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M Reiss

Publications and source records attributed to M Reiss.

At least 19 recordsLinked to original sources
PubMed1995

Missense mutations of the transforming growth factor beta type II receptor in human head and neck squamous carcinoma cells.

In this study, we report the occurrence of missense mutations of the transforming growth factor beta (TGF beta) type II receptor gene in two human squamous head and neck carcinoma cell lines. Both mutations are G:C-->C:G transversions, which result in the replacement of a glutamic acid by a glutamine, and of an arginine by a proline residue, respectively. Moreover, both are located at highly conserved sites within the serine-threonine kinase domain. One of the mutants appears to be defective in its autophosphorylation as well as in the transphosphorylation of the TGF beta type 1 receptor protein, whereas the second mutant appears to be constitutively activated. These are the first reported naturally occurring nucleotide substitution mutations in the T beta R-11 gene in human head and neck cancer cells, which may explain their resistance to TGF beta 1-mediated cell cycle arrest.

Amino Acid Sequence↗
PubMed1995

A study of leg-crossing in a German sample.

When a person is asked to cross their flexed legs then one thigh crossed over the other. This paper reviews the previous literature on leg crossing, and reports new data. In this study about 62% of the population (n = 292) are right leg-crossers, 26% are left leg-crossers, and the remaining 12% report that they have no preference or are indifferent. The incidence of left leg-crossing differs between the sexes, being higher in males, although there seems to be no association with age. Leg-crossing is correlated to some extent with footedness, handedness and eyedness.

Adult↗
PubMed1994

Restoration of differentiation and suppression of tumorigenicity in somatic cell hybrids of human squamous carcinoma cells and keratinocytes.

Somatic cell hybrid cell lines derived from the fusion of human squamous carcinoma cells (FaDu-Hyg) with human keratinocytes were used to examine the relationships between cell differentiation and tumorigenicity. Treatment of the parental keratinocytes or the two hybrid cell lines with the combination of calcium and fetal bovine serum increased the expression of the envelope precursor, involucrin, 4- to 8-fold, whereas it remained unchanged in FaDu-Hyg cells. Similarly, calcium- and serum-treated keratinocytes and the two hybrid cell lines displayed a 7- to 13-fold increase of the activity of membrane-associated type I transglutaminase, whereas transglutaminase activity in FaDu-Hyg cells did not change appreciably. FaDu-Hyg cells were tumorigenic in vivo, but tumorigenicity was suppressed in both hybrid cell lines. Analysis of additional tumor cell lines indicated that the expression of transglutaminase I and involucrin are under separate genetic control and that loss of transglutaminase activity can result either from a lack of protein or from a defect in the activation step. Thus, keratinization of squamous epithelial cells appears to be controlled by several different recessive genes, which cosegregate with but are probably only partly identical with the genes that suppress tumor formation in vivo.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗