Biomedical subjects

T Aigner

Publications and source records attributed to T Aigner.

At least 73 records · Page 4Linked to original sources

PubMed2000

Rectal stricture associated with the long-term use of ibuprofen suppositories.

Here, we report the case of a 64-year-old woman who suffered from chronic lower backache for which she received ibuprofen suppositories. The patient was admitted to the hospital with a suspected rectal tumor. Clinical examination did not reveal any abnormal finding apart from a mild, bilateral peritibial edema. On rectal examination, an area of stenosis was detected approximately 7 cm above the anal verge. All laboratory parameters, including different tumor markers, were within normal range. Pelvic CT scan and colonoscopy revealed a circular rectal stenosis with severe destruction of the rectal mucosa. The rectal biopsy taken during endoscopy showed severe acute and chronic ulceration, chronic granulation and fibrosis with lymphocytic infiltration. After exclusion of sexually transmitted diseases such as syphilis and lymphogranuloma venerium or exposure to drugs as a possible cause of rectal stenosis, the history in this particular case suggests that the prolonged use of the cyclooxygenase (COX) inhibitor "ibuprofen" as a suppository is the cause of mucosal destruction and rectal stenosis.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Cell differentiation and matrix gene expression in mesenchymal chondrosarcomas.

Mesenchymal chondrosarcomas are small-cell malignancies named as chondrosarcomas due to the focal appearance of cartilage islands. In this study, the use of in situ detection techniques on a large series of mesenchymal chondrosarcoma specimens allowed the identification of tumor-cell differentiation pathways in these neoplasms. We were able to trace all steps of chondrogenesis within mesenchymal chondrosarcoma by using characteristic marker genes of chondrocytic development. Starting from undifferentiated cells, which were negative for vimentin and any other mesenchymal marker, a substantial portion of the cellular (undifferentiated) tumor areas showed a chondroprogenitor phenotype with an onset of expression of vimentin and collagen type IIA. Cells in the chondroid areas showed the full expression panel of mature chondrocytes including type X collagen indicating focal hypertrophic differentiation of the neoplastic chondrocytes. Finally, evidence was found for transdifferentiation of the neoplastic chondrocytes to osteoblast-like cells in areas of neoplastic bone formation. These results establish mesenchymal chondrosarcoma as the very neoplasm of differentiating premesenchymal chondroprogenitor cells. The potential of neoplastic bone formation in mesenchymal chondrosarcoma introduces a new concept of neoplastic (chondrocytic) osteogenesis in musculoskeletal malignant neoplasms, which qualifies the old dogma that neoplastic bone/osteoid formation automatically implies the diagnosis of osteosarcoma.

Apoptosis↗

PubMed2000

Immunolocalization of collagen types II and III in single fibrils of human articular cartilage.

Type II and III fibrillar collagens were localized by immunogold electron microscopy in resin sections of human femoral articular cartilage taken from the upper radial zone in specimens from patients with osteoarthritis. Tissue samples stabilized by high-pressure cryofixation were processed by freeze-substitution, either in acetone containing osmium or in methanol without chemical fixatives, before embedding in epoxy or Lowicryl resin, respectively. Ultrastructural preservation was superior with osmium-acetone, although it was not possible to localize collagens by this method. In contrast, in tissue prepared by low-temperature methods without chemical fixation, collagens were successfully localized with mono- or polyclonal antibodies to the helical (Types II and III) and amino-propeptide (Type III procollagen) domains of the molecule. Dual localization using secondary antibodies labeled with 5- or 10-nm gold particles demonstrated the presence of Types II and III collagen associated within single periodic banded fibrils. Collagen fibrils in articular cartilage are understood to be heteropolymers mainly of Types II, IX, and XI collagen. Our observations provide further evidence for the complexity of these assemblies, with the potential for interactions between at least 11 distinct collagen types as well as several noncollagenous components of the extracellular matrix.

Cartilage, Articular↗

PubMed2000

Cell populations involved in pigmented villonodular synovitis of the knee.

OBJECTIVE: Pigmented villonodular synovitis (PVNS) of the knee is a tumor-like process of uncertain nature. We analyzed the involved cell populations, iron deposition, and cell proliferation in PVNS to propose a pathogenetic concept of this still elusive disease entity. METHODS: The study was performed on a series of 14 cases of localized PVNS of the knee. Histology and histochemistry were used to evaluate basic morphology and iron deposit distribution. Immunohistochemistry was performed to characterize the inflammatory cell infiltrate and to identify the proliferating cell compartments. In situ hybridization analysis using a cDNA probe against type I collagen was utilized to further characterize the mononuclear cell infiltrate. RESULTS: In addition to the classic features (mononuclear cell infiltrate, multinuclear giant cells, iron deposits, and stromal fibrosis) we observed a chronic inflammatory cell infiltrate in all PVNS samples, in which CD8 positive T cells were conspicuous. A high portion of non-phagocytotic cells resorbed iron and became CD68 positive. A proportion of mononuclear cells expressed type I collagen, thus resembling B synoviocytes. CONCLUSION: Our results suggest that preexisting chronic inflammation plays an important pathogenetic role in the PVNS disease process. Chronic inflammation increases the risk of articular bleeding and probably deranges the iron processing capacity of local synovial macrophages. The resulting iron overload could lead to a shift of iron storing cells from synovial macrophages to B synoviocytes and fibroblasts. A perpetuated proliferation and activation of these cells can explain why PVNS behaves like a neoplastic process.

Adult↗

PubMed1999

Is dedifferentiated chondrosarcoma a 'de-differentiated' chondrosarcoma?

Since its first description 30 years ago, dedifferentiated chondrosarcoma has been the prototype of all dedifferentiated sarcomas. The presence of two tumour portions of different mesenchymal differentiation lineages in these neoplasms gives rise to three key questions, which are on the way to being resolved. Does it split up? And if so, how does it split up and when does it split up? Accumulating data provide evidence for a common monoclonal origin of both tumour portions and suggest that dedifferentiated chondrosarcoma is a paradigmatic neoplasm of mesenchymal transdifferentiaton in vivo. Two categories emerge of dedifferentiated chondrosarcomas with different cell biology: the classical one, with a low-grade chondroid component splitting up late, and a second type, with a high-grade chondroid component splitting up early in tumour development.

Bone Neoplasms↗

PubMed1999

Chondroblastoma is an osteoid-forming, but not cartilage-forming neoplasm.

Chondroblastoma is defined as a 'benign tumour, characterized by highly cellular and relatively undifferentiated tissue composed of rounded or polygonal chondroblast-like cells' and the 'presence of cartilaginous intercellular matrix' (WHO). An extensive analysis of the extracellular matrix composition and gene expression pattern of a large series of chondroblastoma cases shows, however, that type II collagen, which is the main component of any cartilage matrix, is not expressed by the neoplastic cells of this tumour entity and is not deposited into the extracellular tumour matrix. Instead, osteoid and fibrous matrix is formed, with its typical biochemical composition. The multifocal expression of aggrecan proteoglycan in most chondroblastomas explains the bluish, pseudo-chondroid appearance of some of the matrix-rich areas of chondroblastomas. This study did not show chondroid matrix formation or chondroblastic cell differentiation in chondroblastomas, suggesting that chondroblastoma should be classified as a specific bone-forming, rather than cartilage-forming neoplasm.

Aggrecans↗

PubMed1999

Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage.

OBJECTIVE: To test for the reexpression of the chondroprogenitor splice variant of the gene COL2A1, type IIA procollagen (containing a cysteine-rich NH2 propeptide), in adult articular chondrocytes in osteoarthritic (OA) joint disease. METHODS: In situ hybridization and immunohistochemical localization were performed on normal and OA articular cartilage specimens. The presence of type IIA procollagen messenger RNA (mRNA) expression was confirmed by Northern blot analysis. RESULTS: In normal articular cartilage, no expression of mRNA or presence of type IIA procollagen was found. In OA articular cartilage, focally intense staining for type IIA protein was detected. Consistent with this, chondrocytes, particularly in the middle zones of articular cartilage, expressed type IIA procollagen mRNA. OA repair cartilage typically showed a broad zone of cells expressing type IIA mRNA and protein. CONCLUSION: Type IIA procollagen is reexpressed by adult articular chondrocytes in OA cartilage degeneration, indicating the potential reversion of the cells to a chondroprogenitor cellular phenotype. The absence of type IIA mRNA and protein in normal adult articular cartilage and its onset in the diseased state suggests type IIA procollagen as a marker of OA.

Adult↗

PubMed1999

Up-regulation of MDC15 (metargidin) messenger RNA in human osteoarthritic cartilage.

OBJECTIVE: The aim of the study was to investigate the messenger RNA (mRNA) expression of the disintegrin metalloproteinase MDC15 (metargidin, or ADAM-15) in normal and osteoarthritic (OA) articular cartilage. METHODS: In situ hybridization experiments and reverse transcription-polymerase chain reaction (RT-PCR) were performed on tissue samples of adult normal and OA articular cartilage. RESULTS: MDC15 mRNA could be detected in normal articular cartilage by RT-PCR using tissue-extracted total RNA as a template. However, the mRNA level remained below the sensitivity of in situ hybridization. In contrast, in situ hybridizations of OA cartilage revealed an intense staining with the MDC15-specific riboprobes. The extension of the analysis to chondrosarcomas showed a strong up-regulation of MDC15 mRNA in these malignant transformed cells. CONCLUSION: Our results demonstrate a markedly strong up-regulation of MDC15 in adult OA and neoplastic cartilage compared with adult normal articular cartilage, indicating a potential role of the disintegrin metalloproteinase in cartilage remodeling.

ADAM Proteins↗

PubMed1999

Pleomorphic adenomas of the parotid express different mesenchymal phenotypes: demonstration of matrix gene expression products characteristic of the fibroblastic and chondrocytic cell lineages.

AIMS: Pleomorphic adenomas of the salivary glands are characterized by their high tissue diversity. Many studies have explored the derivation and differentiation of the neoplastic cells. We investigated the composition of the collagenous extracellular tumour matrix and could show a specific biochemical composition pattern in the different tumour areas. METHODS AND RESULTS: In epithelially differentiated acinar and ductal areas there was positive staining for basement membrane collagen type IV and no, or only scarce, staining for collagen types I, II, III, or VI. Solid areas mostly lacked any extracellular matrix. In areas with fibrous tissue-like appearance, the fibroblast-typical interstitial collagen types I, III and VI were seen. Chondroid areas showed abundantly the characteristic cartilage components, collagen type II and, pericellularly, type VI collagen. CONCLUSIONS: Our data show the presence of fibroblastic and chondrocytic cell differentiation in pleomorphic adenomas. Thus, they confirm that these neoplasms display, besides epithelial cell types, also real mesenchymal cell and tissue types. Differences in the abundance and the biochemical composition of the extracellular tumour matrix account largely for the morphological heterogeneity of pleomorphic adenomas of the salivary glands.

Adenoma↗

PubMed1998

Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland.

Mesenchymal and epithelial cell differentiation are assumed to be dichotomic primary events in embryonic development. In this study, pleomorphic adenomas of the parotid gland were analysed as a model which shows morphological features of both epithelial and mesenchymal tissue types. Using matrix gene expression profiles as a supplementary criterion for the identification of cellular phenotypes, areas with unequivocal epithelial and mesenchymal differentiation could be demonstrated. Many areas displayed a transitional phenotype with cells showing both epithelial and mesenchymal features. The data provide evidence that epithelial-mesenchymal transitions represent the basic principle of the tisuse heterogeneity in pleomorphic adenomas. Thus, pleomorphic adenomas demonstrate the potential of adult (neoplastic) epithelial cells to transdifferentiate into mesenchymal cells in vivo.

Adenoma, Pleomorphic↗

PubMed1998

Severe disturbance of the distribution and expression of type VI collagen chains in osteoarthritic articular cartilage.

OBJECTIVE: The aim of this study was to evaluate the messenger RNA (mRNA) expression and distribution of the major pericellular type VI collagen in normal and osteoarthritic (OA) cartilage. METHODS: Conventional and confocal laser scanning immunohistochemistry, as well as in situ hybridization experiments, were performed for all 3 collagen type VI chains in sections of normal and OA articular cartilage. RESULTS: Normal adult articular chondrocytes were surrounded by a type VI collagen-positive pericellular matrix and showed significant levels of mRNA expression for all 3 type VI collagen chains. In OA cartilage, the expression and overall distribution of type VI collagen was largely increased in the lower middle and upper deep zones. In contrast, the upper zones showed a significant loss of pericellular type VI collagen staining. CONCLUSION: Our results suggest that there is a significant basic turnover of type VI collagen in normal articular cartilage. In OA cartilage, the chondrocytes of the lower middle and upper deep zones account for a net increase in type VI collagen synthesis. The loss of type VI collagen staining in the upper zones is most likely the result of increased protein degradation rather than reduced synthetic activity.

Aged↗

PubMed1998

Variation with age in the pattern of type X collagen expression in normal and scoliotic human intervertebral discs.

The distribution and expression of type X collagen, a calcium-binding collagen, which is a marker of hypertrophic chondrocytes and thought to be involved in cartilage calcification, was examined in situ in nondegenerate (grade I or II) human discs taken at autopsy over a wide age range (fetal->80 years) and also in scoliotic discs removed at surgery. In the fetal vertebral column, type X collagen was strongly expressed in the hypertrophic chondrocytes of the endplate, but was not seen in other areas. In the cartilaginous endplate of adults, it was found over the whole age range examined, with intensity increasing with age. In the disc matrix itself, type X collagen was demonstrated around individual cells from all individuals older than 50 years, but not in any fetal or autopsy disc from individuals younger than 40 years. In scoliotic discs, however, focal type X collagen expression was seen in 3/8 patients younger than 40 years including one 12-year-old. No type X collagen was found in the outer annulus in any autopsy or scoliotic disc, supporting the idea that cells of the outer annulus are phenotypically distinct from cells of the inner annulus and the nucleus. Our results demonstrate for the first time that type X collagen is a possible gene product of the intervertebral disc cells and a potential biochemical component of the disc matrix. They indicate that with age or in scoliosis, some cells from the inner annulus or nucleus of the disc differentiate to the hypertrophic chondrocyte phenotype. This might be the initiating event for the abnormal calcification described in aged and scoliotic discs in other studies.

Adolescent↗

PubMed1998

De-differentiated chondrosarcoma is not a 'de-differentiated' chondrosarcoma.

AIMS: De-differentiated chondrosarcoma is characterized by the presence of two distinct chondroid and nonchondroid tumour portions. The aim of our study was to investigate the distribution of extracellular matrix components in this tumour entity and thus to shed light on its histogenetic origin. METHODS AND RESULTS: Histochemical and immunohistochemical analyses were performed for collagen subtypes I, II, III and VI and cartilage proteoglycans in three samples of de-differentiated as well as conventional chondrosarcomas (various grades). In the chondroid tumour areas of de-differentiated chondrosarcoma, typical cartilage matrix components could be detected similar to chondroid areas of grade 1 and 2 conventional chondrosarcomas. In contrast, the tumour matrix of the nonchondroid portions of de-differentiated chondrosarcomas contained matrix molecules which are typical for fibroblastic tissue. This matrix composition was not identical with less differentiated (nonchondroid) areas of grades 2 and 3 conventional chondrosarcomas. CONCLUSIONS: Our results confirm the chondroid nature of the differentiated portion of de-differentiated chondrosarcoma and indicate a nonchondrocytic nature of the nonchondroid portion. De-differentiated chondrosarcoma should not be considered as a 'de'-differentiated chondrosarcoma (grade 4 neoplasm), but as a tumour entity showing two types of mesenchymal differentiation.

Adult↗

PubMed1998

Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits.

OBJECTIVE: Durable healing of full-thickness articular cartilage defects has been considered for a long time as a highly desirable, but unlikely event to occur. In recent years, conflicting reports on the outcome of in vitro and in vivo studies on chondrocyte and cartilage grafting into animal and human joints have raised new arguments for and against controlled repair of articular cartilage following injury. Some of the problems result from insufficient characterization of implant and repair tissue, and from too short follow up phases. Here we describe a new approach to repair articular cartilage defects in rabbit knees by allografting chondrocytes cultured in agarose gels. DESIGN: The implants were monitored over 6-18 months and graded histologically, immunohistochemically, and electron microscopically, using a grading scale based on seven evaluation criteria. Control implants of pure agarose produced poor fibrous substitute tissue, insufficient healing and incomplete filling of the cartilage defects. After transplantation of allogenic chondrocytes embedded in agarose, the quality of the newly formed repair cartilage was superior with respect to type II collagen and proteoglycan content and cellular architecture when compared with untreated defects. Superficial fibrillation and degradation were significantly diminished or prevented. RESULTS: New subchondral bone formed at the level of the previous subchondral bone. In most cases the repair tissue merged with the host articular cartilage; normal calcified cartilage was the only tissue zone that did not participate in the integration of the transplant. By gross evaluation 24% of grafts showed an extent of recovery never observed in controls. The best results were obtained after 18 months when 47% of the grafts (N = 15) developed a morphologically stable hyaline cartilage. CONCLUSION: These studies demonstrate that agarose-embedded chondrocyte may prove a valuable tool for controlled repair of articular cartilage defects.

Agar↗

PubMed1998

[Matrix gene expression pattern as indicators of the biology of cartilage-forming tumors].

Mesenchymal cells can be characterized by the expression of specific sets of extracellular matrix (ECM) proteins. The aim of our study was to identify such expression pattern in cartilage-forming tumours in order to elucidate the biology of these neoplasms. In situ hybridisation and immunohistochemistry for various ECM components were performed on enchondromas, conventional chondrosarcomas of various grades and dedifferentiated chondrosarcomas. Chondroid areas of all investigated neoplasms showed strong expression of cartilage collagen types II and IX and aggrecan core and link protein. Focally, also the expression of other collagen subtypes such as collagen type X and collagen types I and III was observed. Non-chondroid areas of dedifferentiated chondrosarcomas lacked any expression of the cartilage-typical gene products and were instead positive for interstitial collagen types I, III, and VI. The hallmark of all investigated cartilaginous neoplasms was the expression of the chondrocyte-typical genes. Neoplastic chondrocytes showed the differentiation facettes similar to their physiological counterparts resulting in the high heterogeneity, which is characteristic for chondrogenic neoplasms. A different biology is suggested for dedifferentiated chondrosarcomas, in which the "dedifferentiated" portion is proposed to have a separate (e.g. fibroblastic) mesenchymal origin.

Bone Neoplasms↗

PubMed1998

[Iron deposits, cell populations and proliferative activity in pigmented villonodular synovitis of the knee joint].

Pigmented villonodular synovitis (PVNS) of the knee is a tumor-like process of uncertain nature. A chronic inflammation as well as a neoplastic process have been proposed in the literature. The aim of our study was to characterise the prevalent inflammatory cells, the proliferating cell populations, and the iron deposit distribution in PVNS in order to get insights into pathogenetically relevant processes of this condition. Thirteen cases of PVNS of the knee as well as 8 normal controls were analysed histochemically for iron deposits and immunohistochemically for the distribution of vascular structures and inflammatory cell populations. Collagen type I expressing fibroblastic cells were identified by in situ hybridization. The proliferative cell compartment was characterized using MIB-1 staining. Our analysis showed no correlation between intra- or extracellular iron deposits and proliferation, giant cell formation, vascularity, number of CD 68-positive cells, and foam cell formation. Instead, iron deposits were associated with collagen matrix formation. All PVNS specimens showed a significant increase of chronic inflammatory infiltrates compared to all normal synovial membrane specimens investigated. The identification of the proliferative cell compartments showed that besides fibroblastic cells many of the mononuclear, partly CD 68 positive cells were Ki-67 positive. Foam cells, iron-loaded cells, and giant cells were, however, negative for the Ki-67 antigen. PVNS appears to originate from the interplay of proliferating, partly CD 68 positive mononuclear cells and fibroblasts, both activated by an excessive iron load. Giant cells probably develop by fusion of CD 68-positive histiocytic cells. Foam cells are most likely secondary to fatty tissue destruction.

Antigens, CD↗

PubMed1997

Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage.

OBJECTIVE: To evaluate the anabolic activity of osteoarthritic chondrocytes in situ by investigating the messenger RNA (mRNA) expression of 3 major cartilage components, type II collagen, aggrecan, and link protein: METHODS: In situ hybridization experiments and histochemical analysis for proteoglycan content were performed on parallel sections of normal and osteoarthritic (OA) cartilage specimens. RESULTS: Most chondrocytes in the deeper.zones of OA cartilage showed an increase in mRNA expression, in particular, of type II collagen and to a lesser extent, aggrecan, compared with normal specimens. However, chondrocytes of the upper zone were largely negative for aggrecan or type II collagen mRNA. The expression of link protein mRNA was low in normal and OA specimens. CONCLUSION: These observations suggest that suppression of the anabolic activity of chondrocytes in the upper zones contributes to the metabolic imbalance observed in OA cartilage. Stimulation of matrix anabolism in superficial chondrocytes might be a suitable target for therapeutic intervention.

Aged↗

PubMed1997

Spatial and temporal development of the gliovascular tissue in type II lissencephaly.

Type II lissencephaly is a complex cortical malformation in which mesenchymal and central nervous components are intermingled. It is generally believed that the histological pattern is created by migration of heterotopic neuroblasts into the leptomeninges through defects in the superficial basement membrane. Defects of the extracellular matrix have been suggested to be the primary cause of type II lissencephaly. To elucidate the underlying pathogenetic mechanisms, we immunostained extracellular matrix and basement membrane components of the cerebral cortex from six fetal and two infantile brains. We found that the pattern of collagen subtypes I, III and VI was not altered in type II lissencephaly brains when compared to normal controls. As to the pathogenesis of type II lissencephaly, a polymicrogyria-like pattern is created, which results in considerable cortical enlargement. The microgyri do not fuse but remain separated from each other by gliovascular tissue, i.e., leptomeninges which contain astrocytes. At the interface between the enlarged brain surface and the gliovascular tissue, neuronal migration takes place through gaps in the external basement membrane. Thus, the cortical dysplasia encountered in type II lissencephaly is only due to a limited amount to neuronal heterotopia in the leptomeninges.

Astrocytes↗