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P Geller

Publications and source records attributed to P Geller.

8 recordsLinked to original sources

Caspase 7-induced cleavage of kinectin in apoptotic cells.

Kinectin has been characterized as the first known receptor for the molecular motor kinesin, which is critically involved in microtubule-based vesicle transport and membrane trafficking. Here we identify kinectin as a target for caspase-mediated proteolysis during apoptosis. Treatment of cells with diverse apoptotic stimuli including TNF, anti-Fas, anticancer drugs, gamma-radiation or ceramide leads to rapid proteolytic cleavage of the 160-kDa form of kinectin to a 120-kDa fragment. Evidence is provided that kinectin cleavage is mediated by caspase 7.

Amino Acid Chloromethyl Ketones↗

Frequent alterations in gene expression in colon tumor cells of the microsatellite mutator phenotype.

Tumors of the microsatellite mutator phenotype (MMP) are characterized by the accumulation of many thousands of somatic mutations in tracts of simple repeated sequences or microsatellites. Using arbitrarily primed PCR fingerprinting of RNA (RAP-PCR), we have comparatively analyzed the overall gene expression patterns of several colorectal tumor cell lines with and without the MMP. A reproducible pattern of 30-40 main products was obtained for each fingerprint with a total of about 200 cell transcripts analyzed. Differences in RAP-PCR fingerprints were detected between these tumor cell lines. Some of these expression polymorphisms appeared to be specific for tumor cells of the MMP because they were present in two or more different MMP+ cell lines but absent in all MMP- cell lines analyzed. We also analyzed RNAs prepared from single cell clones isolated from these tumor cell lines. Reproducible differences in the fingerprints were detected between single cell clones from each of the cell lines analyzed. Examples of single cell clone-specific fingerprint differences from one of the MMP tumor cell lines were cloned and sequenced. Differential expression of some of these sequences was confirmed by Northern analysis using the cloned fragments as probes. Similar fingerprint alterations were also observed among single cell clones derived from single cell clones from mutator tumor cell lines, which appeared to exhibit higher clonal variation in gene expression compared with MMP- cells. The detection of inter- and intra-tumor alterations in gene expression by unbiased RAP-PCR show that these fluctuations occur with high frequency in tumor cells of the MMP. These results indicate that the profound genomic instability of tumor cells of the MMP is also reflected in a high incidence of alterations in their patterns of gene expression.

Blotting, Northern↗

Calmodulin inhibits the epidermal growth factor receptor tyrosine kinase.

We demonstrate in this report that the epidermal growth factor (EGF) receptor from rat liver can be isolated by calmodulin affinity chromatography by binding in the presence of Ca2+ and elution with a Ca(2+)-chelating agent. The bulk of the EGF receptor is not eluted by a NaCl gradient in the presence of Ca2+. We ascertained the identity of the isolated receptor by immunoblot and immunoprecipitation using a polyclonal antibody against an EGF receptor from human origin. The purified receptor is autophosphorylated in tyrosine residues in an EGF-stimulated manner, and EGF-dependent phosphorylation of serine residues was also detected. Both the EGF and the transforming growth factor-alpha stimulate the tyrosine-directed protein kinase activity of the isolated receptor with similar affinities. Furthermore, we demonstrate that calmodulin inhibits the EGF-dependent tyrosine-directed protein kinase activity associated to the receptor in a concentration-dependent manner. This inhibition is partially Ca2+ dependent and is not displaced by increasing the concentration of EGF up to an EGF/calmodulin ratio of 10 (mol/mol). In addition, calmodulin was phosphorylated in an EGF-stimulated manner in the presence of a basic protein (histone) as cofactor and in the absence, but not in the presence, of Ca2+.

Animals↗

Mammographic features of intracystic papillary lesions.

In this article, the mammographic findings of ten patients with intracystic papillary lesions are reported. Two of these patients also had sonograms, which confirmed the presence of intracystic papillary fronds. Although not all intracystic lesions can be differentiated from gross cysts, there are several helpful roentgenologic and clinical clues. The tumor presents mammographically as a sharply circumscribed cystic mass with an irregular and sometimes nodular contour, except where tumor breaks through the wall of the cyst to invade the parenchyma. There the borders become shaggy. This tumor should be suspected clinically if a cystic lesion is seen in a postmenopausal woman not taking estrogens. Management depends on a high degree of suspicion, and a sonogram is useful to visualize the papillary fronds in the cysts. Although malignant papillary lesions are often large on presentation, they carry an excellent prognosis that is not related to their size. Treatment consists of either mastectomy or lumpectomy and radiation, with or without dissection of axillary nodes.

Aged↗

Year one dental visit.

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Child, Preschool↗