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Biomedical subjects

T Sauer

Publications and source records attributed to T Sauer.

At least 37 records · Page 2Linked to original sources

Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count.

OBJECTIVE: To determine the aetiology and clinical significance of an elevated platelet count (thrombocytosis) in a large cohort of patients. DESIGN: A retrospective review of the medical records was performed on all patients, who had at least one platelet count > or = 500 x 10(9) L-1. SETTING: Departments of Medicine and Surgery, University of Ulm, Germany. SUBJECTS: A total of 732 patients with thrombocytosis. MAIN OUTCOME MEASURES: Classification of thrombocytosis and thromboembolic complications, and evaluation of laboratory parameters distinguishing between primary and secondary thrombocytosis. RESULTS: Of the total of 732 patients, 89 (12.3%) had primary and 643 (87.7%) had secondary thrombocytosis. Essential thrombocythaemia was observed in 40 of 89 patients (45%) with primary thrombocytosis. The most frequent causes of secondary thrombocytosis were tissue damage (42%), infection (24%), malignancy (13%) and chronic inflammation (10%). Primary thrombocytosis was significantly associated with a higher platelet count and an increased incidence of both arterial and venous thromboembolic complications. In secondary thrombocytosis, thromboembolic events were restricted to the venous system and occurred only in the presence of other risk factors. Mean values of leucocyte count, haematocrit, erythrocyte sedimentation rate, fibrinogen, serum potassium and lactate dehydrogenase were significantly different in primary and secondary thrombocytosis. CONCLUSIONS: The finding of an elevated platelet count on routine blood examination has diagnostic, prognostic and therapeutic implications. It is of clinical importance to distinguish between primary and secondary thrombocytosis, as thrombotic complications occur more frequently in primary thrombocytosis. Unless additional risk factors are present, secondary thrombocytosis is not associated with a significant risk for thromboembolic events.

Adolescent↗

Numerical abnormalities of chromosome 7 in interphase cell nuclei of breast carcinoma have no impact on immunohistochemically determined EGFR status.

AIM OF STUDY: To investigate the relationship between epidermal growth factor receptor (EGFR) status and numerical aberrations of chromosome 7 in breast carcinomas. DESIGN: In situ hybridization (ISH) of interphase cell nuclei on air-dried fine-needle aspirates (FNAC) from 33 breast carcinomas was evaluated for numerical abnormalities in chromosome 6, 7, 12 and 17. Immunohistochemical staining of EGFR was performed on corresponding histological specimens. RESULTS: 78% of the tumours were aneuploid by ISH. Aneusomy of chromosome 7 was found in 18 cases (60%). EGFR overexpression was observed in 30% of the carcinomas, and seven of nine were aneuploid by ISH. The same percentage of chromosome 7 aneusomy was found in both EGFR-positive and -negative cases. Five of seven EGFR-positive tumours revealed aneusomy of chromosome 7. CONCLUSION: Numerical gain of chromosome 7 is a common finding, occurring in about 60% of breast carcinomas. Most EGFR-positive tumours are aneuploid and show numerical gain of chromosome 7, but abnormal numbers of chromosome 7 have no impact on the EGFR status.

Breast Neoplasms↗

Ultrasonography of malignant breast neoplasms. Analysis of carcinomas missed as tumor.

PURPOSE: To analyze the malignant breast neoplasms missed as tumor on ultrasonography (US). MATERIAL AND METHODS: A total of 355 malignant tumors were confirmed at histology among 2,985 consecutive patients who underwent breast US. There were no prospectively recorded mammographic findings in 28 of the 355 tumors. The remaining 327 tumors included 16 ductal carcinomas in situ (DCIS) and 66 invasive carcinomas with suspicious microcalcifications on mammography. Excluding these 82 tumors because US would not have been indicated using strict criteria, a subpopulation of 245 noncalcified invasive malignant tumors remained for analysis. The neoplasms missed as tumor on US were analyzed for the whole tumor group (n=355) and the subpopulation (n=245). RESULTS: 42 (11.8%) of the 355 malignant neoplasms were missed as tumor on US, including 6 (2.5%) of the 243 palpable and 36 (32.1%) of the 1 12 nonpalpable malignancies. Most of the missed tumors were DCIS and microinvasive ductal carcinomas dominated by DCIS. In the subpopulation, 14 (5.7%) of the 245 malignancies were missed as tumor on US, including 4 (2.2%) of the 180 palpable and 10 (15.4%) of the 65 nonpalpable lesions. Of the 245 malignancies, 6 (2.4%) had a normal US finding, including 2 palpable retropapillary tumors and 4 incidental findings at histology. CONCLUSION: Using strict criteria for performing US as an adjunct to mammography, by far the most malignant breast neoplasms are diagnosed as a tumor on US.

Adolescent↗

[Breast conserving surgery for breast cancer--local recurrence].

One of the disadvantages of breast conserving treatment compared with mastectomy is the higher rate of local recurrence. Even though a local recurrence has no influence on survival, it is a psychological trauma for the woman it affects. Breast conserving treatment has been practised at Ullevaal Hospital since 1986. This study is based on data from 216 consecutive cases of breast conserving surgery, from January 1986 to March 1996. Mean observation time was 29 months. Nine (4.2%) patients experienced a local recurrence. Age, histological grade, and the size of the tumor were identified as risk factors, whereas there was no correlation between histology, axillary node involvement, and surgical margins.

Adult↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

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↗