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Biomedical subjects

T Krieg

Publications and source records attributed to T Krieg.

At least 235 records · Page 13Linked to original sources
PubMed1987

[Epidermolysis bullosa hereditaria dystrophica (Hallopeau-Siemens). Case report and therapy trial with (+)-cyanidanol-3 in 3 patients].

The diagnosis of hereditary epidermolysis bullosa dystrophica (Hallopeau-Siemens) in three patients was confirmed by clinical and histological means as well as by electron microscopy. The clinical course was followed for many years. Since (+)-cyanidanol-3 has been shown to reduce the susceptibility of collagen to mammalian collagenase under in vitro conditions, (+)-cyanidanol-3 was used to treat the three patients for a period of 27 weeks. A decrease in the amount of blistering was observed in all three patients.

Adult↗
PubMed1986

[The antinuclear antibody spectrum in circumscribed forms of scleroderma].

Sera from 56 patients with circumscribed scleroderma (CS) were tested for the presence of antinuclear antibodies (ANA) by indirect immunofluorescence on HEp-2-cells. 16 patients (28.6%) had ANA, mostly in low titers of 1: 40 and with uncharacteristic fluorescence patterns. Nucleolar antibodies as in progressive systemic sclerosis were seen in a few cases only. Two female patients demonstrated antibodies with a centromere-like pattern. ANA were most frequently found in patients with atrophodermia idiopathica progressiva (60%) and in linear CS (44%). Rheumatoid factor was present in 62% of patients with linear CS; it was less frequent in other forms of CS. Antibodies against double-stranded DNA were found only in one female patient, but three patients with systemic involvement had antibodies to single-stranded DNA. Antibodies to soluble nuclear Scl-70, Ul-RNP and LA(SSB) antigens or to the cytoplasmatic Ro(SSA)-antigen, respectively, were not detected in the patients with CS. These results demonstrate that humoral autoimmune phenomena may occur in CS, mainly in patients with linear CS. These phenomena, however, are less frequent and specific than in progressive systemic sclerosis or in other collagen vascular diseases.

Adolescent↗
PubMed1986

Defective attachment of dermatosparactic fibroblasts to collagens I and IV.

Attachment of fibroblasts from dermatosparactic sheep and cattle to collagenous substrates (types I and IV) is defective (30-50%) when compared with fibroblasts from normal or heterozygous animals. The difference was independent of the amount of substrate, incubation time and protein synthesis. No differences were observed in the binding to fibronectin or laminin. Reduced attachment to collagen can be partially restored by adding fibronectin. The polygonal morphology of dermatosparactic cells was, however, not altered by attachment and growth on dishes coated with different collagens or fibronectin. Reduced interaction with collagens could be due to changes in specific receptors and may represent a further pathological change in dermatosparactic animals.

Animals↗
PubMed1986

Type III collagen aminopropeptide levels in serum of patients with progressive systemic scleroderma.

Sera from 101 patients with progressive systemic scleroderma were analyzed for circulating aminopropeptides of type III collagen using a radioimmunoassay which measures the intact and degraded forms (Fab assay). About 41% of the patients were found to have values above the normal range. A good correlation was observed between elevated levels of aminopropeptides and the degree of involvement of the skin and internal organs in the patients. Most patients (89%) with an active progression of the disease but not those in a stationary phase showed increased serum levels of aminopropeptides. Treatment with corticosteroids apparently normalized the levels of aminopropeptides. Only minor changes were observed with an antibody-based radioimmunoassay which measures primarily the intact form of the aminopropeptide.

Adult↗
PubMed1986

Modulation of collagen type synthesis in organ and cell cultures of fibroblasts.

Fibroblast cultures are widely used to study abnormalities of collagen metabolism in both inborn and acquired diseases. However, there is reason to question the extent to which the experimental information obtained from in vitro culture systems in fact reflects the in vivo situation. In the present study we analyzed the proportions of collagens I and III synthesized by human and mouse skin fibroblasts maintained under various culture conditions. The amount of type III collagen extracted from skin specimens was lower than that which was newly synthesized in organ culture. Cells obtained by enzymatic disintegration of skin specimens synthesized more type III collagen than fibroblasts grown from explants. However, subcultivation of the enzymatically liberated cells resulted in a continuous decline of type III collagen production which eventually reached levels similar to those observed in explant cultures.

Animals↗
PubMed1986

Contraction of collagen lattices by fibroblasts from patients and animals with heritable disorders of connective tissue.

Fibroblasts derived from patients and animals presenting various heritable connective tissue disorders were investigated for the ability to retract a reconstituted collagen matrix. When seeded into gels, dermatosparactic calf and sheep fibroblasts did not exhibit the elongated shape of normal fibroblasts and did not contract the collagen lattice to the same extent as control fibroblasts. In contrast, several cell strains obtained from patients with Ehlers-Danlos syndrome type VII displayed contractile properties for collagen gels similar to controls. Delayed contraction was noted by two strains of fibroblasts from patients with Ehlers-Danlos syndrome type IV, whereas fibroblasts from patients with osteogenesis imperfecta, Marfan syndrome and cutis laxa had normal retraction properties.

Adult↗
PubMed1986

[Hereditary bullous epidermolyses. Recent aspects of diagnosis and therapy].

The introduction of antibodies specific for distinct basement membrane zone components is helpful in the diagnosis of hereditary mechanobullous diseases. In addition, these reagents have implications for investigation of the pathogenesis of these disorders, which might help to establish the classification based on molecular defects. Antibodies by means of indirect immune fluorescent microscopy can play a key role in the differential diagnosis of junctional and dystrophic types of epidermolysis bullosa. In epidermolysis bullosa hereditaria dystrophica, a disturbance in the regulation of collagenase activity has already been well documented, and several therapeutic approaches have been carried out based on the inhibition of collagenase activity. Concomitant inhibition of collagenolytic activity and stabilization of collagen fibrils might furthermore be helpful in the treatment of these patients. There are already several reports on the therapeutic effects of collagenase inhibitors, and stabilization of collagen fibrils in vitro has been demonstrated by (+)-cyanidanol-3. The preliminary results on therapeutic application of this drug seem to be promising.

Antibodies, Monoclonal↗
PubMed1985

Fibromatosis hyalinica multiplex (juvenile hyalin fibromatosis). Light microscopic, electron microscopic, immunohistochemical, and biochemical findings.

Fibromatosis hyalinica multiplex juvenilis (juvenile hyalin fibromatosis) is a very rare mesenchymal dysplasia, probably inherited as an autosomal-recessive trait. Two nonrelated cases are reported. Among the clinical features, the most impressive lesions are multiple slowly growing subcutaneous nodules, hypertrophic gingiva, flexural contractures with joint stiffness and radiolucent bone destructions. Light microscopic examination of the nodules reveals tumor-like deposits of an amorphous hyaline ground substance with delicate staining properties situated partly between cellular and vascular areas. Ultrastructural characteristics are cystic, dilated rough endoplasmatic reticulum and cystic Golgi vesicles which contain a fine fibrillar material that is also found in the ground substance. Immunohistochemical examination shows collagen type I and type III in the hyaline material, but not type II and type IV. Quantitative biochemical investigation reveals a normal ratio of collagen types I and III.

Adolescent↗
PubMed1985

The fibroblastic nature of dermatofibrosarcoma protuberans: morphological investigations in vivo and in vitro.

Six cases of dermatofibrosarcoma protuberans were studied ultrastructurally. Biopsy material from all six cases as well as cell cultures derived from four cases were examined. In all cases, the tumor cells in vivo and in vitro were related to fibroblasts. The two cases with histiocytoid features and a small spiral pattern exhibited numerous lipid vacuoles but no histiocytic cell markers. In these two cases, cultured cells contained a higher number of intracytoplasmic vacuoles than the control fibroblasts. Two other cases exhibited some basement-membrane-like material surrounding tumor cells. All of the investigated cell strains obtained from the tumors showed synthesis of collagenous proteins similar to that found in fibroblasts. However, the level of total collagen was reduced, and type-III collagen was absent. The morphological variations in these cases of dermatofibrosarcoma protuberans appeared to be related to the histological pattern and may reflect the heterogeneity of normal fibroblasts.

Adult↗
PubMed1985

Collagen synthesis in scleroderma: selection of fibroblast populations during subcultures.

In progressive systemic scleroderma, excessive deposition of collagen leads to fibrosis of several tissues including the skin. It has been found that different populations of fibroblasts are present in scleroderma skin; these can be obtained by establishing cell cultures from different layers of the involved skin. Excessive overproduction of collagen was noted in primary cultures of cells obtained from deeper layers of the skin of patients in an early stage of the disease, whereas control fibroblasts did not manifest significant variations dependent on the layers of skin used to initiate the cultures. The synthesis of type-I and -III collagen was found to be altered concomitantly. The production of collagen and collagenous proteins was then followed during subcultivations of overproducing fibroblasts. In many cell strains, increased synthesis of collagen and/or non-collagenous proteins had already been lost after the first subcultivation, whereas overproduction was stable in others. However, after five passages, most of the cultures showed normal collagen synthesis, which probably indicates a loss of phenotype due to successive subcultures or overgrowth by another population of fibroblasts.

Adult↗
PubMed1985

Collagen biosynthesis in systemic scleroderma: regulation of posttranslational modifications and synthesis of procollagen in cultured fibroblasts.

Activities of prolyl hydroxylase (PH), lysyl hydroxylase (LH), and the collagen glycosyltransferases and the extent of the posttranslational modification of lysine residues in newly synthesized collagen were studied in fibroblast cultures obtained from 9 scleroderma patients. The rate of procollagen synthesis had increased more than 3-fold in 3 scleroderma fibroblast lines, but had not changed to the same extent in the others, even though these did not differ from the "high-producers" histologically, clinically, or immunohistologically. The activities of PH and LH correlated significantly with the rate of procollagen synthesis in the same cell lines (p less than 0.001), but the glycosyltransferase activities were not elevated in the scleroderma fibroblasts. Further studies nevertheless indicated that the extent of the posttranslational modification of lysine residues had not significantly changed in the procollagen synthesized by any of the scleroderma fibroblasts investigated.

Adult↗
PubMed1985

Dermatofibrosarcoma protuberans: altered collagen metabolism in cell culture.

Dermatofibrosarcoma protuberans is a low-grade malignant tumor that grows invasively but rarely forms metastases. Its origin is still controversial. We characterized the synthesis of collagen in detail in cells which were obtained from dermatofibrosarcoma protuberans tumors by enzymatic tissue disintegration. Similar to fibroblasts, all tumor cell strains produced considerable amounts of collagen. However, the rate was reduced compared to normal skin fibroblasts. Cells grown from the tumors synthesized type I collagen, but no type II could be detected. After serial passaging the cultures started to produce type III collagen, which is probably due to a slow overgrowth by normal fibroblasts.

Cells, Cultured↗
PubMed1985

Preparation and properties of alpha 1-proteinase inhibitor concentrate from human plasma.

Alpha 1-proteinase inhibitor (alpha 1-PI) has been prepared as a concentrate in quantities large enough for clinical testing of its safety and efficacy in the treatment of emphysema and other disorders. The alpha 1-PI was purified from Cohn fraction IV-1 paste by polyethylene glycol precipitation and DEAE-Sepharose chromatography. The methods used in the purification are gentle and the resulting product behaves almost identically to the alpha 1-PI from plasma. The protein has been heat treated (60 degrees C, 10 h) to lower the risk of transmission of plasma-borne diseases. This resulted in some aggregation of the protein, but did not cause the generation of new antigenic sites. Half-life studies in animals showed that the protein behaved normally (catabolic t1/2 of 68 h).

Blood Proteins↗
PubMed1984

Effect of retinoids on collagen production by chondrocytes in culture.

The effect of vitamin A and of some of its derivatives on chondrocytes in culture has been studied. In the presence of retinoids the proliferation of the cells decreased and they lost their characteristic polygonal shape and assumed a fibroblast-like morphology. All retinoids also caused dedifferentiation of chondrocytes as indicated by the induction of types I and III collagen. 13-cis retinoic acid (= isotretinoin) was the most active derivative in this aspect. Since appropriate control of the synthesis of extracellular matrix proteins is a prerequisite for their normal physiological function, alterations such as those observed here may be involved in the pathogenesis of side effects which are observed during the treatment of dermatological disorders with retinoic acid derivatives.

Animals↗
PubMed1984

Enhanced chemotaxis of tumor-derived and virus-transformed cells to fibronectin and fibroblast-conditioned medium.

SV40 transformants of human embryo fibroblasts showed an enhanced chemotactic response to fibronectin and conditioned medium of fibroblasts in comparison to the non-transformed cells. An even higher chemotactic response was characteristic for a malignant human fibrosarcoma cell line, whereas cells derived from low-grade malignant dermatofibrosarcoma showed a normal response in the Boyden chamber assay. The high stimulation of chemotaxis is paralleled by a reduced synthesis and an altered deposition of fibronectin in the pericellular matrix of these cells. Both high chemotactic response and lack of deposition of fibronectin may play a role in tissue invasion and formation of metastasis by malignant tumors.

Cell Transformation, Viral↗