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Biomedical subjects

T Moore

Publications and source records attributed to T Moore.

At least 19 recordsLinked to original sources

Epigenetics and imprinting of the trophoblast -- a workshop report.

Genomic imprinting is a remarkable process that causes genes to be expressed or repressed depending on their parental-origin. Imprinted genes play important roles in prenatal growth and organ development. Postnatally, imprinted genes can contribute to the regulation of metabolic pathways and behaviour associated with the control of resources. One of the most important sites of imprinted gene action is the placenta. During this workshop at the 11th meeting of the International Federation of Placenta Associations/European Placenta Group held in Glasgow, a series of short talks were presented providing an overview of the evolution, function and mechanisms of imprinting in mammals with particular reference to the placenta. In addition, epigenetic control of trophoblast development and function were considered. This report summarises the contributions to the workshop.

Animals↗

Prenatal detection of associated anomalies in fetuses diagnosed with cleft lip with or without cleft palate in utero.

OBJECTIVE: The aim of this study was to determine the prenatal detection rate of associated anomalies in fetuses with a suspected cleft lip with or without cleft palate. METHODS: Fetuses with a suspected cleft lip with or without cleft palate, determined by prenatal ultrasound, were prospectively enrolled. Additional anomalies suspected by ultrasound or genetic testing were recorded. Postnatal outcome was obtained. RESULTS: Forty-five fetuses with a cleft lip with or without cleft palate, diagnosed prenatally with either two-dimensional and/or three-dimensional ultrasound, were studied. Postnatal follow-up revealed that 16 (35.6%) of these 45 fetuses had an additional structural or syndromic abnormality. Of the 37 fetuses with prenatally determined 'isolated' cleft lip with or without cleft palate, eight (21.6%) had an additional malformation identified after delivery. CONCLUSION: In pregnancies complicated by a cleft lip with or without cleft palate, patients should be informed of the risks of associated anomalies, some of which may be undetected prenatally.

Abnormalities, Multiple↗

Community-onset methicillin-resistant Staphylococcus aureus in an urban HIV clinic.

OBJECTIVES: To determine the proportion of skin/soft tissue infections (SSTIs) and to determine risks for MRSA infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected out-patients. METHODS: We conducted a prospective study of SSTIs in HIV-infected out-patients. A questionnaire was used to record MRSA risk factors and treatment. In vitro testing for antibiotic susceptibility, inducible clindamycin resistance, panton-valentine leucocidin (PVL) toxin, and the staphylococcal chromosomal cassette mec (SCCmec) type was performed using standardized methods. Treatment outcomes included resolution of primary site of infection, nonresolution of infection and reinfection and were confirmed at clinic visit and/or telephone follow-up. RESULTS: Forty-one of 44 patients had an SSTI caused by MRSA. African-Americans comprised 21 of 41 MRSA patients. The median CD4 count of MRSA patients was 411 cells/microL. Four patients required hospitalization and three patients had secondary bacteraemia. Twenty-one of 41 MRSA patients had healthcare-associated (HCA) MRSA risk factors including a history of prior MRSA infection (n=9) and hospitalization within 6 months (n=11). Other prevalent MRSA risk factors included receipt of systemic antibiotics within 6 months (n=21) and previous incarceration (n=19). Twenty-two patients had a significant non-HIV-related comorbid illness. The majority of isolates were susceptible to trimethoprim-sulfamethoxazole, tetracycline, and clindamycin. Inducible clindamycin resistance was detected in 0 of 16 erythromycin-resistant, clindamycin-susceptible MRSA isolates. Twenty-one of 24 isolates tested positive for SCCmec type IV. Twenty-four of 24 isolates tested positive for the PVL gene. Antibiotic treatment was discordant (bacteria nonsusceptible to antibiotic used) in eight MRSA patients. The primary SSTI resolved in 37 of 40 MRSA patients. Recurrence of infection at a site other than the primary site was relatively common (11 patients). CONCLUSIONS: We found a high rate of MRSA causing SSTI in community-dwelling patients. The majority of isolates were positive for PVL and SCCmec IV, which is typical of community-associated MRSA isolates causing SSTIs in the general population. Inducible clindamycin resistance was not detected. Most patients had MRSA risk factors. The initial site of infection resolved in most cases but subsequent MRSA infection was relatively common.

Ambulatory Care Facilities↗

Evolution of mammalian X chromosome-linked imprinting.

We analyse the evolution of X chromosome-linked imprinting by modifying our previous model of imprinting of autosomal genes that influence the trade-off between maternal fecundity and offspring viability through alterations in maternal investment (Mills and Moore, 2004). Unlike previous genetic models, we analyse X-linked imprinting in the context of populations at equilibrium for either autosomal or X-linked biallelically expressed alleles at loci that influence the fecundity/viability trade-off. We show that selection under parental conflict over maternal investment in offspring can parsimoniously explain the occurrence of sex-specific gene expression patterns, without a requirement to postulate direct selection for sexual dimorphism mediated through imprinting. We note that sex chromosome imprinting causes a small distortion of the post-weaning sex ratio, providing a possible selection pressure against the evolution of X-linked imprints. We discuss our conclusions in the context of recent reports of imprinting of mouse X-linked Xlr genes.

Animals↗

Characteristics and scaling of tungsten-wire-array z -pinch implosion dynamics at 20 MA.

We present observations for 20-MA wire-array z pinches of an extended wire ablation period of 57%+/-3% of the stagnation time of the array and non-thin-shell implosion trajectories. These experiments were performed with 20-mm-diam wire arrays used for the double- z -pinch inertial confinement fusion experiments [M. E. Cuneo, Phys. Rev. Lett. 88, 215004 (2002)] on the Z accelerator [R. B. Spielman, Phys. Plasmas 5, 2105 (1998)]. This array has the smallest wire-wire gaps typically used at 20 MA (209 microm ). The extended ablation period for this array indicates that two-dimensional (r-z) thin-shell implosion models that implicitly assume wire ablation and wire-to-wire merger into a shell on a rapid time scale compared to wire acceleration are fundamentally incorrect or incomplete for high-wire-number, massive (>2 mg/cm) , single, tungsten wire arrays. In contrast to earlier work where the wire array accelerated from its initial position at approximately 80% of the stagnation time, our results show that very late acceleration is not a universal aspect of wire array implosions. We also varied the ablation period between 46%+/-2% and 71%+/-3% of the stagnation time, for the first time, by scaling the array diameter between 40 mm (at a wire-wire gap of 524 mum ) and 12 mm (at a wire-wire gap of 209 microm ), at a constant stagnation time of 100+/-6 ns . The deviation of the wire-array trajectory from that of a thin shell scales inversely with the ablation rate per unit mass: f(m) proportional[dm(ablate)/dt]/m(array). The convergence ratio of the effective position of the current at peak x-ray power is approximately 3.6+/-0.6:1 , much less than the > or = 10:1 typically inferred from x-ray pinhole camera measurements of the brightest emitting regions on axis, at peak x-ray power. The trailing mass at the array edge early in the implosion appears to produce wings on the pinch mass profile at stagnation that reduces the rate of compression of the pinch. The observation of precursor pinch formation, trailing mass, and trailing current indicates that all the mass and current do not assemble simultaneously on axis. Precursor and trailing implosions appear to impact the efficiency of the conversion of current (driver energy) to x rays. An instability with the character of an m = 0 sausage grows rapidly on axis at stagnation, during the rise time of pinch power. Just after peak power, a mild m = 1 kink instability of the pinch occurs which is correlated with the higher compression ratio of the pinch after peak power and the decrease of the power pulse. Understanding these three-dimensional, discrete-wire implosion characteristics is critical in order to efficiently scale wire arrays to higher currents and powers for fusion applications.

Journal Article↗

Assessment of endothelial function in complex regional pain syndrome type I using iontophoresis and laser Doppler imaging.

OBJECTIVES: To assess microvascular endothelial function in patients with complex regional pain syndrome type I (CRPS) compared with healthy controls, as measured by iontophoresis of vasoactive chemicals and laser Doppler imaging. METHODS: Microvascular blood flow was stimulated locally in affected and contralateral limbs of patients with CRPS (n = 17) and in control subjects (n = 16) using iontophoresis of the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial-independent vasodilator sodium nitroprusside (NaNP). Changes in blood flow were measured using laser Doppler imaging. Comparisons were made between right and left limbs and between patients and controls. RESULTS: No significant differences in blood flow [expressed as a median percentage increase from baseline (interquartile range)] were detected between affected and contralateral limbs in patients with CRPS for ACh [affected 237 (95-344); unaffected 251 (152-273)] or for NaNP [affected 102 (49-300); unaffected 190 (53-218)]. In addition, there were no significant differences between patients and healthy controls [controls, ACh 216 (119-316); controls, NaNP: 122 (48-249)]. CONCLUSIONS: In this pilot study, CRPS was not associated with impairment of microvascular endothelial function. This may be a true result or may reflect the diversity of the CRPS disease process.

Acetylcholine↗

Complex regulation and nuclear localization of JRK protein.

The mouse jerky gene and its human orthologue, JRK/JH8, encode a putative DNA-binding protein with homology to the CENP-B (centromere-binding protein B). Disruption of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy. In addition (and similar to a cenp-b null mouse) jerky null mice exhibit postnatal weight loss and reduced fertility. Using fluorescence confocal microscopy, the cellular localization of a JRK-GFP fusion (where GFP stands for green fluorescent protein) was investigated in HeLa cells. JRK-GFP has a dynamic expression pattern in the interphase nucleus, localizing in a small number of punctate nuclear foci and in the nucleolus. The JRK-GFP foci number changes during the cell cycle, but a distinct pattern of three JRK-GFP foci is observed at G(2). The endogenous protein behaves in a similar manner to the GFP-fusion protein. JRK-GFP was found to co-localize with CREST antigens (which recognize the centromere-binding proteins, CENP-A, -B and -C) through S and G(2) phases of interphase and co-localized completely with a subset of PML nuclear bodies at G(2). We speculate that JRK protein associates with a specific chromosomal centromeric locus in G(2), where it associates fully with PML bodies. Research is underway to identify this locus.

Animals↗

Fixed dose combinations for tuberculosis: Lessons learned from clinical, formulation and regulatory perspective.

Worldwide, tuberculosis (TB) remains one of the most important communicable diseases in terms of morbidity and mortality. Its control requires multi-drug therapy for at least six months, which could lead to patient non-compliance, failure of therapy and ultimately resulting in the emergence of drug resistance. Fixed dose combinations (FDCs) in TB therapy reduce the number of tablets to be consumed and thereby increase patient compliance with recommended treatment regimens. Thus, FDCs play a significant role in preventing the emergence of drug resistance and successful treatment. However, the quality of FDCs with respect to variable bioavailability and their registration requirements are major hurdles to their implementation in national TB control programs. It is anticipated that a large global market for FDCs will encourage large-scale production and increased competition, which in turn will result in FDCs at affordable prices. The Global Drug Facility (GDF), established by the World Health Organization (WHO), aims to ensure universal uninterrupted access to quality TB drugs for implementation of directly observed treatment short-course (DOTS) in resource-poor countries. In this program, four FDCs were accepted as the drugs of first choice because of their obvious advantages in controlling TB. This demands the necessity of addressing quality and registration requirements of FDCs systematically. In light of this current knowledge on anti-TB FDCs, their dosage, combinations, available clinical studies and the experiences with TB therapy has been discussed in this article, which should serve as lessons for selection of appropriate FDCs for other diseases such as malaria and AIDS.

Antitubercular Agents↗

Benchmarking and quality in residential and nursing homes: lessons from the US.

BACKGROUND: Performance measurement and benchmarking are common concerns in the delivery of long term care. It is common to measure the performance of providers and to publicly report these data. This paper examines selected technical challenges facing those who design, implement and disseminate health care quality performance measures. METHOD: Review of the application of measures of performance in the US nursing home sector. RESULTS: Using examples drawn from the skilled nursing home arena, problems ranging from data reliability and validity, the multi-dimensional nature of quality measures and selection bias as well as differential measurement abilities are discussed. CONCLUSIONS: Benchmarking of performance is an inherently complex issue. However, to ensure that such comparisons are both fair and valid requires measures to be more technically sophisticated and sensitive to real changes attributable to changes in care.

Benchmarking↗

Paclitaxel and concurrent radiation for locally advanced pancreatic cancer.

PURPOSE: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer. METHODS AND MATERIALS: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m(2) by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments. RESULTS: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%. CONCLUSION: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.

Adult↗

Resolution of chronic parvovirus b19-induced anemia, by use of highly active antiretroviral therapy, in a patient with acquired immunodeficiency syndrome.

We present what is, to our knowledge, the second case report of a patient with acquired immunodeficiency syndrome and transfusion-dependent anemia caused by persistent infection with parvovirus B19. The patient's anemia was successfully treated, and she demonstrated serologic evidence of eradication of parvovirus after having received effective therapy for human immunodeficiency virus infection.

AIDS-Related Opportunistic Infections↗

Control of eye movements and spatial attention.

Several lines of evidence suggest that planning eye movements and directing visuospatial attention share overlapping brain mechanisms. This study tested whether spatial attention can be enhanced by altering oculomotor signals within the brain. Monkeys performed a spatial attention task while neurons within the frontal eye field, an oculomotor area within prefrontal cortex, were electrically stimulated below the level at which eye movements are evoked. We found that we could improve the monkey's performance with microstimulation when, but only when, the object to be attended was positioned in the space represented by the cortical stimulation site.

Animals↗

Direction of motion discrimination after early lesions of striate cortex (V1) of the macaque monkey.

Previous studies have established that humans and monkeys with damage to striate cortex are able to detect and localize bright targets within the resultant scotoma. Electrophysiological evidence in monkeys suggests that residual vision also might include sensitivity to direction of visual motion. We tested whether macaque monkeys with longstanding lesions of striate cortex (V1), sustained in infancy, could discriminate visual stimuli on the basis of direction of motion. Three monkeys with unilateral striate cortex lesions sustained in infancy were tested 2-5 years postlesion on a direction of motion discrimination task. Each monkey was trained to make saccadic eye movements to a field of moving dots or to withhold such eye movements, depending on the direction of motion in a coherent random dot display. With smaller motion displays, monkeys were unable to detect or discriminate motion within the scotoma, although they could discriminate moving from static stimuli. Yet, each monkey was able to discriminate direction of motion when the motion stimulus was larger, but still confined to the scotoma. The results demonstrate that the recovery after infant damage to striate cortex includes some sensitivity to direction of visual motion.

Aging↗

Analysis of infant handling and the effects of female rank among Tana River adult female yellow baboons (Papio cynocephalus cynocephalus) using permutation/randomization tests.

Infant handling has been documented in numerous species. Among cercopithecines, interaction motivations are reported to range from aunting to kidnapping; these interactions are often distressful for both mother and infant. Here we examine handling by adult female yellow baboons (Papio cynocephalus cynocephalus) at the Tana River National Primate Reserve, Kenya, using a relatively new, computer-intensive statistical approach of permutation/randomization tests to deal with repeated measures effects and a skewed sample. We hypothesized 1) a tendency for handlers to handle the infants of females ranked similarly or lower than themselves, and 2) more successful infant handling by higher-ranked females, particularly with very young infants. We collected focal data on 23 females (11 mother-infant pairs) over an 11-mo period, with a total of 303 attempted and/or successful "handles" utilized in the permutation analyses. The general patterns apparent in the data seemed to support our hypotheses. However, the permutation tests showed that while females are somewhat more likely to attempt to handle the infants of females ranked "same or lower" than themselves, lower-ranked females are able to prevent more than three-fourths of the attempted interactions, and there is no statistically significant trend for females to successfully handle these infants. Further refinement of the analyses showed no significant tendencies for females to handle those infants ranked "lower" or "immediately lower" than themselves, casting doubt on the significant finding for "same or lower" attempts. Further, there was no significant effect for higher-ranked females to successfully handle an infant during its first month. Thus, rank does not seem to offer any privileges in terms of handling an infant in this population. We believe the permutation tests are an effective way to analyze repeated measures data and offer a more sensitive analysis tool for determining true significance.

Animals↗

Structure and expression of the genes encoding proteins resident in large peripheral vesicles of Phytophthora cinnamomi zoospores.

Zoospores of Phytophthora spp. contain several characteristic types of peripheral vesicles. One of these, large peripheral vesicles, has been proposed to act as a nutrient store and in P. cinnamomi has been shown to contain three immunologically related high-molecular-weight proteins, designated LPVs. We have used antibodies directed against P. cinnamomi zoospores and cysts to isolate several cDNA clones which are products of the Lpv genes and encode one or more of the LPV proteins present in large peripheral vesicles. Northern blot analysis demonstrated the presence of three large Lpv transcripts (11-14 kb) in RNA isolated from hyphae which had been induced to form sporangia. Coordinate accumulation of the three transcripts occurred after induction of sporangium formation: no transcript was observed in uninduced hyphae and maximum transcript levels of all three transcripts were seen 4-6 h after induction. Genomic Southern blots indicated that P. cinnamomi contains three Lpv genes, presumably corresponding to the three transcripts and proteins seen in Northern and Western blots, respectively. Partial genomic clones representing two of the Lpv genes were isolated and characterized by restriction mapping and partial DNA sequencing. In the regions sequenced, the genes were > 99% identical, the high degree of conservation extending at least 415 bp downstream of their polyadenylation sites. The Lpv coding regions contained a variable number (approximately 12-18) of highly conserved 534 bp repeats, flanked by apparently unique sequences. Variation in the number of repeats in the Lpv genes was responsible for the different sizes of the three transcripts and proteins. Database searches using the Lpv nucleotide and deduced amino acid sequences failed to detect any similar sequences. We discuss the molecular events which may have been involved in the evolution of the Lpv genes and the nature of the products of these genes.

Algal Proteins↗