An evaluation of glutathione S-transferase activity in the Tasmanian lacewing (Micromus tasmaniae) as a biomarker of organophosphate contamination.
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Animals↗
Biomedical subjects
M Longley
Publications and source records attributed to M Longley.
Isolation and mapping of the first ruminant multidrug resistance genes.
The first ruminant multiple drug resistance gene (MDR1) has been cloned and sequenced from sheep. Sequence data revealed the sheep MDR1 gene to have high sequence and structural similarity to other characterized MDR proteins from humans and rodents. A restriction fragment length polymorphism was discovered using the EcoRI enzyme and used to map the MDR1 gene to sheep chromosome 4. Physical mapping using fluorescent in situ hybridisation confirmed this map placement and assigned the MDR1 locus in the region 4q15-q21. The ovine MDR2 gene was also cloned and found to map to the same region as MDR1.
ATP Binding Cassette Transporter, Subfamily B↗
Characterization of pBP614, a putative rolling-circle plasmid from Bacillus popilliae.
A plasmid, pBP614 (5.647 kb), has been isolated from the New Zealand Bacillus popilliae strain 17 and characterized by physical mapping, cloning, and sequencing. An open reading frame was found which could encode a protein with homology to the replication (Rep) proteins of rolling-circle plasmids. The predicted B. popilliae Rep protein shows closest homology to Rep proteins from Bacillus plasmids of the pC194 family. Sequences homologous to plus- and minus-strand replication origins were found. The minus-strand origin shows similarities to the pal-T type family. Taken together, these observations suggest that pBP614 is a rolling-circle plasmid, the first such plasmid characterized from B. popilliae.
Amino Acid Sequence↗
Diverse hypermutability of multiple expressed sequence motifs present in a cancer with microsatellite instability.
Colon cancer and an increasing number of other cancers have been found to exhibit instability of DNA microsatellite sequences. Such tumors have been designated as replication errors (RER) tumors. However, as microsatellites are only rarely found within coding regions of the genome, instability of these sequences cannot directly contribute to carcinogenesis. Recently, we have shown RER colon cancers also demonstrate a marked 100-fold increase in mutation rates measured within an expressed gene, hprt, suggesting the mutator phenotype in these tumors extends beyond microsatellite sequences. To determine whether the RER phenotype indeed destabilizes non-repetitive DNA sequences we have sequenced hprt gene mutations recovered from the RER colon cancer cell line RKO. Greater than 10% of hprt mutants proved to be a single 3 bp deletion located in a nonrepetitive ATTAT sequence motif. Additionally, 1-4 bp deletions or insertions were found to be randomly located throughout the hprt gene. Lastly, one third of hprt mutations proved to be transitions or transversions. The microsatellite instability demonstrated in RKO is thus a global mutator phenotype which destabilizes DNA sequences both inside and outside of repetitive sequence elements and which augments base substitutions as well as frameshifts. These findings extend the characteristics of mutations associated with RER tumors and suggest additional mechanisms by which mutator phenotypes may alter oncogenes and tumor suppressor genes.
Base Sequence↗
Analytical techniques for quantifying direct, residual, and oral exposure of an insect parasitoid to an organophosphate insecticide.
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Administration, Oral↗
Mismatch repair deficiency in phenotypically normal human cells.
Tumor cells in patients with hereditary nonpolyposis colorectal cancer (HNPCC) are characterized by a genetic hypermutability caused by defects in DNA mismatch repair. A subset of HNPCC patients was found to have widespread mutations not only in their tumors, but also in their non-neoplastic cells. Although these patients had numerous mutations in all tissues examined, they had very few tumors. The hypermutability was associated with a profound defect in mismatch repair at the biochemical level. These results have implications for the relation between mutagenesis and carcinogenesis, and they suggest that mismatch repair deficiency is compatible with normal human development.
Base Sequence↗
Ambulance services. Casualty of the 1990s.
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Ambulances↗
Serum insulin-like growth factor binding protein-1 in pregnant women: decreased concentrations following an oral glucose load.
Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in men and in non-pregnant and pregnant women. Peak serum IGFBP-1 levels occurred mid-gestation followed by a slight decline towards term. Women with gestational diabetes had higher serum IGFBP-1 concentrations than apparently healthy women at comparable gestation. Following administration of an oral glucose load, serum IGFBP-1 concentrations were decreased within 2 h in men and in pregnant women while IGF-I levels remained constant. These results suggested that IGFBP-1 regulates IGF-I activity in pregnancy in a similar manner to that in the non-pregnant state.
Administration, Oral↗
Mismatch repair and genetic stability in human cells.
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Alkylation↗
Nucleotide sequence of the human placental alkaline phosphatase gene. Evolution of the 5' flanking region by deletion/substitution.
Three closely related alkaline phosphatase (ALP) genes reside on the long arm of chromosome 2 in man. One of these genes (the placental ALP-1) encodes the classic heat-stable placental alkaline phosphatase. Another gene (the placental ALP-2) is closely related to the placental ALP-1 and may encode the so-called placental ALP-like enzyme of the testis and thymus. The third member of this gene family (the intestinal ALP gene) encodes the intestinal alkaline phosphatase. The expression of the placental ALP-1 and intestinal ALP genes is highly tissue-specific in spite of nearly 90% sequence similarity within their exons. To help determine the basis for this tissue specificity, the nucleotide sequence of the placental ALP-1 gene and some of its 5' flanking region has been determined and analyzed by comparison with placental ALP-2 and intestinal ALP gene sequences. The placental ALP-1 gene transcription unit has 4087 bases between the major cap site and the most distal of several reported 3' ends. The protein coding region is divided by 10 short introns varying in size from 74 to 241 nucleotides. Three of these introns bisect regions of the gene that encode residues conserved between the active site of the Escherichia coli enzyme and the human placental ALP. This result suggests that the human alkaline phosphatase genes have evolved in an intron-independent fashion. A comparison of the placental ALP-1 5' flanking sequence (up to -540) with the analogous sequence of the intestinal ALP gene revealed several deletion/substitutions which could be important in determining the tissue-specific expression of these genes.
Alkaline Phosphatase↗
Two gene duplication events in the evolution of the human heat-stable alkaline phosphatases.
There are at least three alkaline phosphatase (AP) isoenzymes in man: a heat-stable placental enzyme (PLAP), a less heat-stable intestinal form (IAP), and the very heat-labile AP enriched in liver, bone and kidney. In addition to these enzymes, there is a heat-stable activity in the thymus and testis that is similar but not identical to the PLAP (the PLAP-like enzyme). Previous work has demonstrated a close structural relatedness among the IAP, PLAP and PLAP-like enzymes. Thus, it is possible that there are three human genes encoding heat-stable AP enzymes. To test this hypothesis, we have used a PLAP cDNA clone to screen a human genomic library cloned into the phage vector lambda EMBL-3. Three sets of clones were isolated, each bearing a distinct coding region homologous to the PLAP cDNA probe. Nucleotide sequence analysis of the 5' ends of these genes allowed comparison of their derived peptide sequences and positive identification of two of the genes. One of the genes encodes the PLAP (the PLAP-1 gene), another encodes the IAP, and a third closely resembles the PLAP-1 gene, but is distinct from it (the PLAP-2 gene). The PLAP-2 gene is highly homologous (greater than 95%) with the PLAP-1 except in the first exon, where sequences encoding the hydrophobic signal peptide are nearly identical with the same region of the IAP gene. These results demonstrate the existence of a small family of PLAP-related genes which is the result of at least two duplication events during the descent of man.
Alkaline Phosphatase↗
Cloning of a cDNA encoding the rat placental glutathione S-transferase: overproduction of the mRNA in hepatocellular carcinomas.
Rat hepatocellular carcinomas and normal liver have been screened for mRNA sequences which are more abundant in the carcinomas than in livers. The screen was done by differential colony hybridization of a cDNA library constructed from the mRNA of a primary tumor induced by diethylnitrosamine (DEN). One cDNA was isolated which hybridizes to a 900 nucleotide mRNA present in abundance in six chemically induced rat hepatomas (both primary and transplantable), but is not detectable in normal adult or fetal (17 day) liver. The nucleotide sequence of this cDNA is identical to that reported by Suguoka et al. for the placental isoenzyme of rat glutathione S-transferase (GST-P) (Nucleic Acids Res. 13:6049). A comparison of the GST-P amino acid sequence with those of two liver GST isoenzymes (Yal and Yc) shows only 26% overall homology; however, this homology is concentrated in three regions of 50%, 68.2% and 34.5%. Genomic blotting experiments show that the overproduction of GST-P mRNA in three Morris hepatomas is not due to amplification of genomic DNA sequences hybridizing with the GST-P cDNA. However, hybridizing sequences are contained on at least 72 kb of genomic DNA, suggesting great complexity of the rat GST-P locus.
Amino Acid Sequence↗
A developmental model for free vascularized bone transfers in the dog.
An autogenous free vascular bone transfer using a segment of ulna along with its periosteum and vascular pedicle was developed. The vascular pedicle, based on the common interosseous artery and vein, emerged where muscular branches from the cranial interosseous artery enter the extensor carpi ulnaris and lateral digital extensor muscles. Four autogenous heterotopic (ulna to tibia) vascular transfers by microvascular anastomosis and two avascular transfers were performed to compare the osteogenic potential and viability of free revascularized grafts with avascular bone grafts. Successful microvascular anastomosis was demonstrated in three of the four vascular transfers by early bone scanning using technetium-labeled polyphosphate. Radiographically, there was more periosteal new bone and callus formation in the successfully revascularized bone transfers than in the failed vascular transfer and the avascular controls. Histologically, viable bone with an intact medullary and periosteal vascular supply was recognized in the grafts successfully revascularized by microvascular anastomosis.
Animals↗