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Biomedical subjects

R Klingel

Publications and source records attributed to R Klingel.

32 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1991

Distribution of Ha-ras alleles in patients with colorectal cancer and Crohn's disease.

The allele distribution of the Ha-ras gene on chromosome 11p was analysed by the restriction fragment length polymorphism of the enzymes Mspl/Hpall in 238 individuals. The investigation covered 116 patients with colorectal carcinoma and 122 patients with Crohn's disease, representing two patient populations with the same ethnic origin, one with a malignant and the other a benign disease of the same organ system. A total of 17 different alleles were detected belonging to the common, intermediate, and rare classes according to the original nomenclature of Ha-ras alleles. Patients with Crohn's disease showed no difference in the distribution of Ha-ras alleles when compared with expected frequencies. In patients with colorectal carcinoma, the frequency of rare alleles was significantly increased compared with the patients with Crohn's disease (chi 2 = 8.166; Fisher's exact test = 0.005) and with a reference population of 424 cancer free individuals (chi 2 = 49.312; Fisher's exact test = 0.000). Homozygosity was not detected for any rare allele. The occurrence of a rare Ha-ras allele was not linked to the location of the colorectal tumour. These results confirm the hypothesis that unique Ha-ras alleles represent an inherited factor which predisposes the development of colorectal cancer.

Alleles↗
PubMed1991

Stimulation of pancreas and gastric carcinoma cell growth by interleukin 3 and granulocyte-macrophage colony-stimulating factor.

Hematopoietic growth factors have recently been well characterized by complementary DNA cloning. For human epidermal growth factor, granulocyte-macrophage colony-stimulating factor recombinant proteins have been expressed in Escherichia coli. To reduce the toxic side effects of chemotherapy on the bone marrow, recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human interleukin 3 were applied to patients suffering of gastrointestinal cancers. To determine the influence of recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human interleukin 3 on human pancreas and gastric cancer cell cells in vitro, a sensitive microculture test system was established that allows precise quantification of proliferation. A more than twofold enhancement of proliferation was observed by interleukin 3 and granulocyte-macrophage colony-stimulating factor in two of two cell cultures derived from gastric carcinoma cells, while two of nine cultures from pancreas carcinoma cells have shown enhanced cell growth in the presence of recombinant human interleukin 3 or recombinant human granulocyte-macrophage colony-stimulating factor. In comparison, recombinant human epidermal growth factor increased cell growth in two of two gastric and in five of nine pancreas carcinoma cultures. In general, 1-10 ng/mL of the growth factors yielded the highest growth rate, but even 1-pg amounts produced increased cell growth. Expression of messenger RNA for granulocyte-macrophage colony-stimulating factor, interleukin 3, and the oncogene HER2/neu remained undetectable in all of the tested cell lines, while the various abundance of messenger RNA for the epidermal growth factor receptor was different in each cell line. The reported results imply that the hematopoietic growth factors interleukin 3 and granulocyte-macrophage colony-stimulating factor influence cellular growth of pancreas and gastric carcinoma cells by a paracrine mechanism and may possess a more general regulatory function than originally anticipated.

Animals↗
PubMed1990

[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↗
PubMed1990

Expression of epithelial antigens Exo-1 and EPM-1 in human epidermal keratinocyte maturation and benign and malignant neoplasia.

Exo-1, a polar neutral glycolipid, and EPM-1, a high molecular weight glycoprotein, are developmental antigens of human epithelial cells, initially described as components both on the cell surface and in secretions of gastrointestinal epithelial and respective tumors. In order to assess the biological significance of both antigens for epithelial cell differentiation and neoplastic transformation, their expression during human skin development and benign and malignant neoplasia was analyzed in fresh frozen tissue specimens of skin biopsies and of human epidermal keratinocytes growing in experimental model systems. Antigen expression was assessed immunohistochemically with specific monoclonal antibodies. During fetal development Exo-1 was temporarily expressed in intermediate cells but was absent in normal adult human skin. Exo-1 expression reemerged in neoplasias, both benign and malignant, but was restricted to spinous-like differentiated cells. Similarly, Exo-1 was not expressed in transplants of normal keratinocytes mimicking the normal epidermis but was clearly visible in differentiated areas of transplants of malignantly transformed keratinocytes. EPM-1 appeared first in basal epidermal cells in the second half of gestation and remained detectable in the stratum basale of adult skin. While squamous cell carcinomas continued to express EPM-1, it was not detectable in basal cell epitheliomas and in normal epidermis after invasion by neuroectodermal tumor cells. In experimental models, EPM-1 was present in the basal layers of normal human keratinocytes and of transformed keratinocytes with benign growth characteristics whenever a well stratified and keratinized epidermis-like epithelium had formed in transplants. In transformed keratinocytes with malignant growth behavior, EPM-1 was expressed irregularly, as in squamous cell carcinomas in situ. Thus, expression of Exo-1 is a marker for an early embryonic differentiation pathway of human keratinocytes and in adult tissue reveals abnormal differentiation associated with certain stages of hyperproliferation. EPM-1 expression is part of developmental programs and is influenced by microenvironmental interactions and alterations of tissue homeostasis.

Antigens↗
PubMed1990

[Examinations by ocular pressure tonometry].

A new method has recently been suggested for the determination of the outflow resistance in the anterior chamber angle. In this method the intraocular pressure is set to 45 mmHg for 8 minutes. The intraocular pressure is measured after the removal of the suction cup. Values below 7 mmHg are obtained in healthy subjects. Values above 7 mmHg are thought to be indicative for glaucoma. By setting the intraocular pressure to 45 mmHg for the expression of fluid the authors claim to have brought normalization to tonography. We show here in a series of results that we can reproduce the results which have been published by Ulrich et al. For normalization of a tonographic test we need a pressure rise which effects a uniform expression of volume. According to the knowledge presently generally agreed upon a uniform expression of volume is obtained by increasing the intraocular pressure by a constant factor and not by increasing it to a constant level. In 30 healthy volunteers and in 30 glaucoma patients we have increased the intraocular pressure by the constant factor of 1.8. According to our results the glaucoma patients and the healthy subjects can no longer be differentiated. A better differentiation is possible by the initial intraocular pressure. Thus we have shown that the favorable results by ocular pressure tonometry are mainly due to the intraocular pressure before the test. We feel therefore that ocular pressure tonometry should not be incorporated in our diagnostic armamentarium for glaucoma diagnosis.

Diagnosis, Differential↗
PubMed1987

An amplification unit in human melanoma cells showing partial homology with sequences of human papillomavirus type 9 and with nuclear antigen 1 of the Epstein-Barr virus.

By partial homology with the DNA of human papillomavirus type 9 a cellular amplification unit was detected which is amplified in melanoma cells but not in Epstein-Barr virus-transformed B cells of two melanoma patients. A 2.4-kilobase EcoRI fragment of this amplification unit was cloned and designated mel/HPV9. At the chromosomal level we detected mel/HPV9 in homogeneously staining regions or in abnormally banded regions containing different marker chromosomes of both melanoma cell lines. DNA sequence analysis of a part of mel/HPV 9 revealed homology with the third internal repeat array of Epstein-Barr virus nuclear antigen 1.

Antigens, Surface↗
PubMed1987

A common epithelial cell surface antigen (EPM-1) on gastrointestinal tumors and in human sera.

A common epithelial cell surface marker (EPM-1) was defined by two monoclonal antibodies (Pa-25 and Pa-42), raised against a pancreatic tumor cell line (Capan-1). Both monoclonal antibodies were tested on 49 cultured human cell lines and 244 tissue samples and reacted with all 76 tissue samples of 20 different normal epithelial cell types and with 57 of 63 epithelial tumor tissue samples of nonendocrine origin. Included were eight exocrine pancreatic carcinomas. There the percentage of EPM-1 positive tumor cells correlated with tumor grading. EPM-1 was detectable on the cell surface of cultured human cell lines of the pancreas, liver, colon, and mamma. Some epithelial tumor cell lines did not express EPM-1 on the cell surface, but in the cytoplasm. 100 nonepithelial and epithelial endocrine tissue samples as well as 25 nonepithelial cultured tumor and normal cells were unreactive with monoclonal antibodies Pa-25 and Pa-42. These included cells of neuronal, endocrine, and mesenchymal origin. EPM-1 activity was purified from pancreas tumor cells Capan-1 and from human sera by high-performance liquid chromatography and its molecular weight amounts to about Mr 400,000. EPM-1 was detectable in bronchial, intestinal, and pancreatic secretions and saliva and serum by an enzyme-linked immunosorbent assay test. EPM-1 values were high in the sera of normal individuals, but low or not detectable in most sera (21 of 31) of patients with gastrointestinal tumors. EPM-1 represents a novel differentiation marker for epithelial cell types, which should have a central role in the biology of normal and tumorous epithelial cells.

Animals↗
PubMed1987

Secretory epithelial cell marker on gastrointestinal tumors and in human secretions defined by a monoclonal antibody.

A new marker for human secretory epithelial cell types (Exo-1) has been defined by a mouse monoclonal antibody (Pa-G14). The antibody was raised against a human exocrine pancreatic tumor cell line (Capan-1) and tested against 46 cultured human cell types and 228 freshly frozen human tissue sections. It reacted specifically with 28 normal and 55 secretory neoplastic epithelial tissues tested. Eleven different secretory epithelial cell types expressed this antigen, as well as human fetal tissues of the gut and bronchi. One hundred and twenty samples of normal tissues, cells, and tumors of nonexocrine origin were Exo-1 negative. In normal secretory tissues staining was most pronounced at the apical poles and as shown by immunoelectron microscopy in the case of the duodenum, at the microvilli. In cultured Exo-1 positive tumor cells the antigen was not demonstrable on the cell surface but in the cytoplasm after acetone/methanol fixation only. The antigen was identified biochemically as a polar neutral glycolipid and detected in human salivary, bronchial, pancreatic, and intestinal secretions by an enzyme-linked immunosorbent assay, but was not found in sera of healthy controls or patients with gastrointestinal and other tumors. Antigen Exo-1 represents a novel common antigen for normal and tumorous glandular epithelial cells.

Animals↗
PubMed1987

Signet ring stomach cancer: morphological characterization and antigenic profile of a newly established cell line (Mz-Sto-1).

A human gastric signet ring cancer cell line (Mz-Sto-1) was established in tissue culture from the ascites fluid of a 54-year-old patient. The tumor cells growing in tissue culture exhibit the morphological characteristics of signet ring cells in phase contrast and transmission electron microscopy. Mz-Sto-1 cells grow as monolayer with a population doubling time of 28-36 hr during exponential growth phase and show a chromosome number between 72 and 74. In the cellular DNA of Mz-Sto-1 cells no amplification of 19 oncogenes studied is observed, c-myc included. Mz-Sto-1 cells secrete 150-250 ng CEA per 10(7) cell in 3 days, but no AFP. In addition Mz-Sto-1 cells and 2 already established gastric cancer cell lines MKN-28 and MKN-45 express HLA- and blood group related antigens (A, Lewis). HLA-DR antigens, which are regularly detected on normal stomach epithelium, are not found on any of the 3 cultured gastric cell lines. Mz-Sto-1 cells represent the first human gastric cancer cell characterized ultrastructurally as signet ring cells. This line will be a valuable tool to study the biology and genetics of gastric carcinoma, to test cytostatic drugs and to define new antigenic markers for stomach cancer.

Adenocarcinoma, Mucinous↗