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M Helle

Publications and source records attributed to M Helle.

At least 37 records · Page 2Linked to original sources
PubMed1990

Discordant results between radioligand and immunohistochemical assays for steroid receptors in breast carcinoma.

Surgical biopsy specimens of 179 breast carcinoma were studied by steroid-binding and immunohistochemical assays or oestrogen and progesterone receptors (ER, PR) in order to explore reasons for discordant results between the two assay types. Receptor statuses in 18% of ER assays and 30% of PR assays were in disagreement. Immunohistochemistry-positive steroid-binding-negative status predominated among the discordant ER assays, while the discordant PR assays displayed the opposite situation. In discordant assays receptor concentration was significantly more often close to the cut-off (10-50 fmol mg-1) than in the concordant ones. Low binding affinity (high Kd) was also significantly associated with disagreeing assay results. These observations clearly indicate that immunohistochemical ER and PR assays measure high-affinity binding components (i.e. type I receptors) in steroid-binding assays. ER but not PR assays in premenopausal women disagreed more often than those in post-menopausal women. Such factors as histological type, specimen size in steroid-binding assay, grade of malignancy and tumour necrosis were statistically unrelated to agreement or disagreement of receptor assays.

Adult↗
PubMed1990

Comparison of biological and immunological activities of human monocyte-derived interleukin 1 beta and human recombinant interleukin 1 beta.

Recombinant human interleukin 1 beta (rhIL-1 beta) and supernatants of Escherichia coli lipopolysaccharides-stimulated human monocyte (Mo) cultures, containing native human IL-1 beta (nhIL-1 beta), demonstrate significant differences when tested in the mouse co-stimulatory thymocyte (lymphocyte activating factor [LAF]) assay. The aims of the present study were to investigate this characteristic difference between rhIL-1 beta and Mo culture supernatants (Mo supernatants), and to compare the biological and the immunological activity of preparations of rhIL-1 beta and nhIL-1 beta during each step of an identical purification procedure. The biological activity of rhIL-1 beta/nhIL-1 beta preparations was characterized by the use of the LAF assay and the rat islet insulin release assay. An IL-1 beta enzyme-linked immunosorbent assay (ELISA) was established in order to compare the biological and immunological responses of the IL-1 beta preparations. We report that the significant difference between rhIL-1 beta and supernatants of Mo cultures, which was only demonstrable in the LAF assay, is due to the presence of interleukin 6 (IL-6) in the Mo supernatants. We describe a simple cation exchange chromatography separating nhIL-1 beta and IL-6 of Mo supernatants. The highly purified rhIL-1 beta possessing the correct amino-terminal sequence and nhIL-1 beta have identical biological and immunological activities demonstrating a specific biological activity (SBA) of 3 x 10(2) U/ng IL-1 beta. Thus, we have no indications of secondary or tertiary structural differences between rhIL-1 beta and purified nhIL-1 beta. In contrast, both in the LAF assay and in the rat islet insulin release assay the SBA of an amino-extended rhIL-1 beta form, Met-Glu-Ala-Glu-rhIL-1 beta, was only 1-2% of the SBA of rhIL-1 beta, suggesting that structural changes were introduced into the molecule by the amino-terminal extension. In the present study we have demonstrated that systematic combined testing of IL-1 beta preparations in two different biological assays and an immunological assay is useful for the characterization and comparison of the activity of recombinant and native IL-1 beta preparations purified by the use of exactly the same procedures.

Amino Acid Sequence↗
PubMed1989

IL-6 is an intermediate in IL-1-induced thymocyte proliferation.

Both IL-1 and IL-6 have been shown to be comitogenic for lectin-stimulated thymocytes. Thymocytes cultured in the presence of IL-1 produce IL-6 themselves. This IL-6 production is caused by a cell population with low buoyant density. After removal of these cells, IL-6 or IL-2 are still co-mitogenic for thymocytes whereas IL-1 is not. Addition of IL-1 to such thymocytes renders them about 100-fold more sensitive to IL-6. At all conditions proliferation is inhibitable with antibodies to IL-2 and to the IL-2R. Our experiments show that IL-1-driven proliferation of thymocytes is dependent on endogenous IL-6 production and that in the classical thymocyte assay IL-1 has a dual role: it induces IL-6 production and it greatly increases the sensitivity for IL-6.

Adjuvants, Immunologic↗
PubMed1989

Comparison of the effects of recombinant interleukin 6 and recombinant interleukin 1 on nonspecific resistance to infection.

Interleukin 1 (IL 1) is a potent enhancer of nonspecific resistance to infection in mice. Since IL 1 also induces interleukin 6 (IL 6), we tested the hypothesis that IL 6 mediates the effect of IL 1 on nonspecific resistance. In a lethal Pseudomonas aeruginosa infection in granulocytopenic mice, in which 80 ng of recombinant human IL 1 alpha protects against death, IL 6 appeared to be much less effective. Dosages of 8 ng, 80 ng and 320 ng IL 6 did not differ from the control, whereas 800 ng had a marginal protective effect (0.05 less than p less than 0.1). IL 1 and IL 6 did not potentiate each other in animals treated with suboptimal dosages of both cytokines. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in animals treated with 800 ng IL 6 and in control animals, arguing against activation of microbicidal mechanisms. The serum concentration profile of IL 6 after an i.p. injection of 80 ng IL 1 was similar to that after 80 ng IL 6 i.p. Only minute amounts of IL 1 were detected in serum after an i.p. injection of IL 6. Taken these data together, it appears that increased resistance to infection induced by IL 1 is not mediated by IL 6.

Animals↗
PubMed1989

Immunohistochemical versus biochemical estrogen-receptor and progesterone-receptor analysis: correlation with histological parameters.

Human breast carcinomas were evaluated for estrogen and progesterone receptors by immunohistochemistry using monoclonal anti-receptor antibodies (n = 267) and by cytosol steroid-binding assays (n = 212). The estrogen and progesterone receptor contents of the tumors correlated with histological features of differentiation, such as histological and nuclear grade, and with the amount of tumor necrosis and lymphoid infiltration. The correlation of immunohistochemically determined steroid receptor values with histological characteristics was somewhat better than that of biochemically assessed concentrations.

Breast Neoplasms↗
PubMed1988

Interleukin 6 is involved in interleukin 1-induced activities.

Human monocytes produce a number of soluble mediators involved in regulation of inflammation and lymphocyte growth and differentiation such as interleukin 1 (IL 1) and tumor necrosis factor. Recently, the cDNA of another monocyte-derived factor, interleukin 6 (IL 6), was cloned. Herein we show that purified E. coli-derived recombinant IL 6 (rIL 6) is as active as IL 1 in the thymocyte assay. In addition, IL 1 and IL 6 synergize strongly in stimulating thymocyte proliferation. Another property shared by IL 1 and IL 6 is their pyrogenicity. Human rIL 6 induces a monophasic fever after i.v. injection into rabbits. Together with the observation that IL 1 induces IL 6 in a variety of cells including thymocytes, our data suggest that IL 6 is involved in many of the pleiotropic effects of IL 1.

Animals↗
PubMed1988

Functional discrimination between interleukin 6 and interleukin 1.

In this study we have investigated the specificity of bioassays in which interleukin (IL) 1 and/or IL 6 are active. The thymocyte assay cannot be used to discriminate between IL 1 and IL 6; both monokines are active in this assay. Moreover the detection limit for both IL 1 and IL 6 is around 100 pg/ml. IL 6 activity can be measured with a murine hybridoma cell line (B9). The detection limit for human as well as murine IL 6 is about 0.5 pg/ml. The assay is specific for IL 6 and is not influenced by a variety of other cytokines except for murine IL 4 which shows some activity in this variety of other cytokines except for murine IL 4 which shows some activity in this assay. IL 1 can be measured specifically with D10 cells. The detection limit for IL 1 alpha and IL 1 beta is around 1 pg/ml whereas IL 6 is not active in this assay at all. Upon stimulation by IL 1 and/or IL 2 D10 cells produce IL 6. However, this IL 6 does not seem to be involved in the proliferation of these cells.

Animals↗
PubMed1988

Oestrogen receptor content and cancer cell/stroma ratio in mammary carcinoma.

In a study of 86 human breast cancers the volume fraction of the neoplastic epithelium was estimated semiquantitatively and a significant association was found between the oestrogen receptor (ER) content and volume fraction of cancer cells of tumours (p less than 0.00001). Tumours with very low cellularity could thus be falsely ER negative. When quantitative ER concentration is used to predict the response of tumours to hormonal therapy the cellularity of tumours should be taken in consideration. The cellularity was not related to ER positivity. Although a correlation was seen between the contents of oestrogen and progesterone (PR) receptors, no correlation between PR content and volume fraction of the neoplastic epithelium was observed.

Breast Neoplasms↗
PubMed1988

Human milk fat globule antigen III D 5, steroid receptors and histopathologic parameters in breast cancer.

Immunohistochemical reactivity of mammary carcinomas with the monoclonal human milk fat globule (HMFG) antibody III D 5, and the estrogen receptor (ER) and progesterone receptor (PR) status were compared with the histopathology of primary breast cancer. The reactivity with III D 5 has earlier been shown to be associated with the estrogen receptor status of tumours and with a favourable prognosis. The reactivity of tumours with III D 5, as well as the presence of ER and PR correlated significantly with the histological features of differentiation; histological grade, nuclear grade, tumour necrosis and lymphoid infiltration. Reactivity with III D 5 correlated with all these parameters, while the presence of ER did not correlate with the nuclear grade and that of PR correlated only with the nuclear grade and the lymphoid infiltration of tumours. Reactivity of III D 5 may thus have prognostic and therapeutic implications in the management of breast cancer.

Adult↗
PubMed1988

Use of immunohistochemical staining panel for characterisation of ovarian neoplasms.

Eighty five ovarian epithelial and non-epithelial tumours were studied by peroxidase histochemical staining for their reactivity with six monoclonal human milk fat globule (HMFG) antibodies, peanut agglutinin (PNA) lectin, and a monoclonal cytokeratin antibody. HMFG IIIC12 and cytokeratin antibodies distinguished epithelial from non-epithelial tumours. The staining patterns of mucinous and serous tumours were essentially different from each other; poorly differentiated anaplastic carcinomas showed similar antigenic content to that of the serous cystadenocarcinomas. Furthermore, staining with PNA lectin and HMFG antibodies was useful in distinguishing clear cell carcinomas from other malignant epithelial tumours of the ovary.

Adenocarcinoma↗
PubMed1986

Recognition with a monoclonal antibody of a cytoplasmic mammary carcinoma antigen, correlated to the estrogen receptor status.

Immunohistochemical reactivity of mammary carcinomas with monoclonal antibodies (MAbs) to human milk fat globule (HMFG) membrane antigens was compared with the estrogen (ER) and progesterone receptor (PR) status of the tumors. Antibody III D 5 stained 55 of the 74 tumors studied, the reaction being of borderline intensity in 19 cases and unequivocally positive in 36 cases. The staining was always cytoplasmic; in addition occasional extracellular III D 5-positive secretory material was observed. Positive reactivity of the tumor with antibody III D 5 was significantly correlated with ER and/or PR content of the tumors. The presence of extracellular, III D 5-positive secretory material correlated to the ER but not to the PR status of the tumors.

Animals↗
PubMed1986

Reactivity of a monoclonal antibody recognizing an estrogen receptor regulated glycoprotein in relation to lectin histochemistry in breast cancer.

We have raised monoclonal antibodies against human milk fat globule membrane antigens and previously shown that one of them, called III D 5, recognises a glycoprotein associated with estrogen receptor activity of breast cancer. In immunoblotting it was shown that the molecule in human milk exclusively stained with III D 5 also binds peanut agglutinin (PNA) and Ricinus communis. In this study we correlate the staining of III D 5 and binding of lectins to tissue sections fixed in formalin and embedded in paraffin. Similar reactions were seen only with III D 5 and PNA. Our results suggest that III D 5 and PNA detect overlapping antigenic epitopes in mammary carcinoma. This is in keeping with previous results that PNA or III D 5 reactivity is correlated with estrogen receptor status of breast cancer.

Antibodies, Monoclonal↗
PubMed1986

Immunohistochemical reactivity of monoclonal antibodies to human milk fat globule with breast carcinoma and with other normal and neoplastic tissues.

The immunohistochemical reactivity of three monoclonal antibodies, generated against human milk fat globule membranes (HMFG), were studied using peroxidase conjugated secondary antibody or avidin-biotin-peroxidase complex method. Two of the antibodies, III E 8 and III H 2 showed rather broad reactivity, staining all mammary, ovarian, endometrial, cervical and bronchial adenocarcinomas. They also stained all pancreatic adenocarcinomas but only 30% of the carcinomas of the colon. Reaction with prostatic and renal adenocarcinomas varied. No reaction was seen with squamous or transitional cell carcinomas. Antibody III D 5, which previously has been shown to recognize an estrogen receptor activation associated antigen in mammary carcinomas, stained 60% of mammary or gynecological adenocarcinomas. This antibody had a more limited reactivity with other tissues as well, as all intestinal carcinomas were negative. It stained all bronchial adenocarcinomas, however, and 50% of the prostatic carcinomas. The three monoclonal antibodies, although not specific, show a more restricted reactivity than the so far described HMFG antibodies and they may therefore be of value in histopathological diagnosis.

Adenocarcinoma↗
PubMed1986

The prognostic significance of the monoclonal antibody III D 5 to human milk fat globule antigen in breast cancer.

The monoclonal antibody III D 5 identifies an antigen in human milk fat globule membrane, found also on breast epithelial cells. Immunohistochemistry with the antibody was used in the staining of formalin-fixed, paraffin-embedded sections of 80 breast carcinomas. The duration of follow-up of patients was from seven to twelve years. The presence or absence of metastases in regional lymph nodes at the time of primary operation, histological grade and necrosis of tumours correlated highly significantly to the survival of patients. The patients whose tumours exhibited positive staining with the antibody III D 5 had an improved survival-rate compared with those with III D 5 negative tumours. In the patients without metastases at the time of primary operation, the histological grade of primary tumour had only a weak correlation with survival, while the same patients with III D 5 positive tumours had significantly better prognosis compared to the III D 5 negative cases. Inclusion of the III D 5 immunoreactivity with other factors in a prognostic index could permit a more accurate estimation of prognosis in patients with mammary carcinoma.

Antibodies, Monoclonal↗
PubMed1985

The use of radiolabelled monoclonal antibodies to human milk fat globule membrane antigens in antibody-guided tumour imaging, and administration of therapeutic dose of labelled antibody in wide-spread ovarian carcinoma. A preliminary report.

Monoclonal antibodies generated against human milk fat globule membrane antigens were used in antibody-guided tumour imaging and palliative therapy in a case of wide-spread ovarian carcinoma. Antibody III H 2, which previously has been shown to react with 100% of ovarian cystadenocarcinomas showed a strong reactivity with tissue sections obtained from the primary and metastatic tumours of the patient. Immunoglobulins were purified from mouse ascitic fluid containing III H 2 and labelled with 123I or 131I with the iodogen method. 80 MBq (2 mCi) of 123I-labelled antibody was given intraperitoneally in 500 ml of PBS and the uptake of radiolabel was followed daily with emission tomography. Radiolabel was mainly located in the peritoneal cavity; only a very low activity was seen in the thyroid gland and urinary bladder. A therapeutic dose consisting of 600 MBq (15 mCi) of 131I-labelled antibody was followed nine days later and the localization of the antibody was followed.

Antibodies, Monoclonal↗
PubMed1985

Generation of monoclonal antibodies to human milk-fat globule membrane antigens, with special reference to a precipitable secretory product of breast and ovarian carcinomas.

Monoclonal antibodies were generated against protein antigens extracted from human milk-fat globule (HMFG) membranes. Of more than 500 hybridoma clones, 16 secreted antibodies reacting with breast and ovarian carcinoma cells, but not with lymphocytes or macrophages. Five clones were further expanded and characterized; four reacted with plasma membranes of all breast and ovarian carcinomas rested, but also with normal breast. One of the monoclonal antibodies, III D 5, reacted mainly against the cytoplasmic components of breast cancer cells, whereas the reaction with normal or mastopathic breast was against the luminal plasma membranes. The antigen recognized by the antibody was secreted in ascites fluid or pleural effusions of patients with widely spread ovarian or breast carcinomas, and could be demonstrated by immunodiffusion. It is suggested that the antigen is composed of several glycoprotein subunits bearing the same repetitive epitope. This might be the physicochemical basis for its precipitability with a monoclonal antibody.

Animals↗