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Biomedical subjects

W J Murphy

Publications and source records attributed to W J Murphy.

157 records · Page 9Linked to original sources
PubMed1984

DNA rearrangements of the variable surface antigen genes of the trypanosomes.

The trypanosome genome contains several hundred (and perhaps several thousand) genes for the trypanosome variable surface glycoproteins (VSGs). In an individual trypanosome only one of these genes is expressed at a given instant; the others are transcriptionally silent. This differential gene expression is responsible for the sequential antigenic variation displayed by trypanosomes. It is mediated by two types of genomic rearrangements of these VSG genes. The best understood rearrangement type is the formation of a transcriptionally-active expression-linked extra copy (ELC) of a transcriptionally-silent basic copy (BC) gene. This duplication and translocation event places the ELC near a chromosomal end (a telomere) where it is apparently located downstream from a strong promotor. Some VSG genes are not expressed via this ELC mechanism. These genes, which seem to already be near telomeres, are activated by a different non-duplication associated ( NDA ) type of mechanism. We have used recombinant DNA techniques to clone and determine the sequences of genes expressed by both the ELC and NDA mechanisms. Comparison of these sequences reveals that sequences flanking the VSG coding regions are similar. This indicates that there is a sequence correlation between the two mechanisms of expression. We have also shown that when bloodstream trypanosomes expressing a specific VSG via the ELC mechanism are established in culture, the resultant procyclic trypanosomes rapidly stop synthesizing the VSG mRNA (and the VSG) but retain the ELC of the VSG gene. This demonstrates that transcription of an ELC can cease without the loss of that ELC and may indicate the presence of other factors regulating VSG gene transcription.

Animals↗
PubMed1983

Comparison of the expression-linked extra copy (ELC) and basic copy (BC) genes of a trypanosome surface antigen.

A recombinant clone of an expression-linked extra copy (ELC) gene of a trypanosome-variable surface glycoprotein was sequenced. In addition the sequences of the corresponding cDNA and portions of the two basic copy genes were determined. Comparison of these sequences reveals that the 5' boundary of the ELC-transposed segment (2.2 kb) occurs within a repetitive sequence about 700 bp upstream from the start codon of the coding sequence. This sequence does not contain internal symmetries and is not homologous with the repetitive sequence at the 3' boundary. The first 35 nucleotides of the cDNA are different than the corresponding ELC sequence and presumably were transcribed from another genomic location. A restriction fragment containing predominantly sequences outside of the 5' boundary hybridizes to a Pst I fragment whose length is variable in different trypanosome clones. This hybridization pattern is similar to that observed using probes for surface glycoprotein genes that are expressed via the nonduplication-associated (NDA) mechanism rather than the ELC mechanism. This indicates that there is a sequence correlation between these two DNA rearrangement mechanism.

Amino Acid Sequence↗
PubMed1977

Torticollis with hiatus hernia in infancy. Sandifer syndrome.

Two infants with torticollis and hiatus hernia (Sandifer Syndrome) are presented. Both infants improved with medical management. Abnormal head and neck positioning is attributed to esophagitis secondary to gastroesophageal reflux, with or without hiatus hernia. Since esophagitis due to reflux is not necessarily accompanied by vomiting, infants with torticollis shoud be studied for gastroesophageal reflux. If present, medical management is usually successful.

Gastroesophageal Reflux↗
PubMedDate not supplied

Molecular dating and biogeography of the early placental mammal radiation.

The timing and phylogenetic hierarchy of early placental mammal divergences was determined based on combined DNA sequence analysis of 18 gene segments (9779 bp) from 64 species. Using rooted and unrooted phylogenies derived from distinct theoretical approaches, strong support for the divergence of four principal clades of eutherian mammals was achieved. Minimum divergence dates of the earliest nodes in the placental mammal phylogeny were estimated with a quartet-based maximum-likelihood method that accommodates rate variation among lineages using conservative fossil calibrations from nine different nodes in the eutherian tree. These minimum estimates resolve the earliest placental mammal divergence nodes at periods between 64 and 104 million years ago, in essentially every case predating the Cretaceous-Tertiary (K-T) boundary. The pattern and timing of these divergences allow a geographic interpretation of the primary branching events in eutherian history, likely originating in the southern supercontinent Gondwanaland coincident with its breakup into Africa and South America 95-105 million years ago. We propose an integrated genomic, paleontological, and biogeographic hypothesis to account for these earliest splits on the placental mammal family tree and address current discrepancies between fossil and molecular evidence.

Animals↗
PubMedDate not supplied

A radiation hybrid mapping panel for the rhesus macaque.

The genomes of nonhuman primates have recently become highly visible candidates for full genome analysis, as they provide powerful models of human disease and a better understanding of the evolution of the human genome. We describe the creation of a 5000 rad radiation hybrid (RH) mapping panel for the rhesus macaque. Duplicate genotypes of 84 microsatellite and coding gene sequence tagged sites from six macaque chromosomes produced an estimated whole genome retention frequency of 0.33. To test the mapping ability of the panel, we constructed RH maps for macaque chromosomes 7 and 9 and compared them to orthologous locus orders in existing human and baboon maps derived from different methodologies. Concordant marker order between all three species maps suggests that the current panel represents a powerful mapping resource for generating high-density comparative maps of the rhesus macaque and other species genomes.

Animals↗
PubMedDate not supplied

Second-generation integrated genetic linkage/radiation hybrid maps of the domestic cat (Felis catus).

We report construction of second-generation integrated genetic linkage and radiation hybrid (RH) maps in the domestic cat (Felis catus) that exhibit a high level of marker concordance and provide near-full genome coverage. A total of 864 markers, including 585 coding loci (type I markers) and 279 polymorphic microsatellite loci (type II markers), are now mapped in the cat genome. We generated the genetic linkage map utilizing a multigeneration interspecies backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis). Eighty-one type I markers were integrated with 247 type II markers from a first-generation map to generate a map of 328 loci (320 autosomal and 8 X-linked) distributed in 47 linkage groups, with an average intermarker spacing of 8 cM. Genome coverage spans approximately 2,650 cM, allowing an estimate for the genetic length of the sex-averaged map as 3,300 cM. The 834-locus second-generation domestic cat RH map was generated from the incorporation of 579 type I and 255 type II loci. Type I markers were added using targeted selection to cover either genomic regions underrepresented in the first-generation map or to refine breakpoints in human/feline synteny. The integrated linkage and RH maps reveal approximately 110 conserved segments ordered between the human and feline genomes, and provide extensive anchored reference marker homologues that connect to the more gene dense human and mouse sequence maps, suitable for positional cloning applications.

Animals↗
PubMedDate not supplied

Mapping of 53 loci in American mink (Mustela vison).

Fifty-three genes were mapped in the American mink genome using polymerase chain reaction (PCR)-based analysis of a Chinese hamster-American mink somatic cell hybrid panel. Heterologous primers designed for cat gene mapping were used in this study. Forty-nine of these loci were localized into expected chromosome regions according to Zoo-FISH data, whereas four loci--ALPL, CDC20, ERF-2, and Fc(Mv)23617--were mapped out of expected conserved regions. PCR products amplified with primers corresponding to these four markers were partly sequenced and verified using BLAST. The results showed the homology to be more than 90% between mink and human or cat counterparts. At present, the gene map of American mink has expanded to 127 loci.

Animals↗
PubMedDate not supplied

Use of neuroendocrine hormones to promote reconstitution after bone marrow transplantation.

A survey of the previous literature and the data shown here indicate that neuroendocrine hormones such as growth hormone and prolactin may be of potential clinical use after bone marrow transplantation (BMT) to promote hematopoietic and immune recovery. The amounts of hormones used in our model do not promote weight gain suggesting that their lymphohematopoietic actions were independent of their anabolic effects. While the hormones may not produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. IL-2 or G-CSF), their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in the post-BMT setting. However, more work needs to be performed to understand the mechanism(s) of their action, particularly with regard to T-cell function and development.

Animals↗
PubMedDate not supplied

Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30.

GAP31 (Gelonium protein of 31 kDa) and MAP30 (Momordica protein of 30 kDa) are agents isolated from the medicinal plants Gelonium multiflorum and Momordica charantia, respectively. The current study was conducted to investigate the efficacy of GAP31 and MAP30 on estrogen-independent and highly metastatic human breast tumor MDA-MB-231 both in vitro and in vivo. The effect of these agents on the expression of breast tumor antigen HER2 (also known as neu or as c-erbB 2) was also examined. Treatment of MDA-MB-231 breast cancer cells with GAP31 and MAP30 resulted in inhibition of cancer cell proliferation as well as inhibition of the expression of HER2 gene in vitro. When MDA-MB-231 human breast cancer cells were transferred into SCID mice, the mice developed extensive metastases and all mice succumbed to tumor by day 46. Treatment of the human breast cancer bearing SCID mice with GAP31 or MAP30 at 10 micrograms/injection EOD for 10 injections resulted in significant increases in survival, with 20-25% of the mice remaining tumor free for 96 days. Thus, anti-tumor agents GAP31 and MAP30 are effective against human breast cancer MDA-MB-231 in vitro and in vivo. These agents may therefore be a potential therapeutic use against breast carcinomas.

Animals↗