[Brain abscess as an endocranial complication of otologic diseases].
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Adult↗
Biomedical subjects
M Reiss
Publications and source records attributed to M Reiss.
[Human hemispherical specialization with special reference to neuroanatomical asymmetry].
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Cerebral Cortex↗
[Hemispheric specialization in man].
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Brain Damage, Chronic↗
Analysis of PTHRP binding and signal transduction mechanisms in benign and malignant squamous cells.
We have explored a potential autocrine role for parathyroid hormone-related protein (PTHRP) in malignant squamous carcinoma cells (SqCC) and their nonmalignant counterpart, human epidermal keratinocytes (HK). Specific binding of Tyr36 human PTHRP-(1-36)NH2 (125I-[Tyr36]hPTHRP-(1-36)NH2) was identified in 75% of unselected SqCC lines. In contrast, no binding was detected on the mouse keratinocyte line BALB-MK or on five different HK lines. Although each SqCC and keratinocyte line secreted immunoreactive PTHRP into its medium, there was no correlation between PTHRP concentration and number of binding sites. Inhibition of binding by [Tyr36]hPTHRP-(1-36)NH2 yielded half-maximal inhibitory concentration values of approximately 100 nM in all SqCC lines. Affinity cross-linking of SqCC cells revealed 98- and 70-kDa binding proteins with similar affinity (approximately 100 nM). Exposure of fura-2-loaded SqCC cells to PTHRP and PTH resulted in equivalent, dose-dependent transient increases in intracellular calcium [half-maximal effective concentration (EC50) = 0.08 nM]. PTHRP also increased intracellular calcium in HK (EC50 = 0.05 nM). No adenosine 3',5'-cyclic monophosphate (cAMP) response to PTHRP or PTH was elicited in either SqCC or HK, despite brisk isoproterenol responses in both. We conclude that high-capacity low-affinity binding sites for PTHRP are detectable in the majority of SqCC lines but not in HK. These low-affinity binding sites are unlikely to represent receptors. The sensitive intracellular calcium response suggests the additional presence of high-affinity receptors on SqCC as well as on HK. However, the failure of PTHRP or PTH to stimulate cAMP production in otherwise cyclase-competent cells suggests that these are not classical PTH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium↗
Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines.
Dominant-negative and/or loss-of-function mutations of the p53 tumor suppressor gene are frequently found in squamous cell carcinomas of the skin and of the head-and-neck region. In order to identify the precise mechanisms of inactivation of p53 in tumors of this class, we examined the status of p53 RNA, protein and DNA in a panel of eight human squamous carcinoma cell lines (head-and-neck, 3; esophagus, 1; lung, 1; uterine cervix, 2; vulva, 1). Three lines (A253, CaLu-1, SqCC/Y1) failed to express any p53 mRNA. A253 cells contained a single p53 allele without mutations in exons 2-9, suggesting that the lack of transcription was the result of mutations in the regulatory region of the gene. Both p53 alleles were deleted in CaLu-1 cells, whereas the single allele present in SqCC/Y1 cells was rearranged and carried two missense mutations in exon 5. Two cell lines (A431, FaDu) expressed only 50% of the normal level of p53 mRNA, either because only one allele was present (A431), or because only one of the two alleles was transcribed (FaDu). The two cervical carcinoma lines (CaSki, C4-1) expressed normal levels of p53 mRNA, but no wild type protein, presumably as a result of accelerated degradation by the human papillomavirus 16 or -18 E6 oncoprotein present in these cells as previously described (Scheffner et al., Proc. Natl. Acad. Sci. USA 88:5523-5527; 1991). Three of the lines expressed only mutant p53 protein (A431, FaDu, CE-48) resulting from missense mutations in codons 248 and 273.(ABSTRACT TRUNCATED AT 250 WORDS)
Base Sequence↗
Activation of the autocrine transforming growth factor alpha pathway in human squamous carcinoma cells.
Transforming growth factor alpha is an autocrine mitogen for nonneoplastic keratinocytes, which exerts its function by binding to the receptor for epidermal growth factor. In order to determine whether this autocrine pathway is activated in squamous carcinoma cells, we analyzed the production of transforming growth factor alpha as well as the expression and regulation of epidermal growth factor receptors in a panel of human squamous carcinoma cell lines. Immunoreactive transforming growth factor alpha was detectable in squamous carcinoma cells as well as in quiescent nonneoplastic keratinocytes. However, in the absence of exogenous mitogens, only the squamous carcinoma cells secreted the growth factor into the medium, whereas untransformed keratinocytes did not. Each of the squamous carcinoma cell lines expressed significantly greater numbers of cell surface epidermal growth factor receptors than normal keratinocytes. The epidermal growth factor receptor gene was amplified and overexpressed in three of the squamous carcinoma cell lines (A431, CaSki, SqCC/Y1). Two of the squamous carcinoma cell lines (C4-1 and CE-48) displayed a relative inability to down-regulate epidermal growth factor receptors in response to epidermal growth factor. The mechanism of receptor overexpression in the remaining three cell lines (A253, CaLu-1, FaDu) is unexplained. Thus, human squamous carcinoma cell lines frequently exhibit a combination of the constitutive secretion of transforming growth factor alpha and the overexpression of epidermal growth factor receptors. Treatment of these tumor cells with an antibody directed against the ligand-binding domain of the epidermal growth factor receptor inhibited their growth by approximately 50%. These findings suggest that designing strategies to interrupt the transforming growth factor alpha autocrine pathway might lead to new modalities to treat this class of malignant tumors.
Carcinoma, Squamous Cell↗
Tumor necrosis factor stimulates epithelial tumor cell motility.
Cellular motility is a critical function in embryonic development, tissue repair, and tumor invasion. We used assays of scattering (epithelial colony dispersion), cell migration, and cell invasion to study cytokine-regulated motility in epithelial and carcinoma cell lines. Tumor necrosis factor (TNF) stimulated motility in 12 of 14 cell lines in one or more assay systems. The motility-stimulating activity of TNF did not correlate with its antiproliferative activity. In lines whose migration was stimulated by both TNF and scatter factor (SF), a fibroblast-derived cytokine which stimulates epithelial cell motility, saturating concentrations of TNF plus SF induced greater migration than either agent alone. Anti-TNF monoclonal antibody blocked TNF- but not SF-stimulated motility. While various other factors (basic fibroblast growth factor, interleukin 6, interleukin 2, colony-stimulating factor 1) had little or not motility-stimulating activity, phorbol-12-myristate-13-acetate (PMA), a tumor-promoting phorbol ester, scattered and/or stimulated migration in all cell lines studied. Combinations of saturating concentrations of TNF plus PMA or of SF plus PMA induced greater migration than did any agent alone. These findings suggest that (a) carcinoma cell motility may be mediated by multiple biochemical pathways and (b) TNF stimulates epithelial motility by a mechanism different from that of SF and PMA. In vivo, TNF might enhance invasiveness of some carcinomas or stimulate epithelial wound healing.
Animals↗
[Theoretical aspects of handedness].
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Brain↗
Extracellular calcium-dependent regulation of transmembrane calcium fluxes in murine keratinocytes.
Because the level of extracellular Ca2+ is an important stimulus for differentiation of epidermal cells in vitro, we characterized the extracellular Ca(2+)-dependent transmembrane Ca2+ fluxes in BALB/MK mouse keratinocytes. Increasing levels of extracellular Ca2+, ranging from 0.07 to 1.87 mM, stimulated the rate of 45Ca2+ uptake into these cells 10- to 70-fold and doubled the rate of 45Ca2+ efflux. The divalent cations, Ni2+ and Co2+, were able to block the influx of Ca2+, but dihydropyridines and verapamil were not. Furthermore, 10 to 100 microM of the trivalent cation La3+ induced a dose-dependent 2- to 100-fold increase of Ca2+ uptake, independently of the level of extracellular Ca2+. These observations suggest that keratinocytes possess a cell-surface "Ca(2+)-receptor," activation of which stimulates the influx of 45Ca2+ through a type of voltage-independent, receptor-operated Ca2+ channels. Epidermal growth factor induced an accumulation of 45Ca2+ of a much smaller magnitude than elevations of the level of extracellular Ca2+, without a detectable increase of Ca2+ efflux. Thus, the divergent cellular responses of keratinocytes to EGF and extracellular Ca2+ may be due, in part, to the distinct changes in transmembrane Ca2+ fluxes that these two stimuli generate. Treatment of cells with type beta transforming growth factor led to a gradual 6-fold increase of the Ca(2+)-activated rate of Ca2+ uptake over a period of 4 hours, but reduced the Ca2+ efflux by approximately 50% within 10 minutes. Thus, type beta transforming growth factor apparently stimulates Ca2+ influx indirectly, but may control the differentiation of keratinocytes by direct inhibition of Ca2+ efflux pumps.
Animals↗
[The practical significance of laterality].
In the present review the practical relevance and the problems of left-handedness have been discussed. Nowadays the diagnosis of the correct hand for writing and learning to write are very important for left-handers. Laterality is a hybrid phenomenon which concerns not only pedagogics but also many other fields, such as medicine, transport, sport and art.
Child↗
Constitutive expression of the c-fos protooncogene in murine keratinocytes: potentiation of the mitogenic response to insulin-like growth factor 1.
In order to determine the biological effects of activation of the c-fos protooncogene on growth and differentiation of BALB/MK mouse keratinocytes, these cells were transfected with the plasmid pMAN-fos, which encompasses the human c-fos coding region under transcriptional control of a mouse mammary tumor virus promoter, as well as the gene encoding neomycin phosphotransferase. Of approximately 70 individual clones obtained by selection in Geneticin, 5 clones that constitutively expressed c-fos mRNA as well as p55fos protein were selected for phenotypic analysis. Each of these clones displayed density-dependent growth arrest at confluency when deprived of serum and mitogens. DNA synthesis could be reinitiated in quiescent cultures by treatment with epidermal growth factor to a similar extent as in the parental line. In four of five fos transfectants, insulin-like growth factor 1 potentiated the mitogenic response to epidermal growth factor more than 10-fold, compared to only 2.5-fold in the parental cells. The enhanced response to insulin-like growth 1 could not be attributed to changes in the number or the affinity of receptors for the growth factor. Finally, the constitutive expression of c-fos did not interfere with the induction of terminal differentiation by calcium.
Animals↗
High frequency of resistance of human squamous carcinoma cells to the anti-proliferative action of transforming growth factor beta.
Transforming Growth Factor beta is a potent autocrine inhibitor of the growth of untransformed keratinocytes. We found each of eight human squamous carcinoma cell lines to be refractory to the anti-proliferative action of Transforming Growth Factor beta. Although each of these carcinoma cell lines expressed the 53-65 kDa (type I) and the 280-300 (type III) Transforming Growth Factor beta-receptor proteins, the 73-85 kDa (type II) species was detectable in only one of these cell lines. Furthermore, although Transforming Growth Factor beta-sensitive non-neoplastic mouse keratinocytes expressed type II binding proteins, human keratinocytes did not. Our findings suggest that resistance to the growth-inhibitory actions of Transforming Growth Factor beta is a common feature of human squamous carcinoma cell lines but does not correlate with the expression of cell-surface receptors for this growth factor.
Carcinoma, Squamous Cell↗
Psychiatry and the irrational: does our scientific world view interfere with the adaptation of psychotics?
Perhaps even more strongly than others in our contemporary Western world, psychiatrists cling to an exceptionally rigid scientific world view. When psychotic patients speak of such matters as their experiences with spirits or of being possessed or of their preoccupations with meaningful coincidences, psychiatrists discount their views as mere psychotic delusions. We suggest that psychiatrists should deal with their patient's attempts at explaining their symptoms by negotiation and compromise, just as any other physician would do when confronted with patient explanations for symptoms which do not coincide with the tenets of scientific medicine. Rather than relegating the psychotic to a meaning-vacuum by dismissing his or her explanations as totally false and non-negotiable, the therapist should help patients find meaning by linking their views and experiences to those of important thinkers within Western cultures. Almost all elements of psychotic thought including beliefs in disembodied spirits, synchronicity (meaningful coincidences), and the possibility of non-material, actions-at-a-distance can be found among respected Western philosophers, psychiatrists, religious leaders and quantum physicists. An example of the world view of a psychotic patient is presented in which a variety of idiosyncratic beliefs are described including convictions of the reality of synchronicity. We demonstrate that highly similar synchronicity beliefs have been entertained by many major Western intellectuals. We contend that on this basis and along with negotiation and compromise, a therapeutic alliance can be established which may provide a measure of symptom relief as well as improvements in rehabilitation potential.
Cultural Characteristics↗
Uncoupling of the calcium-induced terminal differentiation and the activation of membrane-associated transglutaminase in murine keratinocytes by type-beta transforming growth factor.
Calcium is an important regulator of terminal differentiation of cultured epidermal cells. In order to investigate the relationship between the termination of proliferative activity and the process of keratinization, we studied the time course of events induced by a sudden increase of extracellular calcium (calcium-switch) in cultures of established murine skin keratinocytes (BALB/c MK-1). These cells displayed density-dependent growth arrest without undergoing terminal differentiation in the presence of serum- and mitogen-free medium with a calcium concentration less than 0.10 mM. The calcium-switch alone was sufficient to induce a dose-dependent burst of DNA synthesis, which was followed by a state in which the cells became progressively refractory to mitogenic stimulation with epidermal growth factor. Treatment of cultures with type beta transforming growth factor during the first 6- to 10 h following the calcium-switch completely eliminated the initial burst of DNA synthesis as well as the terminal differentiation in response to calcium. On the other hand, the calcium-switch also caused the induction of a four- to fivefold increase of the activity of the membrane-associated form of transglutaminase that is required for keratinization, which was not affected by the presence of type beta transforming growth factor. These observations suggest that type beta transforming growth factor regulates the calcium-induced terminal cell division independently of the induction of phenotypic markers of keratinization, such as transglutaminase.
Animals↗
Transcriptional activation of the c-myc proto-oncogene in murine keratinocytes enhances the response to epidermal growth factor.
To investigate the relationship between activation of the c-myc proto-oncogene and the controls of cellular growth and differentiation of epidermal cells, a transcriptionally activated c-myc gene (DM-myc) was introduced into the established murine keratinocytes, BALB/MK. Exponential growth rates of myc-transfectants were not significantly different from that of parental BALB/MK cells. C-myc RNA transcripts were not detectable in confluent, mitogen-deprived cultures of parental BALB/MK cells, whereas four out of five clones expressed elevated levels of myc mRNA under these conditions. All of the cell lines, however, displayed density-dependent growth arrest in the G0/1 phase of the cell cycle. Maximal stimulation of quiescent BALB/MK cells with epidermal growth factor (EGF) caused a 70- to 100-fold increase of [methyl-3H]-thymidine incorporation into DNA. In the four subclones that expressed the myc gene, the peak thymidine incorporation into DNA was significantly higher than in BALB/MK cells, ranging from 340- to 650-fold control levels. This increased sensitivity to EGF was not due to autocrine mitogenic activity or to a change of EGF binding. Type beta transforming growth factor strongly inhibited the EGF-induced DNA synthesis in BALB/MK cultures as well as in each of the five transfectants (IC50 4-40 pM). Furthermore, both BALB/MK cells and the transfected subclones could be induced to form cornified cell envelopes by increasing the extracellular concentration of calcium. Thus, the constitutive expression of c-myc in BALB/MK appears to affect predominantly the reinitiation of DNA synthesis by EGF.
Animals↗
Bovine papillomavirus type I induces resistance to Ca+(+)-induced terminal differentiation in murine keratinocytes.
Bovine papillomavirus type 1 (BPV-1) was expressed in established mouse BALB/MK epidermal keratinocytes. In each of the transfected cell lines, DNA synthesis was stimulated by epidermal growth factor (EGF) and inhibited by type beta transforming growth factor to an extent similar to that in parental cells. In contrast, the BPV-1-transfectants were resistant to the induction of terminal differentiation by extracellular Ca(+)+. First, BPV transfectants continued to respond to EGF in the presence of Ca(+)+, whereas the growth of BALB/MK cells was arrested. The characteristics of EGF-binding were identical in the two cell lines. Second, the Ca+(+)-switch failed to induce the activation of epidermal transglutaminase in BPV-1-transfectants. Thus, BPV-1 caused mouse keratinocytes to become resistant to Ca+(+)-induced differentiation without otherwise affecting the control of cell growth.
Animals↗
Prognostic factors in primary breast cancer.
Approximately 25% of women with node-negative breast cancer treated with surgery alone eventually experience a relapse of their disease. Survival in this group of patients correlates with the level of estrogen-receptors and inversely with the size of the primary tumor. Moreover, the rate of tumor growth, as determined either clinically or by using in vitro techniques, such as thymidine-labeling and flow cytometric measurements of DNA content, can be used to identify patients with node-negative breast cancer who have a high probability of recurrence. Based on such an analysis, the subset of patients with slow growing cancers may be spared adjuvant cytotoxic therapy. On the other hand, a rapid tumor growth rate predicts for a higher than usual chance of relapse among patients with node-positive breast cancer. Therefore, this subset of women may benefit from more prolonged and/or intensive adjuvant chemotherapy than is currently recommended. Finally, ongoing studies of structural or functional disturbances of proto-oncogenes in breast cancer can be expected to provide practitioners with additional prognostic indicators that will lead to further improvements in the management of this group of diseases in the near future.
Breast Neoplasms↗
Reinitiation of DNA synthesis in quiescent mouse keratinocytes; regulation by polypeptide hormones, cholera toxin, dexamethasone, and retinoic acid.
Cloned mouse keratinocytes (MK-1 cells) display density-dependent growth arrest when reaching confluency in a serum-free medium with a calcium concentration less than 0.1 mM, supplemented only with insulin and transferrin. In this quiescent state, greater than 95% of the cell population is in the Go/1 phase of the cell cycle. Treatment of quiescent MK-1 cells with 1 to 10 ng/ml epidermal growth factor (EGF) resulted in a sharp burst of DNA synthetic activity. Both insulin and cholera toxin potentiated the mitogenic effect of EGF, but neither agent was necessary or sufficient to induce thymidine incorporation into DNA. Dexamethasone abolished the effect of insulin, but not the mitogenic effect of EGF alone. In contrast, retinoic acid (RA) did not possess any mitogenic effect for quiescent MK-1 cells, nor did it modulate the actions of EGF or dexamethasone. A number of commercially available crude extracts of bovine brain and pituitary were also capable of initiating DNA synthesis in resting MK-1 cells. Finally, transforming growth factor type beta (TGF beta) proved to be a potent inhibitor of the mitogen-induced DNA synthesis in MK-1 cells (IC50:10 pM). This defined culture system is eminently suited to study the regulation of DNA synthesis of epidermal cells. In addition, it can be used as a sensitive bioassay for the detection of epidermal mitogens, as well as inhibitors of DNA synthesis such as TGF beta.
Animals↗