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Biomedical subjects

E Springer

Publications and source records attributed to E Springer.

At least 19 recordsLinked to original sources
PubMed2006

The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals.

CHOP (GADD153) is a protein of the C/EBP family of transcriptional regulators, which dimerizes with other C/EBP members and changes their DNA-binding and transactivation properties. It induces growth arrest and apoptosis after endoplasmatic reticulum stress or DNA damage. CHOP is also expressed during early embryogenesis and upregulated in tumour tissues with defective Wnt signals. We report here that CHOP functions as a specific inhibitor of Wnt/T-cell factor (TCF) signalling. CHOP inhibits TCF-dependent transcription in human embryonic and colon cancer cell lines. Injection of CHOP mRNA into early Xenopus laevis embryos suppresses dorsal organizer formation and inhibits secondary axis formation and TCF-dependent transcription in response to Wnt-8, Dishevelled, beta-Catenin and TCF-VP16. In embryos and human cells, this inhibition depends on the N-terminal transactivation domain of CHOP, whereas the C-terminal dimerization domain is dispensable. CHOP binds to TCF factors, thereby preventing the binding of TCF to its DNA recognition site. Our findings demonstrate a novel function of CHOP as a Wnt repressor.

Amino Acid Motifs↗
PubMed2001

Rac affects invasion of human renal cell carcinomas by up-regulating tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 expression.

Rho-like GTPases, including Cdc42, Rac1, and RhoA, regulate distinct actin cytoskeleton changes required for adhesion, migration, and invasion of cells. Tiam1 specifically activates Rac, and earlier studies have demonstrated that Tiam1-Rac signaling affects migration and invasion in a cell type- and cell substrate-specific manner. In the present study, we examined the role of Tiam1-Rac signaling in migration and invasion of human renal cell carcinomas. Stable overexpression of Tiam1 or constitutively active V12-Rac1 in a human renal cell carcinoma cell line (clearCa-28) strongly inhibited cell migration by promoting E-cadherin-mediated cell-cell adhesion. Blocking E-cadherin-mediated adhesion by E-cadherin-specific HAV peptides allowed cells to migrate, but was not sufficient to antagonize Tiam1- and V12-Rac1-induced inhibition of Matrigel invasion, suggesting that Rac may influence invasion also through other mechanisms. Indeed, Tiam1-mediated Rac activation induced transcriptional up-regulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) and post-transcriptional up-regulation of TIMP-2, whereas secretion and activity levels of their counterparts, matrix metalloproteinase-9 and matrix metalloproteinase-2, respectively, were not affected. Application of recombinant TIMP-1 and TIMP-2 proteins significantly inhibited invasion of mock-transfected clearCa-28 cells, supporting a role of TIMPs in Rac-mediated inhibition of invasion. To our knowledge, this is the first evidence that increased Rac signaling may inhibit invasion of epithelial tumor cells by up-regulation of TIMP-1 and TIMP-2.

Carcinoma, Renal Cell↗
PubMed2001

Chemical development of latent fingerprints: 1,2-indanedione has come of age.

The performance of 1,2-indanedione as a latent fingerprint reagent on some types of paper was found to exceed that of DFO, the leading fluorogenic fingerprint reagent. It even exceeds the performance of the sequence, DFO, followed by ninhydrin. No new prints could be observed when ninhydrin was applied after indanedione. On a large number of actual exhibits (used checks) indanedione developed 46% more identifiable prints than the sequence DFO-ninhydrin. A standard procedure for fingerprint development by indanedione is proposed. Best results are obtained with a 0.2% indanedione solution in HFE7100 solvent containing 7% ethyl acetate, but no acetic acid. It can be recommended to start using 1,2-indanedione, which is already commercially available, in actual fingerprint casework.

Dermatoglyphics↗
PubMed2000

Protein kinase C in human renal cell carcinomas: role in invasion and differential isoenzyme expression.

The role of protein kinase C (PKC) in in vitro invasiveness of four different human renal cell carcinoma (RCC) cell lines of the clear cell type was investigated. Different PKC-inhibitors markedly inhibited invasiveness of the highly invasive cell lines, suggesting an invasion-promoting role of PKC in human RCC. Analysis of PKC-isoenzyme expression by protein fractionation and immunoblotting revealed that all cell lines expressed PKC-alpha, -epsilon, -zeta, -mu and -iota as known from normal kidney tissue. Interestingly, PKC-delta, known to be expressed by normal kidney epithelial cells of the rat, was absent on protein and RNA levels in all RCC cell lines investigated and in normal human kidney epithelial cells. PKC-epsilon expression levels correlated positively with a high proliferation activity, but no obvious correlation between expression levels of distinct PKC-isoenzymes and in vitro invasiveness was observed. However, by immunofluorescence microscopy, membrane localisation of PKC-alpha and PKC-epsilon reflecting activation of the enzymes, was associated with a highly invasive potential. In conclusion, our results suggest a role for PKC in invasion of human RCCs and might argue in favour of a particular role of PKC-alpha and PKC-epsilon. Our results further suggest that organ-specific expression patterns of PKC-isoenzymes are not necessarily conserved during evolution.

Carcinoma, Renal Cell↗
PubMed2000

Reagents for the chemical development of latent fingerprints: scope and limitations of benzo[f]ninhydrin in comparison to ninhydrin.

Benzo[f]ninhydrin was compared to ninhydrin for fingerprint development on paper. Overall, the performance of ninhydrin on exhibits was slightly better than that of benzo[f]ninhydrin. The significant advantages of the benzo[f]ninhydrin over ninhydrin were the much stronger fluorescence it gave after treatment with zinc salts and a slightly quicker reaction under ambient conditions. This fluorescence is, however, similar to that obtained with other reagents, such as DFO or ninhydrin analogs. These advantages apparently are not sufficient to justify regular usage of benzo[f]ninhydrin, especially when one considers its low solubility and high cost.

Benzene↗
PubMed2000

Fingerprints and DNA: STR typing of DNA extracted from adhesive tape after processing for fingerprints.

An exhibit that is often received for examination in cases of robbery or terrorist activity is adhesive tape. This type of exhibit can often, but not always, be successfully processed for fingerprints. The question arises whether or not it is possible to extract and type DNA after the tape has been sequentially processed for fingerprints. In this work, various donors left fingerprints on the adhesive side of tapes. The tapes were then sequentially processed for fingerprints using an alternate light source, cyanoacrylate fuming, and staining with BY-40 and then crystal violet. DNA was subsequently successfully extracted, amplified and typed for six STR loci.

Adhesives↗
PubMed1999

Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties.

Recently, a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer. Therefore, we analyzed the expression of survivin in human renal cell carcinomas (RCCs), known to be largely resistant to chemotherapy. Northern blot analysis and RT-PCR revealed survivin expression in newly established RCC cell lines (n = 11) of all major histological types. Moreover, we identified two novel splice variants of survivin, lacking exon 3 (survivin-deltaEx3) or retaining a part of intron 2 as a cryptic exon (survivin-2B). Both sequence alterations cause marked changes in the structure of the corresponding proteins, including structural modifications of the baculovirus inhibitor of apoptosis protein repeat domain. The role of the novel isoforms in the regulation of apoptosis was assessed in transfection experiments, showing conservation of antiapoptotic properties for survivin-deltaEx3 and a markedly reduced antiapoptotic potential for survivin-2B. In conclusion, our observations suggest a complex regulatory balance between the different isoforms of survivin, which might determine the response to proapoptotic stimuli, not only in human RCCs but also in fetal tissues and other types of cancer.

Alternative Splicing↗
PubMed1998

Short UV luminescence for forensic applications: design of a real-time observation system for detection of latent fingerprints and body fluids.

An assembly that allows a pseudo real-time (one second delay) observation of latent fingerprints by their short ultraviolet luminescence was designed. It is composed of a mercury-xenon lamp and a CCD camera, both water-cooled and computer-controlled. The system is used to study the behaviour of latent fingerprints and stains of body fluids such as blood, semen and saliva under short-UV illumination.

Body Fluids↗
PubMed1998

Visualization of sebaceous fingerprints on fired cartridge cases: a laboratory study.

The visualization and endurance of fingerprints on cartridge cases after the firing process have been examined. Cartridges of M16, AK-47 (Kalashnikov) and Parabellum have been tested. Despite difficulties in visualizing these fingerprints, it was found that in some cartridge cases under laboratory conditions--for instance, on M16 brass cartridges--substantial parts of the fingerprints remain intact after shooting. The careful use of illumination after metal vapor deposition enabled visualization. Different possible mechanisms responsible for the partial destruction of the fingerprints are discussed.

Copper↗
PubMed1995

Partial gene sequences for the A subunit of methyl-coenzyme M reductase (mcrI) as a phylogenetic tool for the family Methanosarcinaceae.

Representatives of the family Methanosarcinaceae were analyzed phylogenetically by comparing partial sequences of their methyl-coenzyme M reductase (mcrI) genes. A 490-bp fragment from the A subunit of the gene was selected, amplified by the PCR, cloned, and sequenced for each of 25 strains belonging to the Methanosarcinaceae. The sequences obtained were aligned with the corresponding portions of five previously published sequences, and all of the sequences were compared to determine phylogenetic distances by Fitch distance matrix methods. We prepared analogous trees based on 16S rRNA sequences; these trees corresponded closely to the mcrI trees, although the mcrI sequences of pairs of organisms had 3.01 +/- 0.541 times more changes than the respective pairs of 16S rRNA sequences, suggesting that the mcrI fragment evolved about three times more rapidly than the 16S rRNA gene. The qualitative similarity of the mcrI and 16S rRNA trees suggests that transfer of genetic information between dissimilar organisms has not significantly affected these sequences, although we found inconsistencies between some mcrI distances that we measured and and previously published DNA reassociation data. It is unlikely that multiple mcrI isogenes were present in the organisms that we examined, because we found no major discrepancies in multiple determinations of mcrI sequences from the same organism. Our primers for the PCR also match analogous sites in the previously published mcrII sequences, but all of the sequences that we obtained from members of the Methanosarcinaceae were more closely related to mcrI sequences than to mcrII sequences, suggesting that members of the Methanosarcinaceae do not have distinct mcrII genes.

Base Sequence↗
PubMed1990

Interferon alfa-2a combined with phototherapy in the treatment of cutaneous T-cell lymphoma.

Escalating doses of recombinant interferon alfa-2a (Roferon-A), administered intramuscularly three times weekly, combined with psoralen plus ultraviolet light irradiation (PUVA), were tested in a phase I trial for the therapy of patients with cutaneous T-cell lymphomas (CTCL). Interferon doses were escalated in groups of three patients from 6 million to 30 million IUs three times weekly. Disease stages ranged from IB to IVB. Eighty percent of the patients entered in this trial had failed at least one prior therapy. Complete remissions were obtained in 12 of 15 patients, and partial responses were seen in two of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 13 months (range, 3-15+). All patients who responded have been maintained on therapy. The dose-limiting toxic effects were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). These side effects were reversible with a decrement in dose or discontinuation of the interferon. No patient tolerated 30 million IU of the interferon for extended periods; the maximally tolerated dose was 18 million IU. Interferon plus PUVA appears to be a highly effective regimen for the treatment of patients with CTCL. Phase II studies investigating this combination, using 18 million IU of interferon alfa-2a three times weekly, should be undertaken to expand these findings, and to attempt to reduce the toxic effects associated with this therapy.

Combined Modality Therapy↗
PubMed1990

Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma.

Eighty-two patients with either mycosis fungoides (MF) or parapsoriasis en plaques were treated with psoralens ultraviolet A light (PUVA). Clinical and histologic parameters were followed for a period from 6 months to 10 years. Complete clinical clearing of lesions was observed in 51 patients (62%) and most of them were in limited-plaque MF group or parapsoriasis en plaque. The mean total dose of PUVA for complete clearing was less for early MF. Thirty-one patients (38%) relapsed and responded to additional PUVA. Patients in early stages of the disease remained clear for up to 68 months after the first course of PUVA. Post-treatment skin biopsies with early MF showed histologic clearing. A new combination therapy for MF is presented in 15 patients. Recombinant interferon alpha-2a (Roferon-A), administered intramuscularly combined with PUVA were tested in a phase I trial. Interferon doses were from 6-30 million units three times weekly. Disease stages ranged from I-B to IV-B. Complete responses were obtained in 12 of 15 patients, and partial responses seen in 2 of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 23 months (range, 3 to 25 months). All responding patients have been maintained on therapy. The dose-limiting toxicities were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). Interferon plus PUVA appear to be highly effective regimens for the treatment of patients with cutaneous T-cell lymphomas.

Adult↗