository-driven online computer system (CardioOP) for teleteaching in Heart Surgery. It supports authoring and multiple re-use of multimedia data for different user groups in different instructional applications and therefore requires a process of content management. METHODS: We defined objectives for a terminological system to support semantic, cross-media type annotation and retrieval of learning objects: domain completeness, German (natural) language processing, multi-user concepts, extensibility and maintenance, content based annotation and technical implementation. Existing terminologies (ICD10, READ V3, Snomed III, UMLS 1997, MESH) have been analysed according to these objectives. RESULTS: We found that the analysed terminologies did not meet our criteria sufficiently. Therefore, we developed a domain-specific thesaurus, the CardioOP-DataClas (CDC). The application of the CDC within a database-driven authoring process using specifically developed tools is reported. CONCLUSIONS: Metadata play an important role in the effective discovery and search, access, integration and management of educational multimedia data in medicine but so far, there is no terminology to support content management for instructional multimedia. We prototypically designed and applied a thesaurus for the CardioOP educational system. Additional work is needed to evaluate the system in terms of user-friend-liness, concept coverage and information retrieval performance.

Cytotoxic and genotoxic effects of paclitaxel (Taxol) and radiation in a squamous cell carcinoma cell line of the larynx.

Paclitaxel (Taxol) is an antimicrotubular agent which blocks the cells in the G2/M phase of the cell cycle. Because of this mechanism it is presumed that this drug could function as a radiation sensitizer. The cytotoxic and genotoxic effects of paclitaxel and a combination of paclitaxel and radiation were studied in the human laryngeal carcinoma cell line HLac 79. The growth of the cells was significantly reduced at concentrations of paclitaxel as low as 10 nM. Flow cytometry data showed a G2/M block after exposure to paclitaxel. Radiation at 12 and 24 h after drug treatment exerted an additive but no radiation sensitizing effect. As genotoxic effect paclitaxel induced multinucleated cells, possibly in a synergistic manner, at low concentrations (10 nM) and radiation doses up to 3 Gy.

[LaMedica. The medical education academy on the internet]. / LaMedica. Die medizinische Lernakademie im Internet.

At present, "modern media" are still a novelty in medical education. The "LaMedica Project"--a program supported by the Federal Ministry for Education and Research--intends to provide an Internet-based education and training system for the entire field of medicine, using all available media resources. This online educational program will provide subjects for medical laypersons as well as medical experts. Various styles of learning and different learning requests will be promoted. The project presented mirrors the cutting edge of database technology, computer-based training and media didactics, critical content processing as well as supplying individual subjects. This report summarizes our 10 months of experience with this program at the Department for Urology and Pediatric Urology of the Johann Wolfgang Goethe University of Frankfurt Main.

[A case-based and multi-media computer learning program on the topic of myocardial infarct, angina pectoris and mitral valve stenosis]. / Ein fallbasiertes, interaktives und multimediales Computerlernprogramm zum Thema Herzinfarkt, Angina pectoris und Mitralstenose.

BACKGROUND: Principles in the field of cognitive psychology and problem-based learning together with recent progress in multimedia technologies are providing the basis for the development of case-based and computer-assisted learning systems. With reference to the information-overload of theoretical and factual knowledge in medical education these programs can be an efficient tool to satisfy the current need for new, practical, skill-related forms of knowledge transfer. METHODS: Apple-Macintosh Computers were selected to develop interactive, multimedia patient-simulations on mitral stenosis, angina pectoris and myocardial infarction. INSTRUCTIONAL AIM AND CONTENTS: The user acquires knowledge and skills about the leading symptoms, differential diagnoses, the use and analysis of laboratory examinations and the process of diagnostic reasoning while working through the computer-simulated cases. PEDAGOGICAL DESIGN AND CONCLUSION: Important pedagogical principles associated with computer-assisted learning were employed in the program. Clinical situations can be simulated repeatedly and for every student in an authentic manner. Therefore the program can serve as a preparation for and a supplement to practical clinical education. Compared to conventional teaching media the development of instructional multimedia software requires a tremendous amount of time and resources. Thus, controlled studies are important to objectify the overall advantages such programs can have.

CardioOp: an integrated approach to teleteaching in cardiac surgery.

INTRODUCTION/PURPOSE: The complexity of cardiac surgery requires continuous training, education and information addressing different individuals: physicians (cardiac surgeons, residents, anaesthesiologists, cardiologists), medical students, perfusionists and patients. Efficacy and efficiency of education and training will likely be improved by the use of multimedia information systems. Nevertheless, computer-based education is facing some serious disadvantages: 1) multimedia productions require tremendous financial and time resources; 2) the obtained multimedia data are only usable for one specific target user group in one specific instructional context; 3) computer based learning programs often show deficiencies in the support of individual learning styles and in providing individual information adjusted to the learner's individual needs. In this paper we describe a computer-system, providing multiple re-use of multimedia-data in different instructional sceneries and providing flexible composition of content to different target user groups. TOOLS AND METHODS: The ZYX document model has been developed, allowing the modelling and flexible on-the-fly composition of multimedia fragments. It has been implemented as a DataBlade module into the object-relational database system Informix Dynamic Server and allows for presentation-neutral storage of multimedia content from the application domain, delivery and presentation of multimedia material, content based retrieval, re-use and composition of multimedia material for different instructional settings. Multimedia data stored in the repository, that can be processed and authored in terms of our identified needs is created by using a next generation authoring environment called CardioOP-Wizard. High-quality intra-operative video is recorded using a video-robot. Difficult surgical procedures are visualized with generic and CT-based 3D-animations. RESULTS: An on-line architecture for multiple re-use and flexible composition of media data has been established. The system contains the following instructional applications (prototypically implemented): a multimedia textbook on operative techniques, an interactive module for problem based-training, a module for creation and presentation of lectures and a module for patient information. Principles of cognitive psychology and knowledge management have been employed in the program. These instructional applications provide information ranging from basic knowledge at the beginner's level, procedural knowledge for the advanced level to implicit knowledge for the professional level. For media-annotation with meta-data a metainformation system, the CardioOP-Clas has been developed. The prototype focuses on aortocoronary bypass grafting and heart transplantation. CONCLUSION: The demonstrated system reflects an integrated approach in terms of information technology and teaching by means of multiple re-use and composition of stored media-items to the individual user and the chosen educational setting on different instructional levels.

Fundamental studies on the Cs dynamics under ion source conditions.

The performance of surface conversion based negative hydrogen ion sources is mainly determined by the caesium dynamics. Therefore, fundamental investigations in vacuum and plasma are performed at a flexible laboratory setup with ion source parameters. Studies on the influence of Cs on the plasma parameters of H2 and D2 plasmas showed that ne and Te in the bulk plasma are not affected by relevant amounts of Cs and no isotopic differences could be observed. The coating of the vessel surfaces with Cs, however, leads to a considerable gettering of hydrogen atoms from the plasma volume and to the decrease of ne close to a sample surface due to the formation of negative ions.

Controllable evaporation of cesium from a dispenser oven.

This instrument allows controlled evaporation of the alkali metal cesium over a wide range of evaporation rates. The oven has three unique features. The first is an alkali metal reservoir that uses a dispenser as a cesium source. The heating current of the dispenser controls the evaporation rate allowing generation of an adjustable and stable flow of pure cesium. The second is a blocking valve, which is fully metallic as is the body of the oven. This construction both reduces contamination of the dispenser and enables the oven to be operated up to 300 °C, with only small temperature variations (<5 °C). By minimizing the temperature variation, the built up of the alkali metal at a cold spot is significantly hindered. The last feature is an integral surface ionization detector for measuring and controlling the evaporation rate. The dispenser oven can be easily transferred to the other alkali-metals.