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Biomedical subjects

J L Williams

Publications and source records attributed to J L Williams.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: a Pediatric Oncology Group (POG) study.

PURPOSE: The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD). PATIENTS AND METHODS: Between August 1992 and December 1993, 51 eligible children < or =21 years of age, 31 male and 20 female, were enrolled in this study which was designed for low stage (IA, IIA, IIIA1) HD. Laparotomy and surgical staging was optional. Five postpubertal patients with Stage IA and IIA disease received only involved-field radiation therapy. The other 46 patients, who form the basis of this report, received combined modality therapy consisting of four courses of doxorubicin, bleomycin, vincristine, and etoposide (DBVE) followed by 2,550 cGy involved-field irradiation. RESULTS: With a median follow-up of 8.4 years, the 6-year overall and event-free survival rates for the 46 patients treated with combination therapy were 98 +/- 2% and 91 +/- 5%, respectively. All patients achieved remission after completion of therapy. There have been four recurrences and a remission death due to gunshot wound. Combined modality therapy was well tolerated. Predominant side effects were gastrointestinal and hemopoietic. There have been no clinically significant cardio-pulmonary side effects so far. CONCLUSION: In clinically staged children with early-stage HD, DBVE and low-dose involved-field irradiation was effective therapy with tolerable side effects and reduced potential for long-term adverse events.

Adolescent↗
PubMed2006

Radiation hybrid mapping of all 10 characterized bovine Toll-like receptors.

Toll-like receptors (TLRs) are cell-surface signalling molecules that recognize a range of highly conserved pathogen molecules and instigate the appropriate immune response. Here, we report the mapping of all 10 characterized bovine TLR genes using a radiation hybrid panel. The genomic organization of the bovine TLRs is similar to that of humans and mice. TLR1, TLR6 and TLR10 map closely together on Bos taurus chromosome 6 (BTA6), while TLR7 and TLR8 map to the X chromosome. TLR2, TLR3, TLR4, TLR5 and TLR9 map to BTA17, BTA27, BTA8, BTA16 and BTA22 respectively. Our increased knowledge of the genomic organization of the bovine TLR genes may promote our understanding of their evolution and help in the identification of bovine genes underlying disease-resistance traits.

Animals↗
PubMed2006

Sequencing, chromosomal mapping, and functional characterization of bovine FLICE-like inhibitory protein (FLIP).

FLICE-like inhibitory protein (FLIP) has been shown in both humans and mice to inhibit apoptosis and NF-kappaB activation induced by pro-inflammatory mediators. The activation of NF-kappaB and the induction of apoptosis are critical events in the pathogenesis of a variety of disease states in cattle, including mastitis. Since FLIP is known to moderate these events in other species, we mapped the bovine FLIP gene, sequenced bovine FLIP cDNA, and characterized its expression in cultured primary bovine endothelial cells. Sequencing of bovine FLIP revealed approximately 83, 74, and 68% amino acid sequence identity to its porcine, human, and murine orthologs, respectively. Bovine FLIP was mapped to chromosome 2 by radiation hybrid mapping. Interestingly the region to which bovine FLIP maps contains a putative quantitative trait locus for functional herd life which is an indicator of a cow's ability to survive involuntary culling due primarily to mastitis and infertility. In addition to sequencing and mapping, the function of bovine FLIP was studied. Over-expression of bovine FLIP protected against bacterial lipopolysaccharide (LPS)- and TNF-alpha-induced apoptosis in bovine endothelial cells consistent with previous studies of human FLIP. In addition, elevated expression of bovine FLIP blocked LPS- and TNF-alpha-induced upregulation of NF-kappaB-dependent gene products as assayed by E-selectin expression. Only the full-length bovine FLIP protein could inhibit NF-kappaB activation induced by LPS, whereas the death effector domain region alone was able to inhibit TNF-alpha-induced NF-kappaB activation. Together, these data demonstrate the conservation of FLIP's ability to inhibit apoptosis and to downregulate NF-kappaB activation across species.

Amino Acid Sequence↗
PubMed2006

Comparative mapping of bovine chromosome 27 with human chromosome 8 near a dairy form QTL in cattle.

In the absence of a complete and annotated bovine genome sequence, detailed human-bovine comparative maps are one of the most effective tools for identification of positional candidate genes contributing to quantitative trait loci (QTL) in cattle. In the present study, eight genes from human chromosome 8 were selected for mapping in cattle to improve breakpoint resolution and confirm gene order on the comparative map near the 40 cM region of the BTA27 linkage map where a QTL affecting dairy form had previously been identified. The resulting map identified ADRB3 as a positional candidate gene for the QTL contributing to the dairy form trait based on its estimated position between 40 and 45 cM on the linkage map. It is also a functional candidate gene due to its role in fat metabolism, and polymorphisms in the ADRB3 gene associated with obesity and metabolic disease in humans, as well as, carcass fat in sheep. Further studies are underway to investigate the existence of polymorphisms in the bovine ADRB3 gene and their association with traits related to fat deposition in cattle.

Animals↗
PubMed2005

Quantitative evaluation of genetic and environmental parameters determining antibody response induced by vaccination against bovine respiratory syncytial virus.

The parameters controlling IgG antibody responses induced by vaccination against bovine respiratory syncytial virus (BRSV) were investigated in 463 Holstein-Charolais crossbred cattle. Pre- and post-vaccination sera were tested by enzyme linked immunosorbent assays (ELISA) for BRSV-specific IgG and IgG2. Year-of-birth, age, sex and pre-existing antibody were significant sources of variation for IgG responses. Pre-vaccination, progeny with a higher proportion of Holstein genes had higher total BRSV-IgG. By Day 35 post-vaccination, heritabilities peaked at 0.26 for total BRSV-IgG and 0.36 for BRSV-IgG1. There was no evidence for interbreed differences between Holstein and Charolais calves, post-vaccination. These results suggest that calf-sire has a major heritable influence on serum IgG levels following BRSV immunisation.

Aging↗
PubMed2005

Characterization of bovine FAS-associated death domain gene.

The FAS-associated death domain (FADD) protein is an adapter/signaling molecule that has been shown to function in human cells to promote apoptosis and to inhibit NF-kappaB activation. Because of the critical role that apoptosis and NF-kappaB play in a variety of disease states, we mapped the bovine FADD gene, sequenced bovine FADD cDNA, and characterized its expression in endothelial cells (EC). Sequencing of bovine FADD revealed approximately 65 and 58% amino acid sequence identity to its human and murine homologues, respectively. Bovine FADD was mapped to chromosome 29 by radiation hybrid mapping. In addition, the functionality of bovine FADD was studied. Expression of a bovine FADD dominant-negative construct blocked bacterial lipopolysaccharide (LPS)- and TNF-alpha-induced apoptosis in bovine EC consistent with previous studies of human FADD. In contrast to human FADD, elevated expression of bovine FADD had no effect on LPS- or TNF-alpha-induced upregulation of NF-kappaB-dependent gene products as assayed by E-selectin expression. Thus, while the role of FADD in mediating apoptosis is conserved across species, its role in regulating NF-kappaB-dependent gene expression is not.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Molecular cloning, expression and radiation hybrid mapping of the bovine deiodinase type II (DIO2) and deiodinase type III (DIO3) genes.

Thyroid hormones play a critical role in mammalian development and metabolism. Their activity is regulated in a complex, tissue-specific manner by three isoforms of deiodinases. The goal of this study was to sequence the full-length bovine type II deiodinase (DIO2) and type III deiodinase (DIO3) cDNAs and characterize mRNA expression levels of each of the three deiodinase isoforms in several bovine tissues. Sequencing of bovine DIO2 and DIO3 cDNAs revealed a high degree of predicted amino acid sequence identity with their orthologs in other mammalian species and demonstrated the conservation of selenocysteine residues within the catalytic domains of both bovine proteins. Bovine DIO2 and DIO3 were positioned on chromosomes 10 and 21, respectively, by radiation hybrid mapping. Expression patterns of the three deiodinase isoforms were similar for deiodinase type I (DIO1) and DIO2 to those observed in other species. Expression level of DIO3 transcripts was greatest in mammary gland and kidney, although low-level expression was detected in most tissues sampled. Results of this work will aid in the study of deiodinase gene expression and thyroid hormone regulation in cattle.

Amino Acid Sequence↗
PubMed2005

Endocytosis of plasma-derived factor V by megakaryocytes occurs via a clathrin-dependent, specific membrane binding event.

Megakaryocytes were analyzed for their ability to endocytose factor V to define the cellular mechanisms regulating this process. In contrast to fibrinogen, factor V was endocytosed by megakaryocytes derived from CD34(+) cells or megakaryocyte-like cell lines, but not by platelets. CD41(+)ex vivo-derived megakaryocytes endocytosed factor V, as did subpopulations of the megakaryocyte-like cells MEG-01, and CMK. Similar observations were made for fibrinogen. Phorbol diester-induced megakaryocytic differentiation of the cell lines resulted in a substantial increase in endocytosis of both proteins as compared to untreated cells that did not merely reflect their disparate plasma concentrations. Factor IX, which does not associate with platelets or megakaryocytes, was not endocytosed by any of the cells examined. Endocytosis of factor V by megakaryocytes proceeds through a specific and independent mechanism as CHRF-288 cells endocytosed fibrinogen but not factor V, and the presence of other plasma proteins had no effect on the endocytosis of factor V by MEG-01 cells. Furthermore, as the endocytosis of factor V was also demonstrated to occur through a clathrin-dependent mechanism, these combined data demonstrate that endocytosis of factor V by megakaryocytes occurs via a specific, independent, and most probably receptor-mediated, event.

Cell Differentiation↗
PubMed2005

Chromosomal mapping and quantitative analysis of estrogen-related receptor alpha-1, estrogen receptors alpha and beta and progesterone receptor in the bovine mammary gland.

Steroid receptors are key transcriptional regulators of mammary growth, development and lactation. Expression of estrogen receptors alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR), and estrogen-related receptor alpha-1 (ERRbeta) have been evaluated in bovine mammary gland. The ERRalpha is an orphan receptor that, in other species and tissues, appears to function in the regulation of estrogen-response genes including lactoferrin and medium chain acyl-CoA dehydrogenase and in mitochondrial biogenesis. Expression of ERalpha, ERbeta, PR and ERRalpha was characterized in mammary tissue obtained from multiple stages of bovine mammary gland development using quantitative real-time RT-PCR. Expression was evaluated in prepubertal heifers, primigravid cows, lactating non-pregnant cows, lactating pregnant cows and non-lactating pregnant cows (n=4 to 9 animals/stage). In addition, ERalpha, ERbeta, PR and ERRalpha were mapped to chromosomes 9, 10, 15 and 29 respectively, by linkage and radiation hybrid mapping. Results indicated that expression of ERalpha, PR and ERRalpha was largely coordinately regulated and they were present in significant quantity during all physiological stages evaluated. In contrast, ERbeta transcripts were present at a very low concentration during all stages. Furthermore, no ERbeta protein could be detected in bovine mammary tissue by immunohistochemistry. The ERalpha and PR proteins were detected during all physiological states, including lactation. Our results demonstrate the presence of ERalpha, PR and ERRalpha during all physiological stages, and suggest a functional role for ERRalpha and a relative lack of a role for ERbeta in bovine mammary gland development and lactation.

Animals↗
PubMed2005

Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle.

Studies with different populations are required to properly characterize the robustness of associations of polymorphisms in candidate genes with economically important traits across beef cattle populations before this sort of genetic information can be used efficiently in breeding and management decisions. The objective of this study was to evaluate the association of previously reported SNP in the bovine leptin gene with carcass and meat quality traits from a large sample of crossbred beef cattle. Five SNP (UASMS1, UASMS2, UASMS3, E2JW, and E2FB) were genotyped on 1,111 crossbred bulls, heifers, and steers. The measured traits included fat, lean, and bone yield (%) by partial rib dissection, grade fat, LM area, HCW, quality grade, LM i.m. fat, and tenderness evaluation of LM and semitendinosus muscle. Only four SNP were analyzed (UASMS1, UASMS2, E2JW, and E2FB), because UASMS1 and UASMS3 were completely linked. A uni-variate mixed-inheritance animal model was used to evaluate the association of either genotypes or haplo-types with the traits. The two leptin exon 2 SNP were associated with fat and lean yield and grade fat (E2JW, P < 0.01; E2FB, P < 0.05), and they interacted in their effect on LM tenderness (P < 0.01). The leptin promoter SNP were either not associated with any of the traits (UASMS2) or with fat yield only (UASMS1). Three haplotypes (TCAC, CCAT, TTAC) were at high frequency in the population (88%) and had similar effects on all the traits. Compared with the common haplotypes, one haplotype (CCTT) showed a significantly different effect on fat and lean yield and grade fat (P < 0.01), and one haplotype (TTTT) had a different effect on LM tenderness (P < 0.03). Therefore, important associations between SNP within the leptin gene with lean yield, fatness (fat yield and subcutaneous fat), and tenderness were detected. Results confirm some of the previously reported associations, but diverge with respect to others, showing that further efforts are required to validate some prospective associations.

Adipose Tissue↗
PubMed2005

In vitro peripheral blood mononuclear cell proliferation in a crossbred cattle population.

Immune function measured by Staphylococcus aureus- and phytohemagglutinin- (PHA-) induced cell proliferation was assessed in a population of 445 genetically defined, F2 and backcross Charolais-Holstein crossbred cattle when the animals were approximately 5 mo of age. Variation in Staph. aureus-induced, PHA-induced, and control proliferation [peripheral blood mononuclear cell (PBMC) and media only] was observed at d 2, 3, 4, 5, 9, and 10 of in vitro culture. The levels of Staph. aureus-induced, PHA-induced, and control proliferation were strongly positively correlated between days of culture within-assay (e.g., between d 2 and d 3 or between d 4 and d 5). Responses were also positively correlated when the same individuals were resampled and the assay repeated within 3 mo. Analyses fitting linear mixed models using REML showed that Staph. aureus-induced and PHA-induced proliferation was significantly associated with control proliferation and the year of birth. The age of the animal at sampling influenced only Staph. aureus-induced proliferation, with Staph. aureus-induced proliferation increasing with the age of the animal. Control proliferation was influenced by a sex x cross interaction, although in this study, sex was confounded by management, as female cattle were housed and reared differently from male cattle. All 3 measures of immune function were influenced by sire, demonstrating that these traits are partially under genetic control, and indicating that it may ultimately be possible to identify quantitative trait loci for these measures of immunity.

Animals↗