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Biomedical subjects

M R Jackson

Publications and source records attributed to M R Jackson.

At least 127 records · Page 7Linked to original sources
PubMed1988

Induction of microsomal epoxide hydrolase by nitrosamines in rat liver. Effect on messenger ribonucleic acids.

Nitrosomethylethylamine and nitrosomethylpropylamine were found to be more potent inducers of rat liver microsomal epoxide hydrolase (styrene oxide hydrolase) than nitrosodiethylamine or nitrosodimethylamine. The time course of induction following a single administration of nitrosodimethylethylamine, nitrosomethylpropylamine or nitrosodiethylamine each showed a delay of 24 hr during which enzyme activity was unaltered. After that time activity increased and reached a maximum at between 72 and 120 hr. Increased enzyme activity following NDEA was paralleled by changes in the content of epoxide hydrolase in microsomes as measured by Western blots. Nitrosamines caused an increase of mRNA for epoxide hydrolase which was detected by probing Northern blots with a [32]-P labelled epoxide hydrolase cDNA and by in vitro translation of polyadenylated mRNA. Both methods showed a maximal increase at 72 hr after nitrosodiethylamine treatment but a significant increase was also observed at 24 hr although at this time no increase in enzyme activity was apparent.

Animals↗
PubMed1988

Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells.

A rat kidney phenol UDP-glucuronosyltransferase cDNA was used to isolate a human liver phenol UDP-glucuronosyltransferase cDNA by screening of a human liver cDNA library in the expression vector lambda gt11. The 2.4-kilobase cDNA contained an open reading frame of 1593 base pairs coding for a protein of 531 residues. The human liver cDNA was subcloned into the vector pKCRH2. Transfection of this recombinant plasmid into COS-7 cells allowed the expression of a protein of approximately 55 kDa. The enzyme synthesized was a glycoprotein, as indicated by a reduction in molecular mass of approximately 3 kDa after biosynthesis in the presence of tunicamycin. The expressed enzyme rapidly catalyzed the glucuronidation of 1-naphthol, 4-methylumbelliferone, and 4-nitrophenol. The use of a related series of simple phenols provided an outline description of the substituent restrictions imposed upon the phenolic structures accepted as substrates. The glucuronidation of testosterone, androsterone, and estrone was not catalyzed by this cloned UDP-glucuronosyltransferase.

Amino Acid Sequence↗
PubMed1988

Examination of the substrate specificity of cloned rat kidney phenol UDP-glucuronyltransferase expressed in COS-7 cells.

A cDNA encoding a rat kidney UDP-glucuronyltransferase (UDPGT) was subcloned into the vector pKCRH2. Expression driven by the SV40 promoter produced enzymatically active UDPGT in COS-7 cells cultured in vitro. The appearance of enzyme activity was associated with an immunodetectable glycosylated UDPGT protein (Mr 53 kDa) in the cells. The expressed enzyme rapidly catalyzed the glucuronidation of 1-naphthol, 4-methylumbelliferone, and 4-nitrophenol. Studies using more than 20 compounds showed that the cloned UDPGT exhibited a restricted specificity towards planar phenols. A crude description of the molecular conformation of 4-alkylphenols accepted within the active site of the protein was obtained. The glucuronidation of morphine, thymol, menthol, testosterone, androsterone, or estrone was not catalyzed by this enzyme.

Animals↗
PubMed1987

The molecular basis of the inherited deficiency of androsterone UDP-glucuronyltransferase in Wistar rats.

A major UDP-glucuronyltransferase isoenzyme in rat liver (51 kDa), corresponding to androsterone glucuronidating activity, has been identified by immunoblot analysis. This isoenzyme is absent from Wistar rats exhibiting the low androsterone (LA) UDP-glucuronyltransferase activity exhibiting the low androsterone (LA) UDP-glucuronyltransferase activity phenotype. Northern blot analysis of total RNA from normal and androsterone glucuronidation deficient Wistar rats demonstrated that the mRNA encoding this protein was not synthesised. Differences in restriction fragment length observed on Southern blotting of genomic DNA from LA Wistar rats indicate that this inherited deficiency is the result of a deletion in the androsterone UDP-glucuronyltransferase gene.

Androsterone↗
PubMed1987

Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA.

A cDNA clone (HLUG 25) encoding the complete sequence of a human liver UDP-glucuronosyltransferase was isolated from a lambda gt11 human liver cDNA library. The library was screened by hybridization to a partial-length human UDP-glucuronosyltransferase cDNA (pHUDPGT1) identified from a human liver pEX cDNA expression library by using anti-UDP-glucuronosyltransferase antibodies. The authenticity of the cDNA clone was confirmed by hybrid-select translation and extensive sequence homology to rat liver UDP-glucuronosyltransferase cDNAs. The sequence of HLUG 25 cDNA was determined to be 2104 base-pairs long, including a poly(A) tail, and contains a long open reading frame. The possible site of translation initiation of this sequence is discussed with reference to a rat UDP-glucuronosyltransferase cDNA clone (RLUG 38).

Animals↗
PubMed1987

The volumetric composition of human term placentae: altitudinal, ethnic and sex differences in Bolivia.

Point counting volumetry has been used to decide whether or not altitudinal, ethnic and sex differences in birth weight in Bolivia are accompanied by changes in placental composition. Sixty eight placentae from healthy, term pregnancies were sampled from populations of Amerindian and non-Indian women living in Santa Cruz (400 m) and La Paz (3600 m). Altitudinal reductions in birth weight were not accompanied by significant alterations in placental weight yet highland placentae were substantially different in histological composition. On average, the highland placenta had a more voluminous intervillous space but reduced volumes of villi, juxtavillous fibrin and non-parenchyma. Whilst Amerindian newborn were heavier, placental weights were similar in both ethnic groups. However, the Amerindian placenta tended to possess more trophoblast and more villous stroma than its non-Indian counterpart. No sex differences were detected save for an interaction effect on fibrin which involved altitude, ethnic group and sex. Findings are discussed in the context of known morphometric and physiological differences between placentae in different experimental groups, notably in other types of pregnancy associated with reduced fetal growth.

Altitude↗
PubMed1986

Induction of UDP-glucuronyl transferase mRNA in embryonic chick livers by phenobarbital.

Administration of phenobarbital to chick embryos increased hepatic microsomal UDP-glucuroyltransferase activity some 25-fold. The large phenobarbital-induced increase of UDP-glucuronyltransferase activity was correlated to an equivalent increase of immunochemically measurable UDP-glucuronyltransferase protein. Poly(A+) RNA isolated from the livers of chick embryos treated with either phenobarbital or saline was translated in vitro. Immunochemical analysis of the translation products indicated that phenobarbital induced a 30-fold increase in UDP-GT mRNA. Fractionation of hepatic poly(A+) RNA from phenobarbital-treated chick embryos by sucrose density gradient centrifugation indicated that the size of the UDP-GT mRNA was 21S. These data show that phenobarbital induction of chick embryo liver UDP-glucuronyltransferase activity correlates with a similar large increase in the level of translatable mRNA for this enzyme.

Animals↗
PubMed1986

Studies of the ferroxidase activity of native and chemically modified xanthine oxidoreductase.

The O2-utilizing (type O, oxidase) form of xanthine oxidoreductase is primarily responsible for its ferroxidase activity. This form of xanthine oxidoreductase has 1000 times the ferroxidase activity of the serum ferroxidase caeruloplasmin. It has the ability to catalyse the oxidative incorporation of iron into transferrin at very low Fe2+ and O2 concentrations. Furthermore, the pH optimum of the ferroxidase activity of the enzyme is compatible with the conditions of pH that normally exist in the intestinal mucosa, where it has been proposed that xanthine oxidoreductase may facilitate the absorption of ionic iron. Modification of the molybdenum (Mb) centres of the enzyme in vitro by treatment with cyanide, methanol or allopurinol completely abolishes its ferroxidase activity. The feeding of dietary tungsten to rats, which prevents the incorporation of molybdenum into newly synthesized intestinal xanthine oxidoreductase, results in the progressive loss of the ferroxidase activity of intestinal-mucosa homogenates. Removal of the flavin centres from the enzyme also results in the complete loss of ferroxidase activity; however, the ferroxidase activity of the flavin-free form of the enzyme can be restored with artificial electron acceptors that interact with the molybdenum or non-haem iron centres. The presence of superoxide dismutase or catalase in the assay system results in little inhibition of the ferroxidase activity of xanthine oxidoreductase.

Animals↗
PubMed1986

The full length coding sequence of rat liver androsterone UDP-glucuronyltransferase cDNA and comparison with other members of this gene family.

Cloned cDNAs coding for hepatic UDP-glucuronyltransferase (UDPGT) have been isolated from a rat liver cDNA library in the expression vector bacteriophage lambda gt11 using anti-UDPGT antibodies. Four different mRNAs have been identified by sequencing of 15 UDPGT cDNA clones. The sequences of the four classes of cDNA were determined to be 85-95% homologous. Restriction fragments were isolated from the cDNA in each class and used as class specific probes. Hybridisation of these probes to northern blots of total RNA prepared from the livers of normal and genetically deficient Wistar rats identified the cDNA in class 4 with androsterone UDPGT. Translation of the cDNA sequence of clone rlug 23, the longest member of class 4, allowed determination of the complete amino acid sequence of androsterone UDPGT.

Amino Acid Sequence↗
PubMed1986

A model for the development and implementation of a quality assurance programme in a long term care facility.

This approach to quality assurance has been successful because of the commitment to the programme by the staff and the assignment of each component function to individuals on staff. Staff assigned are senior staff who hold other positions in the Centre. Because each component is interrelated, the co-ordinator of each function must work with all other co-ordinators. This has proven to be of value in further developing organisational cohesiveness. The overall time required to implement the programme depended on the individual facility and ranged from six months to three years. However, it must be noted that implementation is never completed since the system generates new ideas and innovative approaches to providing care. The components of quality assurance have been in practice for a long time in health care facilities. Each day that managers go to work they set standards for resident care and services. There have been unwritten expectations of staff performance against these standards. What has been required is a systematic and objective methodology to co-ordinate and document all evaluation efforts.

Canada↗
PubMed1985

Cloning of cDNAs coding for rat hepatic microsomal UDP-glucuronyltransferases.

Radioiodinated, affinity-purified, anti-UDP-glucuronyltransferase (UDPGT) antibodies have been used to isolate cDNAs coding for UDPGT(s) from a rat liver cDNA library cloned in the expression vector bacteriophage lambda gt11. The sizes of ten cloned cDNAs range from 0.3-2.1 kb. The identity of the cDNAs was confirmed by the hybrid-select translation and immunochemical analyses. Restriction mapping indicates that two classes of cDNA coding for different UDPGT mRNAs have been cloned.

Animals↗
PubMed1984

Reference intervals for some clinical chemical parameters in the marmoset (Callithrix jacchus): effect of age and sex.

Reference intervals for some clinical chemistry parameters in the marmoset were calculated. The effects of age (250-300 days compared with 500-550 days) and sex on the values found was investigated. Alkaline phosphatase levels decreased with age, young males having higher plasma levels than young females, but no sex differences were discernible for older animals. Levels of gamma-glutamyl transpeptidase and sorbitol dehydrogenase were higher in older males than in younger females. Higher plasma iron levels were found in the males with increasing age. Age and sex effects for protein and albumin were interactive and further interpretation was therefore difficult. No significant age or sex effects were seen for cholinesterase, acetylcholinesterase, isocitrate dehydrogenase, malate dehydrogenase, lactate dehydrogenase, glutamate dehydrogenase, aspartate amino transferase, alanine aminotransferase or bilirubin.

Age Factors↗
PubMed1984

Morphological assessment of testicular maturity in marmosets (Callithrix jacchus).

The onset of spermatogenesis in relation to age, bodyweight and testes weight in 105 marmosets used in safety studies has been reviewed. The histological recognition of adverse effects on spermatogenesis is an important part of these studies and this survey indicates that male marmosets should be at least 50 weeks and preferably 60 weeks of age if an assessment of all stages of spermatogenesis is required for safety evaluation.

Animals↗
PubMed1984

The effect of haemolysis on some clinical chemistry parameters in the marmoset (Callithrix jacchus).

The effect of haemolysis on the levels of commonly analysed plasma constituents was investigated in the common marmoset. Results were divided into a) low levels of extra haemolysis (less than 2 g/l plasma haemoglobin) and b) high levels of extra haemolysis (greater than 2 g/l plasma haemoglobin). Mean changes in plasma constituent levels were examined and the correlation with increased haemolysis measured. Large changes in malate dehydrogenase and lactate dehydrogenase were found at low levels of haemolysis. With higher levels of haemolysis there were statistically significant changes in the levels of alanine aminotransferase, isocitrate dehydrogenase, glutathione reductase, bilirubin, aspartate aminotransferase and sorbitol dehydrogenase. The significance of these findings is considered in relation to the interpretation of changes of plasma constituents as indicators of tissue/organ damage.

Animals↗