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Biomedical subjects

D J Henderson

Publications and source records attributed to D J Henderson.

16 recordsLinked to original sources
PubMed1992

Changes in expression of the cyclooxygenase gene in human fetal membranes and placenta with labor.

OBJECTIVE: Our objective was to examine the expression of the gene coding for cyclooxygenase, the central enzyme in prostaglandin synthesis, in human placenta and fetal membranes during pregnancy and before and after labor at term. STUDY DESIGN: Expression of the gene for cyclooxygenase was examined with Northern hybridization to ribonucleic acid from human placenta throughout pregnancy and human amnion and chorion decidua in the late third trimester. RESULTS: Expression was undetectable in trophoblast during the first and second trimesters. Expression in amnion and trophoblast increased 3.5- and 2.5-fold, respectively, in association with labor. CONCLUSIONS: Our results suggest that the increase in prostaglandin synthesis within the uterus that is seen with the onset of labor is associated with an increase in the expression of the gene cyclooxygenase.

Amnion↗
PubMed1992

Expression of human chorionic gonadotrophin alpha and beta subunits is depressed in trophoblast from pregnancies with early embryonic failure.

The expression of the placental proteins human chorionic gonadotrophin alpha (HCG alpha), beta (HCG beta) and human placental lactogen (HPL) was examined in trophoblast from human normal pregnancy and early embryonic failure (EEF) using Northern blot analysis. Trophoblast from EEF expressed significantly depressed levels of HCG alpha (P < 0.05) and HCG beta (P < 0.01) when compared to normal pregnancy. Levels of expression of HPL in EEF were not significantly different to those from normal pregnancy. The gestational ages of the two groups were not significantly different. Immunocytochemistry on paraffin-fixed tissue sections supported these data and showed that mRNA levels reflected protein production of HCG within the tissue. It appears from these data that the depressed level of HCG found in the serum of women with early pregnancy failure is not solely a consequence of diminished placentation in these pregnancies, or placental necrosis, but that the genes of the alpha and beta HCG subunits are down-regulated. This study further suggests that there are two subsets of women with early pregnancy failure; those with apparently normal levels of placental proteins, and those with severely depressed levels. It would seem likely that these two groups have different aetiologies.

Abortion, Spontaneous↗
PubMed1991

Trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome.

In a series of 14 anembryonic pregnancies, deoxyribonucleic acid from trophoblast was examined with locus-specific minisatellite probes. It was found in each case that trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome. This means that although anembryonic pregnancy shares characteristics with complete hydatidiform mole and androgenetic development in the mouse in that there is no embryo, it does not arise by the same genetic process. Of three anembryonic pregnancies that were successfully karyotyped, two had normal female 46,XX chromosome constitutions and one had an abnormal 47,XX + 16 complement. The sex of the trophoblast in each anembryonic pregnancy was determined with a deoxyribonucleic acid probe with Y-specific bands. A male-to-female ratio of 6:8 was found, which is not significantly different from normal.

Chromosome Mapping↗
PubMed1991

Comparison of the effects of FK-506, cyclosporin A and rapamycin on IL-2 production.

The immunosuppressive compounds FK-506, cyclosporin A (CsA) and rapamycin inhibit both the human and mouse mixed lymphocyte reactions (MLR) with IC50s of 2-5 x 10(-10) M for FK-506 and rapamycin and 10(-8) M for CsA. FK-506 and CsA were also potent inhibitors of A23187/PMA-stimulated IL-2 production by Jurkat and HuT-78 cells but had no effect on the response of mouse CTLL cells to IL-2. IC50 values for inhibition of IL-2 production closely matched those for inhibition of the MLR and both drugs were active only during the first 4-6 hr following stimulation. In contrast, rapamycin was a poor inhibitor of IL-2 production, although it inhibited cellular responses to IL-2. The IC50 values for these two activities indicated that neither alone accounted for rapamycin inhibition of the MLR. FK-506 and CsA affected IL-2 gene transcription in Jurkat cells by the same mechanism. Both inhibited the appearance of the transcription factor, NFAT, whereas rapamycin did not. The appearance of another transcription factor, NFK beta, was unaffected by all three drugs. The effects of FK-506 and CsA on IL-2 gene expression, therefore, are similar even though the two drugs act through distinct cytosolic receptors.

Anti-Bacterial Agents↗
PubMed1990

Transposition of IS117 (the Streptomyces coelicolor A 3 (2) mini-circle) to and from a cloned target site and into secondary chromosomal sites.

IS117, previously known as the 2.6 kb mini-circle, is a transposable element found in Streptomyces coelicolor A 3(2). It integrates predominantly into one preferred site when introduced into the closely related Streptomyces lividans 66, which lacks IS117. This preferred integration site was deleted from the S. lividans chromosome by replacement with an erythromycin resistance gene delivered by a phi C31 phage vector. When IS117 was introduced into the resulting strain it integrated into many other sites, with some indication of site preference. By cloning a 200 bp fragment centred on the preferred integration site onto a low copy number, self-transmissible Streptomyces plasmid derived from SCP2* it was shown that this sequence is sufficient to define the preferred site: IS117 integrates efficiently into this sequence from its preferred site in the host chromosome and at a lower frequency from the plasmid into the preferred site on the S. lividans chromosome.

Base Sequence↗
PubMed1990

Discovery of an insertion sequence, IS116, from Streptomyces clavuligerus and its relatedness to other transposable elements from actinomycetes.

We have identified an insertion sequence, IS116, present in Streptomyces clavuligerus at one copy per genome. The element was discovered as a 1.4 kb insertion into the multicopy plasmid pIJ702 after propagation in S. clavuligerus. The nucleotide sequence of IS116 and the flanking sequences from pIJ702 have been determined. The junctions with pIJ702 show no target site duplication and there are no inverted repeats at the ends of the element. One putative coding open reading frame of 1197 bp was identified which would code for a protein product of 399 amino acids. This protein resembles deduced integrase/transposase proteins specified by three other transposable elements of actinomycetes: IS110 and the mini-circle from Streptomyces coelicolor A3(2), and--most particularly--IS900 of Mycobacterium paratuberculosis. Two regions that are relatively conserved among these gene products show features found in similar positions in many reverse transcriptases. IS116 and IS900 are also closely similar in their general organization and (apparently) in their insertion site specificity, whereas IS110 and the mini-circle are quite different in these features.

Actinomycetales↗
PubMed1990

X chromosome genes involved in the regulation of facial clefting and spina bifida.

Congenital malformations such as cleft palate and spina bifida may be multifactorial in etiology. They occur as a result of both environmental agents and defective genes. Consequently it is both practically and intellectually difficult to study their effects experimentally. The advent of molecular biology technology has enabled many genes on the human chromosome to be mapped and some to be cloned. Using these techniques and families that display common congenital malformations inherited in a purely genetic manner, the genetic defects can be separated from the environmental components. This report documents our studies of several families that have cleft palate or spina bifida as X-linked disorders. Their phenotype is similar to the more common multifactorial cases but segregates as a single gene in an X-linked fashion. Localization of these genes using different X chromosome DNA probes and linkage analysis is the first step towards our understanding of the genetic contribution to the etiology of congenital malformations.

Anencephaly↗
PubMed1989

Structural and functional analysis of the mini-circle, a transposable element of Streptomyces coelicolor A3(2).

The mini-circle is a transposable element which is present in Streptomyces coelicolor A3(2) in both free circular and chromosomally integrated linear forms. The nucleotide sequences of the mini-circle and its preferred site of integration in the Streptomyces lividans TK64 chromosome were determined. Three putative open reading frames were identified in the mini-circle sequence. The mini-circle does not appear to cause a target site duplication on transposition and does not have perfect terminal inverted repeats. The observed site-specificity of the mini-circle is not mediated by extensive homology between the element and the chromosomal integration site. Transposition of the mini-circle into the S. lividans chromosome was demonstrated and found to be some two orders of magnitude less efficient than integration of the circular form of the element, suggesting that the circular form of the mini-circle might be a normal intermediate in the transposition process.

Amino Acid Sequence↗
PubMedDate not supplied

Toward culturally sensitive research in a multicultural society.

Applying research methods and techniques developed in a dominant culture to other cultures can threaten the validity and generalizability of research conducted with other cultures. Guidelines are proposed for increasing the cultural sensitivity of research, and a case example is discussed.

Humans↗