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Biomedical subjects

A Nerlich

Publications and source records attributed to A Nerlich.

At least 55 records · Page 3Linked to original sources
PubMed1997

Localization of transforming growth factor-beta-expressing cells and comparison with major extracellular components in aural cholesteatoma.

Transforming growth factor-beta (TGF-beta) plays an important role in the regulation of extracellular matrix (ECM) deposition by stimulating the synthesis of individual matrix proteins like tenascin and fibronectin. Cholesteatoma shows significant changes in the ECM, supporting the view of a disturbed cell-matrix interaction. The purpose of our present study was to evaluate the distribution of TGF-beta in comparison to the deposition of tenascin, fibronectin, and collagen as major components of the ECM in cholesteatoma (n = 12) by means of histochemistry and immunohistochemistry. We found TGF-beta in lymphocytes and fibrohistiocytes in the stroma of 7 cholesteatomas. In corresponding sections, a marked expression of tenascin and fibronectin was seen manifesting as a continuous band along the epidermal-stromal junction, extending to the deeper stroma. In addition, in those cases of TGF-beta expression, beginning collagen fibril formation was seen in adjacent deeper stroma layers, indicating beginning stromal fibrosis. These results suggest that TGF-beta may be involved in the stimulation of the synthesis of tenascin, fibronectin, and collagen. Furthermore, the enhanced expression of tenascin and fibronectin provides evidence for a deregulated cell-matrix interaction in cholesteatoma associated with the enhanced proliferative process of cholesteatoma formation.

Cholesteatoma, Middle Ear↗
PubMed1997

[Cultivated keratinocytes on micro-carriers: in vitro studies of a new carrier system].

Epidermal grafts from confluently cultivated keratinocytes have been used since the early eighties for the treatment of severe burns, where the shortage of donor sites for split-thickness skin grafts did not allow for adequate wound coverage. The difficult handling of these grafts as well as the advanced differentiation of their epithelial cells into a multilayer sheet poses a problem for their clinical application. The aim of the study was to characterize cultivated keratinocytes, as well as to observe their migration and proliferation from the MC onto a surface. Keratinocytes were isolated from human foreskin and cultivated in serum-free and serum-containing medium according to a modified method by Rheinwald and Green. Collagen-coated Dextran beads were used as MC. The MC were colonized with keratinocytes using the Spinner culture technique. After seeding the colonized MC into culture flasks, their migration and proliferation was monitored regularly through immunohistochemical studies and measurement of the metabolic cell activity. Immunohistological staining proved that the cells isolated from human foreskin represent keratinocytes of the basal type. Keratinocytes, cultivated with serum-containing and serum free medium, both adhered to the surface of the MC, then migrated onto the surface of the flasks and proliferated to form a multilayer of epithelial cells. In the long-term, a flexible epithelial graft consisting of poorly differentiated keratinocytes should be available, which is simple to produce and easy to handle. This would be an alternative method for treating wounds, where the conventional multilayer epithelial graft (ET) is insufficient.

Burns↗
PubMed1996

In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia.

Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-beta 1. In human fetal controls bFGF was the most potent growth factor. Clonal growth the articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-beta 1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect.

Cartilage, Articular↗
PubMed1996

Type II collagenopathies: are there additional family members?

The type II collagenopathies represent a group of chondrodysplasias sharing clinical and radiological manifestations which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal to very mild conditions. Their common molecular bases are mutations in the type II collagen gene (COL2A1). We describe one case of lethal platyspondylic dysplasia, Torrance type, and a variant of lethal Kniest dysplasia, neither of which has been reported as a type II collagenopathy. Biochemical studies of cartilage collagens and morphological analysis of cartilage sections suggest that abnormalities of type II collagen structure and biosynthesis are the main pathogenetic factors in both cases. Thus, the phenotypic spectrum of type II collagenopathies might be greater than hitherto suspected.

Bone Development↗
PubMed1996

Total replacement of the mitral apparatus with a stentless, chordally supported mitral valve allograft: an experimental study.

Mitral valves, including the papillary muscles, were harvested from freshly slaughtered sheep and implanted in 10 recipient growing sheep. A strip of ovine pericardium was used to reinforce the anulus and a patch of expanded polytetrafluoroethylene was used to cover the donor papillary muscle. In four valves the natural chordae tendineae at the anterior cusp were supported by two pairs of 5-0 expanded polytetrafluoroethylene sutures. At the beginning of the experiment two animals died early of valve incompetence. Another animal had to be put to death because of paraplegia after extracorporeal circulation and one died on postoperative day 41 of endocarditis. Six sheep were electively put to death, five after 153 +/- 8 days and one after 43 days. At the time of follow-up, a complete hemodynamic study including echocardiography and stress testing was performed. Heart rate at rest was 91 +/- 14 beats/min, left ventricular systolic pressure 96 +/- 20 mm Hg, left ventricular end-diastolic pressure 11 +/- 5 mm Hg, cardiac output 2.04 +/- 0.40 L/min, and the mean transvalvular pressure gradient was 4.9 +/- 2.8 mm Hg as measured by cardiac catheterization. Echocardiography showed excellent movement of all valve components. However, minor regurgitation was evident in one case. Gross morphologic characteristics showed good healing at the anulus and host papillary muscle; in one case there was a rupture of one small first-order chorda. On radiography no signs of calcification were evident. Light microscopy revealed minor to moderate collagen degeneration in all valve components. However, on electron microscopy the presence of numerous fibroblasts within the long-term implants indicated the biosynthesis of new collagen. In summary, allograft mitral valve replacement seems to be a promising procedure if the chordae tendineae are reinforced by expanding polytetrafluoroethylene sutures.

Animals↗
PubMed1996

Structural and functional changes in diabetic glomerulopathy.

Diabetic nephropathy is characterized by glomerular basement membrane thickening and mesangial expansion. Immunohistochemical studies of diabetic kidneys showed an increased collagen type IV synthesis and deposition in the mesangial matrix, while the glomerular heparan sulfate proteoglycan content was decreased. In nodular glomerulosclerosis massive deposition of collagens III and VI appears, possibly indicating irreversibility of the pathological process. These structural changes seem to be the underlying cause for the alterations of renal functions like persistent albuminuria and proteinura. In a recent study significant glomerular infiltration by macrophages at all stages of glomerulosclerosis was observed. The pathogenesis of the multitude of cellular, structural, and functional abnormalities in diabetic nephropathy is likely to be multifactorial, involving chronic hyperglycemia as well as genetic determinants. In vitro studies with cultured glomerular cells have indicated that hyperglycemia induces transforming growth factor beta, a matrix-producing cytokine. The hyperglycemia-induced cytokine production may involve protein kinase C activation and/or the formation of advanced glucosylation end products. The elucidation of the pathogenesis of diabetic nephropathy may suggest new ways for therapeutic interventions.

Animals↗
PubMed1996

Primary leiomyosarcoma affecting the ankle joint.

In a 50-year-old patient with a malignant tumor of the left distal tibia (stage la, according to Enneking) undermining the cartilage of the ankle joint, an extremely rare primary leiomyosarcoma of bone was diagnosed. The diagnosis of a primary leiomyosarcoma of bone is possible only after a secondary (metastatic) leiomyosarcoma has been excluded. Furthermore, typical histopathological features, including immunohistochemical staining results, are required for the diagnosis. Surgery is the therapy of choice. An R0 resection should always be attempted.

Adolescent↗
PubMed1996

Overexpression of tenascin in cholesteatoma and external auditory meatal skin compared to retroauricular epidermis.

In the present study the distribution of tenascin in cholesteatoma was immunohistochemically investigated. The results were compared with those in external auditory meatal skin and in retroauricular skin of healthy controls. The staining pattern was additionally correlated to the degree of cell proliferation as detected by the monoclonal antibody MIB-1 (Ki-67 antigen). Retroauricular skin showed a limited distribution of tenascin in the papillary dermis and a sparse reactivity of MIB-1 in only a few epithelial cells. External auditory meatal skin revealed a more pronounced reaction for tenascin and MIB-1. In contrast, cholesteatoma tissue exhibited an abundant and continuous expression of tenascin covering the whole stroma compartment. This coincided with a significant increase of MIB-1-positive cells in the basal and suprabasal epithelial layers. Doublestaining experiments revealed most prominent stromal tenascin-expression in areas with marked signs for epithelial proliferation. This suggests that tenascin is selectively increased in response to epidermal hyperproliferation. This matrix protein thus shows a quantitatively and qualitatively enhanced expression under pathological conditions. Moreover, the abundant reactivity for tenascin in the cholesteatoma provides evidence of a deregulated cell-matrix interaction involved in the hyperproliferative process of cholesteatoma formation.

Case-Control Studies↗
PubMed1996

Increased glomerular alpha 1 (IV) collagen expression and deposition in long-term diabetic rats is prevented by chronic glycosaminoglycan treatment.

Diabetic nephropathy is associated with thickening of the glomerular basement membrane and, in particular, with mesangial matrix expansion. Previous studies have indicated that administration of chemically modified, low-anticoagulant heparins prevents some of the morphologic and physiologic alterations occurring in experimental diabetic nephropathy. The effect of prolonged heparin treatment on the glomerular expression and deposition of alpha 1 (IV) collagen, which is a major component of the mesangial matrix, has not been reported previously. Four groups of rats were studied for 12 months: two control groups and two groups of streptozotocin-diabetic rats. One group in each branch received modified heparin continuously from the induction of diabetes. After 12 months synthesis and deposition of alpha 1 (IV) collagglomerula and adjacent tubuli were determined by nonradioactive in situ hybridization and immunohistochemistry. Mesangial cells were localized by Thy 1.1 staining. Long-term diabetes caused a significant increase in alpha 1 (IV) collagen deposition in the mesangial matrix and a more than 2-fold enhancement of glomerular cell alpha 1 (IV) collagen transcript levels, mainly in mesangial cells. The alpha 1 (IV) collagen mRNA levels of proximal tubular cells and visceral epithelial cells were similarly increased. Chronic treatment of diabetic rats with modified heparin completely prevented the increased alpha 1 (IV) collagen deposition and expression. The increased glomerular deposition of alpha 1 (IV) collagen observed in long-term streptozotocin diabetic rats appears to depend on an increased alpha 1 (IV) collagen synthesis. Because chronic application of low-anticoagulant heparin completely prevents the increased alpha 1 (IV) collagen synthesis by mesangial cells, this result suggests a new therapeutic option for the prevention of diabetic nephropathy in humans.

Animals↗
PubMed1995

[Spontaneous hemothorax in dermatomyositis and long-term glucocorticoid treatment].

A 65-year-old woman with dermatomyositis for which she had been treated for ten years with prednisone (latterly 15 mg daily) suddenly experienced severe pain in the left thoracolumbar region. Cardiovascular, pulmonary and vertebral causes of the pain were excluded. But serological tests indicated inflammatory disease and the haemoglobin concentration was low (10.4 g/dl). Left pleural effusions were repeatedly aspirated and some haemorrhagic fluid obtained (haematocrit 0.31 in blood, 0.28 in the pleural effusion). Five days after admission her cardiovascular status became unstable and she developed respiratory failure (haemoglobin 7.6 g/dl). Chest radiograph showed increased pleural effusion. Subsequent thoracotomy revealed a left coagulothorax which was removed and flushed. During this procedure severe bleeding occurred from a covered perforation of the descending aorta, 1.5 x 1.5 cm in size. Although the aortic wall was thin, there was no aneurysm but arteriosclerotic changes and an external erosion near an abscessing mediastinitis, originating from a chronic purulent pleuritis and bronchopneumonia. The severe blood loss caused circulatory failure from which the patient could not be resuscitated.

Aged↗
PubMed1995

Different techniques of laparoscopic end-to-end small-bowel anastomoses.

The aim of the study was to prove that laparoscopic stapling devices can be used to create a bowel anastomosis. Three groups with n = 6 pigs each were subjected to different techniques of small-bowel anastomoses. In groups I and II anastomosing of the bowel ends was carried out with singly placed staples using a hernia stapler. (Group I: Two-thirds of the circumference became inverted and one-third everted. Group II circumferentially everted). In group III triangular everted anastomoses were produced using a linear noncutting stapler. All animals survived the observation period of 14 days and were postmortally examined. Average construction time was 59 min for groups I and III and 47 min for group II. Average diameters were 14 mm, 16 mm, and 18 mm for groups I, II, and III, respectively. There were no significant differences between the techniques concerning the stability of the anastomoses as expressed by bursting pressures. There were two stenoses in group I animals caused by electrocautery during preparation of the bowel ends prior to anastomosing. Anastomotic insufficiencies or fistulas were not observed clinically or with Gastrografin studies. We conclude that anastomoses in the pig can laparoscopically be constructed by employing singly placed staples as well as a linear stapler. Further investigations of these techniques on large bowel and human specimens are required prior to their clinical use in humans.

Anastomosis, Surgical↗
PubMed1995

Expression of osteoblastic markers in cultured human bone and fracture callus cells.

We compared the expression of osteoblastic markers in cultured human cells isolated from fracture calluses of various histological states of development with that in cells from adult and fetal bone. Adult osteoblasts and all callus cells produced almost exclusively type I collagen, whereas fetal osteoblasts produced also considerable amounts of type III collagen in vitro. 1,25-Dihydroxyvitamin D3 induced the synthesis of osteocalcin in all bone and callus cells but to varying extents. Fetal bone cells and early-stage callus cells synthesized less than 10% the amount of osteocalcin produced by adult bone cells. Late-stage callus cells produced intermediate levels of osteocalcin. Fetal bone cells and early-stage callus cells responded to parathyroid hormone with a less pronounced increase in intracellular cAMP than did adult bone cells. Late-stage callus cells showed the best response to parathyroid hormone. The activity of alkaline phosphatase was highest in fetal bone cells. These observations show that cells isolated from fetal bone and from fracture callus tissues express a pattern of markers clearly relating them to the osteoblastic lineage. On the basis of the different patterns of osteoblastic markers expressed in vitro we conclude that functionally distinct subtypes of osteoblasts do exist in different mineralized tissues and at different developmental stages.

Adult↗
PubMed1995

Experimental directional atherectomy injury in arterial vessels: impact of trauma depth on cellular response.

This study investigates cellular alterations after directional atherectomy vessel injury (DI) in an experimental model in 50 pigs. Two hundred arteries were excised at eight different times (2 hours to 21 days) after DI and were examined by electron microscopy and immunohistochemistry. The extent of injury varied with the number of repetitive passes of the atherectomy catheter. According to the extent of injury the vessel segments with DI were assigned to three groups: intima injury (group 1), media injury (group 2), and adventitia injury (group 3). A myoproliferative response was found in relation to DI depth, increasing from group 1 (ratio tissue hyperplasia/media: 0.3 +/- 0.2; p < 0.001) to group 2 (ratio tissue hyperplasia/media: 1 +/- 0.5) and group 3. Intense neutrophil infiltration occurred in groups 2 and 3 (peak 12 hours after DI) and was followed by the early occurrence of synthetic smooth-muscle cells (SMC; > 50% of all SMC present). Volume fraction of desmin and actin was transiently reduced in injured media and myoproliferative tissue (7d: 9% vs > 90% normal media). SMC proliferation started in groups 2 and 3 at 48 hours and peaked at 7 days (+500% vs normal media, p < 0.001). After DI was done, vascular response started immediately and depended on injury depth. A transient myoproliferative response resulted, correlating with the extent of vessel trauma.

Actin Cytoskeleton↗
PubMed1995

Molybdenum co-factor biosynthesis: the Arabidopsis thaliana cDNA cnx1 encodes a multifunctional two-domain protein homologous to a mammalian neuroprotein, the insect protein Cinnamon and three Escherichia coli proteins.

The molybdenum co-factor (Moco) is an essential part of all eukaryotic molybdoenzymes. It is a molybdopterin and reveals the same principal structure in eubacteria, archaebacteria and eukaryotes. This paper reports the isolation of cnx1, a cDNA clone of Arabidopsis thaliana which complements the Escherichia coli Moco mutant mogA. The mapping data of this cDNA correlate well with the mapping position of the A. thaliana molybdenum co-factor locus chl6. As mutants in chl6 are known to be repairable by high concentrations of molybdate, the defective gene is very likely to be involved in the last step of Moco biosynthesis, that is, the insertion of molybdenum into molybdopterin. The protein encoded by cnx1 shows a two-domain structure: the N-terminal domain is homologous to the E. coli Moco protein MoeA, the C-terminal domain is homologous to the E. coli Moco proteins MoaB and MogA, respectively. These homologies show that part of the prokaryotic Moco biosynthetic pathway accomplished by monofunctional proteins in E. coli, is performed by a single multifunctional protein in eukaryotes. In addition Cnx1 is homologous to the eukaryotic proteins Gephyrin, a rat neuroprotein, and Cinnamon, a Drosophila protein with a function in Moco biosynthesis. These proteins also show a two-domain structure but the order of the domains is inversed as compared with Cnx1. Southern analysis indicates the existence of at least one further member, in addition to the cnx1 gene, of this novel gene family in the Arabidopsis genome.

Amino Acid Sequence↗
PubMed1995

Lobar emphysema and atelectasis syndrome, a nosological unity.

Shrinking and atelectatic pulmonary processes--atelectasis syndrome--and lobar emphysema show morphological similarities: congenital malformations of the bronchial structure, external compression of the bronchi as well as inflammatory processes. Ventilation mechanics determine whether in the described processes an atelectasis or an emphysema manifests itself clinically. Usually, one finds over-expansions in connection with atelectasis syndrome and atelectases together with lobar emphysema. Both processes can be reversible, if we are not dealing with bronchial malformations. Longer lasting processes as well as acute, life threatening forms require operation. The belief that atelectasis syndrome and lobar emphysema constitute a nosological unity is illustrated by our cases of 9 patients with atelectasis syndrome and 16 patients with lobar emphysema.

Bronchi↗
PubMed1995

Increased expression of type VI collagen in lung fibrosis.

Pulmonary fibrosis is characterized by disturbances of extracellular matrix protein deposition resulting from fibroblast activation and proliferation. Collagen VI, forming microfibrillar meshworks separate from major fibrillar systems, is thought to serve as an anchoring element between collagen I/III fibrils and basement membranes and as a cell binding substrate. We report on the expression of collagen VI in normal and in fibrotic lungs. Collagen VI is present in vascular and bronchial walls and in the interstitial space of normal lungs. Its turnover is too low to generate a mRNA signal by in situ hybridization. Collagen VI expression is increased in lung fibrosis, and its degree appears independent of the etiology of fibrosis. There was no evidence for differential regulation of gene expression for the alpha 1(VI) and alpha 3(VI) constitutive peptide chains of collagen VI. Collagen VI mRNA is expressed by fibroblasts, mostly with myofibroblast characteristics. Collagen VI was coexpressed with collagen III rather than collagen I in idiopathic bronchiolitis obliterans with organizing pneumonia, acute interstitial pneumonitis of the Hamman-Rich type, and bleomycin-induced fibrosis, but collagen VI overlapped with collagen types I and III in idiopathic pulmonary fibrosis. These coexpression data suggest that collagen VI expression may be an early rather than a late phenomenon in pulmonary fibrosis.

Collagen↗