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Biomedical subjects

U Drews

Publications and source records attributed to U Drews.

At least 19 recordsLinked to original sources
PubMed2005

Pathogenesis of extrahepatic bile duct atresia (EHBA): comprehension from a surgical point of view.

INTRODUCTION: The aim of the study is to establish a complete comprehension of the pathogenesis of Biliary Atresia, and to explain both the variable and redundant pathomorphological, as well as, histological findings. MATERIALS AND METHODS: The pathomorphological and histological findings in 223 patients with histologically evident EHBA were recorded retrospectively (72 patients) or prospectively (151 patients), according to a projected ascending study. These findings were compared with histological findings in human and rat embryos. RESULTS: 1) The pathomorphological findings recorded in patients with EHBA were also found in stages of normal embryogenesis of the bile duct system in human and rat embryos. 2) Each histological finding in Biliary Atresia corresponds to a finding in an interrupted stage of the normal development in human and rat embryos. 3) The findings in patients and embryos can be explained completely by a disturbed intrinsic epithelium/mesoderm interaction. 4) Some findings in Biliary Atresia cannot be explained easily by the assumption of an extrinsic factor. CONCLUSION: There is no finding in Biliary Atresia which cannot be completely explained as the result of an intrinsic developmental error, probably due to disturbances or interruption of epithelium/mesoderm interaction during embryogenesis.

Animals↗
PubMed2005

Muscarinic cholinergic receptors in the human melanoma cell line SK-Mel 28: modulation of chemotaxis.

Primary and metastatic human melanomas express muscarinic receptors. In embryonic tissues, expression of muscarinic receptors is correlated with morphogenesis. The hypothesis has been put forward that muscarinic receptors are involved in morphogenetic movements in the embryo, and in cellular movements in melanoma cells during invasive growth. The purpose of the present study was to characterize the muscarinic receptors in the human melanoma cell line SK-Mel 28 and to test in a Boyden chamber assay whether the chemotactic activity towards fibronectin can be influenced by muscarinic stimulation. In Western blots with the monoclonal antibody M35, muscarinic receptors were localized in a strong band at 66 kDa, and in a weak band at 63 kDa. Western blot with M3 subtype specific antibodies reproduced the line at 66 kDa. RT-PCR revealed mRNA for subtypes M3 and M5. These findings suggest that SK-Mel 28 cells express a large number of subtype M3 and a small number of subtype M5 receptors. Microscopic observation of calcium mobilization after muscarinic stimulation indicated that all cells carried functional muscarinic receptors. A standardized chemotaxis assay was established in modified Boyden chambers using fibronectin as chemotactic agent. After addition of carbachol to the upper compartment, an increase of fibronectin induced chemotaxis of approximately 30% was observed, an effect abrogated by atropine. These results demonstrate that muscarinic cholinergic treatment has a modulatory effect on fibronectin-induced chemotaxis in SK-Mel 28 melanoma cells, indicating that the muscarinic system is involved in regulation of cell movement.

Blotting, Western↗
PubMed2002

Muscarinic receptors in cell lines from ovarian carcinoma: negative correlation with survival of patients.

OBJECTIVES: Tumor cells are similar in many respects to embryonic cells, indicating that embryonic genes are reactivated during malignant growth. In previous studies, we observed muscarinic acetylcholine receptors, which are expressed in embryonic cells during morphogenesis and are also found in human melanomas and melanoma cell lines. We determined the presence of muscarinic receptors in a collection of ovarian tumor cell lines for which clinical data were available. METHODS: Muscarinic receptor status of 39 cell lines derived from 34 patients was determined by Western blotting. RESULTS: Twenty-three cell lines were receptor positive, and 16, receptor negative. Kaplan-Meier analysis of receptor status of the tumor cell lines and survival time of patients from which the cell lines were established showed that expression of muscarinic receptors was associated with a reduced probability (P = 0.025) of survival: This is within the range of other established prognostic factors reported in the literature. CONCLUSIONS: A large percentage of ovarian tumor cell lines express muscarinic receptors. Muscarinic receptor expression is an embryonic trait and is correlated with reduced survival of patients. The results from this study provide further evidence of the involvement of muscarinic receptors in the progression of malignant carcinomas.

Animals↗
PubMed2001

Immunohistochemical localisation of androgen receptor during sex-specific morphogenesis in the fetal mouse.

The distribution of androgen receptors (ARs) in paraffin serial sections of day 17 and day 18 male and female mouse embryos was investigated. In the cranial section of the genital tract AR expression was restricted to Wolffian structures while Müllerian ducts and surrounding mesenchyme were AR negative. In the fusion zone with the urogenital sinus the epithelial components of the vaginal bud were clearly distinguished by differential AR expression, which was faint in the Wolffian ducts, totally missing in the Müllerian ducts, and intense in the sinus ridges with the most intense expression in the morphogenetically active mesenchyme, indicating a new mechanism of negative control of vagina formation via androgens. Expression of ARs outside the genital tract was observed: (1) in loose interstitial mesenchyme extending into the retroperitoneal space up to the coeliac artery, indicating androgen effects during ascent of the kidneys and descent of intraperitoneal organs, (2) in the trigone of the bladder indicating androgen involvement in the development of the vesico-ureteral junction, and (3) in loose mesenchyme between striated muscle fibres and around pelvic skeletal elements, indicating mediation of androgen effects on the musculoskeletal system via loose mesenchyme.

Animals↗
PubMed2001

Induction of bile ducts in embryonic liver by mesenchyme: a new perspective for the treatment of biliary atresia?

Presently only those forms of Extrahepatic Biliary Atresia (EHBA) with minimal or no intrahepatic manifestations can be treated successfully by extensive hepatoportoenterostomy. Intraoperative macro- and microscopic observations show that the typical pathogenetic manifestations in EHBA are most prominent at the porta hepatis. We therefore postulate that EHBA is the result of a defective embryonic development of the porta hepatis. In rat embryos hepatic bile duct formation is initiated at the porta hepatis and in this context mesenchyme from the periportal region seems to play a major inductive role. In order to demonstrate the role of invading periportal mesenchyme for the process of bile duct rudiment formation we established an organ culture model of the embryonic porta hepatis by recombining periportal mesenchyme with peripheral liver fragments from 15 days old rat embryos (Carnegie Stage 21). The degree of mesenchyme invasion as well as the formation of mesenchyme-surrounded liver cell clusters, rosettes or vesicles (bile duct rudiments) were assessed. Mesenchyme from the porta hepatis invaded the peripheral liver fragments and induced the formation of mesenchyme-surrounded liver cell clusters and rosettes with the beginning of lumen formation. Kidney mesenchyme recombined with liver fragments as a mesenchymal alternative showed almost the same effect, lung mesenchyme showed only a very weak inductive effect. To assess the effect of a diffusible factor versus direct cell contact, a millipore filter with and without paraffin coating was interposed between mesenchyme containing tissue and peripheral liver tissue fragments. Without direct cell contact to mesenchyme no hepatoblast cluster or rosette formation could be observed. Comparing this result to the normal development of the liver in rats our investigations suggest that the embryogenesis of the porta hepatis is probably defined by the following two developmental steps: First, differentiation of the intrahepatic bile duct system which is induced by invading mesenchyme originating from the extrahepatic periportal region and realized by epithelium mesenchyme interaction. Second, fusion of extra- and intrahepatic bile duct systems at the level of the later porta hepatis. Disturbances of this complex process can possibly lead to biliary atresia. Further investigations regarding details of the role of the mesenchyme, its inductive factors and the kidney mesenchyme's inductive potential in liver development may provide a new perspective for future treatment of biliary atresia.

Animals↗
PubMed2000

Induction of cellular contractions in the human melanoma cell line SK-mel 28 after muscarinic cholinergic stimulation.

In a previous immunohistochemical study we observed muscarinic acetylcholine receptors in primary and metastatic human melanomas, which were not present in normal skin melanocytes. In the present study we demonstrated the endogenous expression of muscarinic receptors, of choline acetyltransferase and of cholinesterase activity in the human melanoma cell line SK-mel 28. We tested the effect of muscarinic agonists on cellular movements of the melanoma cells in a perfusion chamber by digital video time-lapse microscopy. Within 3 to 10 min after onset of muscarinic perfusion cell body contractions and retraction of cell processes of more than 5 micrometer occurred in about 30% of the melanoma cells. The effect disappeared after addition of atropine. The proportion of reacting cells corresponded to the endogenous expression of muscarinic receptors revealed by immunocytochemistry with the monoclonal antibody M35. The experiments indicate the presence of an autocrine muscarinic cholinergic system in the melanoma cells and demonstrate a direct link between muscarinic receptors and the contractile apparatus. Melanocytes are derived from neural crest cells that express cholinesterase activity and muscarinic receptors during their migratory phase in the embryo. Therefore, re-expression of the muscarinic cholinergic system in tumour cells may be involved in invasive growth.

Acetylcholine↗
PubMed2000

Local mechanisms in sex specific morphogenesis.

Sex determination in mammals occurs on three levels. Segregation of sex chromosomes determines the chromosomal sex. Sry on the Y chromosome induces formation of a testis which in turn regulates via AMH and testosterone the development of the genital tract and the external phenotype. Recently a number of new factors have been described, which affect sexual development but have not yet found a place in the above canonical scheme of sex determination. For the purpose of this review, the factors are aligned according to their quality as transcription factors, steroid hormones, or growth factors. In this web of regulatory factors, the classical sex determining factors have evolved as master mechanisms while others function as slaves, or were totally suppressed. In this context, androgens acquired a dominant role in mammalian development. Androgens determine the morphogenesis of the genital tract. The effects of androgens are mediated by local cellular interactions. In the cranial section of the Wolffian duct the androgen receptor appears in the epithelium and mediates maintenance of the duct via an epithelial factor. In the caudal section of the duct the androgen receptor is expressed in the embryonic mesenchyme. Vesicular glands are induced via a morphogenetically active mesenchymal condensation, while the epithelial buds are primarily AR androgen receptor negative. The dominant role of androgens and formation of a vagina evolved together at the transition to eutherian mammals. Under this aspect, the role of androgens in the development of the vagina is analyzed.

Androgens↗
PubMed1998

Characterization of muscarinic receptors in the human melanoma cell line SK-Mel-28 via calcium mobilization.

In melanoma cells of primary and metastatic human melanomas muscarinic cholinergic receptors are present. Muscarinic receptors were shown to be expressed in morphogenetically active embryonic cells. Therefore, the possibility exists that in melanomas an embryonic trait is re-expressed after transformation. In the present study, we demonstrated the presence of muscarinic receptors in the human melanoma cell line SK-Mel-28 by immunofluorescence with the monoclonal antibody M 35 and characterized the receptors further by measuring calcium mobilization after muscarinic stimulation. Cell suspensions were stained with fura-2 and fluorescence was followed at 380 nm excitation in a fluorimeter cuvette. After the addition of acetylcholine or carbachol a steep decrease in fluorescence intensity indicated calcium mobilization from intracellular stores (peak reaction), which was followed by a constantly lowered fluorescence level indicating a steady influx of extracellular calcium in the presence of agonist. By quantitative evaluation, dose-response curves were obtained from which an ED of 4.3 x 10(-6) M was calculated for acetylcholine and an ED of 2.2 x 10(-5) M was calculated for carbachol. After preincubation with antagonists the dose-response curve of acetylcholine was shifted to the right. The inhibition constant of pirenzepine was calculated as 3.9 x 10(-7) M, of methoctramine as 6.8 x 10(-7) M and of 4-DAMP-mustard as 1.9 X 10(-8) M. Comparison with the data from the literature and those obtained in the chick embryo indicates that the muscarinic receptor in SK-Mel-28 melanoma cells pharmacologically behaves as the M3 type and corresponds to the embryonic muscarinic receptor characterized by us in earlier studies.

Atropine↗
PubMed1998

Immunohistochemical localization of ecdysteroid receptor and ultraspiracle in the epithelial cell line from Chironomus tentans (Insecta, Diptera).

Ecdysteroid receptor (EcR) and its heterodimerization partner, ultraspiracle (USP), were demonstrated in the epithelial cell line from Chironomus tentans by immunohistochemistry. In untreated cells both proteins are present in nuclei as well as in granular compartments of the cytosol. At 1 day after addition of 1-microM 20-OH-ecdysone (20E) total immunofluorescence had increased in the nuclei, whereas the cytoplasmic staining had disappeared. At the 2nd and 3rd days all cells within a vesicle appear identical according to morphological criteria, but the EcR and USP immunoreactivity becomes restricted into patches of neighbouring cells. The hormonally induced changes in the pattern of localization of functional ecdysteroid receptor, the heterodimer of EcR and USP, are discussed in relation to similar effects of 20E on acetylcholinesterase and muscarinic acetylcholine receptor distribution in this cell line.

Animal Structures↗
PubMed1998

Direct and mediated effects of testosterone: analysis of sex reversed mosaic mice heterozygous for testicular feminization.

Sex reversed mice are XX males carrying on one of their X chromosomes a translocation of the sex determining region of the Y (Cattanach's Sxr factor). The phenotype corresponds to the Klinefelter syndrome in man. The X linked Tfm (testicular feminization) mutation in the mouse is a frame shift in the androgen receptor gene leading to complete androgen insensitivity. Due to random X inactivation, sex reversed mice heterozygous for Tfm, are mosaics composed of a variable proportion of androgen insensitive X Tfm and androgen sensitive X+ wildtype cells. In the intersexual genital tract, Tfm cells are maintained as undifferentiated cells in the epididymal duct. To the distorted prostate lobes and bulbourethral glands they contribute some lobules of indifferent urethral glands. A large contribution of Tfm cells allows downgrowth of Wolffian and Müllerian ducts to form a vagina. In the external genitalia the stimulatory effect of testosterone is reduced leading to various degrees of feminization correlating with the proportion of Tfm cells present. In the mosaics effects of testosterone, mediated by local growth factors from the wildtype to the Tfm cells, can be distinguished from direct effects expressed only in the wildtype cells. Mediated effects are embryonic induction and morphogenesis of male organs and postnatal maintenance of organ structure and proliferation. The direct effect is cellular differentiation.

Androgen-Insensitivity Syndrome↗
PubMed1997

Immunohistochemical localization of muscarinic acetylcholine receptors in primary and metastatic malignant melanomas.

In embryos morphogenetically active cells transiently express the cholinergic system comprising cholinesterase activity and muscarinic acetylcholine receptors. Malignant melanomas develop from melanocytes, which are derived from the neural crest. Neural crest cells express the embryonic muscarinic system during migration. Using the monoclonal antibody M35, we now show that normal melanocytes carry no muscarinic receptors, whereas malignant melanoma cells express them again. In primary melanomas and metastatic melanomas, we identified muscarinic receptors in solid strands or groups of atypical cells. In all primary malignant melanomas studied we found inhomogeneous distributions of M35-immunoreactivity subdividing the tumors into three different zones. In the tumor center, groups or single cells often showed only little or even no immunofluorescence. In contrast, pericentrally we detected strong immunostaining in the conglomerations of atypical melanocytes. In the peripheral infiltration zone, intensely fluorescent cells in clusters or single, were spreading into the normal tissue, leading to a more patchy staining pattern. Melanocytes of nevi also possess muscarinic receptors, showing similar distribution patterns as in the melanoma. We suggest that in malignant melanomas muscarinic receptors might play a regulative role in infiltrative growth and metastasis.

Hair Follicle↗
PubMed1996

A model for storage and retrieval of theoretical medical knowledge.

A database model for structure and access of theoretical medical knowledge is presented. The basic principle is the organization of knowledge in three dimensions: Each topic--first dimension--is explained with media--second dimension--in different versions of varying details--third dimension--suitable for different users. Every topic is one database entry. Topics are interconnected with heading and sub-topics (tree structure) and to logically related topics (cross references). Access follows the 3D-concept with initial access by topic, by media, or user specific, and with intra-unit access to related topics, media, and user specific versions. The model is discussed and possible implementations are described.

Computer-Assisted Instruction↗
PubMed1995

Muscarinic receptors in the prenatal mouse embryo. Comparison of M35-immunohistochemistry with [3H]quinuclidinyl benzylate autoradiography.

Muscarinic cholinergic receptors are widespread in nervous tissue and smooth muscle or paracrine epithelial cells of various organs. In the embryo, muscarinic receptors are transitorily expressed in the early blastoderm and later on in blastemic tissues during morphogenesis. Recently, a monoclonal antibody (M35) against muscarinic receptor from calf brain became available. In the present study the use of M35-immunohistochemistry is compared to autoradiographic localization of muscarinic binding sites in the mouse embryo. The aim of the study is to test the suitability of the antibody for localization of muscarinic receptors in embryonic tissues. For autoradiography whole-body sagittal cryostat sections of the 17- and 18-day mouse embryo were covered with LKB-Ultrofilm after incubation with the radioactive ligand [3H] quinuclidinyl benzylate (QNB). For immunohistochemistry cryostat sections of formalin fixed tissues were used. In general, all tissues exhibiting ligand binding were also recognized by the antibody. M35-immunohistochemistry resulted in higher spatial resolution of receptor localization than [3H]QNB autoradiography. Definitive muscarinic receptors were observed in smooth muscle and the epithelial lining of the vasuclar, intestinal, respiratory and urinary system, in the brain, spinal cord and peripheral nerves. The embryonic type of the muscarinic receptor was detected in the mesothelium of lung and liver, in the nephrogenic blastema of the metanephros, and in lung mesenchyme. A large amount of embryonic muscarinic receptors was found in the remnants of the notochord and in the nucleus pulposus of the developing vertebral column. A function in morphogenesis is discussed of the embryonic muscarinic receptor.

Animals↗
PubMed1994

Daudi supernatant, unlike other H-Y antigen sources, exerts a sex-reversing effect on embryonic chick gonad differentiation.

In vitro cultures of intact chick gonads (organ cultures) and reaggregation cultures of dispersed gonad cells (roller cultures) were made. Gonads or gonad cells from 7-day-old chick embryos, at the stage when sex-specific differentiation begins, were cultured in the presence of presumed H-Y antigen-containing supernatants, or co-cultured in the presence of H-Y antigen-producing cell lines. The H-Y antigen-producing cells tested were of human, mouse, bovine and chicken origin. During organ culture, addition of supernatant of the human lymphoma cell line Daudi, or co-culture with Daudi cells, stimulated a clear proliferation of the germinal epithelium in male gonads, indicating feminization. A similar effect was obtained by treatment with estradiol. In reaggregation culture, the increase in nuclear size of germ cells was chosen as a parameter for feminization. A significant increase of germ cell nuclear size was observed in gonads cultured in the presence of Daudi supernatant. In both organ cultures and reaggregation cultures, other tested H-Y antigen sources and semi-purified H-Y antigen fractions did not exert significant effects on differentiation of the gonads or on the average area of the germ cell nuclei. These findings suggest that it is not H-Y antigen, but another protein produced by Daudi cells, that might be responsible for the sex-reversing effects.

Animals↗
PubMed1994

[AnaTü-MidroTutor. An interactive tutoral program for a microscopy course].

The AnaTü-MikroTutor is an interactive tutorial program providing specific information for the microscopic anatomical course. It is offered as additional tool during practical microscopy and can be used for recapitulation of histology. The software is based on MS-DOS and can be implemented on IBM compatible computers. The main menu imitates a microscopic desk with a microscope, folders for microscopic slides and written additional information to each slide. The various functions are activated by mouse click over the respective icons. The program is offered to the students parallel to the microscopic course at 4 workstations and at a single terminal at the microscopic hall during practical microscopy. The main body of the program contains digital images of the microscopic slides of the course of microscopy in Tübingen. Each slide is represented by an overview and up to six magnifications. Legends are available as overlay. In addition, textual information is offered to each slide, which is intended to initiate further studies, explain specific termini or to indicate clinical relevance.

Anatomy↗
PubMed1993

[Comparison of vaginal and abdominal ultrasound measurements with embryologic growth curves in early pregnancy].

Body lengths and chorionic diameters of 225 early pregnancies with known fertilisation age, measured by transvaginal sonography (TVS), were compared with measuring results of measurements from abdominal ultrasound and of embryological specimen from the literature. The TVS measuring results were made according to the Carnegie classification. It is shown that the growth curve obtained by TVS is very similar to valid embryological growth curves, although the "Greatest Length" (GL) is measured by sonography not the Crown-Rump-Length (CRL). Between the sixth and eighth gestational week, the TVS curve shows strong resemblance to abdomino-sonographical curves. After that period, the TVS results tend to be systematically lower. The earliest TVS measurement of the human embryo in possible in the sixth gestational week, one week earlier than with abdominal ultrasound. There is a good correlation between the development of a structure and its earliest detection by TVS, active movements of the embryo can even be shown earlier than assumed by embryologists (stage 20/ninth week of gestation). Due to terminological reasons, in ultrasound the established term "Crown-Rump-Length" should be replaced by "Greatest Length". In a TVS-examination of an embryo (gestational weeks 4 to 11), morphological criteria must be additional contributions to the determination of maturity and integrity of a pregnancy. The application of the specimen-derived Carnegie classification to TVS measurements seem to be possible, as well as the utilization of TVS results in embryology.

Adult↗
PubMed1992

Characterization of the Ca2+ influx into embryonic cells after stimulation of the embryonic muscarinic receptor.

Embryonic cells transiently express an embryonic muscarinic system during morphogenesis. Stimulation of the embryonic muscarinic receptor results in biphasic intracellular Ca2+ mobilization: an initial "peak" due to Ca2+ release from intracellular stores is followed by a sustained "plateau" of enhanced cytoplasmic Ca2+ due to influx of extracellular Ca2+. In the present investigation, we characterized the Ca2+ influx by measuring the cytoplasmic free Ca2+ concentration [Ca2+]i using the Ca2+ indicator fura-2: 1. The increase of [Ca2+]i during the plateau depended linearly on the logarithm of the extracellular calcium concentration whereas the initial peak was almost independent from extracellular calcium. 2. The organic Ca2+ entry blockers verapamil, gallopamil, nifedipine, nitrendipine and the inorganic blockers Mn2+, Mg2+ and La3+ were without effect on both phases of Ca2+ mobilization. Only Ni2+ at concentrations above 1 mM was able to reduce the influx without affecting the intracellular Ca2+ release. 3. Substitution of extracellular Na+ by guanidine+, choline+ or tris+ and membrane depolarisation by increasing the extracellular K+ concentration had no effect on either phase of Ca2+ mobilization. We conclude that a non-voltage dependent, receptor-operated influx mechanism, probably a "second messenger operated Ca2+ channel", is responsible for the Ca2+ influx after stimulation of the embryonic muscarinic receptor.

Acetylcholine↗