Biomedical subjects

R Strohmeier

Publications and source records attributed to R Strohmeier.

12 recordsLinked to original sources

PubMed2007

Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients--a double-blind, randomized study.

BACKGROUND: Classical hormone replacement therapy for hot flashes is contraindicated in breast cancer especially in endocrine responsive disease. PATIENTS AND METHODS: In a double-blind, randomized phase III study, breast cancer patients suffering from hot flashes at least twice a day, who were not taking any medication against hypertension and depression received either clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks. The primary end point was defined as the frequency of hot flashes after 4 weeks of treatment. A self-reported 1-week hot flash and other symptom questionnaire were kept before the start of treatment until the end of treatment course. RESULTS: From April 2002 to October 2004, 80 patients were recruited of whom 64 were assessable for efficacy analyses. Thirty-three received clonidine and 31 venlafaxine, nine patients stopped early because of side-effects and seven withdrew consent. At the end of treatment week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes per day for those receiving clonidine (P = 0.025). CONCLUSION: Venlafaxine is significantly more effective in reducing the frequency of hot flashes in breast cancer patients than clonidine.

Adult↗

PubMed2000

Relation of cell proliferation to expression of peripheral benzodiazepine receptors in human breast cancer cell lines.

Peripheral benzodiazepine receptor (PBR) agonist [(3)H]Ro5-4864 has been shown to bind with high affinity to the human breast cancer cell line BT-20. Therefore, we investigated different human breast cancer cell lines with regard to binding to [(3)H]Ro5-4864 and staining with the PBR-specific monoclonal antibody 8D7. Results were correlated with cell proliferation characteristics. In flow cytometric analysis, the estrogen receptor (ER)-negative breast cancer cell lines BT-20, MDA-MB-435-S, and SK-BR-3 showed significantly higher PBR expression (relative fluorescence intensity) than the ER-positive cells T47-D, MCF-7 and BT-474 (P<0.05). Accordingly, BT-20 and MDA-MB-435-S had the highest capacity for binding [(3)H]-Ro5-4864, while the ER-positive cells exhibited only low binding of the benzodiazepine. PBR expression correlated inversely with cell doubling time (r = 0.78) and positively with Ki-67 expression (r = 0.77). The amount of mitochondria was significantly higher in cells with high PBR expression. As PBR could be demonstrated only after permeabilization of cells, PBR is suggested to be localized within the cytoplasm. Moreover, colocalization of PBR and mitochondria was shown by confocal microscopy analysis. The highest amounts of both PBR and mitochondria were found in cell lines with high mitotic activity. Therefore, it is concluded that the level of PBR is dependent on the number of mitochondria. PBR and its putative endogenous ligand diazepam-binding inhibitor are possibly involved in the regulation of cell proliferation of human breast cancer cell lines.

Benzodiazepines↗

PubMed2000

Cell cycle-related expression and ligand binding of peripheral benzodiazepine receptor in human breast cancer cell lines.

The aim of this study was to measure the expression of peripheral benzodiazepine receptors (PBR) as well as mitochondria content in different phases of the cell cycle of BT-20 and MCF-7 breast cancer cell lines, using two-parameter flow cytometric analyses. The PBR expression as well as mitochondria mass, were found to increase as cells pass through different stages of the cell cycle, whereas the amount of PBR in quiescent cells was very low. Binding capacity for the PBR ligand [3H]-Ro5-4864 was strongly related to the phase of the cell cycle with a positive correlation (r=0.98) with a high percentage of cells in S phase. Incubation of BT-20 cells in serum-deprived medium with nanomolar concentrations of Ro5-4864 caused an increase in S phase cells. This effect was not observed in MCF-7 cells. Using micromolar concentrations of Ro5-4864, both BT-20 and MCF-7 cells were reversibly arrested in the G(0/1) phase.

Breast Neoplasms↗

PubMed1999

Specific binding of benzodiazepines to human breast cancer cell lines.

Binding of [3H]Ro5-4864, a peripheral benzodiazepine receptor (PBR) agonist, to BT-20 human, estrogen- (ER) and progesterone- (PR) receptor negative breast cancer cells was characterized. It was found to be specific, dose-dependent and saturable with a single population of binding sites. Dissociation constant (K(D)) was 8.5 nM, maximal binding capacity (Bmax) 339 fM/10(6) cells. Ro5-4864 (IC50 17.3 nM) and PK 11195 (IC50 12.3 nM) were able to compete with [3H]Ro5-4864 for binding, indicating specificity of interaction with PBR. Diazepam was able to displace [3H]Ro5-4864 from binding only at high concentrations (>1 microM), while ODN did not compete for PBR binding. Thymidine-uptake assay showed a biphasic response of cell proliferation. While low concentrations (100 nM) of Ro5-4864, PK 11195 and diazepam increased cell growth by 10 to 20%, higher concentrations (10-100 microM) significantly inhibited cell proliferation. PK 11195, a potent PBR ligand, was able to attenuate growth of BT-20 cells stimulated by 100 nM Ro5-4864 and to reverse growth reduction caused by 1 and 10 microM Ro5-4864, but not by 50 microM and 100 microM. This indicates that the antimitotic activity of higher concentrations of Ro5-4864 is independent of PBR binding. It is suggested, that PBR are involved in growth regulation of certain human breast cancer cell lines, possibly by supplying proliferating cells with energy, as their endogenous ligand is a polypeptide transporting Acyl-CoA.

Benzodiazepinones↗

PubMed1998

Changes in lymphocyte subsets during normal pregnancy.

Peripheral blood lymphocytes from healthy women were studied during pregnancy and postnatally, and were compared with lymphocytes from an age-matched non-pregnant control group. Compared with non-pregnant women, the total white cell count was significantly increased at all pregnancies and also post-partum. In pregnancy the absolute number and percentage of T lymphocytes was slightly elevated while almost no changes in B cells were found. No significant changes were found in the percentage of suppressor/cytotoxic (CD8+), of helper/inducer (CD4+) T lymphocytes, nor of CD4+/CD8+ ratio at any stage of pregnancy and puerperium. The most remarkable changes of the immune system occurred in the group of HLA-DR+ and CD56+ activated T cells. The cell numbers showed a significant increase in the first trimester (< 14 weeks) and decreased slightly from stage to stage. Lower values in NK (natural killer) cells and higher levels of IL-2 receptor positive T lymphocytes did not reach significant levels of change.

Adult↗

PubMed1997

Lymphocyte subsets in patients with ovarian and breast cancer.

Peripheral blood lymphocytes (PBL) from patients with ovarian or breast cancer or benign lesions of the breast, respectively, have been analysed for expression of phenotypic and activation markers by flow cytometry. The results were compared with those of a control group of healthy women. The relative proportion as well as the absolute counts of B lymphocytes were similar in both groups and in the control group. The absolute number of T cells was decreased in breast cancer patients (p < 0.05). The CD4+/CD8+ ratio was significantly depressed in ovarian cancer patients (p < 0.05), but not in breast cancer patients. In the ovarian cancer group, the percentage of CD3+ T cells expressing HLA-DR (p < 0.05) as well as CD3+ T cells expressing CD16 and CD56 (p < 0.05) was significantly higher. The relative proportion as well as the absolute counts of CD3+ T cells expressing the IL-2 receptor (CD25) were significantly higher (p < 0.001), respectively, in breast cancer patients (p < 0.05). These results suggest that gynaecological cancer is associated with specific alterations in the T cell population.

Adult↗

PubMed1993

Laboratory test of an automated cell analysis system for cervical screening.

An automated cell analysis system (Autoplan-MIAC) for the early detection of precancerous lesions of the cervix was tested under semi-routine conditions in a clinical cytology laboratory. A set of 1500 specimens, highly enriched with abnormal cases, was analysed. Cervical scrapings were collected in suspension and processed by cytocentrifugation for microscopy. Two slides were prepared from each sample: one for staining according to Papanicolaou for the visual reference diagnosis and one for Feulgen staining for automated analysis. The specimens were evaluated in two ways: the first one, which is referred to as the automated machine classification system (AMC), classifies the specimens according to the number and ratio of selected objects (alarms) and is a fully automated system. The second system classifies the specimens after visual evaluation of the stored alarms as they are displayed on a TV monitor, and is designated the interactive machine classification system (IMC). The AMC results showed a false positive rate of 16.5% when the cut-off threshold was selected so that all 117 positively diagnosed specimens were classified 'positive' by the system. In that case 87.4% of the CIN I and 96.9% of the CIN II cases were AMC-positive. The IMC results showed a false positive rate of 2.5%, when 86.3% of the CIN I cases, 96.9% of the CIN II cases and all CIN III and invasive carcinoma cases were positively classified.

Cervix Uteri↗

PubMed1991

Emigration of bilayered epidermal cell sheets from tadpole tails (Xenopus laevis).

Migration of bilayered epidermal cell sheets out of explants of tadpole tails (Xenopus laevis) were investigated with time-lapse cinemicrography using reflection-contrast optics. Cell-sheet formation begins beneath the explant in a region where it is closely attached to the coverslip. A single basal cell extends a lamellipodium through the outer (surface) epidermal layer and starts moving in a direction free of attached cells. This cell remains connected to the following basal cell, which then also extends a lamellipodium onto the glass. The cell sheet develops as increasingly more adjacent basal cells start to migrate. Surface cells do not actively locomote but they remain attached to the basal cells and to adjacent surface cells. Thus, they are transported as an intact cell layer, and consequently the in situ arrangement of the tadpole epidermis is largely preserved in the cell sheet, i.e., basal cells adhere to the substratum and are covered by outer cells (surface cells) which face the culture medium. Basal cells extend lamellae beneath the rear end of the preceding cell, which is slightly lifted off the substratum. The direction of locomotion is determined by the frontal cells. Cell-sheet enlargement and locomotion cease when all the epidermal cells facing the coverslip have left the explant, and the cell sheet and epidermis covering the explant form a continuous layer.

Animals↗

PubMed1990

Interobserver variability in the cytological diagnosis of 1500 Papanicolaou stained cervical monolayer specimens.

Cervical specimens from 1500 patients were prepared by means of a centrifugation procedure to obtain monolayer specimens suitable for automated screening using a machine. After staining according to Papanicolaou, each specimen was diagnosed by four independent cytologists from two different institutes. Within each institute, noncorresponding screening results were discussed to arrive at a conclusion diagnosis. After discussion of the discrepancies between the two centers, the conclusion diagnoses were combined to one final cytological diagnosis for each specimen. This final diagnosis is to be used as a reference diagnosis to evaluate machine classification as obtained by the AUTOPLAN/MIAC system. This system is presently being tested both in Leiden and in Frankfurt for its accuracy of detecting abnormal lesions in cervical specimens. The used diagnostic procedure resulted in a negative reference diagnosis for 1217 of the 1500 specimens; 170 specimens were diagnosed CIN I or II (mild or moderate dysplasia) and 113 specimens had a positive reference diagnosis (CIN III or invasive carcinoma). Based on these three diagnostic classes, the agreement between the four independent cytologists and the reference diagnosis varied between 93.60% and 96.60%, whereas 95.33% of all 6000 diagnoses correlated with the reference diagnosis.

Female↗

PubMed1987

Hydrostatic pressure in epidermal cells is dependent on Ca-mediated contractions.

Volume/osmotic pressure relationships were compared in Xenopus epidermal cells treated with the calcium antagonist lanthanum and in control cells. In lanthanum-treated cells the volume was found to be proportional to the reciprocal of the osmotic pressure in the hypotonic range, but not in the control cells. This difference is interpreted as being caused by contractions of the actomyosin system in control cells, which require external calcium. On the basis of the different slopes of the measurements under these two conditions the contractile force of the cells in isotonic conditions was calculated to be 0.96 x 10(5)Nm-2. The observation that in hypotonic media the cell body is enlarged in the direction of movement provides evidence that the cell body/lamella transition region is the part of the cell that contracts most during locomotion. By analysing cell speed in media with varying osmotic pressures, the relationship between internal pressure and cell locomotion was revealed.

Animals↗

PubMed1984

Control of cell shape and locomotion by external calcium.

Dependence of locomotion of Xenopus laevis epidermal cells on calcium influx from the external medium was investigated. Inhibition of Ca2+ influx by 2 mM La3+ or 4 mM Tb3+ in the culture medium causes an immediate stop to locomotion and a loss of motion at the outer margin of the lamella; microcolliculi disappear and the entire lamella becomes flat and very thin. The cell body region enlarges by spreading into the lamella to an extent approximately coincident with the distribution of myosin. The increase in thickness of this area is the result. The cytoskeletal elements actin, alpha-actinin and myosin become homogeneously distributed throughout the cell and a great number of straight microtubules extend to the margin after 20 min in La3+-containing media. Prekeratin distribution does not change. Reduction of calcium concentration in the external medium by EGTA leads to cessation of cell locomotion. Sr2+ (1-4 mM) is also able to replace calcium for triggering locomotion. These findings point to a control of Ca2+-activated contractions of actomyosin by influx of external Ca2+. According to our model of cell locomotion [14] the contractions generate a hydrostatic pressure extending the lamella by flow of hyaloplasm towards the margin. Small swellings (microcolliculi) appearing thereby will be dislocated by a calcium-dependent sol-gel transformation in this area, which contains actin but not myosin.

Animals↗

PubMed1981

Locomotion of Xenopus epidermis cells in primary culture.

The locomotion of single epidermis cells, grown out from Xenopus laevis tadpole tails has been investigated by time-lapse cinemicrography using phase-contrast and reflection-contrast optics. The cells develop a large, mostly 200-250 nm thick, lamella, which adheres homogeneously to the supporting coverglass and exceeds the projection area of the cell body. From the comparison of RIC-pictures taken at high (1.06) and low (0.62) numerical aperture of illumination (I.N.A.) we deduce that at low I.N.A. the embossment of the medium-facing side of the lamella is visualized. By this method microcolliculi are demonstrated, which form at the edge of the lamellipodium and move backward. They resemble ruffles, but are flatter and no membrane flow towards the perinuclear region is observed. Indirect immunofluorescence reveals an enhanced staining for actin and alpha-actinin in the lamellipodium and in the transition region of cell body and lamella. Tonofilaments do not participate in lamella formation, the relatively few microtubules seem to be oriented in the direction of cytoplasmic flow. Electron micrographs demonstrate the course of fibrils in the cell body and a meshwork of actin filaments and membranous tubules in the lamella. Based on these findings a model for cell locomotion is presented: the motive force is generated by the cell body causing a flow of cytoplasm towards the periphery and extension of the lamella at its edge. The activity of the lamellipodium has to ensure the flat form of the advanced edge; microcolliculi are assumed to represent a small membrane store for the extension of the lamella. The lamellipodium is not involved in the production of motive force. The cell body is anchored to the lamella by radiating fibrils and the fibrillar meshwork is inserted at the 'dorsal' membrane of the lamella and the basal filament cortex of the cell body. This anchorage provides the structural basis for the uptake of lamella material into the cell body in the transition region.

Animals↗