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Biomedical subjects

J L Smith

Publications and source records attributed to J L Smith.

At least 19 recordsLinked to original sources
PubMed2006

Impact of antimicrobial usage on antimicrobial resistance in commensal Escherichia coli strains colonizing broiler chickens.

Escherichia coli strains isolated from commercial broilers and an experimental flock of chickens were screened to determine phenotypic expression of antimicrobial resistance and carriage of drug resistance determinants. The goal of this study was to investigate the influence of oxytetracycline, sarafloxacin, and enrofloxacin administration on the distribution of resistance determinants and strain types among intestinal commensal E. coli strains isolated from broiler chickens. We detected a high prevalence of resistance to drugs such as tetracycline (36 to 97%), sulfonamides (50 to 100%), and streptomycin (53 to 100%) in E. coli isolates from treated and untreated flocks. These isolates also had a high prevalence of class 1 integron carriage, and most of them possessed the streptomycin resistance cassette, aadA1. In order to investigate the contribution of E. coli strain distribution to the prevalence of antimicrobial resistance and the resistance determinants, isolates from each flock were DNA fingerprinted by enterobacterial repetitive intergenic consensus sequence (ERIC) PCR. Although very diverse E. coli strain types were detected, four ERIC strain types were present on all of the commercial broiler farms, and two of the strains were also found in the experimental flocks. Each E. coli strain consisted of both susceptible and antimicrobial agent-resistant isolates. In some instances, isolates of the same E. coli strain expressed the same drug resistance patterns although they harbored different tet determinants or streptomycin resistance genes. Therefore, drug resistance patterns could not be explained solely by strain prevalence, indicating that mobile elements contributed significantly to the prevalence of resistance.

Animals↗
PubMed2006

Altered expression of zinc transporters-4 and -6 in mild cognitive impairment, early and late Alzheimer's disease brain.

Accumulating evidence suggests that a disruption of zinc (Zn) homeostasis may play a role in the pathogenesis of Alzheimer's disease. Although several Zn transporter proteins responsible for the regulation of Zn balance are present in the brain, there has been little study of these proteins in Alzheimer's disease. To determine if alterations of Zn transporter proteins exist, levels of Zn transporter-4, which functions to remove Zn from the cytoplasm to endosomal/lysosomal compartments, and Zn transporter-6, which allocates cytoplasmic Zn to the trans-Golgi network, were measured in the hippocampus/parahippocampal gyrus, superior and middle temporal gyrus, and cerebellum of subjects with mild cognitive impairment, early Alzheimer's disease, late stage Alzheimer's disease, and age-matched controls using Western blot analysis and protein specific antibodies. Our results show that Zn transporter-4 and Zn transporter-6 are significantly (P<0.05) increased in hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and middle temporal gyrus of Alzheimer's disease brain.

Aged↗
PubMed2006

Formation of a new dynamical mode in -uranium observed by inelastic x-ray and neutron scattering.

Phonon dispersion curves were obtained from inelastic x-ray and neutron scattering measurements on alpha-uranium single crystals at temperatures from 298 to 573 K. Both measurements showed a softening and an abrupt loss of intensity in the longitudinal optic branch along [00zeta] above 450 K. Above the same temperature a new dynamical mode of comparable intensity emerges along the [01zeta] zone boundary with energy near the top of the phonon spectrum. The new mode forms without a structural transition but coincides with an anomaly in the mechanical deformation behavior. We argue that the mode is an intrinsically localized vibration and formed as a result of a strong electron-phonon interaction.

Journal Article↗
PubMed2006

Pinning frequencies of the collective modes in alpha-uranium.

Uranium is the only known element that features a charge-density wave (CDW) and superconductivity. We report a comparison of the specific heat of single-crystal and polycrystalline alpha-uranium. In the single crystal we find excess contributions to the heat capacity at 41 K, 38 K, and 23 K, with a Debye temperature ThetaD = 265 K. In the polycrystalline sample the heat capacity curve is thermally broadened (ThetaD = 184 K), but no excess heat capacity was observed. The excess heat capacity Cphi (taken as the difference between the single-crystal and polycrystal heat capacities) is well described in terms of collective-mode excitations above their respective pinning frequencies. This attribution is represented by a modified Debye spectrum with two cutoff frequencies, a pinning frequency V0 for the pinned CDW (due to grain boundaries in the polycrystal), and a normal Debye acoustic frequency occurring in the single crystal.

Journal Article↗
PubMed2006

Management of locoregional stage esophageal cancer: a single center experience.

Therapeutic options for locoregional esophageal cancer (EC) include primary surgery, neoadjuvant or definitive chemoradiation and systemic chemotherapy. The role of surgery in these multimodal strategies has recently been debated and definitive chemoradiation is being offered as an alternative to surgery at many centers. We examined our results with multimodal therapy and surgery in this patient population. We conducted a retrospective analysis of 172 patients with locoregional (AJCC stages I-III) EC treated at RPCI between February 14, 1990 and September 20, 2002. Median age was 65 years (range, 36-95); there were 136 male patients. There were 100 regional (stages IIB-III), 69 local (stages I-IIA) and three in situ cases. Initial therapy was either combined modality (n = 122) or single modality (surgery) (n = 50). There was 0%, 30-day, postoperative mortality. Median survival for all patients was 25.3 months and was better for local stage with surgery alone (75 months) than with neoadjuvant (35.7 months) or definitive chemoradiation (19.1 months, P < 0.001). Survival for patients with regional disease treated with surgery alone, neoadjuvant or definitive chemoradiation was 21.5, 24.4 and 11.8 months, respectively (P = not significant). The associations of prognostic factors with overall survival were evaluated using Cox proportional hazards regression analysis and 2-sided Wald's chi-square test. On multivariate analysis, carefully selected patients treated with surgery alone had better outcomes compared with those treated with definitive chemoradiation (P < 0.001). Patients with locoregional esophageal cancer who are eligible for surgical resection either alone or as a part of multimodal therapy may have better outcomes than those treated with non-surgical approaches.

Adenocarcinoma↗
PubMed2005

4-Hydroxynonenal disrupts zinc export in primary rat cortical cells.

Accumulating evidence implicates oxidative stress in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE) have been demonstrated in AD brain. Proteins responsible for zinc export are localized on the plasma membrane and may be vulnerable to damage from lipid peroxidation. To test this hypothesis, cultured primary rat cortical neurons were incubated with (65)Zn for 1h and then treated with HNE (0-35 microM) for 4 h. Levels of (65)Zn in aliquots of medium were measured at 1, 2, 4h following treatment with HNE and intracellular (65)Zn measured after 4h using liquid scintillation counting. The amount of (65)Zn in medium did not differ significantly. However, a statistically significant (p<0.05) increase of (65)Zn was observed inside cortical neurons after treatment with 20 microM HNE for 4 hours. These data suggest that HNE may impair a protein essential for zinc export leading to increased levels of intracellular zinc.

Aldehydes↗
PubMed2005

Plasma delipidation process induces rapid regression of atherosclerosis and mobilisation of adipose tissue.

Cholesterol is a major component of atherosclerotic plaques. Cholesterol accumulation within the arterial intima and atherosclerotic plaques is determined by the difference of cellular cholesterol synthesis and/or influx from apo B-containing lipoproteins and cholesterol efflux. In humans, apo A-1 Milano infusion has led to rapid regression of atherosclerosis in coronary arteries. We hypothesised that a multifunctional plasma delipidation process (PDP) would lead to rapid regression of experimental atherosclerosis and probably impact on adipose tissue lipids. In hyperlipidemic animals, the plasma concentrations of cholesterol, triglyceride and phospholipid were, respectively, 6-, 157-, and 18-fold higher than control animals, which consequently resulted in atherosclerosis. PDP consisted of delipidation of plasma with a mixture of butanol-diisopropyl ether (DIPE). PDP removed considerably more lipid from the hyperlipidemic animals than in normolipidemic animals. PDP treatment of hyperlipidemic animals markedly reduced intensity of lipid staining materials in the arterial wall and led to dramatic reduction of lipid in the adipose tissue. Five PDP treatments increased apolipoprotein A1 concentrations in all animals. Biochemical and hematological parameters were unaffected during PDP treatment. These results show that five PDP treatments led to marked reduction in avian atherosclerosis and removal of lipid from adipose tissue. PDP is a highly effective method for rapid regression of atherosclerosis.

Adipose Tissue↗
PubMed2005

Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease.

Several studies show increased levels of zinc (Zn) in the Alzheimer's disease (AD) brain. More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD. To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects. To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls. Western blot and dot-blot analysis showed statistically significant (p 0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects. We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls. In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls. Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p 0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY. Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD.

Aged↗
PubMed2005

Effects of orally administered tetracycline on the intestinal community structure of chickens and on tet determinant carriage by commensal bacteria and Campylobacter jejuni.

There is a growing concern that antibiotic usage in animal production has selected for resistant food-borne bacteria. Since tetracyclines are common therapeutic antibiotics used in poultry production, we sought to evaluate the effects of oral administration on the resistance of poultry commensal bacteria and the intestinal bacterial community structure. The diversity indices calculated from terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA amplicons did not indicate significant changes in the cecal bacterial community in response to oxytetracycline. To evaluate its effects on cultivable commensals, Enterococcus spp., Escherichia coli, and Campylobacter spp. were isolated from the cecal droppings of broiler chickens. Enterococcus spp. and E. coli expressed tetracycline MICs of >8 microg/ml and harbored a variety of tet resistance determinants regardless of the tetracycline exposure history of the birds. The enterococcal isolates possessed tetM (61%), tetL (25.4%), and tetK (1.3%), as well as tetO (52.5%), the determinant known to confer a tetracycline resistance phenotype in Campylobacter jejuni. E. coli isolates harbored tetA (32.2%) or tetB (30.5%). Tetracycline MICs remained at <2 microg/ml for Campylobacter isolates before and after tetracycline treatment of the chickens, even though isolates expressing MICs of >16 mug/ml were commonly cultured from flocks that did not receive oxytetracycline. The results imply that complex ecological and genetic factors contribute to the prevalence of antibiotic resistance arising from resistance gene transfer in the production environment.

Animals↗
PubMed2004

Rare beryllium icosahedra in the intermediate valence compound CeBe13.

Single-crystal X-ray diffraction experiments show that the Be atoms in CeBe13 form a Be12 icosahedra, which is a very unusual structural feature due, in part, to the remarkably low valence electron count of Be. Magnetization studies show that CeBe13 displays intermediate valence behavior, in which valence fluctuations between the Ce 4f0 and 4f1 states give rise to enhanced electronic specific heat and magnetic susceptibility. Calculations using ab initio theory were used to determine the electronic structure and bonding and to give insight into the relationship between the crystal structure, the bonding, and the intermediate valence behavior of CeBe13. The hybridization between the localized f electrons and the conduction electrons is responsible for the large values of the electronic specific heat coefficient (gamma approximately 100 mJ/mol K2) and magnetic susceptibility (chi approximately 1 x 10-3 emu/mol), which is in marked contrast to those of ordinary metals that have gamma approximately 1 mJ/mol K2 and chi approximately 1 x 10-5 emu/mol values. The magnetic susceptibility, chi = M/H versus T, of a single crystal of CeBe13 exhibits a broad maximum at Tmax approximately 130 K and is typical of intermediate valence systems with an unusually large energy scale (Kondo), TK approximately 500 K.

Journal Article↗
PubMed2003

Experimental electronic heat capacities of alpha- and delta-plutonium: heavy-fermion physics in an element.

We have measured the heat capacities of delta-Pu0.95Al0.05 and alpha-Pu over the temperature range 2-303 K. The availability of data below 10 K plus an estimate of the phonon contribution to the heat capacity based on recent neutron-scattering experiments on the same sample enable us to make a reliable deduc-tion of the electronic contribution to the heat capacity of delta-Pu0.95Al0.05; we find gamma=64+/-3 mJ K(-2) mol(-1) as T-->0. This is larger than that of any element and large enough for delta-Pu0.95Al0.05 to be classed as a heavy-fermion system. By contrast, gamma=17+/-1 mJ K(-2) mol(-1) in alpha-Pu. Two distinct anomalies are seen in the electronic contribution to the heat capacity of delta-Pu0.95Al0.05, one or both of which may be associated with the formation of the alpha(')-martensitic phase. We suggest that the large gamma value of delta-Pu0.95Al0.05 may be caused by proximity to a quantum-critical point.

Journal Article↗
PubMed2003

Emergence of coherent transport in UBe13: an optical investigation in both the normal and superconducting states.

The far-infrared reflectance of heavy-fermion superconductor UBe13 has been measured from 0.5 K in the superconducting state, to 300 K. Coherent transport, characterized by an optical conductivity that exhibits a renormalized Drude peak at low frequencies, emerges between 45 and 85 K although the dc resistivity of UBe13 continues to increase with decreasing temperature down to approximately 2.5 K. In the superconducting state, the low frequency scattering rate falls abruptly, implying that the formation of the condensate alters dramatically the interaction between the heavy electrons.

Journal Article↗
PubMed2003

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

Chromosome Aberrations↗
PubMed2003

Lymphoproliferative disease in antibody deficiency: a multi-centre study.

We have undertaken a retrospective study of antibody deficient patients, with and without lymphoma, and assessed the ability of specific polymerase chain reaction (PCR) primers to determine if the detection of clonal lymphocyte populations correlates with clinical and immunohistochemical diagnosis of lymphoma. We identified 158 cases with antibody deficiency presenting during the past 20 years. Paraffin-embedded biopsy specimens or slides were available for analysis in a cohort of 34 patients. Of these patients, 29 had common variable immunodeficiency, one X-linked agammaglobulinaemia, one X-linked immunoglobulin deficiency of uncertain cause and three isolated IgG subclass deficiency. We have confirmed that lymphoma in antibody deficiency is predominantly B cell in origin. Clonal lymphocyte populations were demonstrated in biopsies irrespective of histology (16/19 with lymphoma and 11/15 without). Isolated evidence of clonality in biopsy material is therefore an insufficient diagnostic criterion to determine malignancy. Furthermore, our data suggest that clonal expansions are rarely the result of Epstein-Barr virus-driven disease.

Adult↗
PubMed2003

Is subtyping of intestinal metaplasia in the upper gastrointestinal tract a worthwhile exercise? An evaluation of current mucin histochemical stains.

Intestinal metaplasia is a premalignant condition that occurs in the upper gastrointestinal tract and can be subdivided into three types (I, II and III). Previous studies suggest that type III carries the highest cancer risk. The high iron diamine/alcian blue (HID/AB) technique traditionally has been used to identify this subtype; however, the technique uses reagents that are toxic and potentially carcinogenic. Therefore, in this study we evaluate various alternative histochemical techniques. Our results indicated that the only suitable alternative is Gomori's aldehyde fuchsin/AB technique. The study also revealed that subtyping of intestinal metaplasia is a subjective procedure, open to varying interpretation. Consequently, we suggest that previous work linking cancer risk to metaplasia subtypes should be viewed with some circumspection.

Barrett Esophagus↗
PubMed2003

Diagnostic role of tests for T cell receptor (TCR) genes.

Rapid advances in molecular biological techniques have made it possible to study disease pathogenesis at a genomic level. T cell receptor (TCR) gene rearrangement is an important event in T cell ontogeny that enables T cells to recognise antigens specifically, and any dysregulation in this complex yet highly regulated process may result in disease. Using techniques such as Southern blot hybridisation, polymerase chain reaction, and flow cytometry it has been possible to characterise T cell proliferations in malignancy and in diseases where T cells have been implicated in the pathogenesis. The main aim of this article is to discuss briefly the process of TCR gene rearrangement and highlight the disorders in which expansions or clonal proliferations of T cells have been recognised. It will also describe various methods that are currently used to study T cell populations in body fluids and tissue, their diagnostic role, and current limitations of the methodology.

Blotting, Southern↗
PubMed2002

Evidence of electromagnetic absorption by collective modes in the heavy fermion superconductor UBe(13).

We present results of a microwave surface impedance study of the heavy fermion superconductor UBe(13). We clearly observe an absorption peak whose frequency and temperature dependence scales with the BCS gap function Delta(T). Resonant absorption into a collective mode, with energy approximately proportional to the superconducting gap, is proposed as a possible explanation. Fits to the data provide a simple relation between Delta(T) and the collective mode frequency.

Journal Article↗