Regulation of pulmonary endothelial cell shape by Trp-mediated calcium entry.
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Animals↗
Biomedical subjects
T Moore
Publications and source records attributed to T Moore.
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↗
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↗
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↗
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↗
From birds and bees to babies? Can theories on genetic conflict aid the clinician?
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Animals↗
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↗
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↗
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↗
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↗
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↗
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↗
Genomic evolution in mice and men: imprinted genes have little intronic content.
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Animals↗
Diazepam enhances conditioned defeat in hamsters (Mesocricetus auratus).
Male hamsters that have been repeatedly defeated by larger, aggressive males subsequently flee from, rather than attack, nonaggressive male intruders that are introduced into their home cages. We have referred to this generalization of flight in response to nonaggressive intruders as "conditioned defeat" (CD). In an attempt to reverse CD pharmacologically, diazepam (DZP) was administered to hamsters at two different time points relative to CD acquisition and subsequent response generalization tests, which involved the exposure of subjects to nonaggressive intruders (NAIs). In Experiment 1, subjects were given a single injection of one of 4 doses of DZP (0, 2, 6, or 20 mg/kg) immediately following CD acquisition. Twenty-four hours later, contrary to expectations, subjects that had received the 6 mg/kg dose displayed elevated flight responses in the presence of an NAI. Flight responding declined over days except in subjects that received the highest dose. In the second experiment, hamsters were administered a single injection of either 0, 2, or 6 mg/kg DZP just prior to a response generalization test occurring 24 h following CD training. Flight responses to the NAIs were again exaggerated in subjects that were given the 6 mg/kg dose, an effect that persisted several days without further drug administration. The present findings suggest the possibility that benzodiazepines can potentiate fear responses under certain stressful conditions.
Agonistic Behavior↗
Marfan's syndrome: a family affair.
Marfan's syndrome (MFS), a heritable connective tissue disorder, may result in cardiac valvular insufficiency, aortic aneurysm or dissection, dislocated lens, and musculoskeletal abnormalities. During a 20-month period (1994-96), an interdisciplinary health care team at a central Virginia medical center evaluated the histories of 112 persons from 15 different families for the presence of MFS-related traits. Seventy-five had at least one MFS-related trait, and 27 subjects underwent echocardiography to evaluate for aortic root dilatation and valvular lesions. Forty-three patients (57.3%) in the above cohort demonstrated significant cardiovascular lesions, with 20 undergoing cardiac surgery. Thirty-one patients (41.3%) were initially seen with significant ocular lesions, and 38 (50.7%) displayed orthopedic deformities. The health care team developed strategies for long-term management of persons with MFS, including antihypertensive therapy, periodic testing, risk-factor modification, genetic counseling, and surgery for appropriate patients. Proactive, consistent management of MFS families will improve long-term health outcomes for this patient population.
Adolescent↗
Imprinted genes have few and small introns.
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Animals↗
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.
Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.
Alleles↗
Increased nailfold capillary dimensions in primary Raynaud's phenomenon and systemic sclerosis.
The aim of the study was to measure nailfold capillary dimensions and capillary density in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc) compared to control subjects. Ten controls, nine patients with PRP and 10 patients with SSc were studied. All dimensions other than distance between limbs were significantly increased in both the PRP and SSc groups compared to controls (P < 0.01), with the SSc group showing the most marked increases (SSc vs PRP, P < 0.05 for all dimensions). Capillary density was significantly reduced in the SSc group compared to controls (P = 0.004). These results suggest that structural vascular changes occur in PRP as well as in SSc, and that PRP may, therefore, not be entirely benign.
Capillaries↗