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Biomedical subjects

S Schreiner

Publications and source records attributed to S Schreiner.

16 recordsLinked to original sources

Biocompatibility and erosion behavior of implants made of triglycerides and blends with cholesterol and phospholipids.

Triglycerides are a promising class of material for the parenteral delivery of drugs and have become the focus of tremendous research efforts in recent years. The aim of this study was to investigate the biocompatibility of glyceroltripalmitate as well as the influence of cholesterol and distearoyl-phosphatidyl-choline (DSPC) on the erosion behavior of the lipid. For these investigations, two in vivo studies were carried out, in which cylindrical matrices of 2 mm diameter were manufactured and subcutaneously implanted in immunocompetent NMRI-mice. After excision of the implants, tissue reactions of the animals as well as changes in the weight, shape and microstructure of the implants were investigated. The triglyceride and cholesterol showed good biocompatibility, as indicated by their minimal encapsulation in connective tissue and the absence of inflammatory reactions. Increasing the levels of phospholipid in the implants, however, led to an increased inflammatory reaction. In contrast to cholesterol, which did not affect erosion, the incorporation of DSPC into the triglyceride matrices led to clearly visible signs of degradation.

Animals↗

Role of estrogen and progesterone in the regulation of uterine peristalsis: results from perfused non-pregnant swine uteri.

BACKGROUND: Adequate uterine contractility and peristalsis are involved in the transport of semen and gametes and in successful embryo implantation. Estrogen and progesterone fluctuate characteristically during the menstrual cycle. It has been suggested that both hormones influence uterine peristalsis in characteristic ways. METHODS: An extracorporeal perfusion model of the swine uterus was used that keeps the uterus in a functional condition and is suitable for the study of physiological questions. The effects of estrogen and progesterone on oxytocin-induced uterine peristalsis were assessed using an intrauterine double-chip microcatheter. RESULTS: Estrogen perfusion was associated with an increase in intrauterine pressure (IUP) in a dose-dependent manner. There was a significant difference between the IUP increase measured in the isthmus uteri and that in the corpus uteri, resulting in a cervico-fundal pressure gradient. Estrogen perfusion resulted in a significantly higher rate of peristaltic waves starting in the isthmus uteri and directed towards the corpus uteri. Progesterone was able to antagonize the estrogen effect in general. CONCLUSIONS: This study demonstrates that estrogen and progesterone have differential effects in the regulation of uterine peristalsis. The present observation shows that estrogen stimulates uterine peristalsis and is able to generate a cervico-fundal direction of peristalsis, whereas progesterone inhibits directed uterine peristalsis.

Animals↗

Transcriptional activation is a key function encoded by MLL fusion partners.

Chromosomal translocations that fuse the mixed lineage leukemia gene (MLL) to a variety of unrelated partner genes are frequent in pediatric leukemias. The novel combination of genetic material leads to the production of active oncoproteins that depend on the contributions of both constituents. In a search for a common function amongst the diverse group of MLL fusion partners we constructed artificial fusions joining MLL with generic transactivator and repressor domains (acidic blob, GAL4 transactivator domain, Herpes simplex VP16 activation domain, KRAB repressor domain). Of all constructs tested, only MLL-VP16 was able to transform primary bone marrow cells and to induce a block of early myeloid differentiation like an authentic MLL fusion. Interestingly, the transformation capability of the artificial MLL fusions was correlated with the transcriptional potential of the resulting chimeric protein but it was not related to the strength of the isolated transactivation domain that was joined to MLL. These results prove for the first time that a general biological function - transactivation - might be the common denominator of many MLL fusion partners.

Animals↗

[Ultrasound hard tissue detection for registration in orthopedics and traumatology].

The application of x-ray diagnostics for intraoperative navigation and for registration of hard tissue structures is restrained due to high radiation loads and the not given real time ability. Previous approaches with conventional ultrasonic imaging are only interactively applicable due to the high information content of soft tissue optimised B-mode-images. A pure image processing does not allow an automatic identification of individual structures, so that this must be done by the physician. To decrease the high expense of time, this report presents a concept for an adapted chain of rf-signal processing as well as an ultrasonic system for the contrast-enhanced representation of tissue borders. The system permits an exact measurement of the body geometry, which is demonstrated by determining the position of the pelvis entry plane.

Algorithms↗

[Ultrasound control of thermal tissue therapy].

As alternatives to surgical resection and/or supportive to radio- or chemo-therapy of tumors and metastases minimal invasive interstitial thermal treatment procedures by which the tissue is heated up locally to temperatures up to 100 degrees C are used. However beside nuclear magnetic resonance tomography there is no economical, by routine applicable procedure for non invasive therapy control at present disposal. In this work the possibility of non invasive control of thermal therapies by means of temporal and spectral analysis of radio frequency ultrasound signals are evaluated. Two different ultrasonic procedures, the first beeing based on the analysis of local modifications in the time of flight of the ultrasound signal for determination of the temperature distribution in the tissue, the second beeing based on the physical attenuation characteristics of biological tissue and their dependence on the tissue structure are proposed and evaluated for therapy control. With in vitro experiments the possibilities and limitations of both procedures and preliminary results of a prototype control system are demonstrated.

Animals↗

Transformation of acridone synthase to chalcone synthase.

Acridone synthase (ACS) and chalcone synthase (CHS) catalyse the pivotal reactions in the formation of acridone alkaloids or flavonoids. While acridone alkaloids are confined almost exclusively to the Rutaceae, flavonoids occur abundantly in all seed-bearing plants. ACSs and CHSs had been cloned from Ruta graveolens and shown to be closely related polyketide synthases which use N-methylanthraniloyl-CoA and 4-coumaroyl-CoA, respectively, as the starter substrate to produce the acridone or naringenin chalcone. As proposed for the related 2-pyrone synthase from Gerbera, the differential substrate specificities of ACS and CHS might be attributed to the relative volume of the active site cavities. The primary sequences as well as the immunological cross reactivities and molecular modeling studies suggested an almost identical spatial structure for ACS and CHS. Based on the Ruta ACS2 model the residues Ser132, Ala133 and Val265 were assumed to play a critical role in substrate specificity. Exchange of a single amino acid (Val265Phe) reduced the catalytic activity by about 75% but grossly shifted the specificity towards CHS activity, and site-directed mutagenesis replacing all three residues by the corresponding amino acids present in CHS (Ser132Thr, Ala133Ser and Val265Phe) fully transformed the enzyme to a functional CHS with comparatively marginal ACS activity. The results suggested that ACS divergently has evolved from CHS by very few amino acid exchanges, and it remains to be established why this route of functional diversity has developed in the Rutaceae only.

Acyltransferases↗

MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell differentiation.

The translocation t(11;19) is a recurrent feature of a subgroup of acute leukemias occurring in infants. This event fuses the genes MLL and ENL and creates the leukemogenic oncoprotein MLL-ENL. We studied the effect of retroviral MLL-ENL expression in primary mouse hematopoietic cells and show here that MLL-ENL requires the oncoprotein Myc to establish a reversible differentiation arrest of a myelomonocytic precursor population. MLL-ENL-transduced cells proliferated as immature myeloid cells in the presence of interleukin 3. The addition of granulocyte colony-stimulating factor reversed the maturation block set by MLL-ENL and induced the development of mature granulocytes and macrophages accompanied by growth arrest. Gene expression analysis indicated a down-regulation of the proto-oncogene c-myc and of several c-myc target genes during granulocyte colony-stimulating factor-mediated differentiation. The role of c-myc in the MLL-ENL transformation pathway was tested by modulating the effective Myc protein concentrations in MLL-ENL transduced cells. Cotransduction of dominant-negative Myc neutralized the MLL-ENL effect and precluded transformation. In contrast, constitutive expression of Myc cooperated with MLL-ENL and caused the transformation of a cell population with an irreversible maturation arrest.

Animals↗

Control of myeloid differentiation and survival by Stats.

Hematopoiesis involves a complex array of growth factors that regulate the survival and proliferation of immature progenitors, influence differentiation commitment, and modulate end-stage cell functions. This mini-review is focused on the role of Stat activation in the development of myeloid cells in response to hematopoietic cytokines. Much of the evidence implicating Stats in these cellular processes comes from studies of mutant cytokine receptors selectively uncoupled from Stat activation, dominant-inhibitory Stat mutants, and mice with targeted disruptions of Stat genes. Together these approaches provide strong evidence that Stat activation, particularly of Stat3 and Stat5, plays an important role in myeloid differentiation and survival. Oncogene (2000).

Animals↗

An ultrasonic approach to localization of fiducial markers for interactive, image-guided neurosurgery--Part I: Principles.

Fiducial markers are reference points used in the registration of image space(s) with physical (patient) space. As applied to interactive, image-guided surgery, the registration of image space with physical space allows the current location of a surgical tool to be indicated on a computer display of patient-specific preoperative images. This intrasurgical guidance information is particularly valuable in surgery within the brain, where visual feedback is limited. The accuracy of the mapping between physical and image space depends upon the accuracy with which the fiducial markers were located in each coordinate system. To effect accurate space registration for interactive, image-guided neurosurgery, the use of permanent fiducial markers implanted into the surface of the skull is proposed in this paper. These small cylindrical markers are composed of materials that make them visible in the image sets. The challenge lies in locating the subcutaneous markers in physical space. This paper presents an ultrasonic technique for transcutaneously detecting the location of these markers. The technique incorporates an algorithm based on detection of characteristic properties of the reflected A-mode ultrasonic waveform. The results demonstrate that ultrasound is an appropriate technique for accurate transcutaneous marker localization. The companion paper to this article describes an automatic, enhanced implementation of the marker-localization theory described in this article.

Adipose Tissue↗

An ultrasonic approach to localization of fiducial markers for interactive, image-guided neurosurgery--Part II: Implementation and automation.

Registration of image space and physical space lies at the heart of any interactive, image-guided neurosurgery system. This paper, in conjunction with the previous companion paper [1], describes a localization technique that enables bone-implanted fiducial markers to be used for the registration of these spaces. The nature of these subcutaneous markers allows for their long-term use for registration which is desirable for surgical follow-up, monitoring of therapy efficacy, and performing fractionated stereotactic radiosurgery. The major challenge to using implanted markers is determining the location of the markers in physical space after implantation. The A-mode ultrasonic technique described here is capable of determining the three-dimensional (3-D) location of small implanted cylindrical markers. Accuracy tests were conducted on a phantom representing a human head. The accuracy of the system was characterized by comparing the location of a marker analogue as determined with an optically tracked pointer and the location as determined with the ultrasonic localization. Analyzing the phantom in several orientations revealed a mean system accuracy of 0.5 mm with a +/- 0.1-mm 95% confidence interval. These tests indicate that transcutaneous localization of implanted fiducial markers is possible with a high degree of accuracy.

Algorithms↗

The c-Fes family of protein-tyrosine kinases.

The human c-fes protooncogene encodes a protein-tyrosine kinase (c-Fes) distinct from c-Src, c-Abl and other nonreceptor tyrosine kinases. Although originally identified as the cellular homolog of several transforming retroviral oncoproteins, Fes was later found to exhibit strong expression in myeloid hematopoietic cells and to play a direct role in their differentiation. Recent work has shown that Fes exhibits a more widespread expression pattern in both developing and adult tissues, suggesting a general physiological function for this kinase and its closely related homolog, Fer. This review highlights the unique aspects of Fes structure, regulation, and function that set it apart from other tyrosine kinase families.

Animals↗

A robotic system for percutaneous renal access.

PURPOSE: Percutaneous renal access can be challenging, particularly when the collecting system is not distended. Precise entry into a selected calyx facilitates subsequent percutaneous manipulations, but this skill requires extensive experience. In an attempt to improve accuracy while decreasing technical challenges, we developed a robotic system that automates the task of fluoroscopic image-guided percutaneous needle placement. MATERIALS AND METHODS: The prototype system consisted of a three degree-of-freedom robot with a needle injector end-effector. Imaging was provided by a biplanar fluoroscope. After correction of image distortion and fluoroscope calibration, robot to image-space registration was completed. To validate the system's ability to insert a needle into a calyx, ex vivo porcine kidneys suspended in agarose gel and distended with iodinated contrast solution were used as a model. In situ renal access tests with three 20 kg. pigs were performed. Access was confirmed by passing a flexible wire or aspirating iodinated contrast from the collecting system. RESULTS: The diameter of target calyces ranged from 3 to 7 mm. The in vitro accuracy of final needle tip positioning was 0.43 mm. In the ex vivo model, successful "one stick" access occurred on 10 of 12 attempts (83%). In situ access on the first attempt was successful for 6 of 12 target calyces (50%). Needle or tissue deflection accounted for each failure. CONCLUSION: The feasibility of a robotic system to assist in the percutaneous access of small and delicate renal calyces has been demonstrated. Additional work in reducing procedural steps and correcting for tissue deflection during needle passage is necessary to improve accuracy and to allow for clinical application.

Animals↗

Comparison of projection algorithms used for the construction of maximum intensity projection images.

OBJECTIVE: Four methods of producing maximum intensity projection (MIP) images were studied and compared. MATERIALS AND METHODS: Three of the projection methods differ in the interpolation kernel used for ray tracing. The interpolation kernels include nearest neighbor interpolation, linear interpolation, and cubic convolution interpolation. The fourth projection method is a voxel projection method that is not explicitly a ray-tracing technique. The four algorithms' performance was evaluated using a computer-generated model of a vessel and using real MR angiography data. The evaluation centered around how well an algorithm transferred an object's width to the projection plane. RESULTS: The voxel projection algorithm does not suffer from artifacts associated with the nearest neighbor algorithm. Also, a speed-up in the calculation of the projection is seen with the voxel projection method. Linear interpolation dramatically improves the transfer of width information from the 3D MRA data set over both nearest neighbor and voxel projection methods. Even though the cubic convolution interpolation kernel is theoretically superior to the linear kernel, it did not project widths more accurately than linear interpolation. A possible advantage to the nearest neighbor interpolation is that the size of small vessels tends to be exaggerated in the projection plane, thereby increasing their visibility. CONCLUSION: The results confirm that the way in which an MIP image is constructed has a dramatic effect on information contained in the projection. The construction method must be chosen with the knowledge that the clinical information in the 2D projections in general will be different from that contained in the original 3D data volume.

Algorithms↗