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Biomedical subjects

A McClelland

Publications and source records attributed to A McClelland.

At least 55 records · Page 3Linked to original sources
PubMed1990

Sexual abuse of children presenting to the Children's outpatient Department of Port Moresby General Hospital.

Over a one-year period in the Children's Outpatient Department of Port Moresby General Hospital 23 cases of child sexual abuse were diagnosed. 20 (87%) were female. The perpetrator was known to be a male relative or acquaintance in 14 (61%) cases. The patients presented either with a history or overt signs of sexual abuse. With increasing awareness of child sexual abuse as a significant problem in paediatrics there will be an increase in the frequency of diagnosis of this condition in Papua New Guinea.

Child↗
PubMed1989

The major human rhinovirus receptor is ICAM-1.

The major human rhinovirus receptor has been identified with monoclonal antibodies that inhibit rhinovirus infection. These monoclonal antibodies recognize a 95 kd cell surface glycoprotein on human cells and on mouse transfectants expressing a rhinovirus binding phenotype. Purified 95 kd protein binds to rhinovirus in vitro. Protein sequence from the 95 kd protein showed an identity with that of intercellular adhesion molecule-1 (ICAM-1); a cDNA clone obtained from mouse transfectants expressing the rhinovirus receptor had essentially the same sequence as ICAM-1. Thus, the major human rhinovirus receptor is ICAM-1. The gene for this receptor maps to human chromosome 19, which also contains the genes for a number of other picornavirus receptors.

Alkaloids↗
PubMed1987

Molecular cloning of receptor genes by transfection.

We have described a transfection method for the isolation of surface antigen genes which requires no mRNA or protein purification. Application of this technique results in the recovery of the entire gene in a single step since selection for expression of genomic DNA forms the basis of the procedure. Based on our results with the transferrin receptor gene and other systems, it is evident that large transcription units can be transferred and expressed in mouse L-cells. This size consideration represents a major advantage over the use of cosmid shuttle vectors for genomic DNA expression. In the case of genes which code for very long mRNAs this method may also have advantages over cDNA expression systems. Although we have described methods for FACS isolation of transfectants based on the binding of species specific antibodies to surface antigens, other methods of identifying transfected cells could be employed. For example, in combination with an appropriate assay, sib selection of recipient cells could be used to identify genes encoding secreted products. Ligand binding assays could be used for receptors which are not expressed on the host cell. Finally, the development of cDNA expression vectors which produce membrane-associated products would extend this methodology to genes not normally expressed at the cell surface.

Animals↗
PubMed1986

Sequence conservation around the 5' ends of the larval serum protein 1 genes of Drosophila melanogaster.

We have determined the nucleotide sequence at the 5' ends of the genes for the alpha, beta and gamma polypeptides of larval serum protein 1 (LSP1) of Drosophila melanogaster. In their upstream regions, the three genes share homology around the TATA boxes. There is also a homologous region of about 20 nucleotides at positions 200, 216 and 377 upstream from the alpha, beta and gamma genes, respectively. Another 18-nucleotide homology occurs between a sequence 111 nucleotides upstream from the alpha gene and 130 nucleotides upstream of the beta gene. This contains a seven-nucleotide match with a sequence 180 nucleotides upstream from the gamma gene. The sequences corresponding to the 5' non-translated regions of the RNA show two regions of strong homology: one being within the first 20 nucleotides at the very 5' end of the RNA, and the other being between nucleotides 27 and 52 of the three transcripts. The first AUG codon to precede a long open reading frame is found at nucleotides 89, 86 and 83 downstream from the 5' end of the alpha, beta and gamma RNAs, respectively. An extremely conserved nucleotide sequence with an exact homology of 66 nucleotides between the alpha and beta genes, and sharing 27 nucleotides with the gamma gene, is contained within this long open reading frame in the first exon. Conceptual translation of the long open reading frame shows that the hydrophobic nature of the first 20 amino acids of the three polypeptides has been conserved whereas the exact sequence has not. This suggests that the N termini contain signal sequences required for secretion of the protein into the haemolymph. The three genes have intervening sequences ranging from 65 to 68 nucleotides in length at comparable locations close to the 5' end of the genes.

Amino Acid Sequence↗
PubMed1986

Cell proliferation and expression of the transferrin receptor gene: promoter sequence homologies and protein interactions.

A 365-bp fragment from the 5' region of the human transferrin receptor gene has been subcloned and sequenced. This fragment contains 115 bp of flanking sequence, the first exon, and a portion of the first intron. It contains a TATA box, several GC-rich regions, and is able to efficiently promote expression of the bacterial CAT gene in mouse 3T3 cells. Sequence comparisons demonstrate that this DNA segment has homology to the promoter regions of the human dihydrofolate reductase gene and the mouse interleukin 3 gene, as well as to a monkey DNA sequence that has homology to the SV40 origin and promotes expression of an unidentified gene product. Several high molecular mass proteins that interact with the transferrin receptor gene promoter have been identified. The activity of these proteins is transiently increased in 3T3 cells that have been stimulated by serum addition. This increase precedes a rise in transferrin receptor mRNA levels in the cytoplasm, which in turn precedes entry of the cells into S phase. DNase I footprinting of the transferrin receptor promoter reveals several protein binding sites. Two of the sites are within the conserved GC-rich region of the promoter. One of these binding sites probably interacts with Spl, while the second interacts with an uncharacterized protein.

Binding Sites↗
PubMed1986

Transcriptional regulation by iron of the gene for the transferrin receptor.

Treatment of K562 cells with desferrioxamine, a permeable iron chelator, led to an increase in the number of transferrin receptors. Increasing intracellular iron levels by treatment of cells with either human diferric transferrin or hemin lowered the level of the transferrin receptors. By using a cDNA clone of the human transferrin receptor, we showed that the changes in the levels of the receptor by iron were accompanied by alterations in the levels of the mRNA for the receptor. The rapidity of these changes indicated that the mRNA had a very short half-life. By using an in vitro transcriptional assay with isolated nuclei, we obtained evidence that this regulation occurred at the transcriptional level.

Cell Line↗
PubMed1986

Psychological and psychiatric aspects of learning difficulties.

The Warnock Committee (1978) recommended that in the future the educational planning of services for children and young people should be based on the assumption that one in six children at any time and up to one in five at some time in their school career will require some form of special educational provision and the approach should be one of "needs" rather than handicap.

Child↗
PubMed1985

Use of a protein-blotting procedure and a specific DNA probe to identify nuclear proteins that recognize the promoter region of the transferrin receptor gene.

We describe a procedure for detecting high-affinity, sequence-specific DNA-binding proteins from crude nuclear extracts. The technique utilizes electrophoretic transfer of NaDodSO4/PAGE-fractionated proteins onto nitrocellulose filters. Incubation of the filters with a 5% (wt/vol) solution of nonfat dry milk effectively blocks nonspecific and low-affinity DNA-binding sites. Incubation of the blocked filters with radiolabeled DNA under optimal binding conditions and subsequent autoradiography reveals high-affinity DNA-protein interactions. We have used this procedure to identify proteins that bind specifically to the promoter region of the transferrin receptor gene.

Base Sequence↗
PubMed1985

Regional localization of the human transferrin receptor gene to 3q26.2----qter.

Transport of iron across the cell membrane is mediated by the iron-binding serum protein, transferrin, and its cell-surface receptor. Transferrin receptor is required for cell proliferation and may play a functional role in the pathogenesis of iron-storage disorders and some neoplasias. To better understand the possible involvement of transferrin receptor in such disorders, we have determined the chromosomal locus of the receptor gene by in situ hybridization. The human transferrin receptor gene was thus mapped to 3q26.2----qter, a region of chromosome 3 that appears to be involved in metal transport and that is subject to nonrandom structural rearrangements associated with neoplasia.

Chromosome Mapping↗
PubMed1984

The human transferrin receptor gene: genomic organization, and the complete primary structure of the receptor deduced from a cDNA sequence.

Heteroduplex analysis shows that the transferrin receptor gene contains at least 19 distinct coding sequences distributed over 31 kb of genomic DNA. The nucleotide sequence of these coding regions has been determined from a cDNA clone. The sequence contains a single complete open reading frame of 2280 bases which specifies a 760 residue polypeptide with a molecular weight of 85K daltons. The deduced amino acid sequence of the receptor shows that it does not contain an N-terminal hydrophobic signal peptide. We have found a single region of sufficient length and hydrophobicity to span the membrane, located 61 amino acids from the N-terminus. This leads to the prediction that the receptor is oriented in the membrane with a cytoplasmic N-terminus and an extracellular C-terminus. The receptor has no significant homology with transferrin, or with any receptor for which a sequence is available.

Amino Acid Sequence↗
PubMed1984

Gene transfer, expression, and molecular cloning of the human transferrin receptor gene.

We describe the molecular cloning of the human transferrin receptor gene by a gene transfer approach. Mouse Ltk- cells were cotransformed with the herpes simplex thymidine kinase gene and total human DNA. Transformants expressing human transferrin receptor were isolated by selection on hypoxanthine/aminopterin/thymidine (HAT) medium and fluorescence-activated cell sorting of HAT-resistant cells. Thirty-four kilobases of human DNA was isolated by screening a genomic library constructed from the DNA of a secondary transformant. Gene transfer of the cloned DNA established that 31 kb of DNA was sufficient to encode the receptor. A probe from the 5' end of the gene was used to isolate a cDNA clone with an insert of 4.9 kb. Hybridization of the cDNA to the cloned genomic DNA revealed a minimum of 12 exons. They extend over the entire 31 kb of expressing DNA and over 2 kb of adjacent 3' untranslated sequences that are not required for receptor expression in L cells.

Animals↗
PubMed1983

Renal cadmium content in the West of Scotland.

The trace element content of kidneys has been documented in very few international centres. Significant differences can be demonstrated between the cortical and medullary levels of calcium, zinc and cadmium. For the West of Scotland the values for the latter are similar to those found in Scandinavia. There are significantly higher cadmium contents in subjects who smoke and who have evidence of ischaemic heart disease.

Adolescent↗
PubMed1981

The molecular cloning of a dispersed set of developmentally regulated genes which encode the major larval serum protein of D. melanogaster.

We have isolated chromosomal segments of D. melanogaster DNA that encode the alpha, beta and gamma polypeptides of the major larval serum protein (LSP1) from libraries of recombinant phage. The recombinant DNAs hybridize in situ to polytene chromosome regions 11A, 21D of 61A, consistent with the known cytogenetic positions of the alpha, beta and gamma genes, respectively. The three genes each encode a 2.85 kb polyadenylated RNA molecule. We have positioned these coding sequences, by both Southern hybridization analysis and R loop mapping. Heteroduplex analysis reveals comparatively close homology between the alpha and beta genes, less homology between the beta and gamma genes and least homology between the alpha and gamma genes.

Animals↗
PubMed1980

Effects of chlordiazepoxide, food familiarization, and prior shock experience on food choice in rats.

Chlordiazepoxide (5, 10 mg/kg) increased the time devoted to eating familiar laboratory chow without altering the response to a range of novel, palatable foods which were also available to the food-deprived rats. Prior experience with the same range of alternative foods (food familiarization) radically changed the effect of the drug. After familiarization with these foods, chow was virtually ignored as a food choice, indicating its low relative palatability; chlordiazepoxide then prolonged the time eating the familiarized foods without significantly increasing the response to chow. These results are not consistent with an anti-food neophobia action of chordiazepoxide. They suggest instead that chlordiazepoxide enhances feeding responses related to food saliency. Footshock, delivered two days before the food choice test affected performance within the test. Its effects were opposite those of chlordiazepoxide, but they competed additively with the drug's effects. These results indicate that chlordiazepoxide's action was not simply to remove any inhibitory effect on feeding produced by fear; instead the drug promoted approach to food antagonizing any deficit in approach associated with fear. These findings are viewed as consistent with an action of chlordiazepoxide to augment the level of feeding motivation. Chlordiazepoxide (15 mg/kg) may act to overcome food neophobia.

Animals↗