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P Board

Publications and source records attributed to P Board.

29 records · Page 2Linked to original sources
PubMed1995

Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset.

The M1 member of the Mu subclass of glutathione S-transferase (GSTM1) is only expressed in about 50% of individuals. In contrast, GSTT1, a member of the theta class which has been recently shown to be polymorphic, is expressed in 85% of Australian individuals. Previous studies have shown a significant excess of homozygous null GSTM1 genotypes among individuals with colorectal cancer, particularly those with proximal tumours. This suggests that GSTM1 plays a role in susceptibility to this neoplasm. In this study of 132 individuals with colorectal cancer and 200 controls, no significant excess of GSTM1 homozygous null genotypes was found among colorectal cancer patients with either a proximal or distal tumour. This suggests that the association between GSTM1 homozygous null genotypes and colorectal cancer is of smaller effect than has been reported previously using larger sample sizes. We have also examined the frequency of homozygous null GSTT1 genotypes in patients with colorectal cancer. Although the frequency was not significantly different in cases compared to control individuals, GSTT1 null homozygotes were significantly more common in patients who were diagnosed before the age of 70 years than in those who were diagnosed at an older age. This suggests that the GSTT1 genotype, and perhaps also the GSTM1 genotype for which a similar, but non-significant effect was seen, might influence the age of onset of colorectal cancer.

Adenocarcinoma↗
PubMed1994

Glutathione S-conjugate transport by cultured human cells.

Elimination of the products of xenobiotic metabolism is an important step in cellular detoxification and involves a specific transport system or "export pump". ATP-dependent transport of glutathione S-conjugates has previously been demonstrated in a variety of tissues, mainly from rat. However, the characteristics of this pump have not been fully explored in human cells. This study investigated transport of a glutathione S-conjugate, 2,4-dinitrophenyl glutathione (GS-DNP), by a variety of cultured human cell lines. GS-DNP was generated intracellularly after treatment of cells with 1-chloro-2,4-dinitrobenzene and subsequent transport of the conjugate into the extracellular medium was measured spectrophotometrically at 340 nm. Calculation of the initial transport rates at 37 degrees C revealed considerable variation in GS-DNP secretion between cell lines which was statistically significant in some cases. A 2-fold increase in GS-DNP efflux was observed between Jurkat and HL-60 cells (11.360 +/- 3.893 vs. 5.662 +/- 2.263 nmol/10(6) cells/h, P < 0.007). The highest rate of transport was found in HepG2 cells (14.171 +/- 4.790 nmol/10(6) cells/h) whereas the 5637 cell line had the lowest level with a transport rate of 1.475 +/- 0.631 nmol/10(6) cells/h. For each cell line, transport of GS-DNP was almost totally inhibited or markedly reduced on ice. Pre-incubation of cells at 42 degrees C also lowered the initial transport rates compared with cells maintained at 37 degrees C but these were not significantly different except in the case of HeLa cells. ATP levels ranged from 30.5 to 89.3 nmol/mg protein and there was variation in the glutathione content and glutathione S-transferase activities of the cells. This report demonstrates firstly that transport of glutathione conjugates is a feature of many cell types in vitro and secondly that the basal levels of GS-DNP secretion vary significantly between human cells.

Adenosine Triphosphate↗
PubMed1994

Purification, molecular cloning and heterologous expression of a glutathione S-transferase from the Australian sheep blowfly (Lucilia cuprina).

Three glutathione S-transferases from Lucilia cuprina (Australian sheep blowfly) pupae were purified by affinity chromatography and anion-exchange chromatography. One isoenzyme was composed of M(r)-24,800 subunits, and two isoenzymes had subunits of M(r) 23,900. The M(r)-23,900 subunits showed immunological identity and were immunologically distinct from the M(r)-24,800 subunits. All three enzymes were active with the substrate 1-chloro-2,4-dinitrobenzene and had low activity with 1,2-dichloro-4-nitrobenzene. A cDNA clone encoding a M(r)-23,900 subunit (LuGST1) was isolated and sequenced. The sequence has close similarities (> 81%) to that of GSTs from the fruitfly Drosophila melanogaster and Musca domestica (housefly). The deduced amino acid sequence of the Lu GST1 subunit showed no significant similarity to that of the mammalian GSTs to the Alpha, Mu and Pi classes, but shows some similarity (33%) over the first 100 residues with the rat subunit 12 Theta-class GST. Southern blots of genomic DNA hybridized with the LuGST1 cDNA identified many hybridizing fragments. Taken together, these data indicated that the L. cuprina genome contains multiple glutathione S-transferase genes.

Amino Acid Sequence↗
PubMed1993

Evidence against a relationship between fatty acid ethyl ester synthase and the Pi class glutathione S-transferase in humans.

Recently, Bora et al. (Bora, P. S., Bora, N. S., Wu, X., and Lange, L. G. (1991) J. Biol. Chem. 266, 16774-16777) reported the cloning and expression of a human fatty acid ethyl ester synthase III (FAEES-III) cDNA that has only four amino acid substitutions compared with human glutathione S-transferase (GST) GSTP1-1, and, when expressed in MCF-7 cells, the protein has both FAEES and GST activities. By site-directed mutagenesis of a GSTP1 cDNA, we have constructed a clone that encodes the FAEES-III protein described by Bora et al. (1991). The recombinant FAEES-III protein was expressed in Escherichia coli and has been shown to be devoid of FAEES and GST activities. The recombinant FAEES-III protein does not bind to a glutathione agarose affinity matrix, presumably because two of the substituted amino acids, Trp-39-->Cys and Gln-52-->Glu, are thought to contribute to the GST glutathione binding site. One of the base substitutions in the FAEES-III cDNA encodes an extra SacI site not found in the GSTPI cDNA. Polymerase chain reaction amplification of human genomic DNA has identified the GSTPI gene, but no DNA from the proposed FAEES gene with a diagnostic SacI site has been detected. Evaluation of the hybridization pattern of HindIII genomic restriction fragments has identified fragments that contain the GSTPI gene and a pseudogene (Board et al. 1992), and there do not appear to be any hybridizing fragments that could contain the FAEES-III gene. Our results do not provide any evidence in support of a relationship between FAEES-III and GST, and the cDNA reported by Bora et al. (1991) may have resulted from a cloning artifact.

Acyltransferases↗
PubMed1992

Identification of a point mutation in factor XIII A subunit deficiency.

Oligonucleotide primers have been designed for the amplification of all 15 exons of the human coagulation factor XIII A subunit gene. Each exon and its intron flanking regions has been amplified and sequenced from a patient with severe A subunit deficiency. A single G to A transition in the last base of exon 14 has been identified in the homozygous proband and in his heterozygous parents. The mutation would result in the substitution 681 Arg to His in the mature protein product. However, because the mutation is at a splice junction, the deficiency may result from a defect in pre-messenger RNA splicing.

Adolescent↗
PubMed1992

Erythrocyte membrane transport of glutathione conjugates and oxidized glutathione in the Dubin-Johnson syndrome and in rats with hereditary hyperbilirubinemia.

The Dubin-Johnson syndrome is manifested by conjugated hyperbilirubinemia and pigment accumulation in hepatocellular lysosomes. The TR-rat model is a phenotypic model of the Dubin-Johnson syndrome and is characterized by defective ATP-dependent transport of a group of nonbile acid organic anions, including glutathione-S-conjugates and oxidized glutathione, across the bile canaliculus. Similar ATP-dependent transport mechanisms have been described in erythrocytes. Intact erythrocytes and inverted erythrocyte membrane vesicles from Dubin-Johnson patients, TR-rats and appropriate controls were studied with regard to ATP-dependent transport of dinitrophenyl glutathione and oxidized glutathione. No significant differences were observed, indicating that the erythrocyte and canalicular ATP-dependent transporters for these substrates are functionally and potentially genetically distinct.

Adenosine Triphosphate↗
PubMed1990

Genetic heterogeneity of the human glutathione transferases: a complex of gene families.

The glutathione transferases (GSTs) are involved in the metabolism of a wide range of compounds of both exogenous and endogenous origin. There is evidence that deficiency of GST may increase sensitivity to certain environmentally derived carcinogens. In contrast, elevated expression has been implicated in resistance to therapeutic drugs. The GSTs are the products of several gene families. This review summarizes the present knowledge of the genetic interrelationships between the various isoenzymes, their deficiencies and the physical locations of their genes.

Animals↗
PubMed1989

HLA A1, B8, DR3 extended haplotypes in autoimmune chronic hepatitis.

Genetic determinants of the autoimmune type of chronic active hepatitis include the major histocompatibility complex alleles HLA-B8 and HLA-DR3, which are usually present as the haplotype A1, B8, DR3. In certain other autoimmune diseases, an extended haplotype including complement alleles confers a greater relative risk than does B8, DR3. Hence, extended haplotypes were ascertained in autoimmune chronic active hepatitis by typing for HLA, complement alleles C4A, C4B, and Bf, and glyoxalase type 1 or 2. Eight of the 10 B8, DR3 haplotypes were A1, B8, DR3. Of the 8, 7 had the extended haplotype A1, B8, C4AQ0, C4B1, BfS, DR3, but this haplotype occurred in four instances with glyoxalase 2 and in three with glyoxalase 1. Thus, we find that in autoimmune chronic active hepatitis there is a high frequency of null alleles for complement but an extended haplotype does not cause any greater risk for disease than B8, DR3 alone.

Alleles↗
PubMed1978

A new storage medium for canine blood.

A solution consisting of ascorbate phosphate, citric acid, sodium citrate, sodium phosphate, and dextrose was developed to extend the shelf life of canine blood stored for transfusion. The 24-hour poststorage viability remained above 70% for 6 weeks of storage at 4 C. The concentration of 2,3 diphosphoglycerate remained constant for 3 weeks, then declined slowly. After 6 weeks of storage, the 2,3 diphosphoglycerate content was still sufficiently high to allow adequate dissociation of oxygen from oxyhemoglobin in vivo. It was concluded that blood stored up to 6 weeks in this solution would be safe to use for transfusion.

Animals↗
PubMedDate not supplied

College women's awareness and consumption of folic acid for the prevention of neural tube defects.

PURPOSE: Awareness and consumption of folic acid in the context of neural tube defect prevention among college women were assessed. METHODS: Subjects documented folic acid awareness and multivitamin consumption. Beliefs about folic acid before and after an educational intervention were characterized using the Health Belief Model (HBM) and the Fetal Health Locus of Control Scale (FHLCS). RESULTS: Awareness of folic acid was not associated with multivitamin consumption. Belief variables were not associated with awareness or consumption of folic acid. CONCLUSION: This study does not support educational interventions based on the HBM or FHLCS to increase multivitamin consumption among college women.

Adolescent↗