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T Sauer

Publications and source records attributed to T Sauer.

At least 37 records · Page 2Linked to original sources
PubMed1998

nm23 protein expression in fine-needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status, and ploidy.

BACKGROUND: nm23 has been recognized as a potential suppressor gene of metastasis. Reduced nm23 expression in breast carcinoma has been found to correlate with axillary lymph node metastases, high grade tumors, and shorter survival. METHODS: nm23 protein was detected immunocytochemically using an avidin-biotin complex technique. When a few cells showed negative or marked reduced cytoplasmic staining, expression was considered reduced. Cytologic grading was performed on routine fine-needle aspirates (FNAC). Ploidy was determined by in situ hybridization of chromosomes 6, 7, 12, and 17 on interphase cell nuclei from FNAC. When all four chromosomes revealed a disome pattern, the tumor was classified as diploid; mixed disome/aneusome carcinomas as well as those with aneusomy in all four chromosomes were considered aneuploid. RESULTS: Approximately 83% of specimens had reduced expression of nm23 protein. Forty-four of 45 lymph node positive tumors as well as 27 of 29 aneuploid tumors, were found to have reduced nm23 expression. Likewise, 49 of 57 Grade 2 (G2) carcinomas (86%) and 20 of 22 Grade 3 (G3) carcinomas (91%) showed reduced nm23 expression. Twenty-nine of 39 Grade 1 (G1) carcinomas (74%) had reduced nm23 expression. None of the G1 or G2 tumors with full nm23 expression had axillary lymph node metastases. CONCLUSIONS: nm23 protein showed a significant inverse correlation with lymph node status, cytologic grading, and ploidy. The nm23 protein antibody may have potential as a preoperative marker in identifying subgroups of patients who either may have a worse prognosis than expected (e.g., those with G1 carcinomas with reduced nm23 expression) or who may be able to avoid axillary lymph node dissection (e.g., those with G1 carcinoma with full nm23 protein expression). Cancer

Biomarkers, Tumor↗
PubMed1998

An increased risk of cervical intra-epithelial neoplasia grade II-III among human papillomavirus positive patients with the HLA-DQA1*0102-DQB1*0602 haplotype: a population-based case-control study of Norwegian women.

Several recent studies have reported different associations between HLA specificities and human papillomavirus (HPV)-associated disease of the cervix. We report the distribution of DQA1 and DQB1 genes and HPV infection in a population-based case-control study including 92 patients with histologically verified cervical intraepithelial neoplasia grade II-III (CIN II-III) (thus including moderate and severe dysplasia and carcinoma in situ) and 225 control subjects. We found an overrepresentation of the DQA1*0102-DQB1*0602 haplotype among HPV-positive cases compared with controls. The association was even stronger when comparing HPV-16-positive cases with HPV-16-positive controls. In addition, among HPV-16-positive individuals, we observed a decreased frequency of DQA1*0102-DQB1*0604 in cases compared with controls. We were not able to detect any association between CIN II-III and DQB1*03. Compared with previous findings in cervical cancer, our data indicate that carrying the DQA1*0102-DQB1*0602 haplotype gives an increased risk of developing CIN when infected with HPV-16, without influencing progression to cancer.

Adult↗
PubMed1998

Bacterial milking: A novel bioprocess for production of compatible solutes.

A novel biotechnological process called "bacterial milking" has been established for the production of compatible solutes using the Gram-negative bacterium Halomonas elongata. Following a high-cell-density fermentation which provided biomass up to 48 g cell dry weight per liter, we applied alternating osmotic shocks in combination with crossflow filtration techniques to harvest the compatible solutes ectoine and hydroxyectoine. H. elongata, like other halophilic or halotolerant microorganisms, produces compatible solutes in response to the salinity of the medium. When transferred to a low salinity medium (osmotic downshock), H. elongata cells rapidly released their solutes to achieve osmotic equilibrium. Subsequent reincubation in a medium of higher salt concentration resulted in resynthesis of these compatible solutes and-after a defined regeneration time-the procedure could be repeated. By repeatedly performing this "bacterial milking" process (at least nine times) we were able to produce large amounts of ectoines with a biomass productivity of 155 mg of ectoine per cycle per gram cell dry weight. Further purification of the products was achieved by a simple two-step procedure based on cation exchange chromatography and crystallization. The principles described in this article may also be useful for the production of other low-molecular-weight compounds.

Amino Acids, Diamino↗
PubMed1998

Numerical aberrations of chromosome 17 in interphase cell nuclei of breast carcinoma cells: lack of correlation with abnormal expression of p53, neu and nm23 protein.

The genes for p53, neu (c-erbB-2) and nm23 are all located on chromosome 17. Abnormal expression of their protein products is an important prognostic parameter. The aim of this study was to investigate if numerical aberrations of chromosome 17 are reflected in the expression of these markers. The immunohistochemical expression was analysed on histological specimens from 33 breast carcinomas. In situ hybridization (ISH) was performed on interphase cell nuclei in air-dried fine-needle aspirates from the same cases using a digoxigenin-labelled alpha-satellite probe for chromosome 17. ISH for chromosome 6, 7 and 12 was used additionally to give an estimate of ploidy. Of the carcinomas 76% were aneuploid, and numerical abnormalities of chromosome 17 were found in 34%. Abnormal p53 protein was expressed in 15% (five cases). All of these were aneuploid, but only one of them revealed aneusomy of chromosome 17. Neu overexpression was found in 18% of the tumours (six cases). Five of these were aneuploid, whereas two were aneusome for chromosome 17. Four cancers showed full (normal) expression of nm23 protein, whereas 29 had reduced expression. Reduced expression was found in 23 of 25 aneuploid tumours. Numerical aberrations of chromosome 17 were found equally in carcinomas with reduced and full nm23 protein expression. Abnormal numbers of chromosome 17 seem only to have a minor impact on these markers and are not reflected significantly in their expression.

Biomarkers, Tumor↗
PubMed1998

Assessing estrogen and progesterone receptor status in fine needle aspirates from breast carcinomas. Results on six years of material and correlation with biochemical assay.

OBJECTIVE: To evaluate the usefulness of immunocytochemical staining on breast fine needle aspiration (FNA) cytology as a routine procedure for determination of estrogen (ER) and progesterone (PR) receptor status. STUDY DESIGN: FNA cytology material from 864 patients was immunostained for ER and PR using Abbott ER/PR-ICA kits. Percentage of stained nuclei, staining intensity and staining pattern was evaluated. In 259 cases comparison with biochemical assay was possible. RESULTS: Of the cases, 75.6% were ER positive and 65% PR positive, and 61.6% were both ER and PR positive. Approximately 4% of the smears were inconclusive because of scant cellularity. Concordance between the immunostaining and biochemical method was 84% for ER and 71% for PR. Kappa values were 0.61 and 0.4, respectively. Major discrepancies were found in 7.7% of the specimens. CONCLUSION: Inconclusive smears due to scant cellularity is a minor problem. Technical difficulties are few, and false negative and positive staining is rarely seen. The results are comparable to those from the biochemical method, and immunostaining of ER/PR on breast cancer FNA cytology smears is useful as a routine procedure for receptor determination.

Biopsy, Needle↗
PubMed1997

[Fine needle aspiration of tumors of the salivary glands].

Tumours in the large salivary glands i.e. glandula submandibularis and glandula parotis are easily accessible by fine needle aspiration. Because of the great variation in morphology, diagnosis is difficult and requires a high level of experience. In this study, which lasted for 4.5 years, 343 fine needle aspiration were carried out on 343 patients. Cytological diagnoses were made in 336 lesions and histological diagnosis in 113. Four false positives and one false negative resulted in a sensitivity of 96.9% and a specificity of 95.3% with respect to malignancy. All aspirations were carried out by experienced cytopathologists, in close cooperation with an attendant ear, nose and throat specialist.

Biopsy, Needle↗
PubMed1997

Structure and function of the iron-responsive element from human ferritin L chain mRNA.

We report the cloning and functional characterization of the iron responsive element (IRE) of human ferritin light (L) chain mRNA from a cDNA library of primary human T lymphocytes. Comparison of this palindromic cDNA element to the IRE predicted from the reported genomic sequence revealed significant differences, resulting in a stem-loop structure with lower stability than the IRE of the heavy (H) chain mRNA. Nevertheless, the L subunit IRE mediated efficient binding of the iron regulatory protein (IRP) in a manner comparable to that of human ferritin H chain mRNA in vitro. In accordance with previous observations on H form transcripts, the cis-acting regulatory IRE motif of human ferritin L chain mRNA was capable of repressing translation under iron deprivation but permitted mobilization of the transcripts into polysomes following iron repletion in vivo.

Base Sequence↗
PubMed1997

The Origin of Gravitational Lensing: A Postscript to Einstein's 1936 Science Paper

Gravitational lensing, now taken as an important astrophysical consequence of the general theory of relativity, was found even before this theory was formulated but was discarded as a speculative idea without any chance of empirical confirmation. Reconstruction of some of Einstein's research notes dating back to 1912 reveals that he explored the possibility of gravitational lensing 3 years before completing his general theory of relativity. On the basis of preliminary insights into this theory, Einstein had already derived the basic features of the lensing effect. When he finally published the very same results 24 years later, it was only in response to prodding by an amateur scientist.

Journal Article↗
PubMed1997

In situ hybridization of chromosome 6 on fine-needle aspirates from breast carcinomas: comparison of numerical abnormalities and ER/PgR status and staining pattern.

The estrogen receptor (ER) gene is located on chromosome 6. The aim of our study was to investigate whether numerical chromosomal aberrations were reflected in estrogen/progesterone receptor (PgR) status and staining pattern. Fine-needle aspirates from 51 breast carcinomas were investigated immunocytochemically for ER/PgR and by in situ hybridization technique using digoxigenin-labeled alpha-satellite probe for chromosome 6. Cases with > or = 70% two-signal nuclei were regarded as disome; the remaining tumors showed aneusomy with a variable number of signals. Aneusomy was found in 32 tumors (63%), whereas 19 (37%) had a normal number of chromosome 6. Chromosomal gain occurred in all aneusome cases except one. ER- and/or PgR-positive tumors had an equal distribution of disomy and aneusomy. Variable ER staining pattern or ER and/or PgR negativity was associated with numerical aberrations in chromosome 6 in 76% of the tumors. Cancers with uniform ER staining pattern all had normal chromosome number.

Biopsy, Needle↗
PubMed1997

Ploidy analysis by in situ hybridization of interphase cell nuclei in fine-needle aspirates from breast carcinomas: correlation with cytologic grading.

Fine-needle aspirates from 54 breast cancer patients were investigated for numeric aberrations in chromosomes 6, 7, 12, and 17 by in situ hybridization (ISH) of interphase cell nuclei. Ploidy findings were compared with cytologic grading of tumors. Aneuploidy was found in 73% of cases. Chromosomes 6 and 7 showed numeric abnormalities in 63% and 62% of cases, respectively, whereas chromosome 17 retained a disome pattern in 2/3 of the tumors. Thirteen cancers (28% of 47 with four analyzed probes) had a normal signal number in all four chromosomes. In 17 (36%), all four had signal gain. Another 17 showed a mixed disome/aneusome pattern. They presented a continuum of increasing numeric abnormalities, 82% disomy for chromosome 17, and 13 of them were grade 2, indicating intermediate biologic properties. Correlation between grading and ploidy was good, with 10 of 11 grade 1 carcinomas showing diploidy, whereas 33 of 36 grade 2 and 3 tumors had numeric aberrations.

Breast Neoplasms↗
PubMed1997

Dynamics of cell cycle regulators: artifact-free analysis by recultivation of cells synchronized by centrifugal elutriation.

Studies on the molecular properties of cell cycle regulators in animal cells require cell preparations highly enriched in particular cell cycle phases. Centrifugal elutriation is frequently used to synchronize cells because this technique was thought to cause only minimal distortions in protein expression or metabolic functions. However, in primary chicken erythroblasts, we consistently observed artefacts in mitotic cyclin mRNA expression and p70 S6 kinase activity, which were clearly caused by the elutriation procedure. Therefore, we modified the standard protocol by reseeding various elutriated fractions into preconditioned medium, a process termed recultivation, and harvesting after an appropriate amount of time. This avoided the pleiotropic effects caused by stress and lack of growth factor supply during elutriation. Using this recultivation procedure, highly synchronous progression starting from any given cell cycle phase could be achieved for a variety of cell types, including primary, factor-dependent cells of hematopoietic origin. Mitotic cyclin expression and S6 kinase activity was found to be normal again in recultivated cultures, as opposed to elutriated ones. Finally, monitoring of mitosis-specific cyclin A degradation in recultivated G2 phase cells showed that recultivation provided an excellent tool to follow cells through M phase into G1 without the requirement for a chemical cell cycle block.

Animals↗
PubMed1997

Correlation between polymerase chain reaction and cervical cytology for detection of human papillomavirus infection in women with and without dysplasia.

The aim of this study was to compare the ability of two methods, the polymerase chain reaction (PCR) and cervical cytology, to detect HPV infection. The study population included 222 randomly selected women without dysplasia (controls) and 91 women with histologically confirmed dysplasia (CIN II-III) (cases). In women without dysplasia, 8.6% had cytological signs of HPV infection, whereas 15.3% were HPV DNA positive by PCR. In women with dysplasia, 72.5% had cytological signs of HPV infection, whereas 90.1% were HPV PCR positive. The statistical agreement between the two diagnostic methods was low (controls: kappa = 0.26, cases: kappa = -0.03). In total, PCR failed to detect 17 of 85 women with cytological signs of HPV infection, whereas cervical cytology failed to detect 48 of 116 HPV PCR-positive women. In women with dysplasia, but not in women without dysplasia, the oncogenic HPV types were associated with cytological signs of HPV infection.

Adult↗
PubMed1997

Prognosis of radically operated breast carcinoma patients. A retrospective study of 167 consecutive patients with emphasis on histopathological grading, reproducibility and mean nuclear area.

A retrospective study of 167 consecutive radically treated breast cancer patients with histopathologically confirmed ductal carcinoma is presented. The aim was to establish the prognostic significance and reproducibility of histopathological grading done independently by two pathologists. Further-more, the value of measurements of mean nuclear area (MNA) in the primary tumour was assessed. The two pathologists reviewed the same histological sections using a three-point scoring system based on tubular structures, number of mitoses and nuclear pleomorphism. Grading was identical for 70% of the tumours (Kappa value 0.51). With increasing MNA, the fraction of poorly differentiated tumours increased. In the univariate analysis, tumour-related survival was significantly related to histopathological grading when G3 tumours were compared to G1/G2 tumours (p < 0.05). In the multivariate analysis, tumour size (pT category), lymph-node status and grading were the only significant factors influencing patient outcome (p < 0.05). MNA had no significant prognostic value. A combination of tumour size and histopathological grading identifies a group of node-negative patients (pT2 G2/G3) who may have a less favourable prognosis and for whom adjuvant treatment may be beneficial.

Adult↗
PubMed1996

A population-based case-control study of human papillomavirus-type-16 seropositivity and incident high-grade dysplasia of the uterine cervix.

In order to study the association between seropositivity against human papillomavirus-type-16 capsids and CIN II-III in the general population in ages at which high-grade cervical dysplasia arises, 90 cases and 216 controls participating in a population-based case-control study of incident CIN II-III, were analyzed for the presence of HPV antibodies, HPV DNA and for the influence of behavioral factors. A significantly higher proportion of cases than controls were seropositive. Of HPV-16-DNA-positive cases and controls, 42 and 14% respectively were seropositive. A similar proportion of seropositivity was found among the 172 cytologically normal, HPV-DNA-negative controls. However, seropositivity was closely linked to the sexual history of the women. Logistic-regression analyses, adjusting for sexual behavior, smoking history and educational level, revealed that CIN II-III was associated with HPV-16 seropositivity and with HPV DNA. Controlling for the presence of HPV DNA indicated that antibodies were not independently associated with CIN. The low correlation between the presence of HPV antibodies and DNA, the finding that the association between seropositivity and CIN depended on the presence of HPV DNA, and the association of seropositivity with sexual history, may be explained by serology detecting both past and present persistent infections and presence of HPV DNA, reflecting mostly transient infections in controls and persistent infections in cases.

Adult↗
PubMed1996

Palmitoylation of endothelin receptor A. Differential modulation of signal transduction activity by post-translational modification.

Post-translational modifications such as phosphorylation and palmitoylation play important roles for the function and regulation of receptors coupled to heterotrimeric guanyl nucleotide-binding proteins. Here we demonstrate that the human endothelin receptor A (ETA) incorporates [3H]palmitate. Mutation of a cluster of five cysteine residues present in the cytoplasmic tail of ETA into serine or alanine residues completely prevented palmitoylation of the receptor. The ligand binding affinity of the non-palmitoylated ETA mutants was essentially unchanged as compared to the palmitoylated wild type ETA suggesting that the replacement of the cysteine residues did not alter the overall structure of the receptor. Furthermore, the ligand-induced stimulation of adenylyl cyclase by the mutant ETA was unaffected by the mutation. In contrast, the mutated non-palmitoylated receptors but not the wild type receptor failed to stimulate phosphatidylinositol hydrolysis by phospholipase C activation upon challenge by endothelin-1. Furthermore, the mutant receptors failed to stimulate the ligand-induced transient increase in the cytoplasmic calcium seen with the wild type ETA. Endothelin-1 induced mitogenic stimuli via the wild type receptors but not through the mutated receptors suggesting an important role for phospholipase C in this signal transduction pathway. The differential regulation of distinct signal transduction pathways by post-translational modification suggests that palmitoylation of the ETA provides a novel mechanism of modulating ETA receptor activity.

Amino Acid Sequence↗