PubMed Health⌕ Search

Biomedical subjects

R A Sutherland

Publications and source records attributed to R A Sutherland.

13 recordsLinked to original sources

A first look at platinum in road-deposited sediments and roadside soils, Honolulu, Oahu, Hawaii.

Platinum (Pt) has become globally distributed by anthropogenic inputs, primarily from automobile emissions resulting from degradation of catalytic converters. These inputs are greatest in urban areas, with the major sinks being road sediments and roadside soils. Limited data are available on the distribution of Pt in the environment. No data for Pt in road-deposited sediments are presently available from the United States, and only a few studies offer a limited perspective of Pt in urban soils in the United States. This investigation represents the first study in the United States to characterize Pt concentrations and enrichment ratios in both road sediments and roadside soils in an urban (nonindustrialized) basin in Honolulu, Hawaii. Two independent analytical techniques-cathodic stripping voltammetry and lead-fire assay followed by ICP-AES-were used to quantify Pt in environmental media. Data from 10 road sediments confirm Pt contamination, with a median concentration of 33 ng g(-1) and a range of 15-160 ng g(-1). Upper soil horizons in roadside areas also exhibited contamination, with a median Pt value of 14 ng g(-1) (range 2-160 ng g(-1)), but significantly lower than road sediments. Computation of robust enrichment ratios using baseline soil, geology, and tree bark data indicated that road sediments had a median Pt enrichment of 9 (range 4-46), upper soil horizons a median of 4, and lower horizons 1.1. The latter were not found to differ significantly from Pt baseline concentrations. However, several roadside sites exhibited significant enrichment with depth, which may indicate potential Pt mobility in this environment. These data support a substantial loading of Pt in the urban environment of Hawaii. Further work is required to characterize the distribution of other autocatalyst-associated noble metals palladium (Pd) and rhodium (Rh) in the environment.

Cities↗

Vaccination with Her-2/neu DNA or protein subunits protects against growth of a Her-2/neu-expressing murine tumor.

The present study utilizes an in vivo murine tumor expressing human Her-2/neu to evaluate potential Her-2/neu vaccines consisting of either full length or various subunits of Her-2/neu delivered in either protein or plasmid DNA form. Our results demonstrate that protective immunity against Her-2/neu-expressing tumor challenge can be achieved by vaccination with plasmid DNA encoding either full length or subunits of Her-2/neu. Partial protective immunity was also observed following vaccination with the intracellular domain (ICD), but not extracellular domain (ECD), protein subunit of Her-2/neu. The mechanism of protection elicited by plasmid DNA vaccination appeared to be exclusively CD4 dependent, whereas the protection observed with ICD protein vaccination required both CD4 and CD8 T cells.

Animals↗

CD8+ T cells recognize an inclusion membrane-associated protein from the vacuolar pathogen Chlamydia trachomatis.

During infection with Chlamydia trachomatis, CD8(+) T cells are primed, even though the bacteria remain confined to a host cell vacuole throughout their developmental cycle. Because CD8(+) T cells recognize antigens processed from cytosolic proteins, the Chlamydia antigens recognized by these CD8(+) T cells very likely have access to the host cell cytoplasm during infection. The identity of these C. trachomatis proteins has remained elusive, even though their localization suggests they may play important roles in the biology of the organism. Here we use a retroviral expression system to identify Cap1, a 31-kDa protein from C. trachomatis recognized by protective CD8(+) T cells. Cap1 contains no strong homology to any known protein. Immunofluorescence microscopy by using Cap1-specific antibody demonstrates that this protein is localized to the vacuolar membrane. Cap1 is virtually identical among the human C. trachomatis serovars, suggesting that a vaccine incorporating Cap1 might enable the vaccine to protect against all C. trachomatis serovars. The identification of proteins such as Cap1 that associate with the inclusion membrane will be required to fully understand the interaction of C. trachomatis with its host cell.

Animals↗

Metal extraction from road sediment using different strength reagents: impact on anthropogenic contaminant signals.

Washoff of road deposited sediment into storm drain systems is one of the major contributors to nonpoint source pollution in urban fluvial networks. These sediments contain a variety of potentially toxic organic and inorganic contaminants. Road sediment from 13 locations in an urban (non-industrialized) drainage basin, and soil from 10 background (control) locations were collected to assess total and labile fractions of Al, Co, Cu, Fe, Mn, Ni, Pb and Zn. Four digestions, of varying strength, were used to assess contaminant levels, these included: a total four-acid digestion, a microwave-assisted digestion with concentrated nitric acid (USEPA Method 3051), a 0.5 M 'cold' HCl, and a 0.05 M EDTA (pH 7). Road sediment data indicate that Al, Co, Fe, Mn and Ni were primarily lithogenic in origin, while Cu, Pb and Zn showed very significant anthropogenic signals, most probably from vehicle-related sources. Median Pb concentration enrichment ratios for the EDTA extraction were about 42, indicating an extreme anthropogenic signal. The weak extractants (HCI and EDTA) are considered in this study to be superior in their ability to characterize the degree of anthropogenic contamination and should be utilized more widely in environmental contaminant studies.

Chelating Agents↗

Metal phase associations in soils from an urban watershed, Honolulu, Hawaii.

Soils of Manoa watershed, Hawaii, have received varying inputs of anthropogenic trace metals, with roadside soils primarily influenced by automobile contributions. A four-stage sequential extraction procedure was used to fractionate 13 topsoil (0-2.5 cm) and 13 subsoil (7.5-10.0 cm) samples into: (i) an adsorbed, exchangeable and carbonate (AEC) phase; (ii) a reducible phase; (iii) an oxidizable phase; and (iv) a residual phase. Phases (i)-(iii) were considered 'labile', with the residual fraction 'non-labile' under normal circumstances. An examination of eight elements (Al, Co, Cu, Fe, Mn, Ni, Pb and Zn) indicated that Pb was the trace metal most impacted by anthropogenic inputs. Roadside soil Pb enrichment was apparent with data from a 0.5 M HCI leach exhibiting a maximum concentration of 1000 mg/kg compared with a median background value of 12 mg/kg. Sequential extraction results indicated the following order with respect to phase dominance for Pb: reducible > residual > oxidizable > AEC. The identification of the reducible phase as the primary pool of available Pb supports previous work from temperate roadside soil environments. The reducible phase is characterized by hydrous Fe and Mn oxides and mobilization of fixed elements can occur with decreases in pH and redox potential. Iron was the least labile of the elements examined with only 5-6% of total Fe removed by the first three steps of the extraction procedure. Lead had the highest labile percentage with average values between 74 and 81%. Therefore, results from this study support earlier research in this watershed which identified Pb as the primary trace metal of concern from a contamination perspective.

Humans↗

Characterization of selected element concentrations and enrichment ratios in background and anthropogenically impacted roadside areas.

Previous research by the National Contaminant Biomonitoring Program found fish from Manoa Stream, Hawaii, to have the highest concentrations of Pb in the nation. To explore possible source linkages we sampled background (uncontaminated) soil, roadside soil, and road deposited sediment in Manoa watershed and analyzed them for total and extractable concentrations of Al, Co, Cu, Fe, Mn, Ni, Pb, and Zn. Our concentration and enrichment ratio data indicate that Al, Co, Fe, Mn, and Ni were controlled by natural source variations, and Cu, Zn, and particularly Pb were anthropogenically enhanced. Labile Pb concentrations, extracted with either dilute HCl or EDTA, reached a maximum of 3,560 mg/kg compared to background values of <10 mg/kg. Additionally, 25% of the 169 contaminated samples analyzed had EDTA-extractable Pb enrichment ratios > or =11.5, where a value of 1 separates uncontaminated from contaminated media. Given the proximity of most samples to roadways it is reasonable to conclude that automotive emissions plus vehicle wear were the primary contributors of trace metals to the roadside system. These data are discussed in context with previous work on the fluvial bed sediments in this watershed in an attempt to examine the potential linkage with the biological accumulation of Pb in fish from Manoa watershed.

Animals↗

Multi-element analysis of road-deposited sediment in an urban drainage basin, Honolulu, Hawaii.

Road-deposited sediment (RDS) and its associated contaminant load play a critical role in degrading receiving water bodies. Few quantitative multi-element RDS studies exist, and there are none from Hawaii. This lack of baseline data combined with concerns with high concentrations of Pb and Cu in fish and enrichment of Cu, Pb and Zn in bed sediments from Manoa Stream, Hawaii, lead to a detailed characterization of RDSs in Manoa basin. Data for a total analysis of 23 elements using inductively coupled plasma atomic-emission spectrometry and instrumental neutron activation analysis and 16 elements using a 0.5 M HCl partial leach are presented for RDSs and background soils. Concentration data, comparisons with environmental guidelines, and concentration enrichment ratios (CERs) all indicate that RDS in Manoa has a significant degree of anthropogenic pollution. The most environmentally important elements were Pb, Sb and Zn. Concentrations of these elements, primarily vehicle contributed, compare favorably with those from other studies of RDS. The high mean concentration of Pb (151 mg/kg) compared to background soils (13 mg/kg) indicates remobilization of Pb previously stored in soils and transported to road surfaces by water erosion processes. The higher Pb CER(Total) in RDSs compared to bed sediments from Manoa Stream suggests a potential link via ubiquitous storm drains and subsequent dilution with less contaminated fluvial sediments. Data from the HCl leach also support Pb and Zn as having significant anthropogenic signals, and Cu having a moderate signal. These data indicate that RDSs in Manoa basin are generally contaminated with certain potentially toxic elements and the legacy of past use of leaded gasoline is still a concern in this urban drainage system.

Journal Article↗

Cellular signaling in the bladder.

Embryologically, the urinary bladder is formed from endodermally derived epithelial cells and mesenchymal cells from the urogenital sinus and allantois. Experimentally, we have shown that bladder mesenchyme differentiates into bladder smooth muscle via an unknown signaling mechanism that originates from the urothelium. It is hypothesized that this signaling between the cellular types, occurs via growth factors. Evidence supporting this hypothesis is that a number of known growth factors, such as TGF beta 2 and 3, KGF and TGF alpha, as well as their receptors are regulated as a function of bladder development and are also modulated during experimental bladder outlet obstruction. Furthermore, growth factors most likely affect extracellular matrix degradative proteins which play a role in bladder remodeling during development, as well as in partial outlet obstruction. There is certainly impressive cellular communication that occurs during development and also occurs postnatally; such as during bladder injury. We have recently shown that KGF is directly responsible for the proliferation of urothelium during bladder injury. This normally quiescent cell, which in humans turns over once every six months to a year when injured, has the incredible ability to immediately proliferate covering the exposed areas of bladder muscle and submucosa. This proliferation is due to the direct effects of KGF, a classic paracrine growth factor which is secreted by the stromal compartment of the bladder and acts directly on the urothelium which harbors the receptor. The bladder also has an uncanny ability to regenerate. In a model to study the basic science behind bladder regeneration, a partial cystectomy was performed and an acellular tissue matrix devoid of all cellular elements was sutured to the defect. Within four days, the urothelium completely covered the acellular matrix, and within two weeks native smooth muscle was seen streaming into the acellular matrix in association with a new epithelium. It is hypothesized that cellular interactions between the epithelium and the mesenchyme, as we have shown in bladder differentiation, are encouraging the new growth of smooth muscle. For the bladder to be a safe and effective storage chamber the ideal cellular lining should be urothelium. Cells from the gastrointestinal are not optimal for this purpose since they either secrete or absorb electrolytes. We believe that the cellular interactions that occur between the urothelium and the foreign intestinal stroma will in time change the phenotype of the urothelium. Newer strategies for bladder replacement which take into account cellular signaling are critical for our young patients with neurogenic bladder disorders.

Animals↗

A CD2/CD28 chimeric receptor triggers the CD28 signaling pathway in CTLL.2 cells.

We are evaluating strategies to enhance the in vivo proliferation and function of adoptively transferred antigen-specific T cells. Although the CD28 costimulatory pathway is important for T cell activation and proliferation, the expression of the ligands for CD28 is highly restricted. We have generated a chimeric receptor composed of the signaling domains of CD28 and the extracellular domain of CD2 which binds the widely expressed ligand CD58. The CD2/CD28 chimeric receptor was introduced into CTLL.2 cells via retrovirus infection and was shown to be expressed on the cell surface. By monitoring early and late components of the CD28 signaling pathway, the chimeric receptor was demonstrated to trigger the CD28 pathway in response to CD2 cross-linking. The possible utility of the CD2/CD28 chimeric receptor for adoptive immunotherapy is discussed.

Animals↗

Mesenchymal-epithelial interactions in the bladder.

During bladder development, undifferentiated mesenchymal and epithelial cells undergo an orderly sequence of differentiation defined by the expression of smooth-muscle (alpha-actin, myosin, vinculin, desmin, vimentin, and laminin) and epithelial (cytokeratins 5, 7, 8, 14, 18 and 19) protein markers. This process requires mesenchymal-epithelial interactions with bladder epithelium (urothelium) necessary for the differentiation of bladder smooth muscle. Peptide growth factors such as keratinocyte growth factor (KGF) and transforming growth factors (TGF) alpha and beta are likely candidates as mediators of these mesenchymal-epithelial interactions. Transcripts for KGF, TGF alpha, and TGF beta are regulated during bladder development and during smooth-muscle hypertrophy secondary to bladder-outlet obstruction. Finally, two experimental bladder models--(1) partial outlet obstruction and (2) regeneration of bladder smooth muscle into an acellular tissue matrix--are described in the context of mesenchymal-epithelial interactions in the bladder.

Animals↗

Using fragment lengths from incomplete digestion by multiply cleaving enzymes to map antibody binding sites on a protein.

The problem of mapping the positions of the unique binding sites of several monoclonal antibodies on a linear protein structure is considered. Data giving the incidence of binding of individual antibodies to fragments of the protein obtained from it by the incomplete chemical or enzymatic digestion are used to formulate a series of linear programming problems. The solution to these problems shows which orderings of binding sites are possible, and gives upper and lower bounds for the relative positions of the sites.

Algorithms↗

Statistical analysis of gamma-emitting radionuclide concentrations for three fields in southern Saskatchewan, Canada.

During 1988, the spatial variability of the natural gamma-emitting radionuclides (238U, 232Th, and 40K) and the artificial radionuclide 137Cs were studied in three near-level unfertilized fields in Saskatchewan, Canada. One field was used as a native (uneroded) control site; the other two sites have been cultivated, one since 1979 and the other since at least the 1940s. The two cultivated sites have been eroded by aeolian processes and tillage practices. Autocorrelation analysis indicated that most of the radionuclides were not serially correlated for the two depth increments sampled (0-15 cm and 15-30 cm). Autocorrelation is a necessary procedure when equally spaced transect sampling is employed, since sample independence cannot be assumed. Robust and nonrobust statistical summaries are presented for the selected gamma-emitting radionuclide concentrations. Robust statistical estimates of location and dispersion are favored when distributions are not normal or when the distribution is skewed. Median concentrations for the three fields indicated that 238U, 232Th, 40K, and 137Cs were similar to areas in the U.S. and to other areas in southern Saskatchewan. Median 238U activity concentrations were between 31.4 and 34.1 Bq kg-1; 232Th concentrations were between 29.6 and 31.2 Bq kg-1; 40K concentrations were between 471 and 502 Bq kg-1; and 137Cs concentrations were between 10.0 and 12.6 Bq kg-1. The variability of natural radionuclides in a given field for a specific depth increment was generally low, with coefficients of variation less than or equal to 10%. The variability of 137Cs concentrations was greater, ranging from 18% to 23%. Nonparametric tests indicated a significant decrease in 214Bi concentration (238U indicator corrected for 222Rn) with depth of the 1979 field, and an increase in 228 Ac (232Th) with depth in the 1940s field. Significant differences in concentration between fields were indicated for all radionuclides except for 228 Ac. The possible reasons for differences in depth and between fields are briefly discussed.

Cesium Radioisotopes↗