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Biomedical subjects

R Hähnel

Publications and source records attributed to R Hähnel.

At least 19 recordsLinked to original sources
PubMed2004

Reduced breast cancer risk with increasing serum folate in a case-control study of the C677T genotype of the methylenetetrahydrofolate reductase gene.

Breast cancer risk may be associated with folate status or the C677T genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. We compared serum folate concentrations and C677T genotype in 141 breast cancer patients and 109 age-matched controls. Serum folate was significantly lower in cases compared to controls (geometric means, 5.7 versus 6.6 microg/l; P=0.005). Breast cancer risk was not associated with C677T genotype. After adjusting for age of menarche, parity, alcohol intake and total fat intake we observed reductions in odds ratios for breast cancer risk comparing the highest with the lowest quartiles of serum folate concentrations of 0.23 (95% confidence interval (CI) 0.09, 0.54) for the entire group, 0.27 (CI 0.09, 0.80) for the wild-type and 0.08 (CI 0.01, 0.52) for the heterozygous C677T genotype. We conclude that for the whole group, and the wild-type and heterozygous C677T genotypes, increased serum concentrations of folate were associated with reduced risks of breast cancer.

Adult↗
PubMed1996

Expression of the PIP/GCDFP-15 gene and survival in breast cancer.

Expression of the PIP/GCDFP-15 gene was determined by measuring PIP/GCDFP-15-mRNA in breast carcinomas of 91 patients. The patients were followed-up for an average of 47 months after initial diagnosis and treatment of the disease. There were no deaths in the group of 14 patients with tumours of high PIP/GCDFP-15-mRNA levels, while 16 of 77 patients of the group with low PIP/GCDFP-15-mRNA tumour levels died. A similar advantage for high PIP/GCDFP-mRNA expression was observed with regard to disease free survival.

Bacterial Proteins↗
PubMed1994

Expression of stromelysin-3 and nm23 in breast carcinoma and related tissues.

Biological functions proposed for the ST3 and nm23 genes in tumour development and progression seem to be directly opposed. Stromelysin-3 (ST3) is a putative member of the matrix metalloproteinase family. ST3 has been implicated in the progression of epithelial malignancies, specifically with regard to an invasive (and therefore potentially metastasizing) phenotype. The nm23 gene, on the other hand, encodes a nucleoside diphosphate kinase which allegedly has a metastasis-suppressor-type function. It was therefore of interest to compare the expression of ST3 and nm23 in various surgically excised normal and neoplastic breast tissues. RNA was isolated from over 200 surgical specimens and studied by Northern blots. Normal breast tissues did not express ST3, and ST3 expression was detected in only 1 of 20 normal axillary lymph nodes. None of 7 fibroadenomas expressed ST3. In contrast, 60% of primary and metastatic breast carcinomas contained ST3-mRNA. The expression of ST3 was mainly confined to invasive carcinomas and was observed less frequently in pure ductal carcinoma in situ (DCIS) lesions. Our results support the suggestion that ST3 expression is related to the malignant process in breast cancer. The role of nm23 is far less clear-cut.

Biopsy↗
PubMed1994

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1994

Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue.

Expression of the hormone-regulated genes, pS2, prolactin-inducible protein (PIP) and fatty acid synthetase (FAS), was investigated by Northern blotting in primary breast carcinoma, metastatic breast cancer in axillary lymph nodes, in uninvolved breast tissue from mastectomies and in normal lymph nodes. There were considerable differences in expression of the genes between the tissues. The proportion of tissues containing PIP-mRNA decreased from uninvolved breast tissue to primary breast carcinoma to metastatic carcinoma. The reverse applied to FAS-mRNA which was found more often in metastatic cancer than in primary cancer, and least frequently in uninvolved breast tissue. Yet another pattern was observed for pS2 expression. The highest proportion of tissues demonstrating gene expression was found in primary breast cancer with both metastatic tumor and uninvolved breast tissue expressing the gene less frequently. pS2-mRNA and PIP-mRNA could only rarely be detected in trace amounts in normal lymph nodes. In contrast, FAS-mRNA was present in about one third of normal lymph nodes. Only pS2-mRNA showed an association with estrogen and progesterone receptor status.

Blotting, Northern↗
PubMed1993

Stromelysin-3 expression in breast cancer biopsies: clinico-pathological correlations.

Stromelysin-3 expression was studied by Northern blotting in 222 tissue samples including primary and metastatic breast carcinoma and normal breast tissue. Uninvolved breast tissue from mastectomy specimens, normal breast tissue from reduction mammoplasties and normal lymph nodes did not contain stromelysin-3 mRNA. About 62% of primary and metastatic breast carcinomas, but only 1 of 10 in situ ductal carcinomas, expressed stromelysin-3. Stromelysin-3 mRNA was found more often in estrogen-receptor-positive carcinomas and in histological grade-1 carcinomas. There was no significant correlation between stromelysin-3 expression and other prognostic factors, including tumor size, lymph-node involvement, age of patient, vascular invasion and cathepsin-D.

Axilla↗
PubMed1993

Expression of the pS2 gene in normal breast tissue.

pS2 expression in normal breast tissue removed for cosmetic reasons was significantly lower than in uninvolved breast tissues from mastectomies for breast carcinomas. It is speculated that the presence of the carcinoma, or factors related to its development, could be the reason for this difference.

Breast↗
PubMed1993

Expression of the pS2 gene in breast cancer--a comparison of pS2 protein radioimmunoassay and immunohistochemistry.

pS2 expression was studied in a series of 82 primary breast carcinomas using and comparing a radioimmunoassay (RIA) technique and immunohistochemistry (IPOX). There was close correlation of the results obtained with each technique. Accurate and reliable determination of pS2 status in breast cancer can be made on the basis of immunohistochemistry using formalin fixed paraffin embedded sections. Immunohistochemical determination of pS2 status may be used in situations where the RIA technique cannot be applied, i.e. instances when fresh tumor tissue is not available.

Breast Neoplasms↗
PubMed1992

Expression of the pS2 gene in breast tissues assessed by pS2-mRNA analysis and pS2-protein radioimmunoassay.

The expression of the pS2 gene in breast tissues was assessed by measuring pS2-protein using a radioimmunoassay, and by determining pS2-mRNA using Northern blotting. There was a good correlation between the two measurements, indicating that expression of the pS2 gene in breast tissues may be assessed by either method. Since radioimmunoassay is technically easier and more efficient than Northern blotting, radioimmunoassay will be the method of choice in routine applications.

Blotting, Northern↗
PubMed1990

Isolation of untransformed bovine estrogen receptor without molybdate stabilization.

A low concentration estrogen-derivatized affinity resin has been used in a rapid, single step purification of the untransformed estrogen receptor from calf uterine cytosols prepared without sodium molybdata. The procedure isolates the Mr 65,000 estrogen receptor in association with the bovine heat shock protein hsp90. Small amounts of proteolyzed receptor ranging in size from Mr 50,000 to 60,000 are also present in the purified extracts. Results from affinity chromatography of receptor cytosols either untreated or presaturated with estradiol suggest that two proteins of Mr 22,000 and 38,000 are co-purified with the untransformed receptor complex and may represent additional nonhormone-binding components of the native receptor form. Some indication of the stability of protein-protein interactions within the oligomeric complex has been derived from differential salt elution studies with heparin-sepharose and affinity gel-immobilized untransformed receptor. On size exclusion high performance liquid chromatography the untransformed complex eluted with a Stokes radius of 75 +/- 2 A (n = 18), but was shown to be sensitive to extended ultracentrifugal analysis dissociating to the receptor homodimer, sedimentation coefficient 5.3 +/- 0.3 s (n = 5). Preliminary data on urea- and heat-induced transformation of the isolated receptor to the DNA-binding state is presented.

Animals↗
PubMed1990

Interaction of bovine estrogen receptor with immobilized zinc.

The metal-binding properties of partially purified untransformed or salt-dissociated bovine estrogen receptors were studied using zinc-chelated iminodiacetic acid gels. Only the salt-dissociated 5S receptor is retained by the metal-chelated resin, and this interaction is dependent on the presence of dithiothreitol. The untransformed 9S receptor is not retained, indicating that the zinc-interacting amino acid residues may be masked by receptor-associated proteins such as 90K heat-shock protein or because of an unfavorable receptor conformation.

Animals↗
PubMed1989

The interaction site for tamoxifen aziridine with the bovine estrogen receptor.

Calf uterine estrogen receptor was covalently labeled with [3H]tamoxifen aziridine during affinity chromatography purification. After carboxymethylation, affinity labeled receptor was digested with trypsin under limit conditions and the labeled peptides were fractionated by reversed-phase high performance liquid chromatography into one major and two minor components. Sequence analysis of the dominant labeled fragment indicated the facile cleavage of label during Edman degradation but identified two peptides, both derived from the extreme carboxyl terminus of the steroid-binding domain. The 17 residues of one peptide were fully conserved in all estrogen receptors. This fragment contained five nucleophilic amino acids and was considered as the more favored interaction site for tamoxifen aziridine. A corresponding region of the glucocorticoid receptor has recently been identified as one of three major contact sites for glucocorticoids (Carlstedt-Duke, J., Strömstedt, P.-E., Persson, B., Cederlund, E., Gustafsson, J.-A., and Jörnvall, H. (1988) J. Biol. Chem. 263, 6842-6846). A comparison of amino acid physical characteristics in the hormone-binding domains of human estrogen and glucocorticoid receptors demonstrated an excellent structural correlation between the two regions and delineated elements in the estrogen receptor which may be directly involved in estradiol binding.

Amino Acid Sequence↗
PubMed1989

Metabolism of androstenedione by placental microsomes in pregnancy hypertension.

The metabolism of [19-3H3]androstenedione by human placental microsomes was studied in vitro by radiometric analysis which distinguishes between 19-hydroxylation and elimination of the C-19 carbon. The ratio of the metabolic products tritiated water/tritiated formic acid is significantly greater for microsomes from patients with pregnancy hypertension when compared with normotensive pregnant women. This indicates that aromatization (2-hydroxylation) is deficient in pregnancy hypertension.

Androstenedione↗
PubMed1989

Identification of the major sources of error in estrogen receptor measurements for individual laboratories using both tissue and cytosol samples.

The major sources of error between laboratories performing estrogen receptor measurements in tissue samples were identified for 17 participating laboratories in a trial conducted by the Australasian Quality Assurance programme. Both tissue and cytosol samples were provided, and the In-House assays were compared with the ER-EIA kit (Abbott Laboratories, U.S.A.) as a reference assay. For both the In-House and Abbott assays, tissue samples resulted in a between laboratory CV of about 55% and a within laboratory CV of about 30%. In contrast to tissue samples, the between laboratory CV for cytosol samples was reduced to 41% for the In-House assays and to 33% for the Abbott assay, whereas the within laboratory CV was reduced to 10% for both types of assay. The different methods of tissue homogenization by themselves were not found to be sources of error, and protein extraction efficiency from tissue was strongly correlated with protein measurement (P less than 0.0005). The major sources of error due to protein measurement, cytosol preparation, In-House and Abbott assays were evaluated for individual laboratories. The results indicated absence of any major sources of error for four laboratories, while one, two and three or more sources were indicated for seven, three and three laboratories respectively. The conclusion that about half the participants need to improve their ER assays was confirmed by three independent reviews. Furthermore, the trial demonstrated that tissue samples are essential as quality assurance material for a realistic assessment of ER assays in biopsy specimens.

Animals↗
PubMed1989

Sources of improvement in between laboratory variation in estrogen and progestin receptor measurement using tissue samples during the Australian Quality Assurance Programme.

Tissue and cytosol samples were compared as quality control material for assessment of between and within laboratory error in measurement of estrogen and progestin receptors (ER and PR) in a series of four trials for a total of 17 participating laboratories during the Australasian Quality Assurance Programme. For tissue samples, a substantial reduction in between laboratory CVs for both ER and PR from about 90 to 50% was achieved during the programme. In contrast, for cytosol samples a substantially lower between laboratory CV of about 30% was obtained. Tissue sample heterogeneity could be excluded as a major source of variation between laboratories. The likely source of the observed improvement in CV for tissue samples during the trials was due to a reduction of the initial under-estimation of receptor concentration in tissue samples by some of the participants. Although cytosol preparation from tissue samples was shown to be one major source of error, other sources of error such as the receptor assay itself and the associated protein measurements were identified. It is concluded that fragmented tissue samples are essential for a realistic assessment of between laboratory error in receptor measurements in biopsy material such as obtained from clinical breast cancer samples.

Animals↗
PubMed1989

Plasma 19-hydroxyandrostenedione and androstenedione levels in hydatidiform moles and early pregnancies with and without hypertensive diseases.

Because of the association of preeclampsia with hydatidiform mole, and since levels of 19-hydroxyandrostenedione (19-OH-A) and androstenedione (A) are raised in hypertensive diseases of pregnancy, we compared plasma 19-OH-A and A in hydatidiform mole patients with control early pregnant women. Both steroids were significantly elevated in 27 patients with partial or complete hydatidiform moles, as compared with the levels in 36 control pregnancies at similar stages of gestation.

Androstenedione↗