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Biomedical subjects

Robert J Baker

Publications and source records attributed to Robert J Baker.

31 records · Page 2Linked to original sources
PubMed2003

Analogies between the reactivities of an anionic gallium(I) heterocycle and N-heterocyclic carbenes toward metallocenes.

The synthesis, spectroscopic and structural characterization of the novel nickel-gallium(I) heterocycle complex, [{Ga[N(Ar)C(H)]2}2Ni(mu-Cp)K(tmeda)(mu-Cp)K(mu-C7H8)0.5]infinity, Ar = C6H3Pri2-2,6, are reported. The compound is polymeric in the solid state and reacts with an N-heterocyclic carbene to give the neutral, square planar complex, trans-[Ni{C[N(Me)C(Me)]2}2{Ga[N(Ar)C(H)]2}2]. Analogies between the reactivities of the gallium(I) heterocycle and isoelectronic N-heterocyclic carbenes are discussed.

Journal Article↗
PubMed2003

The synthesis of phosphorus heterocycles from tetra-tert-butyltetraphosphacubane.

Tetra-tert-butyltetraphosphacubane, P(4)C(4)(t)Bu(4), reacts with water in the presence of 'GaI' to yield two products, namely 4,6,7,8-tetra-tert-butyl-1,2,3-triphospha-5-phosphoniatetracyclo[3.2.1.0(2,4).0(3,8)]oct-6-ene tetraiodogallate(III), (C(20)H(37)P(4))[GaI(4)], and triiodo(3,5,7,8-tetra-tert-butyl-1,2,4lambda(5),6-tetraphosphatetracyclo[4.1.1.0(2,5).0(7,8)]octan-4-one)gallium(III), [GaI(3)(C(20)H(38)OP(4))], both of which have been structurally characterized. The X-ray crystal structure determination of the former compound shows it to be an ion-separated salt, while the latter compound is a neutral phosphinite complex of GaI(3).

Journal Article↗
PubMed2003

Subgenome-specific markers in allopolyploid cotton Gossypium hirsutum: implications for evolutionary analysis of polyploids.

We developed a set of genetic markers specific to the A and D genome types of cotton using representational difference analysis (RDA). These markers produce amplification products with genomic DNA from allotetraploid cotton Gossypium hirsutum. One of the markers is a polymorphic amplified restriction fragment (PARF) - a sequence found in both A and D genomes but differently flanked by restriction sites. Results of phylogenetic analysis of the PARF sequences from diploid cottons and from allotetraploid G. hirsutum agree with a previous observation of the interlocus concerted evolution (sequences corresponding to A and D genomes are homogenized to a D genome-type sequence). Our study shows how RDA can be used to develop genome-specific markers that can be used to study molecular evolution of allopolyploids.

DNA, Plant↗
PubMed2003

The reaction of 'GaI' with a 1,3-diyne: synthesis, characterisation and reactivity of a novel C-C coupled ene-diyne-bis(gem-organodigallium(III)) complex.

Treatment of 'GaI' with a 1,3-diyne, Me3SiC[triple bond]CC[triple bond]CSiMe3, leads to C-C coupling reactions and the isolation of the novel organogallium species, [Ga4I8[C8(SiMe3)4]], as two isomeric forms; their X-ray crystal structures show them to contain the first structurally authenticated gem-organodigallium fragments and to exhibit rare examples of Ga-alkyne pi-interactions.

Journal Article↗
PubMed2003

Exposure to chronic, low-dose rate gamma-radiation at Chornobyl does not induce point mutations in Big Blue mice.

Empirical genetic effects resulting from low-dose rate irradiation and chronic, cumulative exposure are poorly characterized. Expected effects are based on epidemiological studies and downward, linear extrapolations from nonthreshold models derived from acute, high-dose exposures. These extrapolations and their associated risk coefficients have no experimental support, and because of their inherent uncertainty they are the subject of considerable debate. The expectation of deleterious genetic effects resulting from low-dose rate irradiation and chronic exposure is in need of empirical assessment because this type of exposure is typical of those encountered in occupational, residential, and environmental settings. Recent acute low-dose (<10 cGy) studies using cytogenetic and point mutation endpoints indicate that observed effects range from those lower than spontaneous to an increase in the frequency of point mutations. Using the Big Blue assay, we examined the ability of chronic, continuous gamma-irradiation (2.3 x 10(-3) cGy/min) in the Chornobyl environment to induce point mutations. This system has demonstrated a significant point mutation sensitivity (4.5-fold increase) to acute, high-dose (1-3 Gy) gamma-radiation. Mutant frequencies and the mutation spectra were examined in exposed and reference samples of Big Blue mice following 90 days exposure (cumulative absorbed dose = 3 Gy) to the Chornobyl environment. No significant increase in the mutant frequency or bias in the mutational spectrum was observed in exposed individuals. This finding suggests that low-dose rate gamma-irradiation at Chornobyl does not induce point mutations and that cumulative, chronically absorbed doses do not induce the same genetic effects as acute doses of the same magnitude.

Animals↗
PubMed2003

Cytotoxic drugs enhance the ex vivo sensitivity of malignant cells from a subset of acute myeloid leukaemia patients to apoptosis induction by tumour necrosis factor receptor-related apoptosis-inducing ligand.

We have studied the actions of tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) on cells isolated from patients with acute myeloid leukaemia (AML). Apoptosis induction was initially assessed by quantitative morphological analysis. Only 2/19 isolates showed a > 10% increase in apoptotic cells following TRAIL treatment. However, incubation with TRAIL combined with fludarabine, cytosine arabinoside or daunorubicin resulted in additive or super-additive apoptosis induction in approximately half of the isolates. Molecular evidence of super-additive apoptosis induction by TRAIL and cytotoxic agents was obtained by quantification of caspase 3 activation, detected by Western blot analysis of poly (ADP ribose) polymerase cleavage. The ability of TRAIL and daunorubicin to induce super-additive apoptosis correlated with the ability of these agents to activate caspase 8 and to augment cellular levels of the truncated pro-apoptotic form of the BCL-2 family member BID. Our data suggest that co-administration of TRAIL with conventional cytotoxic drugs may be of therapeutic value in some patients with AML.

Acute Disease↗
PubMed2003

mtDNA perspective of chromosomal diversification and hybridization in Peters' tent-making bat (Uroderma bilobatum: Phyllostomidae).

We compared sequence variation in the complete mitochondrial cytochrome-b gene with chromosomal and geographical variation for specimens of Peters' tent-making bat (Uroderma bilobatum). Three different chromosomal races have been described in this species: a 2n = 42 race from South America east of the Andes, a 2n = 44 from NW Central America and 2n = 38 from the rest of Central America and NW South America. The deepest nodes in the tree were found within the South American race (42 race), which is consistent with a longer history of this race. Average distance among races ranged from 2.5 to 2.9%, with the highest amount of intraracial variation found within the 2n = 42 race (1.7%), intermediate values within the 2n = 38 race (0.9%) and lowest within the 2n = 44 race (0.5%). Variation among chromosomal races accounted for over 55% of molecular variance, whereas variation among populations within races accounted for 6%. The 2n = 38 and 2n = 44 races hybridize in the coastal lowlands of Honduras, near the Gulf of Fonseca. Introgression between these two races is low (two introgressed individuals in 45 examined). Clinal variation across the hybrid zone for the cytochrome-b of U. bilobatum, is similar to clinal variation reported for chromosomes and isozymes of this species. Mismatch distribution analyses suggests that geographical isolation and karyological changes have interplayed in a synergistic fashion. Fixation of the alternative chromosomal rearrangements in geographical isolation and secondary contact is the most likely mechanism accounting for the hybrid zone between the 2n = 38 and 2n = 44 races. If a molecular clock is assumed, with rates ranging from 2.3 to 5.0% per million years, then isolation between these races occurred within the last million years, implying a relatively recent origin of the extant diversity in Uroderma bilobatum. None the less, the three chromosomal races probably represent three different biological species.

Animals↗
PubMed2003

Mitochondrial DNA heteroplasmy in laboratory mice experimentally enclosed in the radioactive Chernobyl environment.

Mitochondrial DNA heteroplasmy using the protein-coding cytochrome b (Mtcyb) gene was assessed in laboratory mice (C57BL/6 and BALB/c) exposed to the Chernobyl environment. Subacute to subchronic (30-40 days) exposure resulted in a cumulative radiation dose of 1.2-1.6 Gy ( approximately 0.04 Gy/day). Mice were sampled prior to introduction into the enclosures and again after removal from the enclosures. Nucleotide variation (site heteroplasmy) in 306 pre-exposure Mtcyb gene copies (122400 base pairs) was compared to variation in 354 postexposure gene copies (141600 base pairs). Five mutant copies, each characterized by a single nucleotide substitution, were observed (four in the pre-exposure samples, one in a postexposure sample). The frequencies of mutant gene copies and nucleotide substitutions in pre-exposure and postexposure samples were not significantly different. This suggests that this type of exposure (i.e. low dose rate) does not pose a significant mutation risk to the Mtcyb gene in digit tissue. Furthermore, no significant radiation risk to analogous human tissues may exist when occupational exposures involve low dose rates such as these. Finally, linear, cumulative models of genetic risk currently used to estimate radiation-induced effects are likely to be inappropriate for low-dose-rate exposures and need to be re-evaluated critically.

Animals↗
PubMed2002

Utility of chromosomal position of heterochromatin as a biomarker of radiation-induced genetic damage: a study of Chornobyl voles (Microtus sp.).

Biomarkers that effectively document effects of chronic multi-generational exposure to contaminated environments on chromosomes would be valuable in risk assessment, remediation, and environmental decisions. Native, free-ranging populations of voles inhabiting the highly radioactive regions surrounding Reactor 4 of the Chornobyl Nuclear Power Station provide a model system to evaluate biological and chromosomal effects of chronic multi-generational exposure to radioactivity and other reactor meltdown-related pollutants. Here, we explore the utility of heterochromatic elements as potentially informative biomarkers for genetic damage in voles from the radioactive environments surrounding Chornobyl. We analyzed chromosomal positions of heterochromatin from Microtus arvalis and M. rossiaemeridionalis using fluorescent in situ hybridization. Although intrapopulational variation existed in chromosomal position and abundance of heterochromatin, none of that variation could be assigned to environmental exposure.

Animals↗
PubMed2002

K-ras oncogene DNA sequences in pink salmon in streams impacted by the Exxon Valdez oil spill: no evidence of oil-induced heritable mutations.

It was hypothesized in previous studies that the Exxon Valdez oil spill in Prince William Sound, Alaska, induced heritable mutations and resulted in mortality of pink salmon (Oncorhynchus gorbuscha) embryos. In one of these studies, laboratory exposure of pink salmon embryos to crude oil resulted in apparent mutation-induction in exon 1 and exon 2 of the K-ras oncogene, but no fish from the area impacted by the oil spill were analyzed. We assessed K-ras exon 1 and exon 2 DNA sequences in pink salmon from five streams that were oiled and five streams that were not oiled by the Exxon Valdez oil spill in Prince William Sound, and two streams with natural oil seeps and one stream without seeps on the Alaska Peninsula. Of the 79 fish analyzed for exon 1 and the 89 fish analyzed for exon 2, none had the nucleotide substitutions representing the mutations induced in the laboratory study. Other variable nucleotides occurred in similar proportions in oiled and non-oiled streams and probably represent natural allelic variation. These data do not support the hypothesis that heritable mutations in the K-ras gene were induced by the Exxon Valdez oil spill or oil seeps.

Alaska↗
PubMed2002

Assessing the genotoxicity of chronic environmental irradiation by using mitochondrial DNA heteroplasmy in the bank vole (Clethrionomys glareolus) at Chornobyl, Ukraine.

This study was designed to investigate whether or not chronic exposure to Chornobyl radiation poses a molecular genetic risk to mammals by examining a relatively rapidly evolving genetic system, mitochondrial DNA (mtDNA). More mtDNA mutations (approximately 19%) and an increase in mtDNA heteroplasmy (approximately 5%) occurred in the cytochrome b gene of an exposed mother-embryo set when compared to a relatively unexposed mother-embryo set. However, this increase was not statistically significant (p > 0.05). Our results, in conjunction with previous molecular genetic research on small mammals from Chornobyl, suggest that chronic exposure to environmental ionizing radiation does not increase the number of nucleotide substitutions, as predicted by studies using acute or subacute exposures. Thus, cumulative models of radiation risk would not appear to follow simple linear functions derived from high doses and dose rates. The equivocal nature of research regarding the effects of the Chornobyl accident indicates that future research is warranted such that models of chronic environmental exposure can be developed or refined. Although additional study is required to properly validate mtDNA heteroplasmy as a useful effect biomarker, examination of these data does not indicate that a significant risk to mtDNA exists in native rodents chronically exposed to both internal and external radiation.

Animals↗