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M Gorry

Publications and source records attributed to M Gorry.

5 recordsLinked to original sources
PubMed1999

Fine mapping of the split-hand/split-foot locus (SHFM3) at 10q24: evidence for anticipation and segregation distortion.

Split-hand/split-foot malformation (SHFM, ectrodactyly, or lobster-claw deformity) is a human limb malformation characterized by aberrant development of central digital rays with absence of fingers and toes, a deep median cleft, and fusion of remaining digits. SHFM is clinically heterogeneous, presenting both in an isolated form and in combination with additional abnormalities affecting the tibia and/or other organ systems, including the genitourinary, craniofacial, and ectodermal structures. Three SHFM disease loci have been genetically mapped to chromosomes 7q21 (SHFM1), Xq26 (SHFM2), and 10q24 (SHFM3). We mapped data from a large Turkish family with isolated SHFM to chromosome 10q24 and have narrowed the SHFM3 region from 9 cM to an approximately 2-cM critical interval between genetic markers D10S1147 and D10S1240. In several instances we found evidence for a more severe phenotype in offspring of a mildly affected parent, suggesting anticipation. Finally, data from this family, combined with those from six other pedigrees, mapped to 10q24, demonstrate biased transmission of SHFM3 alleles from affected fathers to offspring. The degree of this segregation distortion is obvious in male offspring and is possibly of the same magnitude for female offspring.

Chromosome Mapping↗
PubMed1996

Structure and sequence of human FGF8.

Recent evidence indicates that Fgf8 is expressed during vertebrate development in multiple locations involved in the patterning and outgrowth of important embryo structures. Cloning and analysis of the murine gene revealed at least eight potential protein isoforms that share a common carboxyl region, encoded by exons 2 and 3, but possess different amino termini, generated by alternative splicing of RNA encoded by multiple 5' exons (exons 1A, 1B, 1C, and 1D). We now report the cloning and sequence of the human FGF8 gene. Human FGF-8 isoforms are identical to their murine counterparts in the common carboxyl region. Four of the human isoforms are identical to, or very similar to, the murine isoforms in the amino termini. However, four of the potential murine isoforms do not have corresponding human isoforms due to marked sequence divergence, leading to a blocked reading frame in exon 1B of FGF8. The lack of the four murine isoforms in humans raises the question of their function in murine development.

Amino Acid Sequence↗
PubMed1990

Effect of endotoxin-induced cell injury on 70-kD heat shock proteins in bovine lung endothelial cells.

Heat shock proteins (HSPs) have been remarkably conserved throughout evolution. It has been assumed that induction of HSPs remains a stereotypic response to injury, important for survival of eukaryotic cells during euthermic injury. However, there are few studies of this phenomenon in endothelial cells, and none in pulmonary endothelial cells. We studied the induction of synthesis of 70-kD proteins in bovine pulmonary artery endothelial cells (BPAECs) in response to heat shock and to euthermic injury induced by bacterial endotoxin. First, in response to heat, BPAECs showed rapid and reversible heat-induced synthesis of 70-kD proteins, readily detectable by one-dimensional SDS-PAGE of [35S]methionine-labeled BPAECs. Heat shock at 42 degrees C for 3 h or 43 degrees C for 2 h suppressed total protein synthesis by 30% (P less than 0.001) but an increased rate of synthesis of 70-kD protein continued, representing an increasing fraction of total protein synthesis. Heat-induced synthesis of 70-kD protein returned to baseline levels 8 h after heat shock. Northern analysis showed that mRNA for a protein homologous to a conserved amino acid sequence in the family of species-homologous 70-kD heat shock proteins (HSP 70) was induced by a 15-min incubation at 42 degrees C and remained detectably increased for 6 h. We next assessed whether euthermic injury by bacterial endotoxin (LPS) generated a similar response. LPS was cytotoxic by BPAECs as assessed morphologically, by release of 51Cr from prelabeled cells, and by a significant suppression of total protein synthesis (range, 35 to 70%; P less than 0.001). Despite cytotoxicity, LPS did not induce 70-kD protein at a level that could be detected by SDS-PAGE, and no increase in mRNA for HSP 70 was detected by Northern analysis. LPS-injured BPAECs remained "competent" to induce both 70-kD proteins and mRNA for HSP 70 in response to heat shock. We conclude that at least quantitatively, induction of HSP 70 by BPAECs is not a stereotypic response to injury but rather is at least relatively injury-specific. However, competence to induce HSP 70 appears to be extremely resilient: it is retained in dysfunctional BPAECs in the face of profound inhibition of global protein synthesis, suggesting an important homeostatic role.

Animals↗
PubMed1990

Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase.

Hydroxyl radical scavengers and xanthine oxidase inhibitors protect cultured bovine pulmonary endothelial cells (BPAEC) from lytic injury by the endotoxin lipopolysaccharide (LPS). We hypothesized that exposure of BPAEC to cytotoxic concentrations of LPS activated intracellular xanthine oxidase, and that intracellular iron-dependent hydroxyl radical formation (a Fenton reaction) ensued, resulting in cell lysis. To test this, the protective effects of deferoxamine against H2O2 and LPS-induced cytotoxicity to BPAEC was assessed by 51Cr release. Preincubation with 0.4 mM deferoxamine conferred 67 +/- 15% (mean +/- SE) protection from LPS-induced cytotoxicity but 48 h of preincubation were required to induce significant protection. Significant protection form a classical Fenton reaction model, injury by 50 microM H2O2, could be induced by a 1-h preincubation with a 0.4 mM deferoxamine. The dissociated time course suggested that deferoxamine might work by different mechanisms in these models. The effects of LPS and deferoxamine on BPAEC-associated xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity were assessed using a spectrofluorophotometric measurement of the conversion of pterin to isoxanthopterin. BPAEC had 106 +/- 7 microU/mg XD+XO activity; XO activity constituted 48 +/- 1% of total XO+XD activity. LPS at a cytotoxic concentration did not alter XO, XD, or percent XO. Deferoxamine had striking proportional inhibitory effects on XO and XD in intact cells. XO+XD activity fell to 6 +/- 1% of control levels during a 48-h exposure of BPAEC to deferoxamine. Deferoxamine did not inhibit XO+XD ex vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗