Biomedical subjects

J Fitzgibbon

Publications and source records attributed to J Fitzgibbon.

At least 37 records · Page 2Linked to original sources

PubMed1998

Isolation and chromosomal localization of two human CDP-diacylglycerol synthase (CDS) genes.

Phototransduction in Drosophila is a phosphoinositide-mediated signaling pathway. Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in this process, and its levels are tightly regulated. A photoreceptor-specific form of the enzyme CDP-diacylglycerol synthase (CDS), which catalyzes the formation of CDP-diacylglycerol from phosphatidic acid, is a key regulator of the amount of PIP2 available for signaling. cds mutants develop light-induced retinal degeneration. As part of a search for novel genes that may be involved in eye disease in human, using Drosophila phototransduction genes as a model system, two human CDP-diacylglycerol synthase genes (CDS1 and CDS2) were cloned and sequenced. Radiation hybrid panel mapping and fluorescence in situ hybridization were used to localize the genes to chromosomes 4q21 and 20p13. As yet, no known retinal diseases map to either of these regions.

Amino Acid Sequence↗

PubMed1998

Interlaboratory concordance of DNA sequence analysis to detect reverse transcriptase mutations in HIV-1 proviral DNA. ACTG Sequencing Working Group. AIDS Clinical Trials Group.

Thirteen laboratories evaluated the reproducibility of sequencing methods to detect drug resistance mutations in HIV-1 reverse transcriptase (RT). Blinded, cultured peripheral blood mononuclear cell pellets were distributed to each laboratory. Each laboratory used its preferred method for sequencing proviral DNA. Differences in protocols included: DNA purification; number of PCR amplifications; PCR product purification; sequence/location of PCR/sequencing primers; sequencing template; sequencing reaction label; sequencing polymerase; and use of manual versus automated methods to resolve sequencing reaction products. Five unknowns were evaluated. Thirteen laboratories submitted 39043 nucleotide assignments spanning codons 10-256 of HIV-1 RT. A consensus nucleotide assignment (defined as agreement among > or = 75% of laboratories) could be made in over 99% of nucleotide positions, and was more frequent in the three laboratory isolates. The overall rate of discrepant nucleotide assignments was 0.29%. A consensus nucleotide assignment could not be made at RT codon 41 in the clinical isolate tested. Clonal analysis revealed that this was due to the presence of a mixture of wild-type and mutant genotypes. These observations suggest that sequencing methodologies currently in use in ACTG laboratories to sequence HIV-1 RT yield highly concordant results for laboratory strains; however, more discrepancies among laboratories may occur when clinical isolates are tested.

Codon↗

PubMed1997

Molecular evolution of the cottoid fish endemic to Lake Baikal deduced from nuclear DNA evidence.

Lake Baikal in Eastern Siberia contains a remarkable flock of 29 species of teleost fishes of the suborder Cottoidei (sculpins, bullheads) that are endemic to the lake and its associated rivers and occupy all depth habitats down to over 1500 m. The species are divided into three families, the Cottidae with 7 species, the Abyssocottidae with 20 species, and the Comephoridae with 2 species. Nucleotide sequences of the rod opsin gene from 12 of these species, plus a non-Baikal marine species, have been used to examine the evolutionary relations and the divergence time of the flock. Phylogenetic trees, generated by neighbor-joining and maximum parsimony, indicate that the unique Comephoridae family with its viviparity and unusual appearance is closely related to the Cottidae and Abyssocottidae, whereas the genus Cottocomephorus, at present placed in the Cottidae, was the first to diverge from the ancestral species and forms a separate lineage. The major adaptation to deep water would appear to be of relatively recent origin, and there is evidence that the ancestral species occupied a shallow-water-marine or brackish habitat. Estimates of antiquity obtained from synonymous substitutions place the origin of the species flock at around 4.9 million years ago.

Animals↗

PubMed1996

Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci.

The human genome contains a group of gene families whose members map within the same regions of chromosomes 1, 6, and 9. The number of gene families involved and their pronounced clustering to the same areas of the genome indicate that their mapping relationship is nonrandom. By combining mapping data and sequence information for the gene families, we have determined that these sequences are part of a large region that spans several megabases. This region is present in three copies: on the long arm of human chromosome 1, the short arm of chromosome 6, and the long arm of chromosome 9. We have characterized the phylogenesis of two of the gene families involved and propose an evolutionary route for the creation of the three regions. Our analysis led us to predict and demonstrate the presence of two loci, a PBX locus on chromosome 6 and a NOTCH locus on chromosome 1. The discovery of this triplicated region increases our understanding of the evolution of the human genome and may have considerable practical implications for gene mapping prediction and novel approaches to isolating new gene family members and uncloned disease loci.

Animals↗

PubMed1996

Human guanylate kinase (GUK1): cDNA sequence, expression and chromosomal localisation.

Guanylate kinase (GK) catalyses the conversion of GMP to GTP as part of the cGMP cycle. In mammalian phototransduction, this cycle is essential for the regeneration of cGMP following its hydrolysis by phosphodiesterase. Mutations in different parts of this signalling cascade lead to retinal degeneration in humans. Protein studies have localized a locus for GK to a region of human chromosome 1 that also contains an autosomal recessive form of retinitis pigmentosa (RP12) and Usher's type 11a (USH2A). We report the sequence of this human GK (GUK1) and a further refinement of its localization to 1q32-41, placing it in the same interval as USH2A.

Amino Acid Sequence↗

PubMed1996

Spectral tuning and molecular evolution of rod visual pigments in the species flock of cottoid fish in Lake Baikal.

Lake Baikal in Eastern Siberia is the deepest and one of the largest and most ancient lakes in the world. However, even in the deepest regions, oxygenation levels do not fall below 75-80% of the surface levels. This has enabled a remarkable flock of largely endemic teleost fish of the sub-order Cottoidei to colonize all depth habitats. We have previously shown that species that occupy progressively deeper habitats show a blue shift in the peak wavelength of absorbance (lambda max) of both their rod and cone visual pigments; for the rod pigments, a number of stepwise shifts occur from about 516 nm in littoral species to about 484 nm in abyssal species. By sequencing the rod opsin gene from 11 species of Baikal cottoids that include representatives from all depth habitats, we have been able to identify four amino acid substitutions that would account for these shifts. The effect of each substitution on lambda max is approximately additive and each corresponds to a particular lineage of evolution.

Amino Acid Sequence↗

PubMed1995

The rhodopsin-encoding gene of bony fish lacks introns.

A study of the sequences of the rhodopsin-encoding genes (Rh) in eight fish species from two of the major subdivisions of the teleosts reveals that no introns are present in the coding region. This contrasts with the opsin-encoding genes of all other vertebrates where either four or five introns are invariably found. Phylogenetic analysis shows that this intronless teleost Rh is homologous to the intron-containing Rh of amphibia, birds and mammals. Possible mechanisms for intron loss are discussed, including replacement by homologous conversion of Rh with a processed cDNA.

Amphibians↗

PubMed1995

Regional localization of 64 cosmid contigs, including 18 genes and 14 markers, to intervals on human chromosome 9q34.

A fluorescence in situ hybridization map of distal human chromosome 9q has been produced by mapping cosmid clones to metaphase chromosomes with balanced reciprocal translocations. This is a very accurate method of mapping, as clones are localized by their position with respect to the breakpoint in addition to cytogenetic banding. By using three lymphoblastoid cell lines with translocation breakpoints within 9q34, we have localized 18 genes and 14 DNA markers to one of four intervals on the chromosome. Cosmid contigs exist around 16 of these genes and 12 of these markers. A further 43 contigs have also been mapped, but they are as yet anonymous.

Animals↗

PubMed1995

Chromosomal localization of three mouse diacylglycerol kinase (DAGK) genes: genes sharing sequence homology to the Drosophila retinal degeneration A (rdgA) gene.

There is growing evidence to support some form of light-activated phosphoinositide signal transduction pathway in the mammalian retina. Although this pathway plays no obvious role in mammalian phototransduction, mutations in this pathway cause retinal degenerations in Drosophila. These include the retinal degeneration A mutant, which is caused by an alteration in an eye-specific diacylglycerol kinase (DAGK) gene. In our efforts to consider genes mutated in Drosophila as candidates for mammalian eye disease, we have initially determined the map position of three DAGK genes in the mouse.

Animals↗

PubMed1995

Cosmid contigs spanning 9q34 including the candidate region for TSC1.

The tuberous sclerosis disease gene TSC1 has been mapped to 9q34. However, its precise localisation has proved problematic because of conflicting recombination data. Therefore, we have attempted to clone the entire target area into cosmid contigs prior to gene isolation studies. We have used Alu-PCR from irradiation hybrids to produce complex probes from the target region which have identified 1,400 cosmids from a chromosome-specific library. These, along with cosmids obtained by other methods, have been assembled into contigs by a fingerprinting technique. We estimate that we have obtained most of the region in cosmid contigs. These cosmids are a resource for the isolation of expressed genes within the TSC1 interval. In addition, the cosmid contig assembly has demonstrated a number of previously unknown physical connections between genes and markers in 9q34.

Animals↗

PubMed1995

Localisation of the gene encoding diacylglycerol kinase 3 (DAGK3) to human chromosome 3q27-28 and mouse chromosome 16.

The gene encoding a 90 kDa diacylglycerol kinase protein, DAGK3, that is predominately expressed in the retina, was localised by fluorescence in situ hybridisation to human chromosome 3q27-28. This was subsequently confirmed by mapping of its mouse homologue to chromosome 16, a region syntenic to this part of human chromosome 3. No retinopathies have so far been assigned to this region.

Animals↗

PubMed1994

Localisation of the human blue cone pigment gene to chromosome band 7q31.3-32.

Blue cone pigment (BCP) is one of three types of cone photoreceptors responsible for normal colour vision. In this study, the BCP gene has been localised to chromosome 7q31.3-32 by fluorescent in situ hybridisation of cosmid clones containing the gene. This is consistent with previous mapping of the BCP gene to chromosome 7q31-35.

Cells, Cultured↗

PubMed1994

Localization of the gene encoding human phosphatidylinositol transfer protein (PITPN) to 17p13.3: a gene showing homology to the Drosophila retinal degeneration B gene (rdgB).

The human gene for phosphatidylinositol transfer protein (PITPN) has previously been shown to share sequence and functional homology to part of the Drosophila retinal degeneration B gene (rdgB). In view of the possible involvement of the PITPN locus in the etiology of retinal disease, the gene has been mapped to human chromosome 17p13.3 and mouse Chromosome 11.

Animals↗

PubMed1993

Localization of the retinoid X receptor alpha gene (RXRA) to chromosome 9q34.

The retinoid X receptor alpha is one of a number of retinoic acid receptors which are members of the steroid/thyroid hormone superfamily. Localization of RXRA was achieved using the polymerase chain reaction on a panel of somatic cell hybrids. A cosmid clone was isolated using the RXRA PCR product, and this was used to further localize the gene by fluorescence in situ hybridization to chromosome 9q34 distal to the dopamine beta hydroxylase gene (DBH). This mapping position was confirmed by PCR on a panel of translocation hybrids.

Animals↗

PubMed1993

Mapping of RXRB to human chromosome 6p21.3.

Retinoid X Receptor beta (RXRB) is a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). We have confirmed the localization of RXRB to chromosome 6 and we have mapped the gene to chromosome 6p21.3-p21.1 by PCR amplification of 5' untranslated sequence in panels of rodent-human somatic cell hybrids and to 6p21.3 by fluorescent in situ hybridization.

Animals↗

PubMed1993

Cutaneous sarcomas and sarcomatoid neoplasms of the skin.

Cutaneous sarcomas and sarcoma-like lesions pose special problems for pathologists. These lesions manifest a great deal of clinical and histological overlap, and they may be virtually impossible to separate from one another on conventional microscopy. Spindle-cell squamous carcinoma (SCSC), sarcomatoid malignant melanoma (SCMM), and fibrohistiocytic tumors, such as "atypical fibroxanthoma" (AFX) and superficial malignant fibrous histiocytoma (SMFH), comprise the group of neoplasms in this category that pose the greatest diagnostic difficulty. All may or may not show attachments between dermal tumor cells and the overlying epidermis; all may be composed of varying proportions of fusiform and pleomorphic cells; and all may demonstrate the presence of "divergent" differentiation into bone, cartilage, or myogenous tissues. Electron microscopy and immunohistology usually are required to identify these tumors with certainty. The usefulness in doing so is supported by differing biological behaviors in this context. SCMM shows the greatest tendency for recurrence and metastasis, followed in relative order by SMFH, SCSC, and AFX.

Aged↗

PubMed1992

Migraine.

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Adult↗

PubMed1989

Drug-related emergencies in athletes.

Drug use among athletes, both amateur and professional, is a problem that will remain with us. Athletes will use the drugs that are considered recreational by the general population as well as some that may help them in their individual sport. Team physicians, coaches, and trainers must be aware of the most frequently used and abused drugs, their side effects, interactions, and emergency management. In addition, they must be aware of their athletes who have a drug-related problem in order to advise them and get appropriate medical help. Remember that an athlete may have a significant drug problem yet continue to function well on the team. Early recognition and intervention may save one or many lives. The following are the responsibilities for coach, trainer, and team physician: (1) know what drugs athletes use and their pharmacology; (2) know one's limitations and how to access community resources; (3) know the laws related to drug/ETOH abuse and treatment; (4) understand the management of acute drug ingestion; and (5) know how to be supportive to the athletes.

Doping in Sports↗