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J Hilgers

Publications and source records attributed to J Hilgers.

At least 73 records · Page 4Linked to original sources

Chromosomal mapping of the mouse IL-4 and human IL-5 genes.

We mapped the mouse interleukin (IL)-4 gene on chromosome 11 by restriction fragment length polymorphism using recombinant inbred mouse strains. The human IL-5 gene was mapped on chromosome 5q 23.3-31.1 by in situ hybridization. Because the granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-3 genes were previously mapped on mouse chromosome 11 (within a 230-kb region) and human chromosome 5, the IL-4 and IL-5 genes are likely to cluster on the same chromosomes with the GM-CSF and IL-3 genes in both species.

Animals↗

Human milk-fat globule membrane antigens (Mam-3 group) in normal cycling endometrium and endometrial carcinomas--an immunohistochemical study. A preliminary report.

The expression of Mam-3 antigens in normal human endometrium and endometrial carcinomas was investigated employing the monoclonal antibodies 67D11 (anti Mam-3a), 115H10 (anti Mam-3b), and 115C2 (anti Mam-3c). Dewaxed sections of formalin-fixed, paraffin-embedded curettings of 9 proliferative-, 6 interval-, 13 secretory endometria, as well as 16 endometrial carcinomas were used. In normal cycling endometrium the Mam-3a, -3b and -3c antigens were detected at the apical membrane of surface and/or glandular epithelium only, but to a different degree. The Mam-3a antigen was only detected in the surface epithelium of 66% of proliferative and 33% of interval endometrium. The Mam-3b antigen was detected in surface and glandular epithelium of all normal endometria, but was most widespread in proliferative endometrium. The Mam-3c antigen was detected in surface epithelium of proliferative, and interval endometrium especially, and in glandular epithelium in 22% of endometria irrespective of the phase. Increased expression of Mam-3a and -3c antigens was recorded in most carcinomas. A loss of polarity of staining was seen in grade III carcinomas especially, staining of the cytoplasma was recorded in half of the carcinomas. The expression of Mam-3c antigen in carcinomas seemed to decline with increasing grade of anaplasia. All carcinomas expressed the Mam-3b antigen. The present results indicate that the Mam-3a and -3c antigens are tumor-associated antigens of endometrial carcinomas and that they might be useful as diagnostic tools in endometrial pathology.

Adenocarcinoma↗

Resistance of STS/A mice to lymphoma induction by X-irradiation.

While fractionated X-irradiation induced a high incidence lymphomas in BALB/cHeA mice (77% in females and 86% in males), it induced the disease at an extremely low incidence in STS/A mice (8% in females and 9% in males). The latent period of lymphoma development was short in BALB/cHeA mice, but relatively long in STS/A mice. No significant difference of incidence of the disease between sexes in either strain was observed. F1 hybrid mice showed an intermediate incidence of radiation-induced lymphomas. This suggests that neither resistance of STS/A mice nor susceptibility of BALB/cHeA mice to radiogenic lymphomas is dominant.

Animals↗

Effect of sodium butyrate and other differentiation inducers on poorly differentiated human ovarian adenocarcinoma cell lines.

We have studied the effects of sodium butyrate, retinoic acid, and dimethyl sulfoxide on two human ovarian carcinoma cell lines PE04 and PE01. PE04 cells, after treatment with sodium butyrate at cytostatic doses (2-3 mM for 4 days), exhibited phenotypic changes including induction of alkaline phosphatase and determinants recognized by the monoclonal antibodies 123C3 and 123A8. These effects are not simply the result of cytostasis as they were not produced by dimethyl sulfoxide or retinoic acid. Other markers are also modified by sodium butyrate including lipid, acid mucin, and glycogen. Retinoic acid modulated expression of lipid and CA125, while dimethyl sulfoxide reduced expression of CA125. Other short chain fatty acids such as propionic acid and valeric acid (in addition to butyric acid) also induced alkaline phosphatase and the determinants recognized by 123C3 and 123A8 in PE04 cells. Other differentiation inducers and cytotoxic agents studied did not induce these markers at cytostatic concentrations. The effects of sodium butyrate (and related short chain fatty acids) thus appear to be relatively specific for this cell line.

Adenocarcinoma↗

Characterization and properties of nine human ovarian adenocarcinoma cell lines.

Four series of cell lines have been derived from patients with ovarian adenocarcinoma. Nine cell lines have been established at one from a solid metastasis. Six lines were derived from the ascites or pleural effusion of patients with poorly differentiated adenocarcinoma: PEO1, PEO4, and PEO6 from one patient, PEA1 and PEA2 from a second, and PEO16 from a third. Three lines (PEO14 and PEO23 from ascites and TO14 from a solid metastasis) were derived from a patient with a well-differentiated serous adenocarcinoma. Each set of cell lines was morphologically distinct. The five cell lines PEO1, PEO4, PEO6, PEA1, and PEA2 had cloning efficiencies on plastic of 1-2% and only a few cells in these lines expressed alkaline phosphatase or vimentin. Only a low percentage of these cells reacted with the monoclonal antibodies 123C3 and 123A8 but most reacted with OC125. Conversely the cell lines PEO14, TO14, PEO23, and PEO16 were characterized by low cloning efficiency values (less than 0.05%), marked expression of alkaline phosphatase and vimentin, and good reaction with 123C3 and 123A8 but not OC125. These four cell lines also exhibited dome formation. Four of the cell lines, PEO1, PEO4, PEO6, and PEO16, have been xenografted into immune-deprived mice and found to be tumorigenic.

Adenocarcinoma↗

Receptors for Fc epsilon and Fc gamma are linked on mouse chromosome 1.

Recently isolated cDNA clones for the high affinity Fc epsilon receptors on mast cells and basophils (Fc epsilon RI alpha) and Fc gamma receptors on macrophages and lymphocytes (Fc gamma 2b/gamma 1R) are homologous members of the Ig supergene family. Analysis of the segregation of restriction fragment length polymorphism in crosses of inbred mice now establish that the structural genes encoding both Fc epsilon RI alpha and Fc gamma 2b/gamma 1R are indeed discrete genes and are linked at the distal end of mouse chromosome 1. This finding raises the possibility that a family of Fc receptors could be found in a region that is known to contain immunologically important markers of lymphocyte surface Ag and autoimmune defects.

Animals↗

Monoclonal antibody 123C3, identifying small cell carcinoma phenotype in lung tumours, recognizes mainly, but not exclusively, endocrine and neuron-supporting normal tissues.

Monoclonal antibody (MAb) 123C3 was raised against a membrane preparation of a small cell lung carcinoma (SCLC) specimen and its reactivity on normal tissues was tested. For the endocrine system, positive tissues included: pituitary and adrenal glands, thyrocytes and C-cells of the thyroid, the parathyroids, testis Leydig cells and pancreatic islets. In bronchioles and intestinal epithelium occasional cells, resembling Kultchitsky and enterochromaffin cells, were also positive. Epithelia like rete testis, mammary epithelium and gastric mucosa were positive in all or a significant proportion of cells. The positive cells in mammary epithelium and gastric mucosa were too numerous to represent the endocrine cells only. Neurons were usually negative or weakly positive. Their supportive cells such as glial, Schwann and ganglionic satellite cells were positive. Mesenchymal cell types, such as smooth muscle cells in most organs, cardiac muscle cells, the pia-arachnoid and ovarian stroma cells were positive, indicating that 123C3 reactivity is not confined to epithelial and neuron-supporting tissues. In Western blots of tumour specimens 123C3 recognized a 29 kDa band in reducing conditions, shifting to approximately 150 kDa in non-reducing conditions. Immunofluorescence on live tissue culture cells demonstrated presence of the antigen on the cell surface.

Animals↗

Monoclonal antibodies to epithelial sialomucins recognize epitopes at different cellular sites in adenolymphomas of the parotid gland.

Fourteen monoclonal antibodies (MAbs) to epithelial sialomucins were studied for their immunohistochemical reactivity on serial sections of 14 formalin-fixed and paraffin-embedded adenolymphomas of the parotid gland. Two types of reactivity were observed, suggesting different cellular distribution of the corresponding epitopes. Most antibodies reacted with the luminal membrane of the columnar tumor cells (type-A reaction). The other reaction (type B) was observed with the membrane of basal epithelial cells. The antibodies could be ranked according to their tendency to show type-A and/or type-B reactions. MAb Cal was the only one with a pure type-A reaction. A strong tendency to type-A reactivity (with traces of type-B reactions) was observed for the antibodies HMFG-2, M8, E29 and NCRC-II. Several antibodies gave good type-B reactions in addition to strong type-A reactivity (MAbs 126E7, 115G2, 115D8, 140C1, F36/22, 139H2). MAb DF3 showed equally strong reactions with both cell types. A clear-cut preference of the reactions with basal cells was seen with the antibodies HMFG-1 and 115F5. This subclassification of the antibodies is in accordance with epitope mapping data, obtained by conventional blocking studies reported in the literature.

Adenolymphoma↗

Pre-operative discrimination between benign and malignant ovarian tumors using a combination of CA125 and CA15.3 serum assays.

Serum levels of CA125 and CA15.3 were measured in 70 patients presenting with an ovarian neoplasm, of whom 38 had an ovarian malignancy and 32 a benign ovarian tumor. CA125 levels exceeded 35 U/ml in 71% of ovarian carcinomas and in 25% of benign ovarian tumors. In the entire group of 70 patients, CA125 levels (greater than 35 U/ml) were elevated in 35 patients, of whom 27 had ovarian cancer. CA15.3 levels were found to be elevated (greater than 30 U/ml) in 9% of benign ovarian tumors and in 50% of ovarian malignancies. Of 8 patients with a false positive CA125 (greater than 35) elevation, only one had an elevated CA15.3 level whereas in 27 correct positive patients 19 also had elevated CA15.3 levels. Of all 20 patients with both markers elevated, 19 patients (95%) had ovarian cancer. When a cut-off level of 65 U/ml was used for the tumor marker CA125, all patients with simultaneous elevation of both markers were found to have an ovarian malignancy. Using a panel of CA125 (greater than 35 U/ml) and CA15.3 (greater than 30 U/ml) and requiring a simultaneous marker elevation, the sensitivity of the test decreased from 71% to 50% but the corresponding specificity of the test rose from 75% to 97%. Specificity was as high as 100% if in the same panel of tests a 65 U/ml cut-off for CA125 was taken. A comparison of early stage I-II ovarian cancer with benign ovarian tumors failed to demonstrate a discriminatory capacity of any test or test combination. We conclude that the use of a panel of tumor markers is advantageous in the pre-operative discrimination of benign and malignant ovarian tumors, since the predictive value for malignancy of a combined marker elevation was as high as 100% in the population studied.

Adult↗

Generation of monoclonal antibodies against human carcinosarcoma cell line for identification of myoepithelium and basement membrane.

An immunohistochemical method is described for identification of myoepithelial cells and basement membrane for cryostat tissue sections of normal, benign, and in situ carcinomas of the breast using two monoclonal antibodies 155C1 and 155D10 generated against human breast carcinosarcoma cell line HS578T. In the majority of infiltrating ductal carcinomas of the breast, there was a discontinuity in the myoepithelial cell layer, as a result an intact basement membrane could not be visualized. The reactivity of these two monoclonal antibodies might prove useful in the study of myoepithelial differentiation antigens and in the delineation of basement membrane. Among the other types of tissues studied, prominent staining was present with soft tissue tumors like leiomyosarcoma and synovial sarcoma.

Antibodies, Monoclonal↗

Monoclonal antibody 123C3 in lung tumour classification. Immunohistology of 358 resected lung tumours.

Monoclonal antibody 123C3, raised in The Netherlands Cancer Institute against a membrane preparation of small cell lung carcinoma, was tested on a series of 358 surgically resected primary epithelial lung tumours of various types. 123C3 recognized all small cell carcinomas and carcinoids tested (total: 30 tumours), but also stained a minority of various types of non-small cell lung carcinomas and almost all bronchial gland tumours investigated. Staining for 123C3 in squamous carcinomas or adenocarcinomas, when present, was usually focal and weak or moderately strong, whereas staining of small cell carcinomas and carcinoids was strong and present throughout the tumour. Our results indicate that immunostaining for 123C3 may be of potential interest for the histological typing of lung tumours, particularly when staining results are either strongly positive or completely negative. The positivity found in a fraction of non-small cell lung carcinomas is yet another illustration of the fact that the major types of lung tumours cannot be strictly separated, and that overlaps in differentiation states and antigenic make-up exist between different histological types of lung tumours.

Antibodies, Monoclonal↗

Chromosomal organization of the cytochrome P450-2C gene family in the mouse: a locus associated with constitutive aryl hydrocarbon hydroxylase.

Cytochromes P-450 represent a superfamily of enzymes with a central role in the metabolism of drugs, chemical toxins, and carcinogens. We have used genetic analysis to establish the complexity and catalytic function of a recently identified constitutively expressed murine hepatic cytochrome P-450 encoded by P450-2C. Southern blotting analysis shows that there are at least seven or eight genes within this family in the mouse and rat and that DNA restriction fragment length variants between different mouse inbred strains are observed. Analysis of recombinant inbred strains derived from these parent strains shows (i) these genes are clustered within 1 centimorgan, (ii) this gene family does not correspond to any of the known cytochrome P-450 loci or map near any well-characterized genomic markers, and (iii) this gene family segregates to within 1-2 centimorgans of a locus controlling constitutive aryl hydrocarbon hydroxylase activity in mice. With use of Chinese hamster/mouse somatic cell hybrids, the P450-2C locus was assigned to a region of mouse chromosome 19 that appears to be syntenic with the previously mapped human P450C2C locus on human chromosome 10. By in situ hybridization to mitotic mouse chromosomes, we have localized this region to the tip of chromosome 19. These results are discussed in relation to the physiological roles of this P-450 family in foreign compound metabolism and steroid oxidations.

Animals↗

H-2-linked control of in vitro gamma interferon production in response to a 32-kilodalton antigen (P32) of Mycobacterium bovis bacillus Calmette-Guérin.

A 32-kilodalton protein antigen (P32) was previously purified to homogeneity from culture filtrate of Mycobacterium bovis BCG (J. De Bruyn, K. Huygen, R. Bosmans, M. Fauville, R. Lippens, J. P. Van Vooren, P. Falmagne, H. G. Wiker, M. Harboe, and M. Turneer, Microb. Pathog. 2:351-366, 1987). Spleen cells from BCG-sensitized mice produce significant amounts of gamma interferon (IFN-gamma) in response to this P32 protein. The amount of secreted IFN-gamma is influenced by mouse genotype, with C57BL/6 (H-2b), C57BL/10 (H-2b), and 129/Sv (H-2b) mice producing about four times more than BALB/c (H-2d), CBF1 (H-2d/b), and DBA/2 (H-2d) mice do. Analysis of seven recombinant inbred strains derived from the BALB/c x C57BL/6 cross and of congenic mice differing in major histocompatibility complex-coding chromosome 17 fragments indicates a probable H-2-linked control of this IFN-gamma induction, with H-2b cells producing high titers and H-2d cells producing low titers in response to the P32 antigen.

Animals↗

A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody.

A rat monoclonal antibody, GoH3, recognizes cell surface antigens on epithelial cells in a variety of tissues in both man and mouse. Furthermore, the antibody showed reactivity with endothelial cells and blood platelets. The molecule recognized by GoH3 on platelets was determined by immunoprecipitation, followed by analysis on one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gels. GoH3 precipitated glycoproteins Ic and IIa from both human and mouse platelets. Glycoprotein Ic consists of disulfide-linked heavy and light chains which both appeared to be glycosylated. As determined by enzymatic digestion followed by gel analyses, both "complex" and "high mannose" type of N-linked oligosaccharides are present on the heavy and light chain of human glycoprotein Ic and on the heavy chain of mouse glycoprotein Ic. The light chain of mouse glycoprotein Ic only carries high mannose type of N-linked oligosaccharides. The N-linked glycans on human and mouse glycoprotein IIa are all of the complex type. The glycoproteins Ic and IIa co-sedimented in sucrose gradients and formed complexes upon treatment of intact platelets with the chemical cross-linking reagent dithiobis(succinimidyl propionate). Dissociation of the complex by chaotropic agents followed by immunoprecipitation establishes that the epitope recognized by GoH3 is located on the Ic molecule. These results provide evidence that the two glycoproteins, Ic and IIa, exist as a heterodimer complex in the platelet membrane.

Animals↗