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Biomedical subjects

Richard Smith

Publications and source records attributed to Richard Smith.

At least 91 records · Page 5Linked to original sources
PubMed2003

Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection.

BACKGROUND: A study was designed to estimate relative analytic sensitivity and window-period (WP) closure and to project incremental yield of newer HBsAg tests, pooled-sample NAT, and single-sample NAT, compared to currently licensed HBsAg tests. STUDY DESIGN AND METHODS: HBV DNA and HBsAg test results for 23 HBV seroconversion (SC) panels were first analyzed to construct a model of primary HBV viremia. One-hundred representative samples were then selected from 10 panels and coded with 28 analytical controls. All 128 samples were tested by seven HBsAg tests and by four pooled-sample and three single-sample NAT assay formats. Results were analyzed to obtain differential times to HBV detection and combined with HBV incidence rates to project comparative yields. RESULTS: HBV doubling time during the ramp-up phase was estimated at 2.56 days. HBsAg concentrations at cutoff for new tests ranged from 0.07 to 0.12 ng per mL, compared with 0.13 to 0.62 ng per mL for licensed tests. Estimated viral load at cutoff ranged from 102 to 267 IU per mL for new tests and from 363 to 1069 IU per mL for licensed tests. HBsAg tests detected 31 to 63 percent of early ramp-up phase samples in the 100-member seroconversion panel study, while pooled-sample NAT detected 55 to 71 percent and single-sample NAT, 82 to 99 percent. Compared with currently licensed HBsAg assays, newer HBsAg assays would reduce the WP by 2 to 9 days; pooled-sample NAT would reduce the WP by 9 to 11 days; and single-sample NAT would reduce the WP by 25 to 36 days. CONCLUSION: Newer HBsAg tests would be expected to detect an additional 15 to 21 infected units per 107 donations, compared to licensed HBsAg tests. Sensitivity, WP closure, and yield projections for newer HBsAg assays and pooled-sample NAT are comparable. Single-sample NAT would increase yield by 13 to 15 units per 107 donations over pooled-sample NAT and newer HBsAg assays and by 35 to 50 units per 107 donations over currently licensed HBsAg assays.

Acute Disease↗
PubMed2003

Novel anterior segment phenotypes resulting from forkhead gene alterations: evidence for cross-species conservation of function.

PURPOSE: Mutations in murine and human versions of an ancestrally related gene usually result in similar phenotypes. However, interspecies differences exist, and in the case of two forkhead transcription factor genes (FOXC1 and FOXC2), these differences include corneal or anterior segment phenotypes, respectively. This study was undertaken to determine whether such discrepancies provide an opportunity for identifying novel human-murine ocular phenotypes. METHODS: Four pedigrees with early-onset glaucoma phenotypes secondary to segmental chromosomal duplications or deletions encompassing FOXC1 and 18 individuals from 9 FOXC2 mutation pedigrees underwent detailed ocular phenotyping. Subsequently, mice with mutations in Foxc1 or a related forkhead gene, Foxe3, were assessed for features of the human phenotypes. RESULTS: A significant increase in central corneal thickness was present in affected individuals from the segmental duplication pedigrees compared with their unaffected relatives (mean increase 13%, maximum 35%, P < 0.05). Alterations in corneal thickness were present in mice heterozygous and homozygous for Foxe3 mutations but neither in Foxc1 heterozygotes nor the small human segmental deletion pedigree. Mutations in FOXC2 resulted in ocular anterior segment anomalies. These were more severe and prevalent with mutations involving the forkhead domain. CONCLUSIONS: Normal corneal development is dependent on the precise dose and levels of activity of certain forkhead transcription factors. The altered corneal thickness attributable to increased forkhead gene dosage is particularly important, because it may affect the clinical management of certain glaucoma subtypes and lead to excessive treatment. The FOXC1 and Foxe3 data, taken together with the novel ocular phenotypes of FOXC2 mutations, highlight the remarkable cross-species conservation of function among forkhead genes.

Animals↗
PubMed2003

Treatment of autoimmune disease by adoptive cellular gene therapy.

Autoimmune disorders represent inappropriate immune responses directed at self-tissue. Antigen-specific CD4+ T cells and antigen-presenting dendritic cells (DCs) are important mediators in the pathogenesis of auto-immune disease and thus are ideal candidates for adoptive cellular gene therapy, an ex vivo approach to therapeutic gene transfer. Using retrovirally transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells, T cell hybridomas, and DCs rapidly and preferentially home to the sites of inflammation in animal models of multiple sclerosis, arthritis, and diabetes. These cells, transduced with retroviral vectors to drive expression of various "regulatory proteins" such as IL-4, IL-10, IL-12p40, and anti-TNF scFv, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental autoimmune encephalitis (EAE), collagen-induced arthritis (CIA), and nonobese diabetic mice (NOD).

Adoptive Transfer↗
PubMed2003

Emission spectroscopy for coal-fired cyclone furnace diagnostics.

Using a spectrograph and charge-coupled device (CCD) camera, ultraviolet and visible light emission spectra were obtained from a coal-burning electric utility's cyclone furnaces operating at either fuel-rich or fuel-lean conditions. The aim of this effort is to identify light emission signals that can be related to a cyclone furnace's operating condition in order to adjust its air/fuel ratio to minimize pollutant production. Emission spectra at the burner and outlet ends of cyclone furnaces were obtained. Spectra from all cyclone burners show emission lines for the trace elements Li, Na, K, and Rb, as well as the molecular species OH and CaOH. The Ca emission line is detected at the burner end of both the fuel-rich and fuel-lean cyclone furnaces but is not detected at the outlet ends of either furnace type. Along with the disappearance of Ca is a concomitant increase in the CaOH signal at the outlet end of both types of furnaces. The OH signal strength is in general stronger when viewing at the burner end rather than the exhaust end of both the fuel-rich and fuel-lean cyclone furnaces, probably due to high, non-equilibrium amounts of OH present inside the furnace. Only one molecular species was detected that could be used as a measure of air/fuel ratio: MgOH. It was detected at the burner end of fuel-rich cyclone furnaces but not detected in fuel-lean cyclone furnaces. More direct markers of air/fuel ratio, such as CO and O2 emission, were not detected, probably due to the generally weak nature of molecular emission relative to ambient blackbody emission present in the cyclone furnaces, even at ultraviolet wavelengths.

Air Pollution↗