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Biomedical subjects

D M Morrow

Publications and source records attributed to D M Morrow.

16 recordsLinked to original sources
PubMed1997

"Break copy" duplication: a model for chromosome fragment formation in Saccharomyces cerevisiae.

Introduction of a chromosome fragmentation vector (CFV) into the budding yeast Saccharomyces cerevisiae results in a targeted homologous recombination event that yields an independently segregating chromosome fragment (CF) and an alteration in the strain's karyotype. Fragmentation with an acentric CFV directed in a centromere-proximal orientation generates a CF that contains all sequences proximal to the targeting segment and results in loss of the endogenous targeted chromosome to yield a 2N-1 + CF karyotype. In contrast, fragmentation with a centric CFV directed in a centromere-distal orientation generates a CF that contains all sequences distal to the targeting segment and retention of the endogenous targeted chromosome to yield a 2N + CF karyotype. We have termed this phenomenon "break copy" duplication. Using yeast strains in which the centromere had been transposed to a new location, it was demonstrated that the centromere inhibited break copy duplication. These data suggest that CF formation is the product of an unscheduled DNA replication event initiated by the free end of the CFV and is analogous to a "half" double-strand break gap-repair reaction. We suggest that break copy duplication may have evolved as a mechanism for maintenance of ploidy following DNA breakage.

Chromosome Aberrations↗
PubMed1996

The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast.

Replication protein A (RPA) is a highly conserved single-stranded DNA-binding protein, required for cellular DNA replication, repair, and recombination. In human cells, RPA is phosphorylated during the S and G2 phases of the cell cycle and also in response to ionizing or ultraviolet radiation. Saccharomyces cerevisiae exhibits a similar pattern of cell cycle-regulated RPA phosphorylation, and our studies indicate that the radiation-induced reactions occur in yeast as well. We have examined yeast RPA phosphorylation during the normal cell cycle and in response to environmental insult, and have demonstrated that the checkpoint gene MEC1 is required for the reaction under all conditions tested. Through examination of several checkpoint mutants, we have placed RPA phosphorylation in a novel pathway of the DNA damage response. MEC1 is similar in sequence to human ATM, the gene mutated in patients with ataxia-telangiectasia (A-T). A-T cells are deficient in multiple checkpoint pathways and are hypersensitive to killing by ionizing radiation. Because A-T cells exhibit a delay in ionizing radiation-induced RPA phosphorylation, our results indicate a functional similarity between MEC1 and ATM, and suggest that RPA phosphorylation is involved in a conserved eukaryotic DNA damage-response pathway defective in A-T.

Ataxia Telangiectasia↗
PubMed1996

Platelet immunoregulatory factors.

A number of soluble and membrane-associated proteins are known to mediate platelet:leukocyte interactions. Platelet-derived factors that have attracted the most attention to date include transforming growth factor beta, interleukin 1 and platelet factor 4. Recently, we have uncovered another protein within platelets that has leukocyte modulatory activity. It was previously characterized as an endometrial glycoprotein named placental protein 14 (PP14) with suppressive effects upon lymphocyte proliferation, pro-inflammatory cytokine production and natural killer cell function. The "hematopoietic" PP14 derived from cells of the megakaryocytic lineage shares this immunosuppressive property, as evaluated by two-way mixed lymphocyte cultures. Interestingly, two alternatively spliced hematopoietic PP14 mRNAs have been cloned which differ in their encoded proteins. Cell-free translation and transfection analyses have verified the translatability of both PP14 mRNA species and allowed for the analysis of their glycosylation properties. PP14, a member of the lipocalin structural superfamily of proteins, now offers an intriguing new link between the coagulation and immune systems.

Blood Platelets↗
PubMed1996

Exploiting the complete yeast genome sequence.

The completion of the genome sequence of the budding yeast Saccharomyces cerevisiae marks the dawn of an exciting new era in eukaryotic biology that will bring with it a new understanding of yeast, other model organisms, and human beings. This body of sequence data benefits yeast researchers by obviating the need for piecemeal sequencing of genes, and allows researchers working with other organisms to tap into experimental advantages inherent in the yeast system and learn from functionally characterized yeast gene products which are their proteins of interest. In addition, the yeast post-genome sequence era is serving as a testing ground for powerful new technologies, and proven experimental approaches are being applied for the first time in a comprehensive fashion on a complete eukaryotic gene repertoire.

Animals↗
PubMed1995

TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1.

Patients with the genetic disorder ataxia telangiectasia (AT) have mutations in the AT mutated (ATM) gene, which is homologous to TEL1 and the checkpoint gene MEC1. A tel1 deletion mutant, unlike a mec1 deletion, is viable and does not exhibit increased sensitivity to DNA-damaging agents. However, increased dosage of TEL1 rescues sensitivity of a mec1 mutant, mec1-1, to DNA-damaging agents and rescues viability of a mec1 disruption. mec1-1 tel1 delta 1 double mutants are synergistically sensitive to DNA-damaging agents, including radiomimetic drugs. These data indicate that TEL1 and MEC1 are functionally related and that functions of the ATM gene are apparently divided between at least two S. cerevisiae homologs.

Ataxia Telangiectasia↗
PubMed1994

Hematopoietic placental protein 14. An immunosuppressive factor in cells of the megakaryocytic lineage.

Placental protein 14 (PP14), an immunosuppressive molecule previously known to be expressed in the female and male reproductive tracts only, was shown to be expressed by hematopoietic cells of the megakaryocytic lineage. Northern blot analysis confirmed the induction specificity of PP14 mRNA in phorbol ester-treated K562 cells. Potent immunosuppressive activity in conditioned medium from phorbol ester-treated K562 cells was attributed to hematopoietic PP14 by anti-PP14 antibody blocking. Immunoprecipitation with anti-PP14 antibodies from conditioned medium revealed two distinct PP14 protein isoforms, designated PP14.1 and PP14.2. Polymerase chain reaction cloning and analysis demonstrated the presence of distinct mRNA counterparts to PP14.1 and PP14.2 that had not been resolved by Northern blot analyses. Hematopoietic PP14.1 mRNA corresponds in size to endometrial PP14 mRNA, whereas the smaller hematopoietic PP14.2 mRNA displays an internal in-frame 66-nucleotide deletion that can be explained by alternative splicing and predicts a 22-amino-acid deletion in the encoded gene product. Both PP14 mRNA isoforms were additionally detected by reverse transcriptase polymerase chain reaction analyses in two human megakaryocytic cell lines and in normal human megakaryocytes and platelets. PP14 mRNA was not detected by reverse transcriptase polymerase chain reaction in a panel of nonhematopoietic, nonendometrial tissues examined. The finding of hematopoietic PP14 within the megakaryocytic lineage provides an additional regulatory link between the coagulation and immune systems in normal and pathological settings.

Base Sequence↗
PubMed1992

Chemical peeling of eyelids and periorbital area.

Chemical peeling promotes formation of new epidermis and new dermal collagen, resulting in skin shrinkage, reduction of wrinkling and crepe paper skin, softening of crow's feet, and, when desired, lightened eyelid color. Chemical peeling may be performed as the only eyelid procedure, simultaneously with CO2 laser surgical blepharoplasty, after healing of cold-steel-scalpel or CO2-laser blepharoplasty, and as a repeated procedure to achieve maximal results.

Adult↗
PubMed1992

CO2 laser blepharoplasty. A comparison with cold-steel surgery.

This study compares and contrasts the use of the CO2 laser with the conventional cold-steel scalpel and electrocautery in cosmetic blepharoplasty. Ten patients underwent bilateral, upper, and lower eyelid cosmetic blepharoplasty using the CO2 laser as the exclusive cutting and cauterizing instrument for one eye, and the cold-steel scalpel and electrocautery as the exclusive cutting instrument and cauterizing tool for the remaining eye. This comparison evaluated administrative factors, procedural ease, and long- and short-term results. The benefits of using the CO2 laser rather than the cold-steel scalpel in blepharoplasty are reduced operative time, less bleeding, superior intraoperative visibility, less bruising and swelling, no pain or discomfort, and a shorter recuperation period. There were no complications with either the scalpel or the laser. Using the laser with standard safety protocols presents no greater risk to the patients undergoing blepharoplasty than does using the cold steel scalpel with an electrocautery device. The disadvantages of using the laser compared with the steel scalpel include the cost of purchasing and maintaining the laser equipment, the need for additional and extensive laser training for surgeons and assistants, and the need for two assistants rather than the one needed for scalpel surgery.

Adult↗
PubMed1992

Protein kinase C isotypes in human erythroleukemia cell proliferation and differentiation.

The human erythroleukemia (K562) cell line is induced to differentiate into megakaryocytic cells by treatment with the tumor promoter phorbol myristate acetate (PMA). PMA-induced differentiation is characterized by (1) almost complete cessation of cellular proliferation, (2) expression of the megakaryocytic cell surface marker glycoprotein IIb/IIIa (gpIIIa), (3) increased secretion of granulocyte/macrophage-colony stimulating factor (GM-CSF) and (4) increased secretion of interleukin-6 (IL-6). PMA-induced differentiation is dose-dependent with maximal activity seen at 10 nM PMA. In contrast, bryostatin (bryo), a structurally distinct protein kinase C (PKC) activator, fails to induce megakaryocytic differentiation or growth arrest at the concentrations tested (0.01-100 nM). Rather, bryo inhibits PMA-induced growth arrest and megakaryocytic differentiation in a dose-dependent fashion (full inhibition at 100 nM). The divergent biological effects of PMA and bryo correspond to the differential activation and translocation of PKC isotypes in K562 cells. PKC isotype analysis demonstrates that undifferentiated cells express both alpha and beta II PKC but no detectable beta I, gamma or epsilon PKC. Treatment of cells with either PMA or bryo leads to rapid translocation of both alpha and beta II PKC from the cytosol to the non-nuclear particulate fraction. However, bryo also induces selective translocation of beta II PKC to the nuclear membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Bryostatins↗
PubMed1989

Directional antisense and sense cDNA cloning using Epstein-Barr virus episomal expression vectors.

A set of Epstein-Barr virus (EBV) episomal expression vectors, incorporating either the Rous sarcoma virus 3' long terminal repeat or the human metallothionein IIA gene promoter, were constructed. The transcriptional cassettes encompassed by these vectors were designed to permit both antisense and sense RNA transcription. A novel methodology was developed for directional cDNA cloning using an oligodeoxyribonucleotide adapter; the EBV episomal vectors alternatively enabled the insertion of cDNA segments in antisense or sense orientations. We propose a strategy for random antisense RNA mutagenesis exploiting this vector system and a method for episome-based directional antisense cDNA cloning and expression, permitting the rapid identification of genes mediating selectable cellular functions.

Base Sequence↗
PubMed1980

Hypersensitivity to aloe.

Hypersensitivity, manifested by generalized nummular eczematous and papular dermatitis, and presumably by contact urticaria, developed in a 47-year-old man after four years of using oral and topical aloe. Patch tests for aloe were positive in this patient.

Aloe↗