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W H Wood

Publications and source records attributed to W H Wood.

13 recordsLinked to original sources
PubMed2006

Gene expression response to cisplatin treatment in drug-sensitive and drug-resistant ovarian cancer cells.

The molecular pathways activated in response to acute cisplatin exposure, as well as the mechanisms involved in the long-term development of cisplatin-resistant cancer cells remain unclear. Using whole genome oligonucleotide microarrays, we have examined the kinetics of gene expression changes in a cisplatin-sensitive cell line, A2780, and its cisplatin-resistant derivative, ACRP. Both sensitive and resistant cell lines exhibited a very similar response of p53-inducible genes as early as 16 h after treatment. This p53 response was further increased at the 24-h time point. These experiments identify p53 as the main pathway producing a large-scale transcriptional response after cisplatin treatment in these cells containing wild-type p53. Consistent with a role for the p53 response in cisplatin sensitivity, knockdown of the p53 protein with small interfering RNA led to a twofold decrease in cell survival in the resistant cells. In addition, our analysis also allowed the identification of several genes that are differentially expressed between sensitive and resistant cells. These genes include GJA1 (encoding connexin 43 (Cx43)) and TWIST1, which are highly upregulated in cisplatin-resistant cells. The importance of Cx43 in drug resistance was demonstrated through functional analyses, although paradoxically, inhibition of Cx43 function in high expressing cells led to an increase in drug resistance. The pathways important in cisplatin response, as well as the genes found differentially expressed between cisplatin-resistant and -sensitive cells, may represent targets for therapy aimed at reversing drug resistance.

Cisplatin↗
PubMed2001

Application of cDNA microarrays to examine gene expression differences in schizophrenia.

Using cDNA microarrays we have investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA neuroarray, comprised of genes related to brain function, was used to screen pools of samples from the cerebellum and prefrontal cortex from a matched set of subjects, and middle temporal gyrus, from a separate subject cohort. Samples of cerebellum and prefrontal cortex from neuroleptic naive patients were also included. Genes that passed a 3% reproducibility criterion for differential expression in independent experiments included 21 genes for drug-treated patients and 5 genes for drug-naive patients. Of these 26 genes, 10 genes were increased and 16 were decreased. Many of the differentially expressed genes were related to synaptic signaling and proteolytic functions. A smaller number of these genes were also differentially expressed in the middle temporal gyrus. The five genes that were differentially expressed in two brain regions from separate cohorts are: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide; sialyltransferase; proteasome subunit, alpha type 1; ubiquitin carboxyl-terminal esterase L1; and solute carrier family 10, member 1. Identification of patterns of changes in gene expression may lead to a better understanding of the pathophysiology of schizophrenia disorders.

Adult↗
PubMed2001

A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity.

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.

cDNA microarray technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to mammalian development have been hampered by the lack of appropriate cDNA collections, particularly for early developmental stages. To overcome this problem, a PCR-based cDNA library construction method was used to derive 52,374 expressed sequence tags from pre- and peri-implantation embryos, embryonic day (E) 12.5 female gonad/mesonephros, and newborn ovary. From these cDNA collections, a microarray representing 15,264 unique genes (78% novel and 22% known) was assembled. In initial applications, the divergence of placental and embryonic gene expression profiles was assessed. At stage E12.5 of development, based on triplicate experiments, 720 genes (6.5%) displayed statistically significant differences in expression between placenta and embryo. Among 289 more highly expressed in placenta, 61 placenta-specific genes encoded, for example, a novel prolactin-like protein. The number of genes highly expressed (and frequently specific) for placenta has thereby been increased 5-fold over the total previously reported, illustrating the potential of the microarrays for tissue-specific gene discovery and analysis of mammalian developmental programs.

Amino Acid Sequence↗
PubMed1979

Microbiologic and antibiotic aspects of infections in the oral and maxillofacial region.

An overview of infection as it applies to the oral and maxillofacial region has been provided. The following conclusions are drawn: odontogenic infections are caused by microbes found in the host's oral flora; cultures of purulent material generally will yield three to six anaerobes and one aerobe, (the aerobe is usually a Streptococcus species); Gram stains of purulent material can aid in therapeutic strategies; anaerobic as well as aerobic cultures are necessary to isolate all pathogens; pathogens found in infections of bite wounds reflect the oral flora of the aggressor; early postoperative wound infections are caused by the host's own flora, whereas later infections may be caused by hospital-acquired bacteria; and hepatitis B and herpes simplex virus are occupational hazards. Recommendations have been made for antimicrobial prophylaxis and for treatment. We recognize that some of these selections may be controversial. For instance, the value of prophylactic antibiotics in orthognathic surgery is not well defined; recommendations were made only in certain instances. However, in severe penetrating maxillofacial injuries with devitalized tissue, recommendations for antibiotics were for broad and prolonged coverage. In this instance, use of antibiotics is considered therapeutic and not prophylactic. In each instance, we tried to validate the selection. Our rationale has been to choose the antibiotics most active against the likely pathogens; additionally, consideration was given to drug toxicity and adverse reactions. We regard penicillin as the preferred agent for prophylaxis and treatment of most odontogenic infections. Alternative drugs include cephalosporins, doxycycline, and clindamycin. Erythoromycin and tetracycline are considered less effective than the former agents. Finally, we believe that successful treatment of infection depends as much on changing the microenvironment of the infected tissue by debridement and drainage as on appropriate antimicrobial therapy.

Actinomycosis↗
PubMed1967

The cell wall of Rickettsia mooseri. I. Morphology and chemical composition.

Cell walls prepared by mechanically disrupting intact Rickettsia mooseri (R. typhi) were examined in an electron microscope and analyzed chemically. Electron micrographs of metal-shadowed and negatively stained rickettsial cell walls revealed no significant differences, except for smaller size, from bacterial cell walls prepared in a similar manner. The chemical composition was complex, and resembled that of gram-negative bacterial cell walls more closely than that of gram-positive bacterial cell walls. R. mooseri cell walls contained the sugars, glucose, galactose, and glucuronic acid, the amino sugars, glucosamine, and muramic acid, and at least 15 amino acids. Diaminopimelic acid, a compound hitherto found only in bacteria and blue-green algae, was demonstrated in rickettsiae for the first time. Teichoic acids were not detected. The compounds identified accounted for about 70% of the dry weight of the cell walls.

Amino Acids↗