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J Bischoff

Publications and source records attributed to J Bischoff.

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

Increased apoptosis coincides with onset of involution in infantile hemangioma.

OBJECTIVE: Hemangioma is an endothelial cell tumor that grows rapidly during infancy and regresses slowly during childhood. However, little is known about the natural history of this common tumor. To gain insight into the cellular mechanisms that underlie the switch from uncontrolled growth to involution of endothelium, we investigated the extent of cellular apoptosis versus proliferation in hemangioma specimens that spanned the natural life cycle of the tumor. METHODS: We analyzed apoptosis and cellular proliferation in frozen sections from 16 hemangioma specimens using the TUNEL assay to detect apoptotic cells and the Ki67 antigen to detect dividing cells. RESULTS: Apoptosis was low in proliferative phase hemangiomas but increased fivefold in involutive phase specimens obtained from children one to four years of age. Immunofluorescence double-labeling experiments showed that at least one third of the apoptotic cells were endothelial. As expected, cellular proliferation was high in specimens up to 2 years of age but decreased significantly thereafter. Apoptosis was consistently low in nine normal skin tissues (newborn to 4 years of age) obtained from discarded pathology specimens. CONCLUSIONS: These results suggest that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating regression of hemangioma.

Age Factors↗
PubMed1997

E-selectin is upregulated in proliferating endothelial cells in vitro.

OBJECTIVE: E-selectin is an endothelial cell-specific membrane glycoprotein that participates in leukocyte adhesion and has also been suggested to function in angiogenesis. To gain further insights into E-selectin, we analyzed E-selectin polypeptide in proliferating versus quiescent bovine capillary endothelial cells and its expression as a function of the cell cycle. METHODS: E-selectin polypeptide was analyzed by immunoadsorption from 35Scysteine-labeled endothelial cells, by enzyme-linked immunosorbent assay, and by fluorescence-activated cell sorting. The distribution of endothelial cells in Gzero/G1, S, and G2/M phases of the cell cycle was determined using propidium iodide staining of DNA. RESULTS: E-selectin was upregulated in subconfluent proliferating bovine capillary endothelial cells compared to confluent quiescent cultures. The upregulation was independent of activation in that E-selectin was further increased by treatment with tumor necrosis factor alpha or lipopolysaccharide. In contrast to E-selectin, P-selectin and platelet-endothelial cell adhesion molecule-1 did not appear to be regulated by the growth state of the endothelial cells. The distribution of E-selectin-positive cells in GzeroG1, S, and G2/M phases of the cell cycle differed from E-selectin-negative cells in that more of the E-selectin-positive cells were in G2 and M. CONCLUSIONS: Increased E-selectin expression under noninflammatory conditions is correlated with cellular proliferation and G2/M phases of the cell cycle. The expression of E-selectin in proliferating endothelial cells in vitro is consistent with the presence of E-selectin in proliferating endothelial cells in vivo (Kräling et al. [18]).

Animals↗
PubMed1997

Vascular expression of E-selectin is increased in estrogen-receptor-negative breast cancer: a role for tumor-cell-secreted interleukin-1 alpha.

Angiogenesis plays an important role in breast cancer growth and metastasis. Multiple adhesion molecules have been shown to perform critical functions in the process of angiogenesis. In this study, we analyzed 15 benign and 22 malignant estrogen-receptor-negative and estrogen-receptor-positive breast specimens for the presence of the endothelial cell adhesion molecules E-selectin and P-selectin. We found that E-selectin's expression was increased in the malignant breast tumors compared with their benign counterparts (23.86% of blood vessels versus 2.47%; P = 0.0005). Furthermore, E-selectin staining was found to be significantly increased in the estrogen-receptor-negative carcinomas compared with the estrogen-receptor-positive ones (P = 0.005). In vitro findings strongly correlated with the in vivo findings and showed a higher degree of E-selectin induction in endothelial cells exposed to conditioned media from estrogen-receptor-negative breast cancer cell lines than from estrogen-receptor-positive ones. The degree of E-selectin induction correlated with the amount of interleukin-1 alpha in the tumor-conditioned media. Neutralizing antibodies to interleukin-1 alpha significantly inhibited the E-selectin expression in endothelial cells exposed to tumor-conditioned media. The results indicate that the endothelial E-selectin expression during angiogenesis is related to breast carcinoma progression in vivo and that this component of angiogenesis may be due directly to tumor-cell-secreted interleukin-1 alpha.

Breast Neoplasms↗
PubMed1996

The angiogenesis inhibitor AGM-1470 selectively increases E-selectin.

The levels of E-selectin mRNA and protein were analyzed in bovine capillary cells treated with or without the angiogenesis inhibitor AGM-1470 (also known as TNP-470). Cells treated with AGM-1470 had a two- to sevenfold (median fivefold) increase in E-selectin mRNA compared with little or no increase in P-selectin, PECAM-1 and VCAM-1 mRNA. E-selectin protein was also significantly increased after exposure to AGM-1470. In contrast, there was no detectable effect on PECAM-1 protein. The increase in E-selectin mRNA and protein was always greater with subconfluent growing cells than with confluent cells. This apparent resistance of confluent endothelial cells to AGM-1470 may be relevant to its specificity in vivo. The fact that the effect of AGM-1470 on E-selectin is relatively selective for subconfluent growing cells may provide a clue as to how AGM-1470 is able to both reversibly inhibit endothelial cell proliferation in vitro and inhibit tumor growth in vivo without apparent effects to quiescent endothelium.

Adrenal Cortex↗
PubMed1996

Hypoxia enhances stimulus-dependent induction of E-selectin on aortic endothelial cells.

In many diseases, tissue hypoxia occurs in conjunction with other inflammatory processes. Since previous studies have demonstrated a role for leukocytes in ischemia/reperfusion injury, we hypothesized that endothelial hypoxia may "superinduce" expression of an important leukocyte adhesion molecule, E-selectin (ELAM-1, CD62E). Bovine aortic endothelial monolayers were exposed to hypoxia in the presence or absence of tumor-necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS). Cell surface E-selectin was quantitated by whole cell ELISA or by immunoprecipitation using polyclonal anti-E-selectin sera. Endothelial mRNA levels were assessed using ribonuclease protection assays. Hypoxia alone did not induce endothelial E-selectin expression. However, enhanced induction of E-selectin was observed with the combination of hypoxia and TNF-alpha (270% increase over normoxia and TNF-alpha) or hypoxia and LPS (190% increase over normoxia and LPS). These studies revealed that a mechanism for such enhancement may be hypoxia-elicited decrements in endothelial intracellular levels of cAMP (<50% compared with normoxia). Addition of forskolin and isobutyl-methyl-xanthine during hypoxia resulted in reversal of cAMP decreases and a loss of enhanced E-selectin surface expression with the combination of TNF-alpha and hypoxia. We conclude that endothelial hypoxia may provide a novel signal for superinduction of E-selectin during states of inflammation.

1-Methyl-3-isobutylxanthine↗
PubMed1996

E-selectin is present in proliferating endothelial cells in human hemangiomas.

E-selectin, an endothelial-cell-specific leukocyte adhesion molecule, may also function in angiogenesis. To investigate its role in a noninflammatory angiogenic disease, E-selectin was analyzed by immunohistochemistry in specimens of proliferative phase and involutive phase hemangiomas. Hemangioma is an endothelial cell tumor of capillary blood vessels that grows rapidly during infancy and regresses spontaneously during childhood. E-selectin expression was high in proliferative phase specimens and was co-localized with dividing microvascular endothelial cells. Relative to the number of blood vessels, E-selectin declined significantly in involutive phase specimens demonstrating that E-selectin correlates with angiogenesis in the tumors. E-selectin was not detected in quiescent endothelium but was co-localized in dividing microvascular endothelial cells in placenta and neonatal foreskin, two tissues with ongoing growth of microvessels. These in vivo studies support the hypothesis that E-selectin functions in angiogenesis and suggest that E-selectin may be a marker for proliferating endothelium.

Antibodies, Monoclonal↗
PubMed1995

Regulation of P-selectin by tumor necrosis factor-alpha.

The levels of P-selectin mRNA and polypeptide were analyzed in bovine capillary cells treated with or without the cytokine tumor necrosis factor-alpha. The 3 kb P-selectin mRNA was upregulated three- to five-fold in cytokine-stimulated cells. The increase in mRNA correlated with a dramatic but short-lived increase in P-selectin polypeptide as determined by metabolic-labeling and immunoadsorption. These data confirm earlier studies on mouse P-selectin expressed in a mouse endothelioma cell line and further indicate that P-selectin function can be regulated not only by rapid translocation to the cell surface but also by cytokine-stimulation of P-selectin biosynthesis.

Animals↗
PubMed1995

Vascular access for haemodialysis--role of the urologist.

Twelve years urological experience at the Klinikum Potsdam with subcutaneous arteriovenous anastomosis as a vascular access for chronic haemodialysis is described. More than 774 access operations have been performed, 344 of them on 255 patients in the last 3 years. The side-to-end anastomosis between radial artery and cephalic vein in the lower arm has proved to be the method of choice. In 187 of the 255 patients (73%) the first operation was successful. Of the other 68, more than 157 operations were necessary for successful vascular access in 55 patients. To summarize, in 242 out of 255 patients (95%) a functioning vascular access was achieved after 1.4 operations per patient. In only 13 patients was it necessary to implant a heterologous vascular graft. In our opinion, the urologist should contribute to the success of treatment for end-stage-renal-disease.

Arm↗
PubMed1995

Approaches to studying cell adhesion molecules in angiogenesis.

Capillaries provide a vast interface between the blood and the tissues that is crucial for regulating nutrient delivery, blood coagulation and transmigration of leukocytes to sites of infection. The growth of new capillaries from pre-existing vessels (angiogenesis) is essential for normal embryogenesis and growth, but also occurs in the development of many diseases. Although relatively little is known about endothelial cell biology, progress is nevertheless being made towards understanding angiogenesis, and several laboratories have begun to identify cell adhesion molecules that may be required for the growth of microvessels.

Journal Article↗
PubMed1994

Evolution of renal replacement therapy in East Germany from 1989 to 1992.

Diminished availability of facilities for renal replacement therapy is known to cause spuriously low acceptance and treatment rates. In this context the evolution of renal replacement therapy in the former German Democratic Republic is a useful model to study and to quantify some of the relevant factors. We performed a survey in all dialysis units for adults in East Germany (excluding East Berlin) by questionnaire, achieving a response rate of 97%. From December 1989 to December 1992 the number of dialysis centres increased from 53 to 96 (+81%), reaching 6.7 centres p.m.p. Of these facilities, 45% were hospital units, 29% private units, and 26% dialysis units run by non-profit health care organizations. The number of dialysis stations for regular dialysis treatment increased from 602 to 1276 (+112%), i.e. 89 stations p.m.p. In parallel, the number of chronic dialysis patients increased from 2127 to 3848 (+81%), i.e. 267 patients p.m.p. A more detailed survey was carried out in Thüringen and part of Sachsen, in a region covering 5 million inhabitants. The acceptance rate for chronic dialysis treatment has increased from 49 to 107 patients p.m.p. (+115%). The average age of new patients increased from 49 to 59 years, the proportion of patients aged > or = 65 years increased from 16 to 42% and the proportion of diabetics from 13 to 35%. Introduction of alternative treatment modalities became possible, with 2.3% of the patients receiving haemofiltrations and 3% CAPD. The proportion of HBs-antigen-positive patients decreased from 14.2% to 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis.

To identify cell adhesion molecules required for angiogenesis, we used an in vitro model in which bovine capillary endothelial cells can be induced to form capillary-like tubes. Monoclonal antibodies directed against the carbohydrate epitopes sialyl Lewis-X and sialyl Lewis-A inhibited capillary formation. We postulated that a member of the selectin family of adhesion molecules may be involved in capillary formation because these proteins bind to sialyl Lewis-X/A-containing ligands. We isolated a 2.8-kilobase complementary DNA from a bovine capillary endothelial cell cDNA library which encodes a polypeptide with 71% identity to human E-selectin. We report here that antibody directed against the bovine E-selectin inhibited capillary formation, suggesting that in addition to its role in leukocyte adhesion to endothelium, a form of E-selectin is involved in capillary morphogenesis.

Amino Acid Sequence↗
PubMed1993

Isolation and characterization of a bovine cDNA encoding a functional homolog of human P-selectin.

A cDNA encoding a homologue of human P-selectin has been isolated from a bovine capillary endothelial cDNA library. The 2.7 kb cDNA encodes a 646 amino acid polypeptide with 77% identity to the human P-selectin except that it lacks three of the consensus repeat domains found in human P-selectin. Human P-selectin, expressed in platelets and endothelium, is a Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. To determine if bovine P-selectin exhibits a similar binding activity, its cDNA was expressed in COS cells and the ability of the transfectants to bind HL-60 human myelogenous leukemia cells was examined. The bovine P-selectin bound the myeloid cells in a manner similar to human P-selectin, indicating that the altered domain structure of bovine P-selectin does not affect P-selectin function in this in vitro cell adhesion assay.

Amino Acid Sequence↗
PubMed1992

1-Deoxymannojirimycin inhibits capillary tube formation in vitro. Analysis of N-linked oligosaccharides in bovine capillary endothelial cells.

Capillary endothelial cells can be induced to form capillary-like structures in vitro by plating on fibronectin-coated dishes (Ingber, D. E., and Folkman, J. (1989) J. Cell Biol. 109, 317-330), thereby mimicking angiogenesis. To assess the role of glycoproteins bearing asparagine-linked oligosaccharides in this process, we tested the effect of oligosaccharide processing inhibitors on the formation of capillary tubes. Deoxymannojirimycin, a compound that prevents synthesis of hybrid and complex-type oligosaccharides, inhibited the formation of capillary tubes. In contrast, swainsonine, an inhibitor that blocks synthesis of complex- but not hybrid-type oligosaccharides, did not inhibit tube formation. Lectin affinity chromatography of 2-[3H] mannose-labeled glycopeptides from endothelial cells induced to form tubes did not reveal a striking difference in the spectrum of oligosaccharides compared to uninduced cells. Since endothelial cells formed tubes normally in the presence of swainsonine, we analyzed glycopeptides from swainsonine-treated induced and uninduced cells. Cells induced to form tubes were enriched in monosialylated hybrid-type oligosaccharides sensitive to alpha-fucosidase, beta-galactosidase, and beta-N-acetylhexosaminidase, suggestive of sialyl Lewis-X determinants. We used an enzyme-linked immunoassay to measure sialyl Lewis-X epitopes on capillary endothelial cells and found that both induced and uninduced cells expressed sialyl Lewis-X epitopes. Deoxymannojirimycin and, to a lesser extent, swainsonine reduced the level of sialyl Lewis-X epitopes in cells induced to form capillary tubes, but neither compound affected the level of epitopes in cell monolayers. We conclude that synthesis of at least hybrid-type oligosaccharides is required for capillary tube formation in vitro and that an increase in monosialylated, fucosylated glycans on asparagine-linked oligosaccharides occurs during this process.

1-Deoxynojirimycin↗
PubMed1990

Isolation, characterization, and expression of cDNA encoding a rat liver endoplasmic reticulum alpha-mannosidase.

We have isolated a cDNA encoding an endoplasmic reticulum alpha-mannosidase, an asparagine-linked oligosaccharide processing enzyme, from a rat liver lambda gt11 library. Two degenerate oligonucleotides, based on amino acid sequence data from the purified enzyme, were used as primers in the polymerase chain reaction with liver cDNA as a template to generate an unambiguous cDNA probe. The cDNA fragment (524 base pair) obtained was then used to isolate cDNA clones by hybridization. We isolated two overlapping clones which were used to construct a full-length cDNA of 3392 base pairs. A single open reading frame of 1040 amino acids encodes a protein with a molecular mass of 116 kilodaltons containing the six known peptide sequences. The deduced amino acid sequence revealed no classical signal sequence or membrane-spanning domain. The alpha-mannosidase encoding cDNA can be expressed transiently in COS cells using the mammalian expression vector pXM, causing a 400-fold increase in alpha-mannosidase activity as well as a dramatic increase in immunoreactive polypeptide. The rat liver endoplasmic reticulum alpha-mannosidase bears striking homology to the vacuolar alpha-mannosidase from Saccharomyces cerevisiae.

Amino Acid Sequence↗
PubMed1990

Investigation into the combined effects of ethanol and cadmium on rat liver and kidneys.

To examine the combined hepatotoxic and nephrotoxic effects of cadmium and ethanol, rats maintained on an ethanol containing liquid diet (5% w/w) were given cadmium either acutely (3 x 1 mg/kg IP) or subacutely (about 14 mg/kg/day PO for 6 weeks). Parameters tested were cadmium, zinc and copper contents of blood and various organs, metallothionein (MT) contents, polysome profile of liver and kidneys, serum SDH and GPT levels and creatinine clearance. Ethanol reduced the hepatic MT contents without altering the polysome profile and the zinc and copper contents. Cadmium on the other hand raised the MT contents in liver and kidneys. This effect of cadmium predominated in the combined treatment. Morphological examination and functional tests (SDH, GPT, creatinine clearance) indicate that cadmium does not enhance the toxic effects of ethanol, and vice versa.

Alanine Transaminase↗
PubMed1988

The H1 and H2 polypeptides associate to form the asialoglycoprotein receptor in human hepatoma cells.

Antibody-induced degradation and chemical cross-linking experiments have been carried out to assess the nature of the interaction between the two asialoglycoprotein-receptor polypeptides, H1 and H2, synthesized in HepG2 cells. Incubation of HepG2 cell monolayers with anti-H1 antibody caused a specific and equal loss of both H1 and H2 polypeptides. The same result was obtained with anti-H2 antibody. Control serum did not affect the level of H1 or H2 not did anti-H1 or anti-H2 antibodies affect the level of the transferrin receptor. The chemical cross-linking reagent, difluorodinitrobenzene, has been used to demonstrate that H1 can be cross-linked to H2 in HepG2 cell microsomal membranes. Dimer and trimer species with apparent molecular masses of 93 and 148 kD, respectively, were readily observed upon chemical cross-linking and some dimers and trimers were immunoreactive with both anti-H1 and anti-H2 antibodies. The putative trimer, possibly two H1 and one H2 molecules, is a minimum estimate of the true size of the asialoglycoprotein receptor in intact HepG2 cell, and it is possible that larger hetero-oligomeric forms of the receptor exist. The results of both types of experiments indicate that H1 and H2 form an oligomeric complex in HepG2 cells and thus, both polypeptides constitute the human asialoglycoprotein receptor.

Antibody Specificity↗