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Biomedical subjects

J D Lee

Publications and source records attributed to J D Lee.

At least 19 recordsLinked to original sources

Ultrafast Fano resonance between optical phonons and electron-hole pairs at the onset of quasiparticle generation in a semiconductor.

Based on the many-body time-dependent approach applied to the ultrafast time region, we investigate the dynamics of creation of an optical phonon incorporating with the electron-hole continuum in a semiconductor. In the transient Fano resonance, due to an interference between those sharp (optical phonon) and continuum (electron-hole pair) quasiparticles, we find the robust destructive interference at birth of them, i.e., tau approximately 0 if the created phonon is coherent under the irradiation of ultrashort optical pulses. The origin is found to be the potential scattering of the electron-hole pair by the q=0 coherent phonon. This finding agrees well with the recent experiment.

Journal Article↗

An observational case study of ozone and precursors inflow to South East England during an anticyclone.

Summertime photochemical air pollution episodes within the United Kingdom have been proposed via modelling studies to be strongly influenced by regional scale inflow of air from the continental European boundary layer. We present a vertically resolved case study using measurements made from the NERC/Met Office BAe 146 research aircraft on 18th August 2005 over the South East of England and the North Sea during a weak anticyclone centred over Northern Europe. The vertical distribution of ozone, CO, NO(x), peroxyacetyl nitrate (PAN) and a wide range of both nonmethane hydrocarbons (NMHC) and oxygenated volatile organic compounds (OVOCs) were determined between 500 ft (approximately 152 m) and 7000 ft (approximately 2134 m) over the East Anglia coastline and 50 km inland. In excess of 80 ppbV ozone was observed within inflowing boundary layer air over the North Sea coast in a broad N-S sloping feature around 60 km wide. The inflowing feature of European origin was also observed further inland within the boundary layer albeit with lower, more variable, ozone mixing ratios. The increased variability in ozone over land was a product of titration by fresh surface emissions of NO via rapid upward transport in thermals, a hypothesis supported by the observed vertical wind speed component. Fast boundary layer mixing over land was further illustrated by a uniform distribution in reactive alkenes. A comparison between aircraft and surface O(3) UK AUN (Automatic Urban Network) measurements showed good agreement with the inland site, Sibton, but marked differences with the coastal monitoring site at Weybourne, potentially due to gradients established by ocean deposition in stably stratified marine air.

Air Pollutants↗

Optical absorption of semiconducting and metallic nanospheres with the confined electron-phonon coupling.

We study the optical absorption, especially the (far-) infrared absorption by phonons, of semiconducting and metallic nanospheres. In the nanoscopic sphere, phonons as well as states of electronic excitations are quantized by confinement. It is also known that in the nanoscopic geometry, the confined electron-phonon interaction has a different form from the usual one in the bulk. First, we analyze the phonon and electron contributions to the dielectric response of nanospheres like epsilon(q,omega)=epsilon(ph)(q,omega)+epsilon(el)(q,omega) or 1epsilon(q,omega)=1epsilon(sc-ph)(q,omega)+1epsilon(el)(q,omega) from the confined electron-phonon interaction for three cases: the intrinsic semiconductor, the doped semiconductor, and the metal. From the dielectric response, the optical absorption spectra are calculated within the semiclassical framework concentrating on the (far-) infrared region and compared to the spectra without imposing confinement. Nontrivial differences of the spectra with confined phonons stem from two features: the electron-phonon coupling matrix has a different form and the phase space q of the confined phonon is reduced because of its quantization to q(n). Finally, size distribution effects in an ensemble of isolated nanospheres are briefly discussed. Those effects are found to be important in metallic spheres with rapid sweepings of resonances by a small change of the sphere size.

Journal Article↗

Measurement and modelling of air pollution and atmospheric chemistry in the U.K. West Midlands conurbation: overview of the PUMA Consortium project.

The PUMA (Pollution of the Urban Midlands Atmosphere) Consortium project involved intensive measurement campaigns in the Summer of 1999 and Winter of 1999/2000, respectively, in which a wide variety of air pollutants were measured in the UK West Midlands conurbation including detailed speciation of VOCs and major component analysis of aerosol. Measurements of the OH and HO2 free radicals by the FAGE technique demonstrated that winter concentrations of OH were approximately half of those measured during the summer despite a factor of 15 reduction in production through the photolysis of ozone. Detailed box modelling of the fast reaction chemistry revealed the decomposition of Criegee intermediates formed from ozone-alkene reactions to be responsible for the majority of the formation of hydroxyl in both the summer and winter campaigns, in contrast to earlier rural measurements in which ozone photolysis was predominant. The main sinks for hydroxyl are reactions with NO2, alkenes and oxygenates. Concentrations of the more stable hydrocarbons were found to be relatively invariant across the conurbation, but the impacts of photochemistry were evident through analyses of formaldehyde which showed the majority to be photochemical in origin as opposed to emitted from road traffic. Measurements on the upwind and downwind boundaries of the conurbation revealed substantial enhancements in NOx as a result of emissions within the conurbation, especially during westerly winds which carried relatively clean air. Using calcium as a tracer for crustal particles, it proved possible to reconstruct aerosol mass from the major chemical components with a fairly high degree of success. The organic to elemental carbon ratios showed a far greater influence of photochemistry in summer than winter, presumably resulting mainly from the greater availability of biogenic precursors during the summer campaign. Two urban airshed models were developed and applied to the conurbation, one Eulerian, the other Lagrangian. Both were able to give a good simulation of concentrations of both primary and secondary pollutants at urban background locations.

Acetone↗

Acinic cell carcinoma on the lower lip resembling a mucocele.

A 64-year-old woman presented with a 2-week history of an asymptomatic mass involving the lower lip. Histopathological examination showed a well-circumscribed tumour composed of many lobules separated by thin, fibrous connective tissue. Individual lobules were composed of round or polyhedral tumour cells, which had a characteristic finely granular and vacuolated cytoplasm and eccentric hyperchromatic nuclei. Positive staining was observed with Periodic acid-Shiff, and immunohistochemistry for cytokeratin, alpha-1 antitrypsin, and S-100 protein resulting in a final diagnosis of acinic cell carcinoma. Acinic cell carcinoma represents a well-established, although uncommon, entity in the classification of neoplasms of salivary gland origin. The parotid salivary gland is the most frequent site of acinic cell carcinoma, whereas the lip is a particularly unusual site. The unusual presentation of this tumour may lead to confusion with a mucocele. Given these findings, we suggest that acinic cell carcinoma should be considered in the differential diagnosis of any mucocele-like mass on the lower lip.

Biomarkers, Tumor↗

CARDS on the table: should everybody with type 2 diabetes take a statin?

BACKGROUND: Vascular complications are a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The recently published Collaborative Atorvastatin Diabetes Study (CARDS) showed that atorvastatin (10 mg, once daily vs. placebo) markedly reduces vascular events in this high-risk population. The participants (n = 2838) were fairly typical T2DM = 2838) patients without cardiovascular disease and with at least one other risk factor: hypertension, retinopathy, albuminuria or current smoking. In the treatment group, coronary events were reduced by 36% (p = 0.001) and stroke by 48% (p = 0.001). The trial was terminated two years early on ethical grounds. The number needed to treat (NNT) was 27 for four years to prevent one event. However, the benefit may have been greater since a proportion of the placebo group received statin therapy. The benefit from statin treatment was independent of sex, age, baseline lipid levels, was independent of sex, age, baseline lipid levels, systolic blood pressure, retinopathy, albuminuria, systolic blood pressure, retinopathy, albuminuria, smoking or HbA smoking or HbA(1c). The frequency of adverse events did not differ between the groups. These findings support those of other statin trials. SCOPE: CARDS does not comment on renal function. However, other trials suggest that statins preserve renal function in those with and without DM. We discuss the CARDS study in this context in this brief overview paper. CONCLUSIONS: the evidence shows that we need to control glucose to prevent microvascular complications, to lower cholesterol to prevent macrovascular disease and to lower blood pressure to prevent both. It may be that the benefit of statins extends beyond a threshold low-density lipoprotein cholesterol level in patients with T2DM. More trials are needed in this field.

Atorvastatin↗

Two high-speed, portable GC systems designed for the measurement of non-methane hydrocarbons and PAN: results from the Jungfraujoch High Altitude Observatory.

Near real-time measurements of light non-methane hydrocarbons (NMHCs) and peroxyacetyl nitrate (PAN) have been performed in the free troposphere using two fast gas chromatography (GC) instruments designed for use on aircraft. A GC-helium ionisation detector (HID) system measured 15 C(2)-C(5) hydrocarbons with 5 min time resolution and a dual channel GC-Electron Capture Detector (ECD) measured PAN with 90 s resolution. Both instruments had low parts per trillion by volume (pptV) detection limits and ran continuously at the remote Jungfraujoch (JFJ) research station in the Swiss Alps (46.55[degree]N, 7.98[degree]E), 3580 m above mean sea level (AMSL), during February/March 2003. Carbon monoxide, ozone, nitrogen oxide and nitrogen dioxide and all odd nitrogen species (NO(y)) were also measured continuously. Hydrocarbons and CO were strongly correlated in all air-masses whilst PAN exhibited both positive and negative correlations with respect to O(3), dependent on age and origin of the air-mass sampled. PAN was found to contribute [similar]20% to the NO(y) sampled on average. The experiment, as well as providing interesting datasets from this remote location, also demonstrated that when optimised, GC techniques have the potential to measure at a time resolution significantly greater than is traditionally considered, with high sensitivity and low uncertainty.

Air Pollutants↗

Recalculation of cardiovascular risk score as a surrogate marker of change in clinical care of diabetes patients: the Alphabet POEM project (Practice Of Evidence-based Medicine).

AIMS: To assess the impact of evidence-based strategies on the care of subjects with diabetes, in particular on their coronary heart disease (CHD) risk, using the Alphabet Strategy template and coronary heart disease (CHD) risk calculators as novel audit tools. METHODS: Diabetes and cardiovascular parameters were collected on 400 consecutive type 2 diabetes patients attending the outpatient clinic. The subjects were men and women aged 21-75 years with necessary follow-up data from referral or first chronological available letter in the notes (T(0)) to the most recent follow-up visit (T(fu)). The disease risk scores: a significant reduction in average follow-up period was 5 years. Absolute CHD risk was calculated using the Framingham risk function and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. The results were analysed using Student's paired t-test and chi-squared test. RESULTS: (T(0) vs. T(fu)): Advice: smoking status improved 18.3 vs. 15.5%: p = 0.3. Blood pressure: systolic blood pressure improved 145.8 +/- 21.1 vs. 140.1 +/- 20.5mmHg: p < 0.0001. Diastolic blood pressure improved 82.0 +/- 12.2 vs. 76.5 +/- 11.0mmHg: p < 0.0001. Cholesterol: total cholesterol improved 5.8 +/- 1.6 vs. 4.9 +/- 1.0 mmol/L: p < 0.0001; high density lipoprotein (HDL) cholesterol improved 1.05 vs. 1.26 mmol/L: p < 0.001. Diabetes control: glycated haemoglobin (HbA1c)% worsened 7.9 +/- 1.8 vs. 8.1 +/- 1.5: p < 0.0001. However, when adjusted for duration of diabetes, this improved non-significantly by 12% overall. Eye examination: improved 86.5 vs. 97.5%: p < 0.001. Feet examination: improved 69.8 vs. 83.5%: p < 0.001. Guardian drugs: significantly more patients were on aspirin (29.0 vs. 83.5%: p < 0.001), angiotensin converting enzyme (ACE) inhibitors (32.0 vs. 64.5%: p < 0.001), and lipid lowering therapy (16.8 vs. 55.0%: p < 0.001). Heart Framingham 10-year absolute cardiac risk was achieved (20.6 +/- 10.04% vs. 16.7 +/- 9.1%: p = 0.001). Using the UKPDS risk engine, there was a non-significant reduction in absolute CHD risk over the follow-up period (23.8 +/- 14.8% vs. 23.7 +/- 15.5: p = NS). There were significant improvements between age-adjusted risk score (T(adj)) and follow-up values (T(fu)) (Framingham: 23.67% (T(adj)) vs. 16.7% (T(fu)); UKPDS 31.2% (T(adj)) vs. 23.7% (T(fu))). For UKPDS stroke risk, a significant improvement was seen from T(adj) to T(fu) (19.0% (T(adj)) vs. 16.4% (T(fu)): p < 0.001), with a significant deterioration noted between T(0) and T(fu) (11.5% (T(0)) vs. 16.4% (T(fu)): p < 0.0001). CONCLUSIONS: The Alphabet Strategy is a novel evidence-based approach to clinical diabetes care, which produced a statistically significant improvement in most of the assessed parameters. The Alphabet Practice Of Evidence-based Medicine (POEM) template is a useful clinical tool for diabetes care and audit. It includes most of the components of diabetes audit required by the National Service Framework (NSF) and the United Kingdom GP contract.

Adult↗

The cerebrovascular response to traditional acupuncture after stroke.

Acupuncture is useful in treating the nausea and vomiting related to chemotherapy, adult postoperative surgery pain and postoperative dental pain. We obtained single-photon emission computed tomography (SPECT) brain perfusion images of six patients with middle cerebral artery occlusion obtained before and after acupuncture and compared the changes in regional cerebral blood flow (rCBF) to those in normal control. Images were obtained before and after acupuncture at six traditional acupoints (LI 4, 10, 11, 15 and 16 and TE5) in the affected arm. The baseline image was subtracted from the postacupuncture image, to produce a subtraction image displaying only voxels with values >2 SD from the mean and those voxels were coregistered to the baseline SPECT or T2-weighted MRI. Similar images were obtained before and after acupuncture of eight normal volunteers. Statistical parametric mapping with a threshold of P =0.001 and a corrected P of 0.05 was performed for group comparison between postacupuncture and baseline SPECT. Focally increased CBF was seen in all patients especially in the hypoperfused zone surrounding the ischaemic lesion, the ipsilateral or contralateral sensorimotor area, or both. Normal subjects showed increased rCBF mainly in the parahippocampal gyrus, premotor area, frontal and temporal areas bilaterally and ipsilateral globus pallidus. Acupuncture stimulation after stroke patients appears to activate perilesional or use-dependent reorganised sites and might be a way of looking at brain reorganisation.

Acupuncture Therapy↗

Thyrotoxic autoimmune encephalopathy: a repeat positron emission tomography study.

Thyroid related autoantibodies have been related to the development of encephalopathy, known as Hashimoto's encephalopathy. However, their relation with the encephalopathy occurring in patients with Graves' disease has not been well established. The case is reported of a 51 year old woman presenting with subacute progressive dementia with evidence of hyperthyroidism. She had Graves' disease associated with high titres of thyroid related autoantibodies. Her encephalopathy was not improved by antithyroid drugs, but promptly responded to corticosteroid treatment, and stabilised with a gradual reduction of thyroid related autoantibody titres. Brain positron emission tomography initially showed a diffuse and multifocal cerebral hypometabolism with subsequent normalisation on her clinical recovery, which was consistent with the acute and reversible cerebral inflammation probably mediated by autoimmune mechanisms.

Autoantibodies↗

Primary human parvovirus B19 infection in an HIV infected patient on highly active antiretroviral therapy.

Adults developing primary human parvovirus B19 (B19) infection may present with arthralgia, fever, and maculopapular rash. Recovery is linked to the development of specific neutralising antibodies. In immunosuppressed patients, including those with HIV infection, such humoral responses are impaired and severe chronic bone marrow suppression and arthritis may occur.

AIDS-Related Opportunistic Infections↗

Strong spin-fluctuation effects on the photoemission line shape in the normal state of high-T(c) cuprates.

We have studied the quasiboson model for photoemission from cuprates in the normal state, where quasiparticles are coupled to collective spin excitations strongly enhanced near momentum (pi,pi). The present model has a benefit to describe the observed crossover from the overdoped to the underdoped cases because it is in principle an infinite-order theory in the limit of narrow bandwidth. The anomalous dependences of the photoemission line shape on the momentum and hole concentration are consistently understood within the model with no adjustable parameter except for a doping-independent coupling constant.

Journal Article↗

Extracellular signal regulated kinase 5 (ERK5) is required for the differentiation of muscle cells.

Extracellular signal regulated kinase 5 (ERK5) is a novel member of the mitogen-activated protein kinase (MAPK) family with a poorly defined physiological function. Since ERK5 and its upstream activator MEK5 are abundant in skeletal muscle we examined a function of the cascade during muscle differentiation. We show that ERK5 is activated upon induction of differentiation in mouse myoblasts and that selective activation of the pathway results in promoter activation of differentiation-specific genes. Moreover, myogenic differentiation is completely blocked when ERK5 expression is inhibited by antisense RNA. Thus, we conclude that the MEK5/ERK5 MAP kinase cascade is critical for early steps of muscle cell differentiation.

Animals↗

Ubiquitination-dependent mechanisms regulate synaptic growth and function.

The covalent attachment of ubiquitin to cellular proteins is a powerful mechanism for controlling protein activity and localization. Ubiquitination is a reversible modification promoted by ubiquitin ligases and antagonized by deubiquitinating proteases. Ubiquitin-dependent mechanisms regulate many important processes including cell-cycle progression, apoptosis and transcriptional regulation. Here we show that ubiquitin-dependent mechanisms regulate synaptic development at the Drosophila neuromuscular junction (NMJ). Neuronal overexpression of the deubiquitinating protease fat facets leads to a profound disruption of synaptic growth control; there is a large increase in the number of synaptic boutons, an elaboration of the synaptic branching pattern, and a disruption of synaptic function. Antagonizing the ubiquitination pathway in neurons by expression of the yeast deubiquitinating protease UBP2 (ref. 5) also produces synaptic overgrowth and dysfunction. Genetic interactions between fat facets and highwire, a negative regulator of synaptic growth that has structural homology to a family of ubiquitin ligases, suggest that synaptic development may be controlled by the balance between positive and negative regulators of ubiquitination.

Animals↗

Sightless has homology to transmembrane acyltransferases and is required to generate active Hedgehog protein.

Proteins of the Hedgehog (Hh) family act as important developmental signals in a variety of species [1]. Hh proteins are synthesized as full-length precursors that are autocatalytically cleaved by their C-terminal domains to release the signaling N-terminal domains [2]. The addition of a cholesterol molecule to the C terminus of the signaling domain is concomitant with cleavage [3]. Vertebrate Sonic hedgehog (Shh) proteins have also been shown to acquire a fatty acid chain on the N-terminal cysteine of this domain [4], which is required for a subset of their in vivo functions [5, 6]. A mutation of the corresponding cysteine in Drosophila Hh transforms it into a dominant-negative protein [6]. We have identified a novel gene, sightless (sit), which is required for the activity of Drosophila Hh in the eye and wing imaginal discs and in embryonic segmentation. sit acts in the cells that produce Hh, but does not affect hh transcription, Hh cleavage, or the accumulation of Hh protein. sit encodes a conserved transmembrane protein with homology to a family of membrane-bound acyltransferases. The Sit protein could act by acylating Hh or by promoting other modifications or trafficking events necessary for its function.

Acylation↗

An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development.

The Drosophila Hedgehog protein and its vertebrate counterpart Sonic hedgehog are required for a wide variety of patterning events throughout development. Hedgehog proteins are secreted from cells and undergo autocatalytic cleavage and cholesterol modification to produce a mature signaling domain. This domain of Sonic hedgehog has recently been shown to acquire an N-terminal acyl group in cell culture. We have investigated the in vivo role that such acylation might play in appendage patterning in mouse and Drosophila; in both species Hedgehog proteins define a posterior domain of the limb or wing. A mutant form of Sonic hedgehog that cannot undergo acylation retains significant ability to repattern the mouse limb. However, the corresponding mutation in Drosophila Hedgehog renders it inactive in vivo, although it is normally processed. Furthermore, overexpression of the mutant form has dominant negative effects on Hedgehog signaling. These data suggest that the importance of the N-terminal cysteine of mature Hedgehog in patterning appendages differs between species.

Acylation↗

BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase.

Activation of the mammalian mitogen-activated protein kinase known as BMK1 is required for growth factor-induced cell proliferation. To understand the mechanism by which BMK1 mediates this cellular response, this kinase was used as bait in a yeast two-hybrid-based library screening. Here, we report the identification of serum and glucocorticoid-inducible kinase (SGK) as a cellular protein that physically interacts with BMK1. During growth factor-induced cell stimulation, BMK1 activates SGK by phosphorylation at serine 78. This BMK1-mediated phosphorylation event is necessary for the activation of SGK and, more importantly, for cell proliferation induced by growth factors.

Cell Division↗

Nitric oxide synthase activity in peripheral polymorphonuclear leukocytes in patients with chronic congestive heart failure.

Increased activity of inducible nitric oxide synthase (NOS) has been found in cardiac tissue and in skeletal muscle from patients with chronic congestive heart failure (CHF). There have been few reports investigating NOS activity in other organs or in peripheral blood cells from patients with chronic CHF. To examine whether NOS activities in peripheral polymorphonuclear leukocytes (PML) are increased in patients with chronic CHF and to determine whether a correlation exists between disease severity and NOS activity in PML of patients with chronic CHF, we assessed the levels of NOS activity in PML by measuring the capacity of isolated PML to convert 3H-L-arginine to 3H-L-citrullin in 70 Japanese patients with chronic CHF and in 24 age-matched healthy volunteers. The levels of NOS activity in PML were significantly greater in patients with chronic CHF than in healthy volunteers (18.0 +/- 0.6% vs 11.5 +/- 0.3%, p <0.01). NOS activity in PML was increased with the severity of New York Heart Association functional class. Among the various neurohumonal factors, the plasma levels of interleukin-6, atrial natriuretic peptide, and norepinephrine showed independent and significant positive relations with levels of NOS activity in PML. Thus, we demonstrated that NOS activity in PML was elevated in patients with chronic CHF in relation to the severity of heart failure, circulating proinflammatory cytokines, and neurohormonal factors.

Adult↗