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Biomedical subjects

R M Schmitt

Publications and source records attributed to R M Schmitt.

11 recordsLinked to original sources

Embryonic stem cells and in vitro hematopoiesis.

To study hematopoietic differentiation a variety of in vitro systems have been established using hematopoietic precursors derived from various explanted adult and fetal tissues. In this prospective we describe and discuss the potential of a novel system for studying the earliest stages of hematopoietic development. In addition, some of the applications of this system as a unique in vitro model for studying other developmental systems are discussed. Murine embryonic stem cells (ESC), which are totipotent and can be maintained undifferentiated indefinitely in vitro, have the capacity to differentiate in vitro into hematopoietic precursors of most, if not all, of the colony forming cells found in normal bone marrow. This potential can be exploited to study the control of the early stages of hematopoietic induction and differentiation. Recent results have indicated that there is a strong transcriptional activation, in a well defined temporal order, of many of the hematopoietically relevant genes. Examples of the genes expressed early during the induction of hematopoiesis include erythropoietin (Epo) and its receptor as well as the Steel (SI) factor (SLF) and its receptor (c-kit). Several other genes, including CSF-1, IL-1, and G-CSF were expressed during the later stages of hematopoietic differentiation. Contrasting with these observations, IL-3 and GM-CSF were not expressed during the first 24 days of ES cell differentiation suggesting that neither factor is necessary for the induction of hematopoietic precursors. Although these studies are just beginning, this system is easily manipulated and gives us an approach to understanding the control of the induction and differentiation of the hematopoietic system in ways not previously possible.

Animals

Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression.

A novel system to study early hematopoietic development is described. This report documents the in vitro capacity of murine embryonic stem (ES) cells to differentiate into hematopoietic precursors of most, if not all, of the colony-forming cells found in normal bone marrow. This system is used to correlate the genetic expression of cytokines, their receptors, the beta-globins, and the hematopoietic cell surface markers throughout the time course of ES cell differentiation with the hematopoietic development that occurs in these cultures. Our results indicate that there is a strong transcriptional activation, in a well-defined temporal order, of most of these genes including erythropoietin (Epo), CSF-1, IL-4, beta-globins, as well as the receptors for Epo, CSF-1, and IL-4. IL-3 and GM-CSF were not expressed during the first 24 days of ES cell differentiation. In contrast, the Steel (Sl) factor (SLF) was expressed early and underwent substantial up-regulation during this differentiation, and its receptor, c-kit, was expressed relatively constantly throughout the culture period. Our results are consistent with the conclusion that SLF, Epo, IL-4, and IL-6 are important during the early stages of ES cell differentiation and hematopoietic development. Furthermore, these results argue strongly that IL-3 and GM-CSF are not critical to early hematopoiesis. This system offers a unique in vitro model for studying hematopoietic development at the earliest possible stages.

Animals

Endosonography of pararectal lymph nodes. In vitro and in vivo evaluation.

One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.

Acoustics

A 100-element ultrasonic circular array for endoscopic application in medicine and NDT.

In this paper we focus on a new developed ultrasonic circular array for endoscopic application in medicine and NDT. The new device consists of 100 strip elements. The diameter of this array is just 10 mm. The arrays are conceived for frequencies between 3.5 and 7.5 MHz, the band width has an amount of 50%. The mathematical algorithm, monochromatic and broadband simulations of the soundfield are shown and problems with grating lobes are discussed. Furthermore the process of manufacturing is discussed and partially depicted. We present the final results and ultrasonic images obtained from tissue aquivalent phantoms representing medical application and from special test specimens representing NDT- Application.

Algorithms

The effect of acute and chronic femoral artery ligation on the blood flow through the gastrocnemius muscle of the rat examined using laser Doppler flowmetry and xenon-133 clearance.

In this investigation the resting gastrocnemius muscle blood flow of the anaesthetized rat was evaluated using a recently developed laser Doppler flowmeter and the xenon-133 clearance technique. The perfusion of the microvasculature of the muscle was measured in normal control rats and in animals in which the supplying femoral artery had been acutely (1 h-1 week) or chronically (8-12 weeks) ligated. The laser Doppler flowmeter allowed continuous measurements of the muscle perfusion. Such measurements revealed a rhythmic fluctuation in the perfusion of the gastrocnemius muscle. The xenon-133 clearance technique did not allow continuous recording of muscle blood flow and rhythmical flow changes could not be observed. Acute ligation of the femoral artery reduced the mean muscle perfusion by 41% and 52% when assessed by laser Doppler flowmetry and xenon-133 clearance respectively. In comparison to animals without femoral artery ligation the hyperaemic response, following release of a tourniquet around the thigh or of an abdominal aortic occlusion, was markedly attenuated. Chronic ligation of the femoral artery reduced the mean muscle perfusion by 33% and 32% when assessed by laser Doppler flowmetry and xenon-133 clearance respectively. In these animals the hyperaemia, following tourniquet-induced muscle ischaemia, was reduced, compared to normal animals, but was more pronounced than observed in acutely ligated animals. In the chronically ligated animals abdominal aortic occlusion did not produce sustained muscle ischaemia and consequently no hyperaemic response was observed upon release of the aortic occlusion. We conclude that, as judged by the comparability of the results obtained using xenon-133 clearance, the laser Doppler flowmeter is a useful and sensitive new tool for the examination of the perfusion of tissue blood flow. The results suggest that chronic ligation of the rat femoral artery induces circulatory changes which mimic those seen in claudicants.

Animals