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Biomedical subjects

T Moore

Publications and source records attributed to T Moore.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Non-invasive assessment of vascular reactivity in forearm skin of patients with primary Raynaud's phenomenon and systemic sclerosis.

We have non-invasively assessed neurovascular control mechanisms in forearm skin of 10 healthy control subjects, eight patients with primary Raynaud's phenomenon (PRP) and 10 patients with systemic sclerosis (SSc) by iontophoresing acetylcholine (endothelial dependent), sodium nitroprusside (endothelial independent) and adrenaline, and measuring subsequent blood flow responses by dual-channel laser Doppler. Because basal forearm blood flow is low, adrenaline response was assessed by attenuation of reperfusion hyperaemia following 60 s of upper arm occlusion. Reperfusion hyperaemia prior to adrenaline iontophoresis differed significantly between groups (F2.21 = 4.3, P = 0.03), being lowest in the SSc and highest in the PRP group. However, the degree of attenuation of this hyperaemia by adrenaline did not differ between groups and all groups demonstrated similar vasodilatory responses to acetylcholine and to sodium nitroprusside. These findings may reflect that abnormalities in vascular tone in patients with Raynaud's phenomenon are local to the digits, or that vasoactive agents not examined in this study play a key role.

Acetylcholine↗
PubMed1996

Describing and analyzing constipation in acute care.

Many patients in acute care hospitals experience constipation, yet the literature on constipation focuses on long-term care and does not provide tools for describing and analyzing bowel management from the perspective of health care professionals or patients. The article describes the development of a bowel management task force at one acute care hospital and the initial steps taken to improve clinical quality in this area. A multifaceted approach was used to collect baseline data on practice, expectations, and problems related to bowel management. Valuable data were obtained from both patients and health care providers that have provided direction for improving clinical outcomes and patient satisfaction.

Constipation↗
PubMed1996

Growth phase-dependent transcription of the sigma(54)-dependent Po promoter controlling the Pseudomonas-derived (methyl)phenol dmp operon of pVI150.

Transcription from Pseudomonas-derived -24, -12 Po promoter of the pVI150-encoded dmp operon is mediated by the sigma 54-dependent DmpR activator in response to the presence of aromatic pathway substrates in the medium. However, global regulatory mechanisms are superimposed on this regulatory system so that the specific response to aromatic effectors is absent in cultures until the stationary phase is reached. Here we genetically dissect the system to show that the growth phase response is faithfully mimicked by a minimal system composed of the dmpR regulatory gene and the Po promoter regulatory region and can be reproduced in heterologous Escherichia coli. Using this system, we show that the growth phase-dependent DmpR-mediated response to aromatic compounds is limited to fast-growing cultures. Thus, during exponential growth of cultures in minimal media containing different carbon sources, the response to aromatics is immediate, while the response is suppressed in cultures grown on rich media until the exponential-to-stationary phase transition. Elements known to be involved in the DmpR-mediated transcription from Po were analyzed for the ability to influence the growth phase response. Most dramatically, overexpression of DmpR was shown to completely abolish the growth phase response, suggesting that a negatively acting factor may mediate this level of regulation. The possible mechanism of action and integration (of the specific regulation of the dmp operon-encoded catabolic enzymes with the physiological status of the bacteria are discussed.

Bacterial Proteins↗