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Biomedical subjects

M Fritsch

Publications and source records attributed to M Fritsch.

At least 91 records · Page 5Linked to original sources
PubMed1995

Influence of extracellular matrices on ganglioside pattern of two hepatoma cell lines with different adhesive properties.

A cell culture model was developed to investigate the involvement of gangliosides in cell-matrix adhesion. Two cell lines with different adhesive properties derived from solid Morris hepatoma 7777 were established. Cultured in horse serum-containing medium, the adhesive cell line (MH 7777A) adheres and spreads on uncoated culture dishes, whereas the revertant cell line (MH 7777A > N) does not adhere and grows in suspension. The adhesiveness of both cell lines is dependent on the coating protein used (none, bovine serum albumin, fibronectin or collagen I) and the horse serum concentration in the culture medium. Both cell lines, although of the same origin, differed in their ganglioside composition. The most abundant ganglioside of both MH 7777A and MH 7777A > N cell lines was fucosyl-GM1, 0.78 and 0.72 microgram per mg cellular protein, respectively. The GM3 and GD1a content of MH 7777A > N cells was significantly higher than that of MH 7777A cells. Furthermore, a matrix-dependency of the ganglioside pattern of both cell lines was demonstrated.

Animals↗
PubMed1995

An estrogen-independent MCF-7 breast cancer cell line which contains a novel 80-kilodalton estrogen receptor-related protein.

Long-term growth of estrogen-responsive human breast cancer cell lines in estrogen-free media leads inevitably to the development of estrogen-independent growth. We have identified and characterized a unique subclone of the MCF-7 human breast cancer cell line, named MCF-7:2A, which grows maximally in the absence of endogenous estrogens but whose growth is inhibited by the antiestrogens 4-hydroxytamoxifen and ICI 164,384. The MCF-7:2A cells express high levels of estrogen receptor (ER; 477 fmol/mg protein), which can be reduced by growth in 10 nM 17 beta-estradiol (201 fmol/mg protein). Basal progesterone receptor synthesis is very low in the 2A cells (< 1 fmol/mg protein) but can be dramatically increased by 10 nM 17 beta-estradiol (384 fmol/mg protein). Clearly, the pathways that control growth and estrogen-regulated genes such as the progesterone receptor are now dissociated in these cells. MCF-7:2A cells also possess two unique characteristics. First, the MCF-7:2A cells constitutively activate an ER-responsive luciferase reporter construct in the absence of any estrogens, and this activation can be blocked by either 4-hydroxytamoxifen or ICI 164,384. This constitutive activity is not observed in the parental MCF-7 cells. Second, they express an 80-kDa protein that cross-reacts with three distinct antibodies to the ER. The MCF-7:2A cells were subjected to an additional round of limiting dilution subcloning, and 10 independent clones were all shown to express both the 66- and 80-kDa ERs as observed in the MCF-7:2A line. This confirms that both ERs are being expressed in each cell and are not the result of a mixed population of cells. While numerous ER variants have been reported previously, no ER has until now been described that is larger than the wild-type 66-kDa ER. The MCF-7:2A cells provide a unique model to use in the study of ER action and the development of estrogen-independent growth in human breast cancer cells.

Blotting, Western↗
PubMed1994

Determination of alkylphosphocholines by high-performance liquid chromatography with light-scattering mass detection.

A rapid and sensitive method for the determination of five different alkylphosphocholines including the antineoplastic phospholipid analogues hexadecylphosphocholine and octadecylphosphocholine is presented. The method is based on the separation of the lipids by high-performance liquid chromatography and quantitation by light-scattering mass detection. The lower limit of detection is approximately 50 pmol for each alkyphosphocholine tested. Quantitation is linear over the range 0.05-75 nmol. Hexane-isopropanol extracts of cultured cells can be applied to the column without further cleanup. The high resolution of separation and the sensitivity of detection render this method useful for pharmacokinetic investigations dealing with the uptake of alkylphosphocholines into different types of cells.

Animals↗
PubMed1994

Late endogenous potentials in three-tone experiment in short- and long-term abstinent alcoholics.

Information processing (and cognitive ERPs as their concomitants) has been observed to be disturbed in chronic alcoholics and to recover with sustained abstinence. However, some specific components of ERPs appear to remain significantly decreased in long-term abstinent alcoholics. Using a longitudinal design we investigated the effect of abstinence and relapse on P300 and Late Slow Wave. P300 was evoked by a three-tone paradigm, which results in a two-stage process for evaluating and classifying stimuli. The amplitude of P300 in short-term abstinent alcoholics was reduced significantly and recovered with time of abstinence at least partly. In alcoholics abstinent for eight months the mean amplitude was lower than of the control group, but this difference failed to be significant. The long latency of the positive peak at about 600 ms seems to reflect delayed information processing in alcoholics, revealed by two-stage processing. This component arises later in alcoholics whether they stay abstinent or not.

Adult↗
PubMed1994

Long-term Tamoxifen Therapy for the Treatment of Breast Cancer.

Tamoxifen is a nonsteroidal antiestrogen that has become the frontline endocrine therapy for all stages of breast cancer. The drug is the only single-agent therapy that, when used in an adjuvant fashion, produces a survival advantage in postmenopausal women. Survival is longer when the estrogen receptor content of the primary tumor is higher, although receptor-poor patients still have a survival advantage from adjuvant tamoxifen equivalent to that noted with combination chemotherapy. The added advantages of tamoxifen are a maintenance of bone density and a decrease in fatal myocardial infarction. Although side effects from tamoxifen are few, patients must be examined for preexisting endometrial carcinoma before beginning drug use. Tamoxifen does not prevent the growth of endometrial tumors. Spotting and vaginal bleeding in postmenopausal patients taking tamoxifen should be followed up with a thorough gynecological examination. The incidence rate of endometrial cancer for tamoxifen-treated patients is 2 per 1000 patients per year. More than 80% of detected endometrial tumors are stage 1 disease and can be cured by hysterectomy.

Journal Article↗
PubMed1993

Structural characterization of the trypsinized estrogen receptor.

Structural differences between the unoccupied and ligand-occupied rat uterine estrogen receptors (ERs) were investigated using partial proteolysis followed by immunoblotting, affinity labeling, and gel filtration chromatography. Trypsin digestion of the unoccupied ER at 4 degrees C resulted in retention of 70-80% of high-affinity [3H]estradiol binding. Only two fragments of the rat ER were detected after prolonged trypsin treatment of the unoccupied ER followed by affinity labeling with [3H]tamoxifen aziridine. One fragment represents the intact steroid binding domain (28 kDa), and the other fragment is about 10 kDa. The small 10-kDa fragment of the ER detected by denaturing gel electrophoresis is shown to be held in a large oligomeric complex in solution using gel filtration chromatography. This oligomeric complex probably represents the steroid binding domain, which has its tertiary structure maintained predominantly by noncovalent interactions between the trypsin-generated fragments. The estrogen, anti-estrogen, and unoccupied trypsinized ERs all result in similar patterns of fragments after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and detection by immunoblotting. Although no new trypsin cleavage sites were exposed, the sensitivity of the available trypsin sites was altered by heating the ER and, to a lesser extent, by hormone treatment. Gel filtration chromatography of the trypsinized estradiol- and 4-hydroxytamoxifen-occupied ERs demonstrates similar, diffuse peaks centered at about the correct size for the intact steroid binding domain (28 kDa), whereas the trypsinized unoccupied ER results in a sharp, discrete peak centered at about 80 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Perturbations in the model of estrogen receptor regulation of gene expression.

Estrogen receptors are key elements in the mechanisms of action of estrogenic hormones. Models of how estrogens and their receptors interact and subsequently modify gene expression should be reevaluated to explain new data currently available. The following review discusses nuclear localization, DNA binding, and protein structural changes of the estrogen receptor induced by estrogen binding. We also discuss how these phenomena relate to the induction of changes in gene expression.

Animals↗
PubMed1993

[Talking to an "unconscious" patient?].

In our every day practice in intensive care unit, we have the constant worry to join words to our care, is it towards conscious our unconscious patients. This paper is the issue of a work of listening and thinking over from the nursing team, to the testimony of a patient who was in our unit for three months. This person was in the coma for long weeks, and he tells us afterwards about how he experienced this trial.

Communication↗
PubMed1992

A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain.

Upon binding estrogen, the estrogen receptor (ER) is proposed to undergo some form of conformational transition leading to increased transcription from estrogen-responsive genes. In vitro methods used to study the transition often do not separate heat-induced effects on the ER from estrogen-induced effects. The technique of affinity partitioning with PEG-palmitate was used to study the change in the hydrophobic surface properties of the ER upon binding ligand with and without in vitro heating. Upon binding estradiol (E2), the full-length rat uterine cytosolic ER undergoes a dramatic decrease in surface hydrophobicity. The binding of the anti-estrogen 4-hydroxytamoxifen (4-OHT) results in a similar decrease in surface hydrophobicity. These effects are independent of any conformational changes induced by heating the ER to 30 degrees C for 45 min. The use of the human ER steroid binding domain overproduced in Escherichia coli (ER-C) and the trypsin-generated steroid binding domain from rat uterine cytosolic ER demonstrates that the decrease in surface hydrophobicity upon binding E2 or 4-OHT is localized to the steroid binding domain. Gel filtration analysis indicates that the change in surface hydrophobicity upon binding ligand is an inherent property of the steroid binding domain and not due to a ligand-induced change in the oligomeric state of the receptor. The decrease in surface hydrophobicity of the steroid binding domain of the ER upon binding E2 or 4-OHT represents an early and possibly a necessary event in estrogen action and may be important for "tight" binding of the ER in the nucleus.

Animals↗
PubMed1992

DNA allosterically modulates the steroid binding domain of the estrogen receptor.

The ability of DNA to allosterically alter the conformation of the estrogen receptor's (ER) steroid binding domain was investigated. Using dissociation kinetics we observed that when DNA was bound to the DNA binding domain of the rat uterine ER the rate of estrogen dissociation from the steroid binding domain increased almost 2-fold. This change in the rate of estrogen dissociation depended on the concentration of DNA used and correlated with the thermodynamic binding affinities (Kd) of the ER for two different DNA sequences. We were unable to detect a DNA-induced change in the trypsin cleavage pattern of the amino terminal end of the ER. Using a whole cell dissociation kinetic assay with MCF-7 breast cancer cells we observed a 7-fold slower rate of estrogen dissociation from the ER within the cell than from the ER in vitro. This suggests that additional factors, other than DNA binding, may modify the steroid binding domain within the cell. We conclude that DNA can allosterically modulate the structure of the steroid binding domain of the ER, and we hypothesize that this conformational change may be necessary for the full transcriptional activity of the ER.

Allosteric Regulation↗
PubMed1990

Diagnosis and management of paragangliomas of the skull base.

In appropriately selected patients, glomus tumors of the head and neck are best treated surgically. Unresectability is not a factor in therapeutic planning for local disease control. Existing techniques and exposures for tumor removal can be reliably applied to these paragangliomas, with acceptable morbidity and mortality. A team approach to this problem is mandatory.

Adult↗
PubMed1990

Preservation of hearing in neurofibromatosis 2.

Preservation of hearing in the neurofibromatosis 2 (central neurofibromatosis) patient has been infrequently documented. This goal can be attained in selected patients and should be more frequently accomplished in the future with improved diagnostic capabilities and improved surgical techniques. We report three patients in whom this elusive goal has been accomplished.

Adolescent↗
PubMed1985

[The handicapped, no future?].

Over a period of 17 years, 455 disabled individuals in all have moved out of the Senator-Neumann-Heim, a residential and rehabilitation facility for persons with severe physical disablement. Of these, 151 had participated in educational and/or vocational rehabilitation measures. 33 of the current 136 residents participate in educational programmes, another 34 are settled in gainful employment. A detailed description of the various types of schooling, as well as of preparatory services and incidence of university studies, serve to illustrate the potential held by effective, individualized preparation for vocational integration. The essential factor for settlement in gainful activity had invariably been sound, requirements-oriented, successfully completed vocational training, either in a vocational training center, or in the dual system of industrial training and professional school. Issues relative to daily working hours, psychosocial follow-up, residential possibilities, partnerships, are discussed.

Activities of Daily Living↗
PubMed1983

Direct and reversible inhibition of estradiol-stimulated prolactin synthesis by antiestrogens in vitro.

The antiestrogens tamoxifen and monohydroxytamoxifen inhibited the estradiol-stimulated increase in prolactin synthesis by dispersed cells in culture derived from immature rat pituitary glands. Monohydroxytamoxifen had a relative binding affinity for the estrogen receptor similar to that of estradiol, whereas tamoxifen's relative binding affinity was approximately 3%. This was consistent with the observation that monohydroxytamoxifen was 30 times more potent than tamoxifen as an antiestrogen in vitro. To avoid the possibility that tamoxifen was fractionally metabolized to monohydroxytamoxifen by the pituitary cells, the p-methyl, p-chloro, and p-fluoro derivatives of tamoxifen that are unlikely to be converted to monohydroxytamoxifen were tested for activity. The substitution did not have a detrimental effect on their ability to inhibit the binding of [3H]estradiol to either rat uterine or pituitary gland estrogen receptors. Similarly, the derivatives of tamoxifen inhibited estradiol-stimulated prolactin synthesis at concentrations that were consistent with their relative binding affinities. Although it is clearly an advantage for tamoxifen to be metabolized to the more potent antiestrogen monohydroxytamoxifen, we have shown that this is not a prerequisite for the antiestrogenic actions of tamoxifen. With the direct actions of antiestrogens established, the pituitary cell system was validated for further structure-activity relationship studies. Overall, the inhibition of estradiol-stimulated prolactin synthesis by antiestrogens is competitive and reversible with estradiol, an effect that can be explained by interactions with the estrogen receptor system.

Animals↗
PubMed1981

[Self-determination of the disabled (author's transl)].

Self-determination of the disabled is examined in the present paper on the criteria stated in the constitutional document of the Federal Republic of Germany, and in the United Nations' Declaration on the Rights of Disabled Persons, with a view to determining the extent to which disabled people are infringed upon in practising self-determination. It is shown that restrictions in self-determination are directly related to the severity of the disability, arising in particular from dependence on personal care, wheelchair dependence, financial difficulties, and in an institutional setting. Self-determination is a central concern in the entirely of disability work in the Federal Republic of Germany. Its implementation can be achieved only if a greater level of awareness and acceptance on the part of the non-disabled is brought about, as a basis of the will for positive partnership with the disabled. The disabled must equally accept the changes necessary to their lifestyles, in order to translate their right to fully develop their personality into actually self-determined life.

Activities of Daily Living↗