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T Moore

Publications and source records attributed to T Moore.

At least 73 records · Page 4Linked to original sources
PubMed1998

DMSO produces a new subgel phase in DPPC: DSC and X-ray diffraction study.

Equilibrium phases and the kinetics of subgel phase transformation of dipalmitoylphosphatidylcholine (DPPC) hydrated with mixtures of dimethylsulfoxide (DMSO)/water have been studied using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The rate of gel-to-subgel transformation is decreased with a small increase in X, the DMSO/water mole fraction, but then speeds up and becomes faster than in pure water by X = 0.16. The DSC scans show multiple subgel peaks, some of which can be attributed to impacted domain growth. For X greater than 0.10, XRD shows that there is a new, stable subgel phase, S, which also accounts for some of the multiplicity of DSC peaks. Our electron density profiles show that the thickness of the bilayer in the S phase is greater than in the usual C subgel phase. We suggest that the S subgel phase is characterized by different headgroup ordering and smaller chain tilt angle than in the C subgel phase. Electron density profiles show that increasing X decreases the water space between bilayers in all phases, subgel, gel and fluid (L alpha). For X = 0.20, a different gel phase is also observed that may be due to subtle changes in the orientation of chain tilt first observed in partially dehydrated DMPC. The dehydrating effect of DMSO explains the results of a previous study, confirmed in this study, that increasing the concentration of DMSO raises the main transition temperature and eliminates the ripple phase.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Tumor remnants within giant cells following irradiation of cutaneous squamous cell carcinoma.

BACKGROUND: The histopathologic effects of curative doses of radiation therapy on cutaneous squamous cell carcinoma (SCC) have not been well described in the dermatologic literature. OBJECTIVE: To understand the histopathologic process of cutaneous SCC involution following radiation treatment. METHODS: Hematoxylin-eosin stain and immunoperoxidase stains for keratin were performed on tissue from the site of a primary cutaneous SCC 2 months after completion of fractionated radiation therapy (7000 cGy total) but prior to clinical involution. RESULTS: Histopathological examination of the irradiated SCC revealed dermal keratin pearls and keratinocytic necrosis resembling apoptosis as well as inflammation and foreign body giant cell reaction. Immunoperoxidase staining for keratin revealed cellular remnants of cutaneous SCC without intact keratinocytic nuclei within giant cells. CONCLUSION: Complete clinical resolution of the SCC over the next several weeks without recurrence after 15 months confirmed the histopathologic findings of tumor destruction by primary radiation therapy.

Aged↗
PubMed1998

A cellular protein binds vaccinia virus late promoters and activates transcription in vitro.

Available evidence indicates that the transcription of the late class of vaccinia virus genes requires the participation of several virus-encoded proteins in addition to the viral RNA polymerase. In this report we describe the identification of a protein present in extracts of uninfected HeLa cells that binds avidly to viral late promoter DNA. The protein bound specifically to several different vaccinia virus late promoters but not an early nor an intermediate promoter. DNase I footprinting localized the protein's binding site to nucleotides surrounding the transcriptional start site of the I1L promoter. Optimal promoter binding required sequences in the highly conserved TAAAT motif at the transcriptional start site as well as sequences immediately upstream; however, one variation on the motif's sequence did not affect promoter binding by the protein. Partially purified late promoter binding protein (LPBP) was capable of stimulating the transcription activity of extracts depleted of LPBP on a late promoter-driven template, establishing LPBP as a transcription activator in vitro. These results suggest that a cellular protein is responsible for targeting vaccinia virus late promoters for initiation of transcription.

Binding Sites↗
PubMed1998

Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes.

In vitro manipulation of preimplantation mammalian embryos can influence differentiation and growth at later stages of development. In the mouse, culture of embryonic stem (ES) cells affects their totipotency and may give rise to fetal abnormalities. To investigate whether this is associated with epigenetic alterations in imprinted genes, we analysed two maternally expressed genes (Igf2r, H19) and two paternally expressed genes (Igf2, U2af1-rs1) in ES cells and in completely ES cell-derived fetuses. Altered allelic methylation patterns were detected in all four genes, and these were consistently associated with allelic changes in gene expression. All the methylation changes that had arisen in the ES cells persisted on in vivo differentiation to fetal stages. Alterations included loss of methylation with biallelic expression of U2af1-rs1, maternal methylation and predominantly maternal expression of Igf2, and biallelic methylation and expression of Igf2r. In many of the ES fetuses, the levels of H19 expression were strongly reduced, and this biallelic repression was associated with biallellic methylation of the H19 upstream region. Surprisingly, biallelic H19 repression was not associated with equal levels of Igf2 expression from both parental chromosomes, but rather with a strong activation of the maternal Igf2 allele. ES fetuses derived from two of the four ES lines appeared developmentally compromised, with polyhydramnios, poor mandible development and interstitial bleeding and, in chimeric fetuses, the degree of chimerism correlated with increased fetal mass. Our study establishes a model for how early embryonic epigenetic alterations in imprinted genes persist to later developmental stages, and are associated with aberrant phenotypes.

Alleles↗
PubMed1998

Thermography and nailfold capillaroscopy as noninvasive measures of circulation in children with Raynaud's phenomenon.

OBJECTIVE: To determine in a pilot study the feasibility of noninvasive techniques of (a) measurement of rewarming response after a standard cold challenge test (using thermographic imaging) and (b) measurement of nailfold capillary dimensions using video capillaroscopy, in the assessment of children presenting with Raynaud's phenomenon (RP). METHODS: Ten children with RP and 10 age matched healthy controls were studied. No child had definite evidence of underlying connective tissue disease. RESULTS: Children with RP had abnormal rewarming curves. The gradient of the rewarming curve was significantly lower in children with RP (median 1.5 vs 5.0 degrees C/min in controls; p = 0.015), and there was a trend for the lag time (the interval between the end of the cold challenge and the onset of rewarming) to be increased in children with RP (median 4.7 vs 0.5 min in controls; p = 0.08). Capillary dimensions were measured in 7 of the children with RP, and were similar to those of healthy controls. CONCLUSION: Thermography and nailfold capillaroscopy are feasible in children and should be further evaluated.

Adolescent↗
PubMed1997

Multiple imprinted sense and antisense transcripts, differential methylation and tandem repeats in a putative imprinting control region upstream of mouse Igf2.

The mouse insulin-like growth factor 2 (Igf2) locus is a complex genomic region that produces multiple transcripts from alternative promoters. Expression at this locus is regulated by parental imprinting. However, despite the existence of putative imprinting control elements in the Igf2 upstream region, imprinted transcriptional repression is abolished by null mutations at the linked H19 locus. To clarify the extent to which the Igf2 upstream region contains autonomous imprinting control elements we have performed functional and comparative analyses of the region in the mouse and human. Here we report the existence of multiple, overlapping imprinted (maternally repressed) sense and antisense transcripts that are associated with a tandem repeat in the mouse Igf2 upstream region. Regions flanking the repeat exhibit tissue-specific parental allelic methylation patterns, suggesting the existence of tissue-specific control elements in the upstream region. Studies in H19 null mice indicate that both parental allelic methylation and monoallelic expression of the upstream transcripts depends on an intact H19 gene acting in cis. The homologous region in human IGF2 is structurally conserved, with the significant exception that it does not contain a tandem repeat. Our results support the proposal that tandem repeats act to target methylation to imprinted genetic loci.

Alleles↗
PubMed1997

Hadamard conjugations and modeling sequence evolution with unequal rates across sites.

This paper considers the many different distributions that may approximate the distribution of site rates in DNA sequences and shows how the Hadamard conjugation may be modified to take these into account. This is done for both 2-state and 4-state data. Distributions which give simple closed forms include the gamma (gamma) distribution, the inverse Gaussian distribution (which is similar to the lognormal), and a mixture of either of these with a proportion of sites which cannot change (invariant sites). It is seen that the tail of a distribution can have major effects upon the coefficient of variation of site rates. Because the Hadamard conjugation can be used to either correct data or predict the data given the model (i.e., the likelihood of site patterns), light is shed on properties of maximum likelihood tree selection with unequal site rates. Analysis of rRNA shows how unequal rates across sites can change the optimal tree. Maximum likelihood analysis also shows that distinct distributions fit each data set, with the gamma often not being the best. Analyzing both these data and a long stretch of primate mtDNA reveals evidence of many "hidden" multiple substitutions, while signals not corresponding to the preferred biological tree generally decrease an unequal rates are allowed for. Last, we discuss the expected behavior of sequences evolving by models where stabilizing selection alone explains unequal site rates. Such models do not explain "synapomorphies" or informative changes in ancient molecules, because while stabilizing selection can vastly decrease change at a site, it will also vastly accelerate back-substitution (leaving only a covarion model to explain old synapomorphies). When and why models allowing a continuous distribution of site rates (e.g., gamma) will approximate covarion evolution requires further study.

Algorithms↗
PubMed1997

Functional characterization of equine neutrophils in response to calcium ionophore A23187 and phorbol myristate acetate ex vivo.

Equine neutrophils (PMN) play a critical role in inflammatory processes in horses. The objective of this study was to characterize equine PMN function ex vivo following stimulation with calcium ionophore A23187 (A23187) and phorbol myristate acetate (PMA). These stimulants trigger different branches of the PMN activation process that occurs in vivo. Equine PMN were isolated from the whole blood of six clinically normal geldings using a one-step discontinuous Percoll gradient technique. Neutrophil aggregation, degranulation, and superoxide anion production were evaluated in assay systems which had previously been established to quantitate PMN function. Dose-response curves for A23187 and PMA were derived for the three functions. Results indicate that equine PMN aggregation and superoxide anion production are more responsive to activation by PMA as the maximum change in percent transmittance and maximum nanomoles of superoxide anion produced following PMA stimulation (60.8% and 10.4 nmol per 10(6) cells, respectively) were greater than those values stimulated by A23187 (41.5% and 5.2 nmol per 10(6) cells, respectively). However, degranulation was found to be more responsive to A23187 stimulation (maximum percent degranulation: 56.1%) than to PMA stimulation (maximum percent degranulation: 30.7%). Dose-response curves following A23187 and PMA stimulation revealed that superoxide anion production had the lowest threshold concentration among the three functions. Degranulation had the highest threshold concentration among the three functions for both stimulants. Results indicate that equine PMN functions differ in their dependence on second messengers in the activation pathway. These functions also occur in a dose-dependent manner and differ in the threshold concentrations required for their stimulation.

Animals↗
PubMed1997

A 1.1-Mb transcript map of the hereditary hemochromatosis locus.

In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein. Several members of the butyrophilin family and the RoRet gene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently "shuffled" into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology of HLA-H to MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.

Amino Acid Sequence↗
PubMed1997

Changing cancer outcome: the role of LSUMC Minority-Based Clinical Community Oncology Program.

The National Cancer Institute has recognized the need for minority participation in clinical trials as a means to enhance cancer outcomes in minority populations and to validate the outcomes of clinical research. In 1994, Louisiana State University Medical Center in New Orleans was granted an award by the National Cancer Institute to establish a Minority-Based Clinical Community Oncology Program. This article outlines the Louisiana State University's Minority Based Clinical Community Oncology Program. During the initial funding period, the Program has established a regional network of cancer physicians and healthcare professionals to provide state-of-the-art cancer treatment and prevention trials to South Louisiana for indigent and minority populations who otherwise would have little access to this care. Because of the success of the Program in patient accrual to both cancer treatment and cancer prevention and control protocol trials, Louisiana State University Medical Center has applied for a continuation of funding for the Program for the next five years.

Clinical Trials as Topic↗
PubMed1997

Maternal melanoma metastatic to the placenta: a case report and review of the literature.

Metastases of maternal cancer to the placenta and fetus are rare in cases of maternal primary malignancy. This report describes a case of malignant melanoma metastatic to the placenta, reviews the literature, and discusses the clinical significance. A 33-year-old woman presented at 30 weeks' gestation with multiple metastases from a malignant melanoma diagnosed 4 years previously. Rapid maternal deterioration necessitated premature cesarean delivery, and maternal death occurred 7 days later. The placenta showed multiple metastases of malignant melanoma. The infant, however, is alive and well at 7 months of age. Melanoma in pregnancy rarely results in metastasis to the conceptus, but when it does occur there may be fatal consequences to the fetus. Therefore, the placenta should be thoroughly examined for metastasis, which, if present, should alert the clinician to monitor the infant for development of malignant disease.

Adult↗
PubMed1996

Nucleotide sequence of a 28-kb mouse genomic region comprising the imprinted Igf2 gene.

The mouse insulin-like growth factor II gene (Igf2) is physically linked to the insulin II gene (Ins2) and both are subject to tissue-specific genomic imprinting. The paternal-specific expression of Igf2 has been associated with hypermethylation of some CpG sites in the 5' flanking region and in the body of the gene. As a first step in analyzing the structural features of this imprinted locus, we here report the complete nucleotide sequence of Igf2, including all introns and the intergenic region adjacent to Ins2. This 28-kb segment of mouse chromosome 7 exhibits 80% overall identity with the corresponding rat sequence and has a high GC content of 52%. In addition to the known CpG island within the second Igf2 promoter, another island was identified approximately 2 kb 5' to the first exon. Other features of this locus include a 35-fold tandem repeat of an 11-bp sequence that overlaps Igf2 pseudo-exon 2, and a B2 repeat element in the intergenic region between Ins2 and Igf2. The GC-richness and the presence of CpG islands associated with tandem repeats are common features of imprinted genes and thus may play a role in the imprinting mechanism.

Animals↗
PubMed1996

Regional distribution of neurotrophin receptors in the developing auditory brainstem.

Neuron survival and axonal regeneration become severely limited during early postnatal development. In conjunction with our recent organotypic analysis of regeneration in the auditory midbrain, we wished to determine whether neurotrophins could serve as a trophic substance during the postnatal period. Therefore, the current study examines the development of three neurotrophin receptor tyrosine kinases (TrkA, TrkB, and TrkC) in the gerbil auditory brainstem. Immunoreactivity to TrkA, the nerve growth-factor receptor, was observed in nonneuronal cells during the first two postnatal weeks. In the cochlear nucleus of mature animals, however, there was a TrkA-positive neuronal subpopulation. In contrast, immunoreactivity to TrkB and TrkC (the receptors for brain-derived neurotrophic factor and neurotrophin-3, respectively) displayed a widespread distribution in the auditory brainstem. At postnatal day 0, TrkB and TrkC staining was virtually absent from auditory nuclei, although immunopositive neurons were present in the mesencephalic trigeminal nucleus. By postnatal day 7, TrkB- and TrkC-positive neurons were present in most brainstem auditory nuclei. At postnatal day 15, TrkB immunoreactivity was observed throughout the inferior colliculus (IC), the cochlear nucleus, the medial and lateral nuclei of the trapezoid body, and the lateral superior olive, whereas TrkC labeled only a subpopulation of neurons within the central nucleus of the IC. The TrkB immunoreactivity was present on both neuronal somata and dendrites, whereas TrkC was generally restricted to cell bodies. At postnatal day 30, TrkB immunostaining was observed on most neurons of the IC. The medial and lateral nuclei of the trapezoid body displayed extremely strong TrkB staining, followed by the cochlear nucleus. In contrast, the TrkC immunostaining was decreased dramatically by postnatal day 21. Observations at the ultrastructural level confirmed a neuronal localization of TrkB and TrkC. Immunostaining for both receptors was restricted largely to the postsynaptic density of synaptic profiles in both dendrites and somata. In summary, this study illustrates a differential pattern of immunoreactivity between three neurotrophin receptors during development. The general increase of TrkB expression is well correlated with the onset of sound-evoked activity in this system, and its synaptic localization suggests that it may be involved in the modulation or maintenance of postsynaptic physiology.

Animals↗
PubMed1996

Haemophilus influenzae type b (Hib) vaccination and uptake predictors in Northern Ireland.

In order to study selected factors affecting the uptake of Haemophilus influenzae type b (Hib) vaccine a case control study was undertaken in residents of the Southern Health and Social Services Board in Northern Ireland. Standard data from the child health computer system were used. Residents in the catchment area of the health board born between 1 January and 30 June 1993 were defined as cases (unvaccinated) and controls (vaccinated). The uptake of Hib vaccination and odds ratios for factors associated with non-completion of vaccination were calculated. Overall uptake of Hib vaccination exceeded 97%. Children of mothers who smoked or children who had two or more younger siblings were less likely to have been vaccinated.

Analysis of Variance↗