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Thomas Wood

Publications and source records attributed to Thomas Wood.

7 recordsLinked to original sources
PubMed2005

Gene expression profile of an adenomyoepithelioma of the breast with a reciprocal translocation involving chromosomes 8 and 16.

Myoepithelium is an integral part of the mammary ductal and lobular architecture, positioned between luminal cells and the basement membrane. We describe the first report on cytogenetic findings in an adenomyoepithelioma of the breast with a balanced t(8;16)(p23;q21), and provide gene expression profile using Affymetrix GeneChip U95AV2 (Affymetrix, Santa Clara, CA). Differential analysis identified 857 genes with 2-fold or more mRNA change in comparison to pooled normal breast control; immunohistochemical analysis was used to confirm these results in a limited number of genes. Expression results were grouped based on the chromosomal location of the genes and associated protein function, and identified several potential pathogenetic mechanisms (autocrine and paracrine growth stimuli) in the development of myoepithelial tumors.

Aged↗
PubMed2004

Synthesis and structural characterization of trivalent amino acid derived chiral phosphorus compounds.

Reaction of the N-toluenesulfonyl derivatives of (S)-alanine, phenylalanine, and valine (4-6) with PhPCl(2) gave in high yield the 4-methyl, benzyl, and isopropyl derivatives (7-9) of 2-phenyl-1-p-toluenesulfonyl-1,3,2-oxazaphospholidin-5-one. The ratios of the (2S,4S)/(2R,4S) diastereomers (cis/trans isomers) were 1:1, 2:1, and 10:1 for the methyl, benzyl, and isopropyl derivatives 7a,b, 8a,b, and 9a,b, respectively. For 7a,b, both isomers could be crystallized, but for the others only the major isomers were isolable. The X-ray crystal structure of 9a shows that the isopropyl and phenyl groups are mutually cis and that the tolyl moiety is oriented s-trans to both the isopropyl and phenyl groups. Reaction of 6 with Cl(2)PCH(2)CH(2)PCl(2) (10) gave a 56:38:7 mixture of the cis/cis, cis/trans, and trans/trans diphosphorus heterocycles 11a-c. The major isomer could be crystallized and isolated free of the other diastereomers. Reaction of 6 with EtPCl(2) gave a 6:1 mixture of cis/trans isomers of the ethyl-substituted heterocycles 12a,b as an inseparable oil but allowed confirmation of the structure of 11a. Slow epimerization at phosphorus may occur by inversion but more likely by ring opening/closure, since 7b, 9a, and 11a give rise upon standing in solution to mixtures containing starting material and 7a, 9b, and 11b, respectively, along with the free amino acid derivatives 4 and 6. The NMR spectra, and in particular the coupling constants between the alpha-hydrogen atom of the amino acid moiety and phosphorus, were used to establish the identities of the cis and trans isomers. Reaction of 9a with (THF)W(CO)(5) gave the phosphorus-ligated adduct (9a)W(CO)(5) (13), and the IR spectrum of this complex shows that 9a is a strongly electron-withdrawing ligand. The geometry of the sulfonamide moiety is discussed in detail, as are the (1)H NMR coupling constants. The data are consistent with the presence of little steric interaction between the cis isopropyl and phosphorus substituent in 9a, 11a, and 12a and orientation of the tolyl moiety s-cis to the isopropyl group in 9b, 12b, and 13.

Amino Acids↗
PubMed2004

Intestinal expression of mutant and wild-type progastrin significantly increases colon carcinogenesis in response to azoxymethane in transgenic mice.

BACKGROUND: The authors recently reported that transgenic mice (hGAS) expressing pharmacologic levels of progastrin (PG) (> 10 nM to 100 nM) exhibited increased susceptibility to colon carcinogenesis in response to azoxymethane (AOM). It is not known whether PG functions as a cocarcinogen at the concentrations observed in patients with hypergastrinemia (approximately 1.0 nM). METHODS: The authors generated transgenic mice that overexpressed either wild-type (wtPG) or mutant (mtPG) human PG in the intestinal mucosa using the murine fatty acid binding protein (Fabp) promoter. Fabp-PG mice and their wild-type littermates were treated with AOM, and their colons were examined for preneoplastic (aberrant crypt foci [ACF]) and neoplastic (adenomas [Ads] and adenocarcinomas [AdCas]) lesions after 2 weeks and 6 months of treatment. RESULTS: ACF and tumors were significantly more common (by a factor of approximately 2) in colon specimens from both Fabp-wtPG mice and Fabp-mtPG mice relative to wild-type mice. It is noteworthy that the multiplicity of ACF and the total number of small and large Ads and AdCas were significantly greater in colon specimens from Fabp-PG mice compared with colon specimens from wild-type mice, irrespective of gender. CONCLUSIONS: The results of the current study suggest that at concentrations (approximately 1.0 nM) far lower than the ones observed in hGAS mice, PG functions as an equally potent cocarcinogen and significantly increases the risk of colon carcinogenesis in response to AOM. Thus, PG may represent a clinically relevant target molecule in patients with hypergastrinemia or colon carcinoma.

Animals↗
PubMed2002

Deletion of functional gastrin gene markedly increases colon carcinogenesis in response to azoxymethane in mice.

BACKGROUND & AIMS: We recently reported that transgenic mice overexpressing progastrin were at a higher risk for developing colon cancers in response to azoxymethane (AOM), whereas mice overexpressing gastrin-17 were at a reduced risk. To examine further the role of gastrins in colon carcinogenesis, we generated gastrin gene knockout mice (GAS-KO). METHODS: The height and proliferative index (PI) of colonic crypts were similar in GAS-KO and wild-type (WT) mice, suggesting that the absence of gastrins in GAS-KO mice did not significantly affect the growth of colonic mucosa. GAS-KO and WT mice were treated with AOM for 3-4 weeks; control mice received saline. RESULTS: Colonic proliferation in response to AOM was significantly increased in GAS-KO vs. WT mice. Aberrant crypt foci (ACFs) were similarly increased significantly by approximately 2-5-fold in GAS-KO vs. WT mice after 2 weeks of AOM treatment. Female GAS-KO mice developed adenomas (Ads) and adenocarcinomas (AdCAs) at earlier times ( approximately 10 months) than the male GAS-KO mice and the male and female WT mice ( approximately 12 months). The total numbers of Ads and AdCAs were significantly higher in GAS-KO than in WT mice. CONCLUSIONS: These results suggest the novel possibility that loss of gastrin expression (and hence amidated gastrins) significantly increases susceptibility to colon carcinogenesis in response to AOM. Previous studies with FVB/N transgenic mice similarly suggested a protective role of amidated gastrins against colon carcinogenesis, which supports the present findings of an increase in colon carcinogenesis in GAS-KO mice lacking normal physiological levels of amidated gastrins.

Animals↗
PubMedDate not supplied

Age-associated changes in gene expression patterns in the liver.

Aging is one of the least clearly understood biological processes. Alteration of oxidation/reduction (redox) enzymes has been demonstrated with aging; however, a systematic analysis of expression patterns has not been performed. The liver plays a key role in homeostasis and detoxification; therefore alteration of hepatic gene expression with aging may affect outcome after surgery. The purpose of our study was to assess changes in gene expression patterns in aged livers from both rats and humans using gene array analysis. Total RNA was extracted from young (2-month-old) and aged (2-year-old) rat livers, as well as young (1-year-old) and aged (78-year-old) human livers. Gene expression patterns were compared using Affymetrix GeneChip arrays. The expression pattern of selected genes was confirmed by reverse transcription-polymerase chain reaction. A threefold or greater change in gene expression was noted in 582 genes in the aged rat livers and 192 genes in the aged human livers. Comparison of the genes that were increased with aging demonstrated some similar patterns of expression in the rat and human livers, particularly in members of the antioxidant family and the cytochrome P-450 genes. Our findings demonstrate changes in the expression pattern of genes in the liver with aging. Concomitant increases in the expression of important antioxidant and detoxifying genes were noted in the livers of both rats and humans. This induction pattern suggests a complex link between changing hepatic detoxification/redox capability and senescence.

Aged↗
PubMedDate not supplied

Small-scale electrical resistivity tomography of wet fractured rocks.

This paper describes a series of experiments that tested the ability of the electrical resistivity tomography (ERT) method to locate correctly wet and dry fractures in a meso-scale model. The goal was to develop a method of monitoring the flow of water through a fractured rock matrix. The model was a four by six array of limestone blocks equipped with 28 stainless steel electrodes. Dry fractures were created by placing pieces of vinyl between one or more blocks. Wet fractures were created by injecting tap water into a joint between blocks. In electrical terms, the dry fractures are resistive and the wet fractures are conductive. The quantities measured by the ERT system are current and voltage around the outside edge of the model. The raw ERT data were translated to resistivity values inside the model using a three-dimensional Occam's inversion routine. This routine was one of the key components of ERT being tested. The model presented several challenges. First, the resistivity of both the blocks and the joints was highly variable. Second, the resistive targets introduced extreme changes the software could not precisely quantify. Third, the abrupt changes inherent in a fracture system were contrary to the smoothly varying changes expected by the Occam's inversion routine. Fourth, the response of the conductive fractures was small compared to the background variability. In general, ERT was able to locate correctly resistive fractures. Problems occurred, however, when the resistive fracture was near the edges of the model or when multiple fractures were close together. In particular, ERT tended to position the fracture closer to the model center than its true location. Conductive fractures yielded much smaller responses than the resistive case. A difference-inversion method was able to correctly locate these targets.

Electricity↗