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Biomedical subjects

S D Porter

Publications and source records attributed to S D Porter.

18 recordsLinked to original sources
PubMed1999

Changes in chromatin organization at the neutrophil elastase locus associated with myeloid cell differentiation.

Neutrophil elastase, proteinase-3, and azurocidin are primary components of neutrophil azurophilic granules and are encoded by closely linked genes (gene symbols ELA2, PRTN3, and AZU1, respectively) in a region of approximately 50 kb. These genes are coordinately expressed in a granulocyte-specific fashion, but the mechanisms defining this pattern of expression are unknown. To understand the role of chromatin organization in governing the expression of ELA2, PRTN3, and AZU1, we mapped this region of chromosome 19 and identified the adipsin (complement factor D) gene in proximity to the 3' end of ELA2. We then examined the changes in chromatin structure at the locus which accompany myeloid cell differentiation and identified 17 DNase I hypersensitive sites (DHS 1 to 17) in U-937 cells, an early myelomonocytic cell line expressing high levels of neutrophil elastase. Chemically induced differentiation and concomitant downregulation of AZU1, PRTN3, and ELA2 transcription in U-937 cells is not accompanied by changes in the DHS-pattern. Mature neutrophils, however, do not carry any of these hypersensitive sites, indicating a large degree of chromatin remodeling at this locus accompanying terminal granulocytic differentiation. Sixteen of the 17 DHS identified in U-937 cells are also present in the HL-60 myelomonocytic cell line. Hematopoietic cell lines representing the early erythroid and lymphocyte lineages, and a nonhematopoietic cell line display a subset of the hypersensitive sites. The altered chromatin structure specific to cells that actively transcribe the AZU1-PRTN3-ELA2 genes suggests that chromatin reorganization is an important mechanism regulating the myeloid-specific transcription of this gene cluster.

Chromatin↗
PubMed1999

Distal upstream tyrosinase S/MAR-containing sequence has regulatory properties specific to subsets of melanocytes.

A distal upstream regulatory element of the mouse tyrosinase gene has locus control region (LCR)-like activity and is required for position-independent expression of linked genes. It consists of a DNAse I hypersensitive site, which has enhancer activity in neural crest-derived melanocytes, embedded within a scaffold/matrix attachment region (S/MAR), both of which are necessary for LCR activity. To address the role of the S/MAR in position-independent expression, we assessed the ability of a fragment containing most of the S/MAR to insulate a transgene from position effects. The S/MAR sequence showed a striking cell type specificity in its function in all six multicopy transgenic lines, dampening position effects considerably in cutaneous melanocytes while allowing no expression in other neural crest-derived melanocytes, and causing elevated expression in ocular melanocytes derived from the neural tube. The specificity of transgene expression in the eye suggested the presence of both positive and negative regulatory elements in this enhancer/S/MAR region, which was confirmed by transient transfection analyses. This is the first known regulatory element to exhibit different activities in melanocytes of different developmental origins.

Animals↗
PubMed1997

A microcomputer-based activity meter for multiple animals.

We describe and validate a computer-video system that records and displays in real-time the activity of multiple specimens in a user-defined space, at user-defined intervals. The computer program uses image subtraction algorithms to record changes in video images, and stores observations in column format or as a series of 2-D matrices. The program was tested under various lighting conditions, backgrounds, specimen size and specimen speed. An AV model of Macintosh computer with video input from a camera or video cassette recorder was used to record and analyze the mechanical movement of spots on a turntable and the locomotor activity of an ant colony. The limitations and potential applications of the program are discussed.

Animals↗
PubMed1995

Prolactin (PRL)-dependent expression of a zinc finger protein-encoding gene, Gfi-1, in Nb2 lymphoma cells: constitutive expression in autonomous sublines.

The proliferation of cultured rat Nb2 lymphoma cells is dependent on prolactin (PRL) acting as the principal growth factor. Previously, PRL-independent Nb2 sublines were obtained by PRL starvation of the parent line and cloning of surviving cells. Development of PRL independence was in some cases found to be associated with a reciprocal translocation involving chromosome 14 at breakpoint 14p22. In the present study, a novel, 14p22 zinc finger protein-encoding gene, Gfi-1, has been examined for a role in Nb2 cell proliferation. PRL-dependent Nb2 cells expressed the gene during active growth; in comparison, in stationary, early G1-arrested cells obtained by an 18 hr lactogen starvation, Gfi-1 gene expression was markedly decreased. Addition of PRL to such stationary cells led to induction of Gfi-1 gene expression within a few hr with a maximum in late G1. Actively growing cells from 5 different PRL-independent Nb2 sublines, cultured in chemically defined, mitogen-free medium, expressed the gene constitutively. In two sublines, carrying the 14p22 rearrangement, the gene was markedly overexpressed. The results suggest the Gfi-1 gene product has a regulatory role in Nb2 cell mitogenesis and that unscheduled activation could contribute to loss of PRL dependency.

Animals↗
PubMed1994

Three spontaneous mutations at the albino locus in SELH/Bc mice.

The SELH/Bc inbred mouse stock has produced an unusually high number of spontaneous mutations, including sph2Bc, nuBc, a recessive lens opacity, and three mutations at the c locus. Classical genetic and molecular genetic studies were done to investigate the origin of the albino locus mutations. Southern blots probed with the mouse tyrosinase cDNA showed that two of the mutations, cBc and c2Bc, are deletions of exons 1, 2 and 3. The third mutation, c3Bc, showed a disruption, either a rearrangement or an insertion, in the region of exon 1. The deletion of the cBc mutation is anticipated to be large as the mutation has inactivated the Mod-2 locus 2 cM away, and an essential locus for post-implantation survival outside the c-Mod-2 interval, whereas the c2Bc mutation is viable and fertile in homozygotes. Homozygotes for c3Bc are also viable and fertile. We conclude that at least some of the molecular events leading to the three albino mutations were independent. The mutations differ from each other and from the classical albino point mutation. All three new mutations originated from parents who were germline mosaics, and the mutational events were therefore all postmeiotic. All three mosaics shared one common ancestor six generations previously, raising the possibility that an instability of the albino locus might have been inherited. SELH/Bc mice may provide an animal model for the study of mechanisms underlying genetic instability.

Albinism↗
PubMed1994

A distal tyrosinase upstream element stimulates gene expression in neural-crest-derived melanocytes of transgenic mice: position-independent and mosaic expression.

We have assessed the importance of a melanocyte-specific DNase I hypersensitive site and matrix attachment region situated 15 kb upstream of the mouse tyrosinase gene by analysis in transgenic mice. Transgenes containing all, part, or none of this region linked to the tyrosinase promoter and human tyrosinase cDNA were introduced into genetically albino mice, and pigmentation and transgene message levels were analyzed in the resulting transgenic lines. The effect of the upstream region was to enhance significantly gene expression in melanocytes, and to provide position-independent expression of the transgene. Two exceptions to complete position independence were seen; these lines displayed a mosaic expression pattern in which the transgene was expressed fully in some melanocyte clones but less so in others, resulting in transverse stripes of colours ranging from near white to dark grey. Unexpectedly, pigmentation in the eye of all transgenic lines containing the upstream region was nonuniform, in that the neural-crest-derived melanocytes of the choroid and anterior iris contained significantly more pigment than those derived from the optic cup (retinal pigment epithelium and posterior iris). Transgenes containing a small part or none of the upstream region were expressed poorly and in a position-dependent manner; of those lines that were visibly pigmented, expression was equal in the neural crest and optic-cup-derived cells of the eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Stability of polygyne and monogyne fire ant populations (Hymenoptera: Formicidae: Solenopsis invicta) in the United States.

Over the past decade, polygyne red imported fire ants (Solenopsis invicta Buren) have been found at more and more sites across the southeastern United States. The objective of my study was to determine if polygyne (multiple-queen) populations are expanding and at what rate this might be occurring. More than 200 sites were inspected for polygyny in Florida and several other southeastern states. These sites were reinspected 1-3 yr later. Results showed that polygyne populations were not expanding rapidly in the areas studied (i.e., > 4-6% per yr); however, more data will be needed to determine if polygyne populations are expanding slowly (i.e., 1-2% per yr). Overall, polygyne and monogyne sites were about 95% stable from year to year; in other words, they did not commonly switch back and forth from one form to the other. As expected, average mound densities in the Florida survey (62 sites) remained relatively constant from 1990 to 1992.

Analysis of Variance↗
PubMed1991

Distribution and density of polygyne fire ants (Hymenoptera: Formicidae) in Texas.

Multiple-queen or "polygyne" Solenopsis invicta Buren colonies are a serious economic and environmental concern because they occur in much higher densities than the monogyne form. Polygyne colonies have been found at numerous locations in the United States; nevertheless, the frequency and distribution of this form are poorly known. Almost 700 roadside sites in 168 Texas counties were surveyed. Polygyny was discovered at 54% of the infested sites. Polygyne populations were scattered in a mosaic across Texas. The frequency of polygyny varied somewhat with geographic region, but the pattern was generally unrelated to habitat and environmental conditions. Polygyne sites averaged more than twice as many mounds per hectare as monogyne sites. Populations of monogyne and polygyne forms were slightly lower in cooler and drier portions of the state. Mounds of both forms were about the same size. Polygyny was correlated with lower rates of sexual production and reduced numbers of native ants. The high frequency of polygyny in Texas indicates that the fire ant problem in the state is much greater than previously realized.

Analysis of Variance↗
PubMed1968

Seat belt injuries.

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Abdominal Injuries↗
PubMed1968

Biliary hypoplasia.

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Bile Ducts, Intrahepatic↗
PubMedDate not supplied

Homoeo-domain homology in yeast MAT alpha 2 is essential for repressor activity.

The MAT alpha locus of the yeast Saccharomyces cerevisiae encodes two regulatory proteins, alpha 1 and alpha 2, which are responsible for determining the alpha-cell type. MAT alpha 1 is a positive regulator of alpha-cell-type-specific genes, and MAT alpha 2 is a negative regulator of a-cell-type-specific genes. MAT alpha 2 also determines the a/alpha diploid cell type, in conjunction with the MATa product, a1, by repressing haploid cell-type-specific genes. The MAT alpha 2-encoded protein binds specifically in vitro to a DNA sequence found upstream of several a-specific genes and is thus thought to exert its control directly at the transcriptional level of target genes. In an initial attempt to understand the molecular basis of the interaction of alpha 2 with DNA, we have saturated with missense mutations the segment of alpha 2 that is weakly homologous to a conserved prokaryote DNA-binding structure and to a portion of the higher eukaryote homoeo domain to ascertain the possible functional significance of this homology in alpha 2. We report here that most of the amino-acid residues in alpha 2 which correspond to conserved amino acids in the prokaryote DNA-binding proteins and in the homoeo domain are essential for the two repressor activities of alpha 2, that is, the repression of a-specific genes and of haploid-specific genes. Mutations in a subset of these amino-acid residues more severely affect the ability to repress a-specific genes than haploid-specific genes.

Genes, Regulator↗