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M Haase

Publications and source records attributed to M Haase.

At least 37 records · Page 2Linked to original sources
PubMed1998

Expression of the extracellular matrix signaling molecule Cyr61 is downregulated in prostate cancer.

BACKGROUND: Prostate cancer (CaP) is one of the most common neoplasms in the USA and Europe. We used differential display PCR (DD-PCR) to identify genes related to the development of prostate cancer. METHODS: The RNA of 4 patients with untreated CaP was analyzed for differentially expressed genes. Using DD-PCR, we identified a downregulated cDNA-fragment in these prostate cancer cells. This fragment (N7) was cloned and further analyzed by CMRT-PCR, Northern-blot analysis, and in situ hybridization. RESULTS: Sequence analysis revealed that N7 is identical to the 3'-untranslated region of the recently described immediate early gene Cyr61. Comparative multiplex RT-PCR with sequence specific primers showed that Cyr61 is downregulated in the tumor tissue of 7 out of 13 patients. By in situ hybridization we could demonstrate that the expression of Cyr61 is restricted to the epithelium of the prostate. Immunohistochemical analysis showed that Cyr61 protein could be found in the epithelium of normal prostatic tissue, whereas prostate cancer tissue showed a marked decrease of Cyr61 protein expression. CONCLUSIONS: Cyr61 is a member of the emerging family of extracellular signaling proteins and enhances the effect of bFGF. The changed pattern of expression Cyr61 might therefore contribute to the altered interactions between epithelial and stromal cells in prostate carcinoma.

Animals↗
PubMed1998

Splenunculus mimicking late local recurrence of renal cell carcinoma.

We report on a case of a splenunculus found in the renal fossa 14 years after left transperitoneal radical nephrectomy and splenectomy for renal cell carcinoma. The significance of splenunculi in differential diagnosis of space occupying lesions in the left renal bed is discussed.

Carcinoma, Renal Cell↗
PubMed1997

Cellular distribution of c-Jun and c-Fos in rat lung before and after bleomycin induced injury.

C-Jun and c-Fos transcription factors have been associated with enhanced cellular proliferation. We studied their cellular distribution in normal and fibrotic rat lung. Pulmonary fibrosis was induced by intratracheal administration of bleomycin. In normal rat lung, c-Jun and c-Fos are present in alveolar macrophages and type II pneumocytes, in the bronchiolar epithelium and in smooth muscle cells of bronchioli and blood vessels. Subcellular fractionation of proteins revealed a predominant presence of both c-Jun and c-Fos in the heavy membrane fraction containing mitochondria and secretory granules. This was confirmed by immunoelectron microscopy, which also revealed a different localization of c-Jun and c-Fos in different cell types. Whereas in type II pneumocytes and in macrophages cytoplasmic c-Jun and c-Fos is associated with mitochondria, in Clara cells of the bronchial epithelium only secretory granules contain c-Jun and c-Fos. In addition, c-Jun is strongly present in the nuclear fraction. In the fibrotic rat lung c-Jun and c-Fos are located in the same cell types as in control lungs. In addition, fibroblasts contain c-Jun and c-Fos in areas of proliferation whereas in areas of complete fibrosis there is only a very weak expression of c-Jun and c-Fos.

Animals↗
PubMed1997

Heterotopic ossification after total knee arthroplasty. 54/615 cases after 1-6 years' follow-up.

We found heterotopic ossifications in 54 (9%) of 615 cases after total knee arthroplasty. The largest ossifications were located in the anterior distal femur. In 12 cases smaller ossifications were found in other knee regions. The development of heterotopic ossification showed a positive correlation with hypertrophic arthrosis and a negative correlation with rheumatoid arthritis. We propose a new 3-grade classification which refers only to the anterior distal femoral region. Grade III heterotopic ossifications occurred in 4 patients (4 knees) who had clinical symptoms; 2 were successfully reoperated with removal of the ossifications. Prophylaxis should be considered in patients with marked hypertrophic arthrosis or marked periosteal damage to the anterior distal femur.

Aged↗
PubMed1997

The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B.

The natural occurring pigment curcumin, a major component of the spice tumeric, has been described to have antioxidative, anti-tumorpromoting, anti-thrombotic and anti-inflammatory properties. It appears, that the pleiotropic effects of curcumin are at least partly due to inhibition of the transcription factors NF-kappa B and AP-1. This study investigates the effect of curcumin on the TNF alpha induced expression of endothelial Tissue Factor (TF), the central mediator of coagulation known to be controlled by AP-1 and NF-kappa B. When bovine aortic endothelial cells (BAEC) were preincubated in the presence of curcumin, TNF alpha induced TF gene transcription and expression were reduced. Transient transfection studies with TF-promoter plasmids revealed that both, NF-kappa B and AP-1 dependent TF expression, were reduced by curcumin action. The observed inhibitions were due to distinct mechanisms. Curcumin inhibited TNF alpha induced I kappa B alpha degradation and the nuclear import of NF-kappa B. In contrast, inhibition of AP-1 was due to a direct interaction of curcumin with AP-1-binding to its DNA binding motif. Thus, curcumin inhibits NF-kappa B and AP-1 by two different mechanisms and reduces expression of endothelial genes controlled by both transcription factors in vitro.

Animals↗
PubMed1996

Immunolocalization of cathepsin D in pneumocytes of normal human lung and in pulmonary fibrosis.

Cathepsin D expression has been assessed by immunohistochemistry and immunoelectron microscopy in fetal, normal adult and injured lungs of human beings. In addition to the well known positivity of alveolar macrophages and the bronchial epithelial cells, normal type I and to a lesser extent type II pneumocytes showed a granular, cytoplasmic staining pattern. Using immunogold labelling of lowicryl embedded human lung, cathepsin D was present in lysosomes of epithelial cells. Double immunofluorescence labelling employing type I and type II specific antibodies or lectins confirmed the epithelial staining for cathepsin D. At the terminal sac period during lung development cathepsin D appears in the alveolar epithelium. In fibrotic specimens, enhanced immunoreactivity was found in epithelial and non-epithelial cells. Proliferative epithelial formations were strongly stained with cathepsin D antibodies, whereas detached, desquamated epithelial cells were weakly positive or negative. We suggest that cathepsin D plays a role in the remodelling process during fibrogenesis.

Adult↗
PubMed1996

Stability testing requirements for vaccines--draft guidelines of the International Conference on Harmonization.

The International Conference on Harmonisation (ICH) process considers ways in which the technical requirements for assuring the quality, safety and efficacy of medicines can be made more compatible. At present, divergencies can make it necessary for companies to repeat tests or present the data in different formats to satisfy the requirements of different health authorities. In this context, I report that agreement on Step 2 of an ICH guideline on stability testing of biotechnological/biological products has been reached. This guideline will be of significant benefit in reducing the need to repeat costly and lengthy storage trials for biologicals to meet differing requirements. This guideline will be an annex to the ICH Harmonized Tripartite Guideline on Stability Testing of New Drug Substances and Products published in 1993. According to its present scope it covers vaccines consisting of well-characterized proteins and polypeptides and conventional vaccines after consultation with the appropriate regulatory authorities. The purpose of stability studies is to establish how the quality of a drug substance (bulk material) and a drug product (final container product) varies with time under the influence of a variety of environmental factors such as temperature, humidity and light, and enables recommended storage conditions, re-test periods and shelf lives to be established. The guideline contains specific advice for the selection of batches, the stability-indicating profile, storage conditions, testing frequency, test procedures and test criteria, specifications, long term-, stress- and accelerated testing, labelling, etc. and a glossary which defines certain of the traditional terms used in the biologics field. Therefore, it will help in informing the industry and the regulatory authorities of the important factors in stability testing of biological/biotechnological products.

Drug Packaging↗
PubMed1995

Mechanism of the tumor necrosis factor alpha-mediated induction of endothelial tissue factor.

This study examines the regulation of the human tissue factor (TF) promotor in vitro and in vivo. Transient transfections were performed in bovine aortic endothelial cells to investigate the role of two fundamentally different AP-1 sites and a closely located NF-kappa B site in the human TF promoter. The NF-kappa B site is functionally active, since overexpression of NF-kappa B(p65) resulted in induction of TF mRNA and activity. Promoter analysis showed that NF-kappa B induction was dependent on the integrity of the region from base pair -188 to -181. Over-expression of Jun/Fos resulted in TF induction of transcription and protein/activity. Functional studies revealed that the proximal AP-1 site, but not the distal, was inducible by Jun/Fos heterodimers. The distal AP-1 site, which has a G-->A switch at position 4, was inductible by Jun homodimers. Electrophoretic mobility shift assays, using extracts of tumor necrosis factor alpha (TNF alpha)-stimulated bovine aortic endothelial cells, demonstrated TNF alpha-inducible binding to the proximal AP-1 site, comprising JunD/Fos heterodimers. At the distal AP-1 site, only minor induction of binding activity, characterized as proteins of the Jun and ATF family, was observed. Consistently, this site only marginally participates in TNF alpha induction. Functional studies with TF promotor plasmids confirmed that deletion of the proximal AP-1 or the NF-kappa B site decreased TNF alpha-mediated TF induction to a higher extend than loss of the distal AP-1 site. However, integrity of both AP-1 sites and the NF-kappa B site was required for optimal TNF alpha stimulation. The relevance of these in vitro data was confirmed in vivo in a mouse tumor model. Expression plasmids for a dominant negative Jun mutant or I-kappa B were packaged in liposomes. When either mutated Jun or I-kappa B were injected intravenously 48 h before TNF alpha, a reduction in TNF alpha-mediated TF expression in the tumor endothelial cells was observed. Simultaneously, fibrin/fibrinogen deposition decreased and free blood flow could be restored. Thus, TNF alpha-induced up-regulation of endothelial cell TF depends on a concerted action of members of the bZIP and NF-kappa B family.

Animals↗
PubMed1995

Criteria for investigation of the product equivalence of monoclonal antibodies for therapeutic and in vivo-diagnostic use in case of introduction of changes in the manufacturing process.

The development of a monoclonal antibody for therapeutic or in vivo-diagnostic use from the first description to clinical trials and compilation of the dossier for granting the license requires a time consuming and expensive program. Due to its long development time, a particular monoclonal antibody can be subjected to a series of changes and improvements in manufacturing technology before licensure. In addition, the application for marketing authorization of biotechnology-derived medicinal products is not to be considered as an endpoint of a drawn-out development process which ends with license, because changes, amendments or improvements of the manufacturing process occur after a marketing authorization for a monoclonal antibody has been granted. Most of these changes, even minor qualitative and quantitative changes in the active substance itself, would require a new application according to the legal regulations of the European Union and of the national drug laws of the Member States. The paper proposes a procedure to take previously evaluated development-related data into account by evaluation of the product equivalence of both antibody forms ascertained before and after introduction of changes in the manufacturing process. The thorough in vitro analysis of parameters such as isotype, subclass, affinity, microheterogeneity, molecular weight, primary and secondary structure, structural integrity of the antibody molecule, glycosylation pattern, specificity, cross-reactivity and biological potency with subsequently performed pharmacological/toxicological evaluation of biodistribution, half life and safety provide sufficient data for decision on the need for further clinical trials.

Animals↗
PubMed1993

Cellular localization of tissue factor in human breast cancer cell lines.

Expression of tissue factor (TF), the cellular receptor of clotting factor VII/VIIa, is a feature of certain malignant tumours. The TF gene has been classified as an immediate early gene responsive to serum and cytokines. Thus, the regulation of TF gene expression seems to play a role in cell growth. Recently, we have shown that constitutive TF expression in MCF-7 breast cancer cells is modulated by such growth factors as EGF, TGF alpha, and IL-1. The present study deals with the immunocytochemically detectable cellular distribution of TF in human breast cancer cell lines MCF-7 and MaTu stimulated by EGF and TGF alpha. In MCF-7 cells growing logarithmically, stimulation led to a significant increase of TF mRNA after 2 h (in situ hybridization, Northern blot) and to maximum TF expression after 6 h (immunohistochemistry). When decorated by monoclonal antibodies, TF protein showed a pronounced localization at ruffled membrane areas, cell edges, and processes of spreading cells after 6 and 20 h. In more flattened cells TF was concentrated in peripheric lamellae and microspikes communicating with neighbouring cells. After epithelial colony pattern had established, TF was predominantly accumulated at the intercellular boundaries. The vary same distribution patterns as seen in MCF-7 cells were true for the stimulated MaTu cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Changes in cytokeratin, vimentin and desmoplakin distribution during the repair of irradiation-induced lung injury in adult rats.

The expression of cytokeratins, desmoplakin and vimentin has been studied immunohistochemically in the rat lung injured by x-irradiation using 14 well characterized monoclonal antibodies. A time-dependent relationship between the cytokeratin expression pattern and the morphological alterations observed was apparent. A cytokeratin 8 and 18 expression in normally cytokeratectable even at 3-6 h after irradiation. Between 14 days and 2 months, a remarkable heterogeneity in the epithelial cell cytokeratin pattern and an increasing immunoreaction for desmoplakin was found. In terminal bronchial epithelial cells, a heterogeneous CK8, 18 and 19 staining and a neoexpression of cytokeratins 4 and 7 was detected. Finally, peribronchiolar and vascular smooth muscle cells were cytokeratin-positive. At 6 months after irradiation, cytokeratin 13 and vimentin were focally present in bronchial epithelial cells and atypical type I and II pneumocytes as well as scattered epithelioid cell complexes were noted. During the course of injury, a loss of type III alveolar epithelial cells was found, which was characterized in the rat by a specific globular cytokeratin pattern and restricted immunoreactivity with cytokeratin-specific antibodies. These results show that the expression pattern of cytokeratins is a sensitive marker in monitoring epithelial alterations during lung injury.

Animals↗
PubMed1991

[Morbidity studies in children's nurseries].

In 1986-1988 the indices of absence morbidity taken from monthly reports of crèches were registered in 8 crèches of Dresden and were compared with the real total morbidity, which had been registered with help of a symptom catalogue for one year. The total morbidity amounted to more than the double of absence morbidity, the total of the illness days per case amounted to 8.42 days and the days of absence morbidity amounted 7.3. The description of infection groups with help of quarters (according to Adam) on the basis of the registered total morbidity showed differences with regard to: average illness period per case (children susceptible to infections: 9.33 d; children robust to infections: 6.82 d) and average recurrence period (children susceptible to infections: 15.7 d; children robust to infections: 78.2 d). Probable causes of susceptibility to infections and conclusions hence to be drawn.

Child Day Care Centers↗
PubMed1990

Monoclonal antibodies for use in man: current regulatory situation in the Federal Republic of Germany.

The article addresses the requirement to be met for approval of monoclonal antibodies with special emphasis on products coupled with radionuclides and on principles for the conduct of clinical trials. According to the German Drug Law monoclonal antibodies are considered as being sera. Therefore, the Paul-Ehrlich-Institut, Federal Office for Sera and Vaccines, is responsible for marketing authorizations. Sera and vaccines need a special manufacturing licence which is given by the competent authority of the Federal State. Batches of monoclonal antibodies can only be marketed if they have been released by the Paul-Ehrlich-Institut; in connexion with batch control the importance of reference preparations is stressed. The standard requirements for the data to be submitted with the applications for marketing authorizations are in accordance with the EEC Council Directives and Notes for Guidance. For the testing of radioactive monoclonal antibodies in clinical trials, compliance with both the Drug Law and The German Radiation Protection Ordinance must be ensured. In addition to the authorizations required for non-labelled monoclonal antibody products, the use of radioactive substances in diagnosis and therapy requires an authorization by the competent Federal State authority. The main purpose of the planning and performance of clinical trials with new monoclonal antibody in diagnosis and therapy must be the comparison with established diagnostic tools and/or established medicinal products of known effect.

Antibodies, Monoclonal↗
PubMed1985

The mouse neutralization test in comparison with the rapid fluorescent focus inhibition test: differences in the results in rabies antibody determinations.

Sixteen lots of rabies immune globulin (RIG) and six lots of rabies immune horse serum (RIS) from different producers were examined for rabies antibody by the standard mouse neutralization test (MNT) and the rapid fluorescent focus inhibition test (RFFIT). An equine rabies standard serum was assayed in parallel. In comparisons of RIS with this standard the MNT and RFFIT gave comparable results. In comparisons of RIG the antibody values in the MNT was two to ten times higher than that in the RFFIT in 15 out of 16 lots. The MNT and RFFIT are thus not fully comparable when measuring rabies antibodies in RIG. The choice of the titration method is obviously important in the measurement of the antibody concentration in RIG or RIS in IU against an equine rabies reference preparation. The described differences could have consequences for the use of RIG.

Animals↗
PubMed1983

[Bacterial antibodies and isoagglutinins in intravenous immunoglobulin preparations].

Various lots of intravenous immunoglobulins for passive immunization should contain almost the same, broad, antibody profile and provoke very low frequencies of untoward reactions. From 1976-1982 a study was undertaken to measure the level of antibodies directed against tetanustoxin, diphtheriatoxin, streptolysin O, staphylolysin, and salmonella in up to 82 lots. It is interesting to note that the measured level of antibodies in intravenous immunoglobulins varied only slightly as well qualitatively as quantitatively with one exception: an immunoglobulin of placental origin. The amount of tetanusantitoxin in the majority of lots of that preparation was ten-fold lower than that of the other immunoglobulins. Intravenous immunoglobulins contain generally 3-6 IE/ml antistaphylolysin, 600-1200 IE/ml antistreptolysin O, 10-20 IE/ml tetanusantitoxin, and 1-2 IE/ml diphtheriaantitoxin. Antibodies to salmonella could not be demonstrated. Some of the lots exhibited isoagglutinins up to a dilution of 1 : 4.

Agglutinins↗