Biomedical subjects

W Götz

Publications and source records attributed to W Götz.

At least 37 records · Page 2Linked to original sources

PubMed2001

Immunohistochemical localization of components of the insulin-like growth factor-system in human deciduous teeth.

To investigate the occurrence of components of the insulin-like growth factor (IGF) system during the resorption process of shedding human deciduous teeth, we investigated sections of 13 decalcified and paraffin-embedded deciduous teeth immunohistochemically with antibodies against IGF-I and -II, six IGF binding proteins (IGFBPs 1-6) and the IGF receptors IGF1R and IGF2R. The teeth were in different stages of resorption and all showed reparative cementum formation. It was found that acellular extrinsic fiber cementum, reversal lines and reparative cellular intrinsic fiber cementum were immunoreactive for both IGFs and various IGFBPs. Therefore, in human deciduous teeth, all subgroups of cementum, but not dentine, may represent sources of components of the IGF system. Odontoclasts did not carry IGFs or the IGF1R, but IGFBPs and the IGF2R. Therefore, these cells, in contrast to osteoclasts, may not respond to IGFs, but may be involved in the release and sequestration of IGFs from cementum during the resorption process. In contrast to odontoclasts, cementoblasts and periodontal ligament (PDL) fibroblasts carried IGF1R. The influence of the IGF system on the function of these cells with respect to periodontal matrix turnover and cementogenesis is discussed. On the behalf of the IGFBP immunoreactivities found, the PDL extracellular matrix can be considered to be a reservoir for IGF system components, where binding proteins may regulate IGF distribution and activity.

Child↗

PubMed2000

Tissue distribution of components of the insulin-like growth factor system in sudden infant death and controls.

Growth factors may be involved in sudden infant death (SID). Among these factors, the insulin-like growth factor (IGF) family is important in human fetal and perinatal organ growth and development. In order to detect probable differences in the occurrence and distribution of components of the IGF system, tissue samples from liver, lung, skin, parotid and thyroid gland, gut and cerebellum from SID children (n=9) and controls (n=6) aged between 14 and 258 days of life (mean 105 days) were stained immunohistochemically using antibodies against IGF-I, IGF-II and their specific IGF-I-receptor (IGF-IR). In contrast to controls in hepatocytes of SID children a reduction or an absence of immunoreactivity for IGF-I and IGF-IR and a weaker staining for IGF-II was detected. IGF-II in smooth muscle layers in the gut and IGF-I in epithelial cells in intestinal specimens also showed a reduced immunoreactivity in SID children and those who died traumatic deaths. In the other organs examined no significant differences in the distribution of the insulin-like growth factor system between the groups could be detected, indicating that in SID children no fundamental differences or alterations in the physiology of the IGF system occur. Because of the decreased immunostaining of IGFs in the liver and intestine of SID cases, a local dysregulation may be discussed.

Autopsy↗

PubMed2000

Extensive glycosylation changes revealed by lectin histochemistry in morphologically normal prenatal tissues of the mouse mutant undulated (un/un).

Recently we observed that in human embryos and fetuses with a variety of malformations, not only malformed tissues, but also several non-malformed tissues displayed alterations in the glycosylation pattern. It was the aim of this work to investigate this more or less inexplicable phenomenon under experimental conditions. To this end, we studied a well known mouse model, the mouse mutant undulated, which has an exactly defined genetic defect (substitution in the pax-1 gene) leading to a localized malformation in the vertebral column. The glycosylation pattern was studied using lectin histochemistry. Distribution of binding sites for the lectins RCA I, Con A, SNA, SBA, PNA, LTA and WGA was studied during the organogenesis stages (i.e., days 11-18). It was striking that in mutants, changes in the glycosylation pattern were found not only in the malformed organ (i.e., vertebral anlage), but also in other embryonic tissues, which showed normal morphology. This suggests that the altered glycosylation seems to be a part of genetically determined phenomena throughout the entire organism. Our results show that a defect in a gene with a very restricted expression can cause universal changes in the glycosylation pattern during development.

Animals↗

PubMed2000

The effect of local injection of botulinum toxin A on the parotid gland of the rat: an immunohistochemical and morphometric study.

PURPOSE: In this investigation, the effect of a local injection of botulinum toxin A on the concentration of acetylcholinesterase in the parotid gland of the rat was examined. MATERIALS AND METHODS: After local injection into the parotid glands of female Wistar rats, the treated glands were excised, and immunohistochemical staining for acetylcholinesterase was performed. To discover possible changes in cell morphology after local application of botulinum toxin A, morphometric measurements also were performed on the excised parotid glands. RESULTS: In contrast to the untreated, physiologic saline-injected, glands, there was a decrease in the concentration of acetylcholinesterase in the glands treated with botulinum toxin. No persistent changes in the number of acinar cells could be observed. CONCLUSIONS: Because the cholinergic pathway of the autonomic nervous system has great importance in the secretion of fluid from the salivary glands, blocking this pathway and local application of botulinum toxin offers a possible therapeutic option for the treatment of hypersalivation in various otolaryngologic and neurologic diseases.

Acetylcholinesterase↗

PubMed2000

Localization of cathepsin D in human odontoclasts. a light and electron microscopical immunocytochemical study.

Odontoclasts are dentine and cementum resorbing cells whose relationship to bone resorbing osteoclasts is not clear. Like osteoclasts, they possess different cathepsins which are involved in mineralized tissue degradation during the tooth root resorption process in deciduous teeth. Whether cathepsin D, which in osteoclasts probably functions as an activator of other cathepsins, can be found in odontoclasts, has, however, not been investigated before. In order to determine its occurrence and localization, cathepsin D immunocytochemistry was applied to paraffin-embedded sections from 30 human deciduous tooth roots undergoing resorption. Using immunogold postembedding immunocytochemsitry on LR-Gold embedded specimens, the distribution of cathepsin D was investigated at the ultrastructural level. We identified tartrate-resistent acid phosphatase-positive mono- and multinuclear odontoclasts near and on the periodontal surfaces of tooth roots. Nearly all of these cells showed cytoplasmic granular cathepsin D immunoreactivity. At the electron microscopical level, gold labelling was seen on vacuoles and vesicles of the odontoclasts, which were identified as secondary lysosomes and phagosomes. Extracellularly it was seen along the ruffled border and in neighboured resorption areas of dentine and cementum. These findings indicate that cathepsin D is secreted into the resorbing area of human odontoclasts in order to participate in degradation of mineralized tooth matrix, but may also function as an activator of other proteases in lysosomal organelles.

Cathepsin D↗

PubMed1999

Immunohistochemical and morphometric investigations of the influence of botulinum toxin on the submandibular gland of the rat.

Immunohistochemical methods were used to study the effects of botulinum toxin A on the concentration of acetylcholinesterase in the submandibular gland of the rat. The toxin was injected into the glands of healthy adult female Wistar rats and immunohistochemistry performed on the excised organs. Morphometric measurements were also carried out to study changes of cell morphology after local applications of botulinum toxin A. Compared with untreated glands or glands injected with saline there was a decrease of acetylcholinesterase in the glands treated with botulinum toxin. As the cholinergic pathway of the autonomic nervous systems plays an important role in eliciting secretion from the salivary glands, inhibition of secretion by local application of botulinum toxin could be considered a therapeutic option for the treatment of various diseases affecting salivary gland function.

Animals↗

PubMed1998

Comparison of lectin binding patterns in malformed and normal human embryos and fetuses.

Altered glycosylation in the course of disease detectable by changes in lectin binding patterns has been well established for adult tissues, but only a few authors have described carbohydrate entities during normal human embryonic and fetal development. Whether alterations in carbohydrate patterns occur in human embryonic and fetal tissues, affected by malformations, remains to be investigated. We, therefore, examined human embryos and fetuses at corresponding developmental stages with and without malformations (spina bifida, exencephaly, cleft lip and cleft palate, and dysmelia) with respect to their lectin binding patterns for the lectins RCA I, PNA, WGA, SBA, SNA, Con A, and LTA. Our results demonstrated that during the development of malformations, the affected tissue sites exhibited a different carbohydrate pattern from normally developed specimens. Furthermore, tissues known to be sites of secondary malformation, accompanying the primary defect, although displaying a histologically normal appearance, also showed an altered carbohydrate pattern. This might indicate a possible general alteration in the carbohydrate pattern in the course of development of malformations in man.

Binding Sites↗

PubMed1998

Mouse insulin-like growth factor binding protein-6: expression, purification, characterization and histochemical localization.

The mitogenic and metabolic activities of insulin-like growth factors (IGF) are modulated by a family of six high affinity IGF binding proteins (IGFBPs). This study describes the expression of the mouse IGFBP-6 which is unique among IGFBPs in its preferential binding of IGF II, in insect cells using the baculovirus system. The purified, O-glycosylated IGFBP-6 was functional as shown by IGF binding and by inhibition of IGF II-stimulated DNA synthesis in human fibroblasts. Specific antibodies generated in chicken against the recombinant IGFBP-6 were used for Western blotting analysis and immunohistochemistry. Strong immunoreactivity was found in ossifying bones of the cranial base, in cell clusters of the pancreas anlage, in the trigeminal ganglion, on myoblasts, on motoneurons of the spinal cord of embryonic mice. In tissues of adult mouse, strong IGFBP-6 immunostaining was present in epidermal and peridermal layers of the skin, in meningeal layers, in long-striated skeletal muscle, and in the Langerhans' islets of the pancreas. No immunopositive staining was observed in lung and liver indicating that sites of synthesis and IGFBP action are different.

Animals↗

PubMed1997

[Recurrent angina pectoris in stress caused by hemangioma of the heart].

We present the case of a 73-year-old man with a 3-week history of recurrent exertional angina confirmed by exercise stress testing. The symptoms were caused by hemangioma situated between the pulmonary artery and the left auricle. The diagnosis was confirmed by ventriculography, coronary angiography, and CT-scanning. The tumor was completely removed through a midline sternotomy without extracorporeal circulation. Histology revealed the diagnosis of a cavernous hemangioma with endothelial lined vascular channels of varying size. The patient made an uneventful recovery and remained asymptomatic during follow up. Cardiac hemangioma are rare tumors of the heart that may cause angina by interfering with the coronary blood flow. Surgery is curative for most patients.

Aged↗

PubMed1997

Changes in lectin binding sites during early human liver development.

In this study we investigated whether changes in glycosylation during liver morphogenesis correlate with the early development of individual structures in the human liver. Therefore, we localized the binding of the lectins from Sambucus nigra (SNA; specific for sialic acid), Triticum vulgare (WGA; specific for N-acetylglucosamine and sialic acid), Ricinus communis (RCA I; specific for beta-galactose), Lotus tetragonolobus (LTA; specific for alpha-fucose) and Concanavalia ensiformis (Con A; specific for alpha-mannose) in the human liver between the 4th and the 12th gestational week (GW). Cell membranes of early hepatocytes (5th-6th GW) showed strong staining for RCA I, which decreased noticeably from the 8th-9th GW onward. Early intrahepatic capillaries (4th-5th GW) showed reactions only for WGA and RCA I. Reactions for SNA occurred later (6th-9th GW). At this time a fine granular staining for SNA was visible at the sinusoidal sides of hepatocytes. The hepatocytes of the outer limiting plate were specifically stained by WGA, Con A, and SNA in the 9th GW and the staining remained visible in developing bile ducts up to the 12th GW. The possible biological significance of the appearance or disappearance of carbohydrate moieties during early human liver development is discussed.

Binding Sites↗

PubMed1997

The oncoproteins c-erb-B2, c-fos and the tumour suppressor protein p53 in human embryos and fetuses.

Oncoproteins and tumour-suppressor proteins are thought to possess an antagonistic function in the regulation of growth and differentiation processes during embryonic and fetal development. In contrast, in the adult, tumour growth is associated with the overexpression of oncoproteins or the malfunction of tumour-suppressor proteins. We examined the occurrence of the tumour proteins c-erb-B2 and c-fos and the tumour-suppressor protein p53 in 17 human embryos and fetuses with the help of immunohistochemistry. C-erb-B2 was detected mainly in embryonic tissue that are not known for c-erb-B2-overexpression in tumours in the adult. In contrast, c-fos was almost always located in fetal tissues corresponding to its location in adult tumours. Staining for p53 was found in a wide variety of embryonic and fetal tissues. C-erb-B2 and p53 were localized in the same tissue structures of the developing skin, heart and muscle. In other tissues, e.g. muscle and bone, c-fos was found together with p53, suggesting an antagonistic action of these proliferative and antiproliferative factors. Furthermore, c-erb-B2. c-fos and p53 appear to be important for growth and differentiation processes in human development as the occurrence of these proteins was not only restricted to specific tissues but also to specific stages of development of these tissues.

Embryo, Mammalian↗

PubMed1997

Immunohistochemical localization of the small proteoglycans decorin and biglycan in human intervertebral discs.

Immunohistochemistry was used to study the presence and distribution of the core proteins of the small proteoglycans decorin and biglycan in the various compartments of human intervertebral discs. Both proteoglycans could be found in the outer tendon-like parts of the annulus fibrosus, indicating their potential role in collagen network formation and biomechanical stress resistance. The loss of both proteoglycans in the annulus of individuals older than 50 years reflects a normal age-related change. In the nucleus pulposus, decorin could be found in fibrillar areas of the interterritorial matrix, thereby indicating co-localization of decorin with fibrils containing type II collagen. Biglycan was present in the extracellular matrix of the nucleus pulposus of adults. The pericellular immunoreactive rims observed around nucleus pulposus cells and giant chondrones indicated local biosynthetic activity for these small proteoglycans. The staining patterns in cartilage endplates resembled those found in human hyaline articular cartilage.

Adolescent↗

PubMed1997

Detection and distribution of the carbohydrate binding protein galectin-3 in human notochord, intervertebral disc and chordoma.

Galectin-3 is an endogenous carbohydrate-binding protein which plays a role in cell differentiation, morphogenesis and cancer biology. We investigated the occurrence and distribution of galectin-3 in the embryonic and fetal human notochord, the developing human vertebral column, adult intervertebral discs and in six chordomas, which are tumors thought to originate from notochordal remnants. By means of Western blots, the expression of galectin-3 was confirmed in tissue probes from the vertebral column region beginning with the 8th gestational week. These results were supported by immunohistochemical data which revealed the presence of galectin-3 in the cytoplasm of cells of the notochord also from the 8th gestational week onwards. Notochordal immunostaining became stronger with increasing gestational age. A persisting notochordal remnant in an adult intervertebral disc and various cells of the nucleus pulposus also contained galectin-3. All chordomas showed moderate or strong immunoreactivity irrespective of their cellular composition. Subcellularly, galectin-3 was localized mostly in the cytoplasm, while a subset of tumor cells also showed nuclear distribution. Differences in staining patterns of chordoma cells could not, in general, be correlated to any histological features of these tumors.

Adolescent↗

PubMed1997

Outcome of cardiopulmonary resuscitation following open heart surgery.

The outcome of cardiopulmonary resuscitation (CPR) following cardiac surgery is not known to date. A retrospective analysis of all patients subjected to CPR during their hospital stay following heart surgery was conducted; 1.4% of patients required CPR 0.5-192 h following surgery. The mean duration of CPR was 42 +/- 29 min. Twenty-nine patients were subjected to emergency rethoractomy and 14 patients received coronary artery bypass grafting. The hospital mortality was 46%. There was a significant correlation of duration of CPR and death (r = 0.44, p = 0.004). The commonest cause of death was consecutive multiorgan failure in 12 patients. Twenty-one patients were long-term survivors without neurological sequelae. Twenty patients were in NYHA class I or II. Ventricular fibrillation and myocardial ischaemia are the commonest conditions leading to CPR in an average population of patients immediately after cardiac surgery. Aggressive treatment and emergency rethoracotomy in most cases results in long-term survival in 50%.

Aged↗

PubMed1996

Localization of large-T oncoprotein during the embryonic and fetal development of transgenic mice.

Oncoproteins are not only involved in the development of tumors but also play a role in physiological regulation in embryonic growth and differentiation. The mechanisms by which regulation is accomplished in embryonic stages differ from postnatal or adult stages. Oncoproteins responsible for tumors in the adult, i.e., products of proto-oncogenes, are prevented from causing tumors in the embryo. If oncogenes are introduced artificially into the embryo. will they be governed by the embryonic regulation described above? To answer this question we used transgenic mice in which the hybrid construct MSV-SV40-Large-T, composed of the Simian-Virus-Oncogene. Large-T with its SV40-promotor and the Moloney Murine Sarcoma Virus (MSV)-enhancer, had been integrated. Under the influence of large-T expression, these animals develop either brain or endocrine pancreas tumors. In the present investigation, we localised large-T expression during development of mouse embryos and fetuses. Interestingly, we saw large-T positive reactions in organ anlagen other than those that later develop tumors. We found large-T antigens in cartilage anlagen, e.g., in ribs and vertebrae, particularly in fetuses of days 14 to 17, and also in a variety of epithelial cells such as in the lung or the choroid plexus. Our results indicate that, as for proto-oncogene products, the effect of an artificially introduced transgenic oncogene product can also be regulated by embryonic cells.

Animals↗

PubMed1996

Expression pattern of type II collagen mRNA during early vertebral development in the human embryo.

The role of extracellular matrix molecules in ontogenetic differentiation processes is a matter of increasing interest. In cartilage development, type II collagen is suspected of promoting chondrogenic differentiation, since its expression has been demonstrated in a range of precartilaginous tissues of vertebrate species. Up to now, no studies supplying a coherent description of type II collagen expression in the skeletogenesis of human embryos including early embryonic stages have been published. In this work, we examine the temporal and spatial distribution of type II collagen mRNA during vertebral column development in human embryos from 4 to 12 weeks of gestation using non-radioactive in situ hybridization. The onset of gene expression was demonstrable in the 5th week in precartilaginous mesenchymal cells and in notochordal cells. Additionally, we found a weaker hybridization signal in the mesenchymal precursors of the intervertebral discs. In the anlagen of the axial skeleton, type II collagen expression decreased during osteogenic reconstruction in the 11th/12th week, whereas expression continued in the notochordal remnants of the future nuclei pulposi. The results suggest a relatively late occurrence of type II collagen in human vertebral development compared with other vertebrate species. The distribution of gene expression is concordant with a possible role of this molecule in promoting differentiation of mesenchymal cells into chondrocytes. The mechanism of this influence remains to be established.

Cartilage↗

PubMed1996

The extracellular matrix proteins fibulin-1 and fibulin-2 in the early human embryo.

Fibulin-1 and fibulin-2, two recently identified extracellular matrix proteins with a homologous domain structure, are known to bind various extracellular ligands and calcium. In this study, they have been localized at the light microscopical level in human embryos of gestational weeks 4-10, using polyclonal antibodies. Identical localization patterns were observed for the two fibulins in most of the tissues. In the heart, the endocardial cushion tissue and endocardium, but not the myocardium, were stained, as were the basement membrane zones and adventitia of blood vessels. Staining was also observed in the perichondrium and calcifying regions of developing bones. Moreover, reactions occurred with the gut subepithelium and epithelial basement membranes of the skin. Differences in staining patterns, however, were observed in various neural structures. Fibulin-1 was prominent in the matrix of the leptomeningeal anlage, in basement membranes of the neuroepithelium and the perineurium of peripheral nerves. Fibulin-2 was detected primarily within the neuropithelium, spinal ganglia and peripheral nerves. The early embryonic expression of both fibulins indicates specific roles during organ development and, in particular, involvements in the differentiation of heart, skeletal and neuronal structures.

Animals↗

PubMed1996

Immunohistochemical localization of insulin-like growth factor binding protein-1, -3 and -4 in human fetal tissues and their analysis in media from fetal tissue explants.

The actions of insulin-like growth factor (IGF) II that are important in the regulation of fetal growth and development, are modulated by IGF binding proteins (IGFBPs). We have determined the cellular distribution of IGF-II and IGFBP-1, -3 and -4 in 12-week gestation human fetal tissues using immunocytochemistry. IGF-II immunostaining was found in all organs examined, with strongest immunoreactivity in spinal ganglia, tubular cells of the mesonephros and peri- and epidermal layers of the skin. The immunoreactivity distribution of all IGFBPs was similar to that of IGF-II except lung, hepatic parenchyma, fibrocytes of connective tissue and cells of the growth plate in the cartilage. When conditioned media from skin, liver, lung and kidney explants were analyzed, phosphorylated IGFBP-1 was only detected in liver samples whereas IGFBP-3 was found in all media. Weak immunoreactivity of IGFBP-4 was seen in media from lung tissue. To determine whether proteolytic degradation of IGFBPs were responsible for the different IGFBP levels, cell-free conditioned media were incubated with recombinant human IGFBPs. At neutral pH only proteolysis of IGFBP-4 was observed in media from skin and lung tissue. Upon acidification of the medium samples, IGFBP-1 fragments were formed in skin-derived medium and IGFBP-3 was cleaved by medium from lung and kidney tissue. Acid-activated proteolytic activity against IGFBP-4 was found in the media from lung and liver. These findings suggest that IGFBP proteases may be important in locally defining the concentrations of IGFBPs and contribute to tissue-specific growth response to IGFs.

Antibodies, Monoclonal↗