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Biomedical subjects

I Guerrero

Publications and source records attributed to I Guerrero.

At least 37 records · Page 2Linked to original sources
PubMed1994

Subcellular localization of the segment polarity protein patched suggests an interaction with the wingless reception complex in Drosophila embryos.

The product of the segment polarity gene patched is a transmembrane protein involved in the cell communication processes that establish polarity within the embryonic segments of Drosophila. Monoclonal antibodies have been raised against the patched protein, and by immunoelectron microscopy part of the patched staining is found associated with discrete regions of the lateral plasma membrane of the embryonic epidermal cells. Using a mutation affecting endocytosis (shibire) we find that patched is a membrane-bound protein, which is internalized by endocytosis, and that the preferential sites of accumulation resemble the described localization of the cell-cell adhesive junctions of the epidermal cells. patched partially co-localizes with the wingless protein in the wingless-expressing and nearby cells, in structures that seem to be endocytic vesicles. These data suggest the interaction of patched protein with elements of the reception complex of wingless, as a way to control the wingless expression.

Animals↗
PubMed1991

Unrestricted expression of the Drosophila gene patched allows a normal segment polarity.

In the Drosophila embryo, mutations in the segment polarity gene patched (ptc) cause the replacement of the middle region of each segment by a mirror-image duplication of the remaining structures, including the parasegmental border. This gene, which encodes a transmembrane protein, is initially expressed in a generalized way at blastoderm, but later stops being transcribed in cells expressing the engrailed gene, and even later in cells in the middle of the parasegment. The genes engrailed (en) and wingless (wg) are also segment-polarity genes, and they are expressed in adjacent stripes flanking the parasegment borders in the embryo; in ptc mutants wg expression extends anteriorly and an ectopic stripe of en expression is induced. The suggestion has been made that ptc must be transcribed in a specific subset of cells to prevent en expression anterior to the wg-expressing stripe. Here we report that unrestricted expression of ptc from a heat-shock promoter has no adverse effect on development of Drosophila embryos. The heat-shock construct can also rescue ptc mutants, restoring wg expression to its normal narrow stripe. The ectopic en stripe fails to appear, but the normal one remains unaffected. The results imply that, despite its localized requirement, the restricted expression of ptc does not itself allocate positional information.

Animals↗
PubMed1989

A protein with several possible membrane-spanning domains encoded by the Drosophila segment polarity gene patched.

The patterning of cells in insect segments requires the exchange of information between cells, which in Drosophila depends on the activity of members of the segment-polarity class of genes. Here we report the molecular characterization of one such gene, patched. We find that patched encodes a large protein with several possible membrane-spanning domains and is expressed in a complex pattern during embryogenesis.

Alleles↗
PubMed1988

Dissociation of c-fos from ODC expression and neuronal differentiation in a PC12 subline stably transfected with an inducible N-ras oncogene.

In order to develop a model system for investigating the role of ras genes in neuronal differentiation, a construct consisting of a mouse N-ras oncogene linked to a dexamethasone-inducible promoter was devised and transfected into a subline of the PC12 rat pheochromocytoma cell line. Clonal lines were isolated which extended neurite-like processes within one day of exposure to dexamethasone. N-ras had a strong antiproliferative effect on these cells. These effects were reversible after removing dexamethasone. Elevation of mRNA for ornithine decarboxylase (ODC) was detected 6-18 hours after induction of N-ras by dexamethasone. The effects of ras on cell division, differentiation and cell size were analogous, but not identical to the effects of NGF on PC12 cells. One NGF action, induction of c-fos mRNA did not occur in ras-induced cells indicating that c-fos induction is unnecessary for both neurite outgrowth and for subsequent induction of ODC mRNA. The ability of ras to induce ODC, a division promoting enzyme, may also be relevant to the transforming actions of ras oncogenes.

Adrenal Gland Neoplasms↗
PubMed1988

Concomitant K- and N-ras gene point mutations in clonal murine lymphoma.

We have surveyed a panel of induced murine lymphomas for c-ras gene mutations. The K-ras gene seems to be preferentially activated in our system, and there are at least two examples of concomitant K- and N-ras gene mutations in the same tumor. This indicates that in some cases additional ras mutations may contribute to tumorigenesis and is evidence for a role of ras activation in tumor progression.

Alleles↗
PubMed1987

Differential expression of the ras gene family in mice.

We compared the expression of the ras gene family (H-ras, K-ras, and N-ras) in adult mouse tissues and during development. We found substantial variations in expression among different organs and in the amounts of the different transcripts originating from each gene, especially for the N-ras gene. The expression patterns were consistent with the reported preferential tissue activation of ras genes and suggested different cellular functions for each of the ras genes.

Aging↗
PubMed1987

Mouse N-ras genes: organization of the functional locus and of a truncated cDNA-like pseudogene.

The N-ras gene was first identified in both humans and mice as a mutationally activated oncogene found in tumors. The nucleotide sequence and intron/exon structure of the coding region of the mouse gene have been determined previously. We have now determined the sequence and intron/exon structure of the 5' and 3' untranslated regions of mouse N-ras. Like its human homolog, the 3' untranslated region of the gene is encoded by two exons, and the 5' region is encoded by one. In addition, we have isolated and sequenced a second mouse gene homologous to N-ras. This locus, which we have named N-ras-2ps, resides at a chromosomal site distinct from N-ras and appears to be a truncated cDNA-like pseudogene.

Animals↗
PubMed1986

Activated N-ras gene induces neuronal differentiation of PC12 rat pheochromocytoma cells.

Activated mouse N-ras gene transfected into PC12 rat pheochromocytoma cells suppressed proliferation and promoted neuronal differentiation. Normal mouse N-ras in a LTR-containing vector caused differentiation with a reduced efficiency, but normal N-ras in a vector lacking LTR sequences failed to alter the PC12 phenotype. Cultures of NGF-resistant PC12 variant subline U7 also showed outgrowth of neurites and cessation of cell division following transfection with the mutated ras gene. The present findings suggest that ras genes can, in certain cells, play a role in promoting differentiation and suppressing proliferation, in contrast to their established oncogenic neoplasia-promoting activity in other cells.

Adrenal Gland Neoplasms↗
PubMed1986

Oncogene activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea.

Thymic lymphomas have been induced by gamma-radiation and treatment with the chemical nitrosomethylurea in different mice strains. As indicated by the NIH 3T3 focus forming assay, a significant percentage of the tumors contain activated oncogenes of the ras family (K or N). Cloning and sequencing has enabled us to identify single base mutations as the only significant alteration present in the activated oncogenes. These alterations result in the substitution of amino-acid 12 or 61 of the p21 product of the ras genes. With the use of synthetic oligonucleotides it has been found that the tumors do not all contain the same mutation and in one case so far the normal allele is absent.

Animals↗
PubMed1985

Loss of the normal N-ras allele in a mouse thymic lymphoma induced by a chemical carcinogen.

Young mice injected with the carcinogen N-nitroso-N-methylurea develop thymic lymphomas 2-4 months later. We previously have shown that these tumors frequently contain an activated N-ras gene that can transform rodent fibroblasts in vitro. We report here the intron/exon structure of such an activated N-ras gene and the sequence of its four coding exons. A single nucleotide change is responsible for the transforming alteration, a C----A transversion in the first base of codon 61. Through the use of synthetic oligonucleotides as hybridization probes, we show that this tumor lacks the normal allele of the N-ras gene. The implications of this finding for oncogene dominance are discussed.

Alleles↗
PubMed1984

Activation of a c-K-ras oncogene by somatic mutation in mouse lymphomas induced by gamma radiation.

Mouse tumors induced by gamma radiation are a useful model system for oncogenesis. DNA from such tumors contains an activated K-ras oncogene that can transform NIH 3T3 cells. This report describes the cloning of a fragment of the mouse K-ras oncogene containing the first exon from both a transformant in rat-2 cells and the brain of the same mouse that developed the tumor. Hybrid constructs containing one of the two pieces were made and only the plasmid including the first exon from the transformant gave rise to foci in NIH 3T3 cells. There was only a single base difference (G----A) in the exonic sequence, which changed glycine to aspartic acid in the transformant. By use of a synthetic oligonucleotide the presence of the mutation was demonstrated in the original tumor, ruling out modifications during DNA-mediated gene transfer and indicating that the alteration was present in the thymic lymphoma but absent from other nonmalignant tissue. The results are compatible with gamma radiation being a source of point mutations.

Animals↗
PubMed1984

Isolation, characterization, and chromosome assignment of mouse N-ras gene from carcinogen-induced thymic lymphoma.

Treatment of mice with the carcinogen N-methylnitrosourea results in the development of thymic lymphomas with frequent involvement of the N-ras oncogene. The activated mouse N-ras gene was isolated from one of these lymphomas and, by transformation in concert with restriction digestion, a map of the gene was prepared and its approximate boundaries were determined. By means of somatic cell hybrids the normal N-ras gene was found to be unlinked to other members of the ras gene family.

Animals↗
PubMed1984

A molecular approach to leukemogenesis: mouse lymphomas contain an activated c-ras oncogene.

By inducing mouse thymomas with carcinogens and gamma-radiation, we have studied the potential of tumor DNA to induce foci in rodent fibroblasts. A high percentage of the tumors used transformed the cultured cells, and the oncogenic phenotype segregated with extra copies of the c-ras gene family. There appears to be selectivity in the activated gene because so far all analyzed tumors induced by carcinogen have activated the N-ras gene, and those induced by radiation have activated the K-ras gene. The K-ras gene is the cellular counterpart of the viral ras oncogene in Kirsten murine sarcoma virus, but the N-ras has not yet been found in a retrovirus. The transformed cells have a marked increase in expression of the oncogene at the RNA and protein level. This model system might be a powerful tool in the study of leukemogenesis.

Animals↗
PubMed1983

Immune deficiency syndrome in children.

The present epidemic of acquired immune deficiency syndrome (AIDS) was originally described in homosexual men and subsequently in intravenous drug abusers, Haitians, and hemophiliacs. Profound defects in cell-mediated immunity (CMI) are associated with Kaposi's sarcoma and a variety of serious opportunistic infections. Recently, we and others have encountered a group of children with an otherwise unexplained immune deficiency syndrome and infections of the type found in adults with AIDS. In this report, we describe eight children from the Newark, NJ, metropolitan area born into families with recognized risks for AIDS. These patients have had recurrent febrile illnesses, failure to thrive, hypergammaglobulinemia, and depressed CMI. Four of these children have died. Our experience suggests that children living in high-risk households are susceptible to AIDS and that sexual contact, drug abuse, or exposure to blood products is not necessary for disease transmission.

Acquired Immunodeficiency Syndrome↗