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Biomedical subjects

B Breyer

Publications and source records attributed to B Breyer.

At least 19 recordsLinked to original sources
PubMed2002

Fluorescence-based functional assay for Wnt/beta-catenin signaling activity.

Aberrant activation of beta-catenin signaling has been implicated in the development of human cancers. As a Wnt signal transducer, beta-catenin forms a complex with the lymphocyte enhancer-binding factor/T cell factor transcription factor and activates downstream targets that promote cell proliferation. Here we developed a Wnt-dependent beta-catenin-mediated heterologous transactivation system, which consisted of a chimeric transcription factor constructed by fusing the GAL4 DNA-binding domain with the full-length beta-catenin, and a GAL4-responsive reporter expressing GFP. The chimeric transcription factor was highly unstable and exerted no detectable transactivating effect on the GAL4-responsive reporter. However, lithium and Wnt1 significantly stabilized this chimeric transactivator, indicating that this transactivation system is regulated by beta-catenin in a Wnt-responsive fashion. Thus, this transactivation system could be used as a functional reporter to identify potential upstream factors that deregulate beta-catenin signaling during tumorigenesis, as well as to screen for potential anti-cancer agents that specifically inhibit beta-catenin signaling in human tumors.

Adenocarcinoma↗
PubMed2001

Tetracycline-regulated gene expression mediated by a novel chimeric repressor that recruits histone deacetylases in mammalian cells.

Regulated gene expression will provide important platforms from which gene functions can be investigated and safer means of gene therapy may be developed. Histone deacetylases have recently been shown to play an important role in regulating gene expression. Here we investigated whether a more tightly controlled expression could be achieved by using a novel chimeric repressor that recruits histone deacetylases to a tetracycline-responsive promoter. This chimeric repressor was engineered by fusing the tetracycline repressor (TetR) with an mSin3-interacting domain of human Mad1 and was shown to bind the tetO(2) element with high affinity, and its binding was efficiently abrogated by doxycycline. The chimeric repressor was shown to directly interact with mSin3 of the histone deacetylase complex. This inducible system was further simplified by using a single vector that contained both a chimeric repressor expression cassette and a tetracycline-responsive promoter. When transiently introduced into mammalian cells, the chimeric repressor system exhibited a significantly lower basal level of luciferase activity (up to 25-fold) than that of the TetR control. When stably transfected into HEK 293 cells, the chimeric repressor system was shown to exert a tight control of green fluorescent protein expression in a doxycycline dose- and time-dependent fashion. Therefore, this novel chimeric repressor provides an effective means for more tightly regulated gene expression, and the simplified inducible system may be used for a broad range of basic and clinical studies.

Base Sequence↗
PubMed2001

Peroxisome proliferator-activated receptors: roles in tumorigenesis and chemoprevention in human cancer.

Peroxisome proliferator-activated receptors are nuclear receptors that were isolated for their ability to modulate lipid metabolism. Similar to other members of the nuclear receptor family, peroxisome proliferator-activated receptors bind ligand as heterodimers and exert their effects via transcriptional regulation through their DNA binding domains. During the past decade, it has become clear that peroxisome proliferator-activated receptors also contribute to a variety of different biologic processes, including atherosclerosis, insulin resistance, and more recently, cancer. In this review, we discuss the evidence for the different peroxisome proliferator-activated receptors' roles in tumorigenesis and also their potential application for the treatment and prevention of neoplastic diseases.

Adenomatous Polyposis Coli↗
PubMed2001

Adenoviral vector-mediated gene transfer for human gene therapy.

Human gene therapy promises to change the practice of medicine by treating the causes of disease rather than the symptoms. Since the first clinical trial made its debut ten years ago, there are over 400 approved protocols in the United States alone, most of which have failed to show convincing data of clinical efficacy. This setback is largely due to the lack of efficient and adequate gene transfer vehicles. With the recent progress in elucidating the molecular mechanisms of human diseases and the imminent arrival of the post genomic era, there are increasing numbers of therapeutic genes or targets that are available for gene therapy. Therefore, the urgency and need for efficacious gene therapies are greater than ever. Clearly, the current fundamental obstacle is to develop delivery vectors that exhibit high efficacy and specificity of gene transfer. Recombinant adenoviruses have provided a versatile system for gene expression studies and therapeutic applications. Of late, there has been a remarkable increase in adenoviral vector-based clinical trials. Recent endeavors in the development of recombinant adenoviral vectors have focused on modification of virus tropism, accommodation of larger genes, increase in stability and control of transgene expression, and down-modulation of host immune responses. These modifications and continued improvements in adenoviral vectors will provide a great opportunity for human gene therapy to live up to its enormous potential in the second decade.

Adenoviridae↗
PubMed1995

Glycoprotein and ganglioside changes in human trophoblasts after exposure to pulsed Doppler ultrasound.

Changes in glycoprotein and ganglioside composition in human trophoblasts (eighth week of gestation) after in vitro exposure to pulsed Doppler ultrasound (pulse duration 1.22 microseconds; repetition frequency 11.1 kHz; center frequency 4 MHz; ISPPA = 175.5 W/cm2; ISPTA = 0.59 W/cm2) were investigated. Evacuated trophoblasts were divided in two halves and insonated for 10 min on top of a 6-cm layer of 5% gelatin in 50-mL tubes (Falcon) at 37 degrees C. One half of each trophoblast was sham insonated and served as an internal control. After insonation trophoblasts were maintained at 37 degrees C for 24 h. Glycoproteins were detected using alpha-D-mannose specific lectins from Galanthus nivalis and Narcissus pseudonarcissus. A decrease in the expression of mannose containing glycoprotein mgp47 and an increase in expression of mgp54 were observed. Ganglioside composition was also significantly altered. Concentrations of two gangliosides migrating similarly to GM2, and one similarly to GQ1, decreased by more than 75%. At the same time, concentrations of one ganglioside migrating similarly to GM3, and two other unidentified gangliosides increased two- to fourfold.

Chromatography, Thin Layer↗
PubMed1993

Characteristics of blood flow in cancer of the uterine cervix.

Blood flow characteristics were measured in patients with histologically proved cervical cancer and compared to normal values. Flow parameters were derived by color and pulsed Doppler ultrasound. The results showed a significant difference in the mean values of resistance index and pulsatility index among the diseased patients and healthy controls. However, the method does not have the required sensitivity for screening purposes, so that its value may mainly be in the follow-up of patients treated conservatively with radiation and chemotherapy.

Journal Article↗
PubMed1991

Possibilities of ultrasound catheters.

Ultrasound catheters offer the possibility of various non-imaging applications. Some of these applications, now in different stages of development, have been studied and will be described here in some detail. Ultrasonically marked catheters have different applications. The catheter has a miniature marker transducer mounted at the tip or some other place of interest. Initially, this device was used to localize the pacing lead tip in the heart. Connected to a transponder of a passive type this device can generate a visible localization mark on the echograph screen. The basically same system can be used for early detection of cracking of the pacing lead insulation. In this case the marker transducer works as a high-frequency signal generator and detects characteristic capacitance changes better than other methods. The electronic circuit for measurement is built into the pacemaker. Other non-imaging applications have also been studied. The marker transducer can be used for echo ranging of the distance between a His bundle fulguration electrode and the structure to be destroyed. Such an automatic 'proximity fuse' can help to avoid the firing of energy at too great a distance from the His bundle. Technology of implantable defibrillators yields the possibility for a double transducer arrangement, one transducer mounted at the patch and the other being the marker transducer. Using on-line distance measurement this arrangement enables early detection of abnormal movement of the ventricle wall, thus detecting deterioration of the muscle function before it is electrically evident. The measurement was simulated in-vitro. Measurement of axial blood flow using transit time methods, instead of Doppler, was also experimentally studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1989

Properties of ultrasonically marked leads.

We have developed an ultrasonic marking system for pacing leads and the electrophysiological study of catheters. The aim of this study was to evaluate the accuracy of our system, its usability in the measurement of performance of implanted leads, and to investigate the potential of electrical shock and ultrasonic hazard. The measurements have shown that different applications require specific electronic design, involving some compromise between accuracy and sensitivity. A higher sensitivity at the beginning of the ultrasonically guided cardiac lead implantation yields poorer accuracy. Quantitative measurements show that accuracy can be subsequently improved by reduction of sensitivity of the marking system. The transponder marking circuit is better suited for general use and the passive electronic circuit is better suited for multiple electrode electrophysiological studies. Experiments concerning electrical safety show that in the worst failure case, the energy of the marking system released within the heart is less than 10(-9) J per pulse within the pacing frequency spectrum and the current was below 50 microamperes. Ultrasound intensities were within the safety limits set by international and national organizations. The experiments using the marking system for detection of the pacing lead failure showed that the system can yield an early warning of the lead malfunction. The system can significantly reduce the exposure of the medical staff and the patients to x rays as well as improve patient follow-up accuracy.

Cardiac Catheterization↗
PubMed1987

Color flow mapping in obstetrics.

Blood flow studies are now used extensively in evaluating fetal peripheral circulation. By using continuous and pulsed Doppler ultrasonic equipment the raw Doppler shifts caused by blood moving in the vessels can be analyzed in different ways. Spectral data can be used to estimate blood velocity and volume in the vessel, and pulsatility characteristics and turbulence. All these data are obtained from very restricted areas within the body so that aiming of the probe is critical, and obtaining data from an area requires long and tedious effort. Color flow mapping which has recently been introduced into clinical practice provides an overview of flow velocities and directions within an area. Color coded flow can be displayed by applying the moving target identification principle (as in radar) to an ultrasonic diagnostic instrument where sound waves are used instead of radio waves. The value of flow mapping has already been recognized in the diagnosis of congenital and acquired heart disease in adults and children. Direct visualization of intracardiac flow provides for a fast and accurate diagnosis of various cardiac defects, such as the ventricular septal defect, without cardiac catheterization. In the present study we have investigated the potential of color flow mapping in obstetrics. 211 pregnant women were examined between the 15th and 40th weeks of pregnancy. 193 of them had normal pregnancies; 18 were abnormal, including 11 cases of insulin dependent diabetes, 2 cases of Rh-immunization, 2 cases of nonimmunologic fetal hydrops, 2 cases of fetal cardiac structural defects and 1 case of intrauterine growth retardation. Intracardiac flow was clearly seen in 78% (35/45) of cases at the gestational age between the 20th and 24th weeks. After the 24th week the heart flow visualization rate gradually decreased to 31% (11/36) before term. In 2 cases of congenital heart abnormality flow mapping enabled clear visualization of reverse flow through the tricuspid valve and diagnosis of valvular insufficiency. The best results in studies of flow in peripheral vessels were obtained from umbilical vessels which were seen in all cases after the 15th week. The flow visualization rate was much lower when the fetal aorta, intrahepatic umbilical vein and internal carotid artery were studied. The comparison between the diameter of the umbilical vein measured on the B-scan and flow width in the same vessel showed no significant difference (t = 0.26; p less than 0.01; N = 209).(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Flow Velocity↗
PubMed1986

The use of ultrasound in developing countries.

In many developing countries ultrasound services are either nonexistent or inadequate, although the diagnostic problems for which ultrasound is particularly suited are common in such countries. In view of this, the World Health Organization (WHO) has outlined the indications for diagnostic ultrasound together with the technical specifications for equipment. Where there are larger hospitals the basic ultrasound services should be complemented with the proposed general-purpose ultrasound scanner while at the level of major medical centres there will be need for a variety of special purpose ultrasonic units, e.g. for cardiac, intraluminal and interventional investigations. The usefulness of any ultrasound appliance depends to a great extent on the skill and experience of the operator. Therefore, WHO provides guidance on the training of general practitioner and expert sonographer that is necessary for proper implementations of this technology. In this review the authors discuss the various problems affecting the use of ultrasound in developing countries.

Developing Countries↗