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Biomedical subjects

T Miller

Publications and source records attributed to T Miller.

At least 37 records · Page 2Linked to original sources

Electron-hole coupling and the charge density wave transition in TiSe2.

Angle-resolved photoemission is employed to measure the band structure of TiSe2 in order to clarify the nature of the ( 2 x 2 x 2) charge density wave transition. The results show a very small indirect gap in the normal phase transforming into a larger indirect gap at a different location in the Brillouin zone. Fermi surface topology is irrelevant in this case. Instead, electron-hole coupling together with a novel indirect Jahn-Teller effect drives the transition.

Journal Article↗

Myopathy with antibodies to the signal recognition particle: clinical and pathological features.

OBJECTIVES: To study myopathies with serum antibodies to the signal recognition particle (SRP), an unusual, myositis specific antibody associated syndrome that has not been well characterised pathologically. METHODS: Clinical, laboratory, and myopathological features were evaluated in seven consecutive patients with a myopathy and serum anti-SRP antibodies, identified over three years. The anti-SRP myopathy was compared with myopathology in other types of inflammatory and immune myopathies. RESULTS: The patients with anti-SRP antibodies developed weakness at ages ranging from 32 to 70 years. Onset was seasonal (August to January). Weakness became severe and disability developed rapidly over a period of months. Muscle pain and fatigue were present in some patients. No patient had a dermatomyositis-like rash. Serum creatine kinase was very high (3000 to 25 000 IU/l). Muscle biopsies showed an active myopathy, including muscle fibre necrosis and regeneration. There was prominent endomysial fibrosis, but little or no inflammation. Endomysial capillaries were enlarged, reduced in number, and associated with deposits of the terminal components of complement (C5b-9, membrane attack complex). Strength improved in several patients after corticosteroid treatment. CONCLUSIONS: Myopathies associated with anti-SRP antibodies may produce severe and rapidly progressive weakness and disability. Muscle biopsies show active myopathy with pathological changes in endomysial capillaries but little inflammation. Corticosteroid treatment early in the course of the illness is often followed by improvement in strength. In patients with rapidly progressive myopathies and a high serum creatine kinase but little inflammation on muscle biopsy, measurement of anti-SRP antibodies and pathological examination of muscle, including evaluation of endomysial capillaries, may provide useful information on diagnosis and treatment.

Adult↗

How successfully do general practitioners diagnose herpetic gingivo-stomatitis clinically?

Herpetic gingivo-stomatitis is a common, often painful affliction of young children. Recently, aciclovir treatment has been found to be effective in hospital-referred cases, an approach limited in general practice where laboratory diagnosis is invariably impractical. This study demonstrated that 49 out of 63 clinical diagnoses of herpetic gingivo-stomatitis [PPV = 78%] made by 27 GPs were subsequently validated by laboratory virus culture. This suggests that herpetic gingivo-stomatitis might be treated with aciclovir in general practice on the basis of a clinical diagnosis alone.

Clinical Competence↗

New experimental limits on strongly interacting massive particles at the TeV scale.

We have carried out a search for strongly interacting massive particles (SIMPs) bound to Au and Fe nuclei, which could manifest themselves as anomalously heavy isotopes of these elements. Our samples included gold from the NASA Long Duration Exposure Facility satellite, RHIC at Brookhaven National Laboratory, and from various geological sources. We find no evidence for SIMPs in any of our samples, and our results set stringent limits (as low as approximately 10(-12)) on the abundances of anomalous Au or Fe isotopes with masses up to 1.67 and 0.65 TeV/c(2), respectively.

Journal Article↗

COMPASS: a complex of proteins associated with a trithorax-related SET domain protein.

The trithorax genes encode an evolutionarily conserved family of proteins that function to maintain specific patterns of gene expression throughout cellular development. Members of this protein family contain a highly conserved 130- to 140-amino acid motif termed the SET domain. We report the purification and molecular identification of the subunits of a protein complex in the yeast Saccharomyces cerevisiae that includes the trithorax-related protein Set1. This protein complex, which we have named COMPASS (Complex Proteins Associated with Set1), consists of seven polypeptides ranging from 130 to 25 kDa. The same seven proteins were identified in COMPASS purified either by conventional biochemical chromatography or tandem-affinity tagging of the individual subunits of the complex. Null mutants missing any one of the six nonessential subunits of COMPASS grow more slowly than wild-type cells under normal conditions and demonstrate growth sensitivity to hydroxyurea. Furthermore, gene expression profiles of strains missing either of two nonessential subunits of COMPASS are altered in similar ways, suggesting these proteins have similar roles in gene expression in vivo. Molecular characterization of trithorax complexes will facilitate defining the role of this class of proteins in the regulation of gene expression and how their misregulation results in the development of human cancer.

Chromatography, Liquid↗

Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes.

Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in vitro. We investigated whether oxidative stress mediates hypertrophy and apoptosis in cyclically stretched ventricular myocytes. Neonatal rat ventricular myocytes cultured on laminin-coated silastic membranes were stretched cyclically (1 Hz) at low (nominal 5%) and high (nominal 25%) amplitudes for 24 hours. Stretch caused a graded increase in superoxide anion production as assessed by superoxide dismutase (SOD)-inhibitable cytochrome c reduction or electron paramagnetic resonance spectroscopy. The role of reactive oxygen species (ROS) was assessed using the cell-permeable SOD/catalase mimetics Mn(II/III)tetrakis(1-methyl-4-peridyl) (MnTMPyP) and EUK-8. Stretch-induced increases in protein synthesis ((3)H-leucine incorporation) and cellular protein content were completely inhibited by MnTMPyP (0.05 mmol/L) at both low and high amplitudes of stretch. In contrast, while MnTMPyP inhibited basal atrial natriuretic factor (ANF) mRNA expression, the stretch-induced increase in ANF mRNA expression was not inhibited by MnTMPyP. In contrast to hypertrophy, only high-amplitude stretch increased myocyte apoptosis, as reflected by increased DNA fragmentation on gel electrophoresis and an approximately 3-fold increase in the number of TUNEL-positive myocytes. Similarly, only high-amplitude stretch increased the expression of bax mRNA. Myocyte apoptosis and bax expression stimulated by high-amplitude stretch were inhibited by MnTMPyP. Both low- and high-amplitude stretch caused rapid phosphorylation of ERK1/2, while high-, but not low-, amplitude stretch caused phosphorylation of JNKs. Activation of both ERK1/2 and JNKs was ROS-dependent. Thus, cyclic strain causes an amplitude-related increase in ROS, associated with differential activation of kinases and induction of hypertrophic and apoptotic phenotypes.

Animals↗

Quantum electronic stability of atomically uniform films.

We have studied the structural stability of thin silver films with thicknesses of N = 1 to 15 monolayers, deposited on an Fe(100) substrate. Photoemission spectroscopy results show that films of N = 1, 2, and 5 monolayer thicknesses are structurally stable for temperatures above 800 kelvin, whereas films of other thicknesses are unstable and bifurcate into a film with N +/- 1 monolayer thicknesses at temperatures around 400 kelvin. The results are in agreement with theoretical predictions that consider the electronic energy of the quantum well associated with a particular film thickness as a significant contribution to the film stability.

Journal Article↗

Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia.

Autosomal dominant myopathy, Paget disease of bone, and dementia constitute a unique disorder (MIM 605382). Here we describe the clinical, biochemical, radiological, and pathological characteristics of 49 affected (23 male, 26 female) individuals from four unrelated United States families. Among these affected individuals 90% have myopathy, 43% have Paget disease of bone, and 37% have premature frontotemporal dementia. EMG shows myopathic changes and muscle biopsy reveals nonspecific myopathic changes or blue-rimmed vacuoles. After candidate loci were excluded, a genome-wide screen in the large Illinois family showed linkage to chromosome 9 (maximum LOD score 3.64 with marker D9S301). Linkage analysis with a high density of chromosome 9 markers generated a maximum two-point LOD score of 9.29 for D9S1791, with a maximum multipoint LOD score of 12.24 between D9S304 and D9S1788. Subsequent evaluation of three additional families demonstrating similar clinical characteristics confirmed this locus, refined the critical region, and further delineated clinical features of this unique disorder. Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2.

Adult↗

Histone deacetylases and cancer: causes and therapies.

Together, histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones. This acetylation affects the regulation of gene expression, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes. HDAC inhibitors are proving to be an exciting therapeutic approach to cancer, but how do they exert this effect?

Acetylation↗

Bacterial community associated with Pfiesteria-like dinoflagellate cultures.

Dinoflagellates (Eukaryota; Alveolata; Dinophyceae) are single-cell eukaryotic microorganisms implicated in many toxic outbreaks in the marine and estuarine environment. Co-existing with dinoflagellate communities are bacterial assemblages that undergo changes in species composition, compete for nutrients and produce bioactive compounds, including toxins. As part of an investigation to understand the role of the bacteria in dinoflagellate physiology and toxigenesis, we have characterized the bacterial community associated with laboratory cultures of four 'Pfiesteria-like' dinoflagellates isolated from 1997 fish killing events in Chesapeake Bay. A polymerase chain reaction with oligonucleotide primers specific to prokaryotic 16S rDNA gene sequences was used to characterize the total bacterial population, including culturable and non-culturable species, as well as possible endosymbiotic bacteria. The results indicate a diverse group of over 30 bacteria species co-existing in the dinoflagellate cultures. The broad phylogenetic types of dinoflagellate-associated bacteria were generally similar, although not identical, to those bacterial types found in association with other harmful algal species. Dinoflagellates were made axenic, and the culturable bacteria were added back to determine the contribution of the bacteria to dinoflagellate growth. Confocal scanning laser fluorescence microscopy with 16S rDNA probes was used to demonstrate a physical association of a subset of the bacteria and the dinoflagellate cells. These data point to a key component in the bacterial community being species in the marine alpha-proteobacteria group, most closely associated with the alpha-3 or SAR83 cluster.

Animals↗

Moderating effect of ear preference on personality in the prediction of sales performance.

This study examined the relationship between ear preference, personality, and performance ratings on 203 telesales staff. Social desirability scores were a significant predictor of two relatively independent sets of supervisor ratings (actual performance and developmental potential) in interaction with ear preference. It was found that the social desirability scale was a significant positive predictor for staff preferring a right ear headset, but a negative predictor for staff preferring a left ear headset. These results were interpreted in terms of different strategies used to achieve successful sales.

Journal Article↗

Uveal tumour resection.

AIM: To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques. METHODS: This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed. RESULTS: 138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of > or =20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had > or =20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas. CONCLUSIONS: 76% of eyes were retained and 53% of these had a final visual acuity of > or =20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not appear to be compromised with eye wall resection and in very thick, more posterior melanomas it appeared that ocular retention and visual results were better than with radiation alone.

Adolescent↗

Increasing longevity and Medicare expenditures.

Official Medicare projections forecast that the elderly population will be less healthy and more costly over the next century. This prediction stems from the use of age as an indicator of health status: increases in longevity are assumed to increase demand for health care as individuals survive to older and higher-use ages. In this paper I suggest an alternative approach, in which time until death replaces age as the demographic indicator of health status. Increases in longevity are assumed to postpone the higher Medicare use and costs associated with the final decade of life. I contrast the two approaches, using mortality forecasts consistent with recent projections from the U.S. Census Bureau and the Social Security Administration. The time-until-death method yields significantly lower-cost forecasts. The hypothetical cost savings from improved health care small, however, relative to the size of the Medicare solvency problem caused by population aging.

Accounting↗

Evaluating the performance of the Lee-Carter method for forecasting mortality.

Lee and Carter (LC) published a new statistical method for forecasting mortality in 1992. This paper examines its actual and hypothetical forecast errors, and compares them with Social Security forecast errors. Hypothetical historical projections suggest that LC tended to underproject gains, but by less than did Social Security. True e0 was within the ex ante 95% probability interval 97% of the time overall, but intervals were too broad up to 40 years and too narrow after 50 years. Projections to 1998 made after 1945 always contain errors of less than two years. Hypothetical projections for France, Sweden, Japan, and Canada would have done well. Changing age patterns of mortality decline over the century pose problems for the method.

Age Factors↗

Three-year update of sildenafil citrate (Viagra) efficacy and safety.

In the three years since its launch, sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been prescribed to more than 10 million patients worldwide and has been further evaluated in clinical studies in diverse patient populations. Significant improvements in erectile function have been demonstrated in double-blind, placebo-controlled trials in patients with ED and underlying diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. Promising results have also been reported for patients with treated prostate cancer, end-stage renal failure, Parkinson's disease, and spina bifida and in multiple organ transplant recipients. Accounts of sildenafil use in clinical practice and postmarketing data reflect clinical trial findings of effectiveness in a broad spectrum of ED aetiologies and overall good tolerability. As in the clinical trials, most adverse events associated with sildenafil use have been transient, mild or moderate effects that rarely lead to treatment discontinuation.

Erectile Dysfunction↗

HARM 2000: crash cost and consequence data for the new millennium.

This paper presents the most detailed and current costs per US motor vehicle crash victim. These unit costs, which include the first keyed to AIS90, are reported by category, body part, whether a fracture/dislocation was involved, and MAIS. This level of detail allows for reliable analyses of interventions targeting narrow ranges of injuries and, hopefully, for the development of a biomechanical injury cost model.

Accidents, Traffic↗

Inotropic stimulation induces cardiac dysfunction in transgenic mice expressing a troponin T (I79N) mutation linked to familial hypertrophic cardiomyopathy.

The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and a high incidence of sudden death, despite causing little or no cardiac hypertrophy. In skinned fibers, I79N increased myofilamental calcium sensitivity (Miller, T., Szczesna, D., Housmans, P. R., Zhao, J., deFreitas, F., Gomes, A. V., Culbreath, L., McCue, J., Wang, Y., Xu, Y., Kerrick, W. G., and Potter, J. D. (2001) J. Biol. Chem. 276, 3743-3755). To further study the functional consequences of this mutation, we compared the cardiac performance of transgenic mice expressing either human TnT-I79N or human wild-type TnT. In isolated hearts, cardiac function was different depending on the Ca(2+) concentration of the perfusate; systolic function was significantly increased in Tg-I79N hearts at 0.5 and 1 mmol/liter. At higher Ca(2+) concentrations, systolic function was not different, but diastolic dysfunction became manifest as increased end-diastolic pressure and time to 90% relaxation. In vivo measurements by echocardiography and Doppler confirmed that base-line systolic function was significantly higher in Tg-I79N mice without evidence for diastolic dysfunction. Inotropic stimulation with isoproterenol resulted only in a modest contractile response but caused significant mortality in Tg-I79N mice. Doppler studies ruled out aortic outflow obstruction and were consistent with increased chamber stiffness. We conclude that in vivo, the increased myofilament Ca(2+) sensitivity due to the I79N mutation enhances base-line contractility but leads to cardiac dysfunction during inotropic stimulation.

Animals↗