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Biomedical subjects

W Dippold

Publications and source records attributed to W Dippold.

At least 37 records · Page 2Linked to original sources

[Acute respiratory failure in tropical malaria during pregnancy. Successful treatment using extracorporeal CO2 elimination].

A 32-year-old woman in the 26th week of pregnancy became ill, 6 days after returning from a trip to Indonesia, with a fever up to 42 degrees C, haemolytic anaemia (haemoglobin 7.6 g/dl) and thrombocytopenia (7,000/microliters). She had not been on any malaria prophylaxis. Chloroquine, quinine and pyrimethamine, administered after macrogametocytes of Plasmodium falciparum had been found in the blood smear, eliminated the parasites from the peripheral blood, but respiratory failure and treatment-resistant pneumonia occurred, leading to the adult respiratory distress syndrome (Morel stage 4). Because of threatened intrauterine death (resulting from premature placental separation during artificial ventilation) the child was delivered by an emergency section. Despite extensive conventional therapeutic measures the mother's respiratory state progressively deteriorated so that extracorporeal membrane CO2 elimination was instituted on the 17th day. First signs of improvement in respiratory functions were noted after six days. The extracorporeal CO2 elimination was discontinued after twelve days, because artificial ventilation could now be adequately controlled. The woman was gradually weaned from the ventilator and discharged home without symptoms after a total of 11 weeks in hospital. Her child has not shown any neurological symptoms.

Acute Disease↗

De novo expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in pancreas cancer.

We examined the expression of intercellular--adhesion molecule-I (ICAM-I, CD54) in 6 surgically removed pancreatic tumors and 8 pancreatic tumor cell lines. Immunohistochemistry revealed a varying percentage of ICAM-I-positive pancreas tumor cells, while normal pancreatic tissue (except for slight reactivity of endothelial cells) was not stained. The presence of the ICAM-I molecule on the cell surface and the expression of ICAM-I mRNA were investigated for 8 different pancreatic tumor cell lines. Three of these (Capan-I, Capan-2, QGP-I) expressed ICAM-I constitutively. In 4 of the ICAM-I-negative pancreas cancer cell lines, it was possible to induce a remarkable expression of ICAM-I by incubating the cells in the presence of inflammatory cytokines, whereas one cell line, 818-4, remained ICAM-I-negative. The responsiveness to either IFN-gamma, TNF-alpha, or IL-I beta treatment was shown to vary from cell line to cell line, indicating complex mechanisms that regulate the expression of ICAM-I at both, the transcriptional and the post-transcriptional level. Interestingly, ICAM-I is shed by pancreatic tumor cells, since soluble sICAM-I was detected in the cell-culture supernatants. In comparison with normal sera, the mean level of sICAM-I in sera of patients with pancreas carcinoma is elevated 2-fold.

Antigens, CD↗

Human complement factor B: functional properties of a recombinant zymogen of the alternative activation pathway convertase.

The human complement factor B is a centrally important component of the alternative pathway activation of the complement system. Here we report the isolation, characterization and eukaryotic expression of the first full length cDNA transcript for human factor B. In a factor B dependent haemolysis assay, the recombinant human factor B generated by transient COS cell transfection was shown to reconstitute haemolytic activity of factor B depleted human serum. To study the biological activities assigned to factor B, the availability of recombinant polypeptides representing definite portions of the human factor B molecule is desirable.

Animals↗

Expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in colonic epithelial cells.

The expression of intercellular adhesion molecule-1 (ICAM-1, CD54) was examined in 16 surgically removed colonic tumours and two colonic carcinoma cell lines. Immunohistochemistry showed a varying percentage of ICAM-1 positive colonic carcinoma cells in 9/16 tissue specimens, while normal colonic tissue (apart from a slight reactivity of endothelial cells) was not stained. The presence of the ICAM-1 molecule on the cell surface and the expression of ICAM-1 mRNA were investigated for two colonic carcinoma cell lines. It was possible to enhance the expression of ICAM-1 considerably by incubating the cells in the presence of inflammatory cytokines in HT-29 and CaCo-2 cells. The responsiveness to either interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha), or interleukin 1 beta (IL-1 beta) treatment was different in each cell line. Interestingly, ICAM-1 is shed by colonic carcinoma cells because soluble sICAM-1 was detected in the cell culture supernatants. In comparison with normal serum samples, the mean value of sICAM-1 in 63 samples of patients with colonic carcinoma and in 20 cases of active inflammatory bowel disease is raised about twofold. It remains to be clarified what part both forms of ICAM-1 play in the course of colonic cancer, ulcerative colitis, and Crohn's disease.

Base Sequence↗

Brucellosis: differential diagnosis of acute abdominal pain.

A 34-year-old Turkish woman presented with septic fever, sweats, arthralgia, and abdominal pain. Further examination revealed generalized lymphadenopathy, hepatosplenomegaly, pancytopenia, and multiple caseous granulomas. Microbiological diagnosis revealed Brucella melitensis type 3 as causative agent. This case report demonstrates that abdominal pain can be a symptom in brucellosis, and caseous granulomas may occur. In our mobile society Brucella infection should be considered as possible differential diagnosis in patients with fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia, although human brucellosis is rare in Germany and other Western countries.

Abdominal Pain↗

[Endogenous and exogenous factors in tumor development and cell differentiation in gastrointestinal tumors].

In recent years, epidemiological and molecular studies revealed very important new insights into the development of tumors in the gastrointestinal tract. Above all, certain forms of nutrition and molecular genetic features and events are responsible for tumor occurrence. This article tries to give a short review of the most important recent findings in this field of research.

Cell Division↗

Immunorecognition of different ganglioside epitopes on human normal and melanoma tissues.

There is increasing evidence that cell-surface gangliosides play a role in tumor growth, progression and metastases. In order to determine the frequency of ganglioside GD3 in patients with metastatic malignant melanoma for further therapeutic trials, GD3 ganglioside expression was determined in 119 tissue samples. Of these melanomas, 93% (111/119) were R-24-positive, which indicates the value of this diagnostic marker for melanoma. To study the structural epitopes of gangliosides, 10 ganglioside antibodies with defined specificities and affinities were tested on over 100 fresh-frozen tissue specimens of human normal and melanoma tissues. All the antibodies tested recognize the ganglioside GD3, but vary in their cross-reactivity with other gangliosides. According to their epitope specificity, they can be divided into 5 groups. For example, the antibodies Z-21 and A-4 react like the previously established MAb R-24 with gangliosides GD3 and GQlb, and one MAb (Q-4) detects all gangliosides containing 2 connected sialic acids (GD3, GD2, GDlb, GTlb, GQlb). Specificity on TLC does not always correlate with specificity to melanoma tissues and vice-versa. For example, MAb A-4, which recognizes only GD3 and GQlb on TLC, shows no specific reactivity on tissues. Furthermore, antibodies with the same ganglioside specificity do not have the same staining pattern on human tissues. For example, MAb Z-21, which is directed against the same gangliosides as MAb R-24 on TLC, does not cross-react with as many neuroectodermal tissues as MAb R-24. Because of their distinct properties, some of these antibodies may be even more useful for immunodiagnosis and immunotherapy of malignant melanoma than MAb R-24.

Antibodies, Monoclonal↗

Immunorecognition of ganglioside epitopes: correlation between affinity and cytotoxicity of ganglioside antibodies.

Cell-surface gangliosides have immunomodulatory effects that are presumed to play a role in tumour growth, progression, metastasis and therapy. To study the epitopes of gangliosides on human malignant melanomas and to search for monoclonal antibodies (Mabs) with superior immunological effector functions, 19 ganglioside antibodies were established. Specificity and affinity of nine antibodies of IgG3 isotype were evaluated by enzyme linked immunosorbent assay and thin layer chromatography with a panel of purified gangliosides. All antibodies recognised the ganglioside GD3, but their epitope specificity divided them into five groups. Their affinity constants for ganglioside GD3 ranged from 4.7 x 10(6) to 2.3 x 10(8), with 2 x 10(7) for Mab R-24. Two antibodies possessed a higher affinity for GD2 than for GD3. The functional properties of the antibodies were investigated in vitro. Differences in the degree of tumour lysis by complement fixation correlated with the affinity constants. Every ganglioside antibody differed in epitope recognition, affinity and cytotoxicity. Therefore some of these antibodies might even be more useful in the immunotherapy of malignant melanoma than Mab R-24.

Antibodies, Monoclonal↗

Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF)-alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.

Antibodies, Monoclonal↗

[The clinical relevance of anti-CEA immunoscintigraphy with the 99mTc-labelled monoclonal antibody BW 431/26. A critical assessment after 119 studies].

The results of 119 radioimmunoscintigraphies (RIS) in 113 patients with the 99mTc-labeled monoclonal anti-CEA-antibody BW 431/26 (Behring) have been analysed. The aim of our study was the estimation of the method's sensitivity and specificity under different aspects to find out for which indications and questions the 99mTc-RIS is useful. Colorectal primary tumours in 19 patients were scintigraphically detected with a sensitivity of 83% and a specificity of 100%; 3 out of 7 other tumour sites were localised correctly. 55 patients were examined during the follow-up of colorectal cancer. There were 17 out of 22 true positive findings of local recurrences (sensitivity 77%, specificity 88%). Liver metastases were imaged as hot lesions with only 41% sensitivity and 86% specificity. The detection of extrahepatic tumour sites is difficult because of the persistently high blood-pool activity of the monoclonal antibody and, in the pelvic area, the unspecific bowel activity. Skeletal metastases were recognised in 7 out of 9 cases. In 14 patients with other non-colorectal carcinomas, RIS was successful in single cases. It is not helpful, however, when searching for tumours of unknown origin or for the screening of patients with elevated CEA levels without tumour history. The high technical, methodological and time effort required by RIS is justified in the follow-up of cancer patients when conventional diagnostic procedures are inconclusive or the status of morphological findings remains unclear. The use of RIS as an unspecific screening tool in tumour diagnosis must be rejected because of the not completely explored risks of the examination. Repeated applications of monoclonal antibodies require controls of the patients' HAMA titers before performing RIS.

Adult↗

Autosomal dominant polycystic kidney disease--in vitro culture of cyst-lining epithelial cells.

The major form of autosomal dominant polycystic kidney disease (ADPKD) in humans is linked to the PKD1 gene on chromosome 16p. The identity of the gene and the underlying pathogenetic mechanisms are not yet defined. Cyst-lining epithelial cells derived from a polycystic kidney were successfully grown in culture and designated MZ-PKD-1 cells. By linkage analysis, the related pedigree of the nephrectomized patient could be linked to the PKD1 gene on chromosome 16p. Thus, these cells exhibit the genotype of a mutated PKD1 gene and represent an in vitro culture model for ADPKD involving chromosome 16p. The antigenic phenotype was characterized immunohistologically by epithelial differentiation antigens and markers of individual nephron segments. An essentially identical antigenic pattern of proximal tubular cells was observed both in vitro and in fresh frozen tissue. Electron microscopy showed the formation of a microvillous-like coating. During growth phases in vitro successive changes in the cell shape were observed. MZ-PKD-1 cells exhibited a limited lifespan ending in replicative senescence. Northern blot analysis of kidney-growth-related genes, c-myc, TGF-alpha, TGF-beta 1, and EGF receptor revealed abundant expression of all of these genes in MZ-PKD-1 cells.

Antibodies, Monoclonal↗

Proliferation of gastrointestinal carcinoma cells by T lymphocyte factors interleukin-3 and granulocyte-macrophage colony-stimulating factor.

Hematopoietic growth factors have been well characterized by cDNA cloning in recent years. In order to determine the influence of rhGM-CSF and rhIL-3 on epithelial cells of the gastrointestinal tract, their influence on in vitro cultured gastric and pancreas cancer cells was determined. A more than two-fold enhancement of proliferation was observed by IL-3 and GM-CSF in Mz-Sto-1 gastric and 818-4 pancreas carcinoma cells, applying a sensitive microculture system which allows precise quantification. The highest growth rates were obtained adding 1-10 ng/ml of the growth factors, but even picogram amounts were effective. Expression of mRNA for GM-CSF and IL-3 remained undetectable in the cell lines, but mRNA for the EGF receptor was demonstrated. However, IL-3 and GM-CSF did not up-regulate mRNA for the EGF receptor. Therefore, the hematopoietic growth factors IL-3 and GM-CSF stimulate proliferation of epithelial cells derived from gastric and pancreas carcinomas by a paracrine mechanism. This effect did not involve an up-regulation of EGF receptor mRNA.

Cell Division↗

[Pseudoxanthoma elasticum (Grönblad-Strandberg syndrome) and rheumatoid arthritis].

A 72-year-old woman, not previously known to have coronary heart disease, was admitted to hospital with an acute anterior wall myocardial infarction. The history revealed that, when about 40 years of age, a coarse skin-fold and yellowish-white xanthoma-like efflorescences had been noted around her umbilicus, the inguinal regions and axillae. These changes subsequently developed into a pathognomonic picture of pseudoxanthoma elasticum (PE), which was a significant factor in the myocardial infarction. At the age of 69 years, rheumatoid arthritis (RA), stage II after Steinbrocker, had been diagnosed on the basis of morning stiffness, symmetrical arthritis in more than three joint regions and the radiological appearance of narrowed joint spaces with erosions. Different pathological mechanisms of PE and RA change the connective tissue metabolism, thus affecting the same target tissue, but there is no known connection between the two diseases.

Aged↗

The role of the Thomsen-Friedenreich antigen as a tumor-associated molecule.

The Thomsen-Friedenreich antigen (Gal-GalNAc) represents a tumor-associated molecule, which is assumed to be one of the few chemically well-defined antigens with a proven association with malignancy. In order to analyze the role of the carbohydrate structure Gal-GalNAc for gastrointestinal tumors, we immunized Balb/c mice with MCF-7 breast tumor cells together with synthetic Gal-GalNAc linked to a BSA carrier. One monoclonal antibody (82-A6) was established which recognizes the Thomsen-Friedenreich antigen according to the biochemical and serological analysis presented here. In contrast to the studies performed in the past, immunohistochemical results using this antibody 82-A6 did not exhibit a reactivity clearly restricted to tumors. Preliminary biochemical analysis revealed that the T-determinant is detectable in the high-molecular weight range (about 1000 kD), suggesting that the Gal-GalNAc epitope is found on mucinlike glycoproteins. Tumor restriction of Thomsen-Friedenreich antigen may therefore be determined either by the protein backbone or by the beta-glycosidic linkage of the carbohydrate structure to the protein.

Antibodies↗