Biomedical subjects

A R Smith

Publications and source records attributed to A R Smith.

At least 19 recordsLinked to original sources

PubMed2005

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.

Journal Article↗

PubMed2005

Therapeutic step and shoot proton beam spot-scanning with a multi-leaf collimator: a Monte Carlo study.

In step and shoot spot-scanning, a small-diameter proton beam is magnetically swept and varied in energy in order to cover the tumour. Initial estimates of the beam size indicate that additional collimating hardware will be needed for lower energy proton beams in order to achieve a clinically acceptable lateral dose falloff at the edge of the proton beam. In this report, we present dosimetric data from Monte Carlo simulations with a model of a simple multileaf collimator which indicate that such a device may be used to improve the lateral dose falloff. The dosimetric quantities relevant to the clinical usefulness of the device are studied, including lateral penumbra, leaf transmission and scalloping effect. Multileaf collimation is compared with a differential spot-weighting technique of sharpening the lateral dose falloff.

Body Burden↗

PubMed2004

Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.

alpha-Lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that LA also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of LA with particular reference to how LA may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.

Animals↗

PubMed2003

Molecular phylogenetics and evolution of the endemic Hawaiian genus Adenophorus (Grammitidaceae).

Recent studies of the phylogeny of several groups of native Hawaiian vascular plants have led to significant insights into the origin and evolution of important elements of the Hawaiian flora. No groups of Hawaiian pteridophytes have been subjected previously to rigorous phylogenetic analysis. We conducted a molecular phylogenetic analysis of the endemic Hawaiian fern genus Adenophorus employing DNA sequence variation from three cpDNA fragments: rbcL, atpbeta, and the trnL-trnF intergenic spacer (IGS). In the phylogenetic analyses we employed maximum parsimony and Bayesian inference. Bayesian phylogenetic inference often provided stronger support for hypothetical relationships than did nonparametric bootstrap analyses. Although phylogenetic analyses of individual DNA fragments resulted in different patterns of relationships among species and varying levels of support for various clades, a combined analysis of all three sets of sequences produced one, strongly supported phylogenetic hypothesis. The primary features of that hypothesis are: (1) Adenophorus is monophyletic; (2) subgenus Oligadenus is paraphyletic; (3) the enigmatic endemic Hawaiian species Grammitis tenella is strongly supported as the sister taxon to Adenophorus; (4) highly divided leaf blades are evolutionarily derived in the group and simple leaves are ancestral; and, (5) the biogeographical origin of the common ancestor of the Adenophorus-G. tenella clade remains unresolved, although a neotropical origin seems most likely.

Base Sequence↗

PubMed2003

Nucleoside diphosphate kinase is a possible component of the ethylene signal transduction pathway.

In etiolated seedlings of Pisum sativum and leaves of Arabidopsis thaliana, in vivo ethylene treatment resulted in an increase in in vitro phosphorylation of 17 kD (P. sativum) or 16 and 17 kD (A. thaliana) polypeptides. These polypeptides were identified as nucleoside diphosphate kinase (NDPK) based on both biochemical properties and interaction with antibodies against NDPK from P. sativum. Using the receptor-directed antagonist of ethylene action 2,5-norbornadiene and the ethylene-insensitive mutants of A. thaliana etr1-1 and eti5, ethylene specificity and receptor dependence of NDPK phosphorylation have been demonstrated. In pea epicotyls, ethylene treatment also led to increase in nucleoside transferase activity unlike in A. thaliana leaves. The increases in nucleoside transferase activity and NDPK phosphorylation were very rapid and transient. The results suggest a role for NDPK as a possible component of the ethylene signal transduction chain.

Arabidopsis↗

PubMed2003

Vascular endothelial dysfunction in aging: loss of Akt-dependent endothelial nitric oxide synthase phosphorylation and partial restoration by (R)-alpha-lipoic acid.

Aging is the single largest risk factor for cardiovascular diseases, which in turn are the leading cause of death of individuals over the age of 65 years. In part, this risk is due to a profound loss of vasomotor function of the major conduit arteries, primarily because of lower levels of endothelial-derived nitric oxide. The mechanisms involved in vascular dysfunction are not entirely understood, but age-related alterations in eNOS (endothelial nitric oxide synthase) activity appear to be a likely source of the aging lesion. However, age-related changes in cell signalling that ultimately affect eNOS phosphorylation and its activity have not been explored. Results in our laboratory indicate that levels of eNOS phosphorylation in aortas from aged F344xBN rats (28-30 months old) are almost 50% lower than in aortas from young animals (3 months old). Lower eNOS phosphorylation is directly attributable to loss of constitutive Akt/protein kinase B activity. The decline in eNOS phosphorylation can be partially restored by treating old rats with (R)-alpha-lipoic acid. These results thus suggest that age-related changes in eNOS phosphorylation may be a significant factor in the overall loss of vasomotor function in the elderly.

Aging↗

PubMed2002

A reappraisal of the reported dose equivalents at the boundary of the University of California Radiation Laboratory during the early days of Bevatron operation.

The Bevatron of the Lawrence Berkeley National Laboratory operated with no permanent shielding-roof from 1954 to 1962. Neutron fluences measured at the laboratory perimeter reached a maximum in 1959, and were reported as an annual dose equivalent of 8.1 mSv (54% of the then operative radiation limit). The addition of temporary local shielding and improved operational techniques subsequently led to a steady decline in dose equivalent at the laboratory perimeter. A permanent concrete shielding-roof was constructed in 1962. In those early years of operation the reported dose equivalent, H, was derived from a measured total neutron fluence, phi, and an estimated spectrum-weighted fluence to dose equivalent conversion coefficient, (g), where H= (g) phi. The uncertainty in H was almost entirely due to the uncertainty in (g). While the measurements of phi were accurate the estimates of (g) were quite crude and depended upon measurements of average neutron energy, on assumptions about the shape of the neutron energy spectrum, and primitive values of fluence to dose equivalent conversion coefficients for monoenergetic neutrons. These early reported dose equivalents were known to be overestimated. This paper has reappraised the dose equivalents in the light of better information now available. Environmental neutron spectra have been calculated which more accurately correspond to the operational conditions of the Bevatron in the 1950s and early 1960s. than did those spectra available at that time. A new fluence to dose equivalent conversion function based on the latest data and for isotropic irradiation geometry was developed. From these two parameters better estimates of the coefficient (g) were determined and compared with the earlier values. From this reappraisal it is shown that the early reported dose equivalents were conservative by a factor of at least five.

Calibration↗

PubMed2002

Dosimetry for ocular proton beam therapy at the Harvard Cyclotron Laboratory based on the ICRU Report 59.

The Massachusetts General Hospital, the Harvard Cyclotron Laboratory (HCL), and the Massachusetts Eye and Ear Infirmary have treated almost 3000 patients with ocular disease using high-energy external-beam proton radiation therapy since 1975. The absorbed dose standard for ocular proton therapy beams at HCL was based on a fluence measurement with a Faraday cup (FC). A majority of proton therapy centers worldwide, however, use an absorbed dose standard that is based on an ionization chamber (IC) technique. The ion chamber calibration is deduced from a measurement in a reference 60Co photon field together with a calculated correction factor that takes into account differences in a chamber's response in 60Co and proton fields. In this work, we implemented an ionization chamber-based absolute dosimetry system for the HCL ocular beamline based on the recommendations given in Report 59 by the International Commission on Radiation Units and Measurements. Comparative measurements revealed that the FC system yields an absorbed dose to water value that is 1.1% higher than was obtained with the IC system. That difference is small compared with the experimental uncertainties and is clinically insignificant. In June of 1998, we adopted the IC-based method as our standard practice for the ocular beam.

Academic Medical Centers↗

PubMed2001

Melatonin receptor RNA is expressed in photoreceptors and displays a diurnal rhythm in Xenopus retina.

Melatonin is an output signal of an endogenous circadian clock of retinal photoreceptors, with highest levels occurring at night. Melatonin synthesized in the retina appears to act as a paracrine signal by binding to specific receptors in the eye. We have previously demonstrated that RNA encoding the Mel(1b) and Mel(1c) melatonin receptor subtypes is expressed in the Xenopus laevis retina. The goal of this study was to determine the distribution of the Mel(1b) and Mel(1c) receptor subtype RNA expression in the retina, and to determine if the level of expression of these receptors exhibits a diurnal rhythm. Sections of frog neural retina were analyzed by in situ hybridization with 35S-labeled Xenopus Mel(1c) and Mel(1b) riboprobes. Hybridization was present in cells of the inner nuclear layer and the ganglion cell layer. Moreover, there was hybridization in the photoreceptors, which has not been previously reported. To test the hypothesis that retinal melatonin receptor mRNA undergoes a diurnal rhythm of expression, total RNA was isolated from frog neural retinas obtained at 3-h intervals during a 24-h period. The total RNA was used in real-time PCR assays to quantify the differences in Mel(1b) and Mel(1c) receptor mRNA expression at various circadian times. Both the Mel(1b) and Mel(1c) receptor RNA demonstrated a diurnal rhythm of expression, with peak levels occurring late in the light period, and lowest levels late in the dark period. These results support the hypothesis that RNA encoding melatonin receptors undergo a diurnal rhythm of expression. To further investigate the possible expression of the Mel(1a) receptor subtype in Xenopus retina, we generated Mel(1a) PCR products in genomic DNA, and in reverse-transcribed neural retina and retinal pigment epithelium (RPE) RNA. The identity of the PCR product was confirmed by sequencing. Therefore, all three known Xenopus melatonin receptor subtypes appear to be expressed in the neural retina and RPE.

Animals↗

PubMed2001

Synthesis, structural characterization, and conformational bias in solution of a sterically congested pyrophosphite: experimental and computational evidence for restricted rotation about an sp3-sp3 P-O single bond.

The synthesis and structural characterization of the sterically congested pyrophosphite 6-[(2,4,8,10-tetrakis(1,1-dimethylethyl)-dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl)oxy]-2,4,8,10-tetrakis(1,1-dimethylethyl)-dibenzo[d,f][1,3,2]dioxaphosphepin, 3, is described. In solution at room temperature, a single species was observed that was consistent with a pyrophosphite structure without any evidence for the tautomeric diphosphine monoxide. Below the coalescence temperature (T(C)), 0 degrees C, three atropisomers were observed with relative absolute configurations of (R,R,R), (R,S,R), and (R,R,S). Ring inversion of the seven-membered rings below the T(C) is slow on the NMR time scale, which leads to observable diastereoisomerism because of the presence of two independent stereoaxes (sp2-sp2 C-C single bond connecting the two aryl rings). Additionally, a rotation about an exocyclic P-O single bond connecting the two seven-membered rings, which constitutes a third stereoaxis, is slowed on the NMR time scale. In the X-ray crystal structure of 3, the solid-state conformation was found to be the same as the major conformation in solution below the T(C), namely, the (R,R,S) atropisomer. The results of a conformational search, performed with a specifically parametrized AMBER force field, were in agreement with the 31P NMR assignment of the major (R,R,S) atropisomer, which was found to be an energy minimum. Additionally, we could independently assign the relative configuration of the minor isomers based on the calculated results.

Journal Article↗

PubMed2001

Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma.

BACKGROUND: Infertility is a common late effect of chemotherapy and radiotherapy, and has a substantial effect on the quality of life for young survivors of cancer. For men, semen cryopreservation is a simple way of preserving reproductive potential but for women, storage of mature eggs rarely proves successful, and the alternative-immediate in vitro fertilisation with cryopreservation of embryos-is not always appropriate. Reimplantation of cryopreserved ovarian tissue has been shown to restore natural fertility in animals. We applied this technique in a woman who had received sterilising chemotherapy for lymphoma. METHODS: A 36-year-old woman underwent a right oophorectomy with cryopreservation of ovarian cortical strips before receiving high-dose CBV chemotherapy for a third recurrence of Hodgkin's lymphoma. 19 months later, when serum sex steroid analysis confimed a postmenopausal state, two ovarian cortical strips were thawed and reimplanted-one onto the left ovary and another at the site of the right ovary. FINDINGS: 7 months after reimplantation of ovarian cortical strips, the patient reported resolution of hot flashes and, for the first time, oestradiol was detected in the serum. This finding was associated with a decrease in the concentrations of follicle-stimulating hormone and luteinising hormone, and ultrasonography revealed a 10 mm thick endometrium, a poorly visualised left ovary, and a 2 cm diameter follicular structure to the right of the midline. The patient had one menstrual period, but by 9 months after the implantation, her sex steroid concentrations had returned to those seen with ovarian failure. INTERPRETATION: Orthotopic reimplantation of frozen/thawed ovarian cortical strips is a well tolerated technique for restoring ovarian function in women treated with sterilising chemotherapy for cancer.

Adult↗

PubMed2001

Horsetails and ferns are a monophyletic group and the closest living relatives to seed plants.

Most of the 470-million-year history of plants on land belongs to bryophytes, pteridophytes and gymnosperms, which eventually yielded to the ecological dominance by angiosperms 90 Myr ago. Our knowledge of angiosperm phylogeny, particularly the branching order of the earliest lineages, has recently been increased by the concurrence of multigene sequence analyses. However, reconstructing relationships for all the main lineages of vascular plants that diverged since the Devonian period has remained a challenge. Here we report phylogenetic analyses of combined data--from morphology and from four genes--for 35 representatives from all the main lineages of land plants. We show that there are three monophyletic groups of extant vascular plants: (1) lycophytes, (2) seed plants and (3) a clade including equisetophytes (horsetails), psilotophytes (whisk ferns) and all eusporangiate and leptosporangiate ferns. Our maximum-likelihood analysis shows unambiguously that horsetails and ferns together are the closest relatives to seed plants. This refutes the prevailing view that horsetails and ferns are transitional evolutionary grades between bryophytes and seed plants, and has important implications for our understanding of the development and evolution of plants.

Biological Evolution↗

PubMed2001

Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration.

OBJECTIVE: To examine (1) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration (AMD) and (2) the relationship in this population between depression, visual acuity, the number of comorbid medical conditions, disability caused by vision loss as measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision-specific Sickness Impact Profile (SIPV), and disability caused by overall health status as measured by the Sickness Impact Profile-68 (SIP). DESIGN: Analysis of cross-sectional baseline data from a randomized clinical trial. PARTICIPANTS: Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced macular degeneration whose vision was 20/60 or worse in their better eye. METHODS: Subjects were interviewed using measures of depression, disability, and chronic medical conditions. Visual acuity was obtained. Nonparametric correlation analyses and linear regression analyses were performed. MAIN OUTCOME MEASURES: Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP. RESULTS: Of the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder, twice the rate observed in previous studies of community-dwelling elderly. Over and above depression (GDS), visual acuity aided in prediction of the level of vision-specific disability (NEI-VFQ and SIPV). CONCLUSIONS: Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration. Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning. Over and above depression, visual acuity aided in predicting vision-specific disability. Treatment strategies that teach patients to cope with vision loss should be developed and evaluated.

Aged↗

PubMed2001

Ethylene signal perception and transduction: multiple paradigms?

Current progress on the mechanisms of ethylene signal perception and transduction are reviewed with an emphasis on reconciling data from molecular genetics and from biochemical approaches. It is proposed that there exist two or more interacting transduction pathways.

Animals↗

PubMed2001

Laparoscopic colposuspension.

Laparoscopic urogynaecology started to develop following the first report of a laparoscopic colposuspension in 1991. The place of laparoscopic treatment of urinary incontinence has yet to be established and, as for all new techniques, case reports, case series and small randomized studies have been reported. Larger randomized studies with adequate power have yet to be reported. Current opinion is divided as to the success of these new operations. Assessment of outcome is further clouded by large variations in technique, such that like is not always compared with like. The present review assesses the recent literature and the place of the traditional colposuspension performed via the laparoscopic route.

Female↗

PubMed2001

Recovery of commercially produced Bacillus thuringiensis var. israelensis and Bacillus sphaericus from tires and prevalence of bacilli in artificial and natural containers.

We conducted surveys to identify the species of spore-forming bacteria present in natural and artificial containers. Most of our samples came from Illinois. Identification was based on the cellular fatty acid composition of the bacterial cell wall. In addition, we utilized a custom database for commercially produced strains of Bacillus thuringiensis var. israelensis (Bti) and B. sphaericus, to differentiate between larvicidal isolates with commercial or native origin. Native Bti was present at low levels in almost all habitats but was not recovered from bromeliads and metal containers. In temporary woodland pools, 27.9% of the colonies recovered were native Bti. We did not recover larvicidal B. sphaericus in untreated habitats. VectoBac and VectoLex were applied to tires containing water and the tires were sampled 3 months and 9 months after treatment. Isolates of Bti and B. sphaericus with commercial origin were recovered as long as 9 months after application. We noticed numerous cadavers of Aedes triseriatus in several tires 9 months after treatment with VectoBac. We could not determine if this mortality resulted from recycling of Bti in these tires or whether insecticidal crystal proteins from the original treatment were resuspended. Bacillus thuringiensis var. israelensis isolates with commercial ancestry were recovered from untreated tires 9 months after application. Isolates of larvicidal B. sphaericus that differed from the bacteria in VectoLex were also recovered from untreated tires.

Animals↗

PubMed2001

2,4-dichlorophenoxyacetate/alpha-ketoglutarate dioxygenases from Burkholderia cepacia 2a and Ralstonia eutropha JMP134.

2,4-Dichlorophenoxyacetate (2,4-D)/alpha-ketoglutarate (alpha-KG) dioxygenase has been purified to apparent homogeneity from Burkholderia cepacia strain 2a, which utilizes 2,4-D as sole carbon source. The enzyme required ferrous ions, and was a homodimer composed of subunits having an Mr of approximately 32,000. The reaction catalysed consumed one mol each of 2,4-D, alpha-KG and dioxygen, with the production of one mol each of succinate, 2,4-dichlorophenol and glyoxylate. Maximum activity was exhibited at pH 7.8 and 25 degrees C, and reactivity was enhanced by the presence of ascorbate and cysteine. Mn2+, Zn2+, Cu2+, Fe3+ and Co2+ were inhibitory, and chemical modification of the dioxygenase revealed that thiol groups were essential for activity. The enzyme was active towards other substituted phenoxyacetates, but reacted most rapidly with 2,4-D. The apparent Michaelis constants for 2,4-D and alpha-KG were 109 and 8.9 microM, respectively. The properties of this enzyme are compared with those of the 2,4-D/alpha-KG dioxygenase from Ralstonia eutropha JMP134, which exhibits a differing N-terminal amino-acid sequence, and a different temperature 'optimum', pH optimum, substrate specificity and sensitivity to thiol-binding reagents.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2001

rbcL data reveal two monophyletic groups of filmy ferns (Filicopsida: Hymenophyllaceae).

The "filmy fern" family, Hymenophyllaceae, is traditionally partitioned into two principal genera, Trichomanes s.l. (sensu lato) and Hymenophyllum s.l., based upon sorus shape characters. This basic split in the family has been widely debated this past century and hence was evaluated here by using rbcL nucleotide sequence data in a phylogenetic study of 26 filmy ferns and nine outgroup taxa. Our results confirm the monophyly of the family and provide robust support for two monophyletic groups that correspond to the two classical genera. In addition, we show that some taxa of uncertain affinity, such as the monotypic genera Cardiomanes and Serpyllopsis, and at least one species of Microtrichomanes, are convincingly included within Hymenophyllum s.l. The tubular- or conical-based sorus that typifies Trichomanes s.l. and Cardiomanes, the most basal member of Hymenophyllum s.l., is a plesiomorphic character state for the family. Tubular-based sori occurring in other members of Hymenophyllum s.l. are most likely derived independently and more than one time. While rbcL data are able to provide a well-supported phylogenetic estimate within Trichomanes s.l., they are inadequate for resolving relationships within Hymenophyllum s.l., which will require data from additional sources. This disparity in resolution reflects differential rates of evolution for rbcL within Hymenophyllaceae.

Journal Article↗