Biomedical subjects

Richard M Higashi

Publications and source records attributed to Richard M Higashi.

7 recordsLinked to original sources

PubMed2006

Integrating contaminant responses in indicator saltmarsh species.

A challenge in environmental management is to provide both methodology and a framework for assessing effects of pollutants in resident species and then applying the findings to management. The Pacific Estuarine Ecosystem Indicator Research (PEEIR) consortium advocates the development of an integrated portfolio of techniques using indicator species selected for various habitat types. We developed such a portfolio for California salt marsh ecosystems and evaluated the feasibility of our approach in management applications. PEEIR is employing a suite of biomarker responses in two indigenous species, the lined shore crab (Pachygrapsus crassipes) and the longjaw mudsucker (Gillichthys mirabilis). Detrimental effects such as apoptosis, endocrine disruption, and ovarian tumors have been observed in G. mirabilis at a site where toxicity test responses were relatively low. With P. crassipes, developmental abnormalities and several markers of decreased reproductive performance were quantified at the same site. Multivariate statistical techniques are used to examine the relationships between the responses and multiple contaminant and natural stressors. For the fish, findings are related to population-level parameters using dynamic energy budget (DEB) models.

Animals↗

PubMed2006

Tidal salt marsh sediment in California, USA. Part 2: occurrence and anthropogenic input of trace metals.

Surface sediment samples (0-5 cm) from 5 tidal salt marshes along the coast in California, USA were analyzed to investigate the occurrence and anthropogenic input of trace metals. Among study areas, Stege Marsh located in the central San Francisco Bay was the most contaminated marsh. Concentrations of metals in Stege Marsh sediments were higher than San Francisco Bay ambient levels. Zinc (55.3-744 microg g(-1)) was the most abundant trace metal and was followed by lead (26.6-273 microg g(-1)). Aluminum normalized enrichment factors revealed that lead was the most anthropogenically impacted metal in all marshes. Enrichment factors of lead in Stege Marsh ranged from 8 to 49 (median=16). Sediments from reference marshes also had high enrichment factors (2-8) for lead, indicating that lead contamination is ubiquitous, possibly due to continuous input from atmospherically transported lead that was previously used as a gasoline additive. Copper, silver, and zinc in Stege Marsh were also enriched by anthropogenic input. Though nickel concentrations in Stege Marsh and reference marshes exceeded sediment quality guidelines, enrichment factors indicated nickel from anthropogenic input was negligible. Presence of nickel-rich source rock such as serpentinite in the San Francisco Bay watershed can explain high levels of nickel in this area. Coefficients of variation were significantly different between anthropogenically impacted and non-impacted metals and might be used as a less conservative indicator for anthropogenic input of metals when enrichment factors are not available.

California↗

PubMed2006

Integrating metabolomics and transcriptomics for probing SE anticancer mechanisms.

Transcriptomics provides the tool for deciphering gene expression networks, and proteomics links these networks to protein products. The third crucial partner is metabolomics, which defines the metabolic network(s) linked to gene expression. NMR and mass spectrometry enable the broad screen analysis of the metabolome and its transformation pathways, transcending classical targeted metabolic studies. These tools were combined to investigate the anticancer mechanisms of different selenium forms in human lung cancer cells. Using 2-D NMR and tandem-MS, we mapped perturbations of 13C labeling patterns in numerous metabolites induced by selenite and selenomethionine. This information was used to interpret selenite-induced changes in gene expression networks. Linking metabolic dysfunctions to altered gene expression profiles provided new insights into the regulatory network underlying the metabolic dysfunctions, enabled the assembly of discrete gene expression events into functional pathways, and revealed protein targets for proteomic analysis.

Animals↗

PubMed2004

Chronic effects of dietary selenium on juvenile Sacramento splittail (Pogonichthys macrolepidotus).

The chronic effects of dietary selenium (Se) exposure in juvenile Sacramento splittail (Pogonichthys macrolepidotus) were investigated in the laboratory. A total of 960 (40 fish per tank, 3 tanks per diet) 7-month-old juvenile splittail were fed one of eight Purified-Casein diets supplemented with selenized yeast for 9 months in a flow-through system. These diets contained the following: 0.4 (control), 0.7, 1.4, 2.7, 6.6, 12.6, 26.0, and 57.6 mg of Se kg(-1) dry weight. Survival, Se tissue concentration, growth, gross morphology, and liver histopathology were assessed at 5- and 9-month of exposure. Mortalities occurred only in the two highest Se treatments and were accounted for 8.3 and 18.3% at 5-month and 10.0 and 34.3% at 9-month, respectively. Liver and muscle Se concentration were significantly correlated with dietary Se concentration. Fish exposed to 0.4-12.6 mg of Se kg(-1) diets had reached equilibrium in liver Se concentration by 5 month. Splittail fed diets at concentrations > or =26.0 mg of Se kg(-1) had not reached equilibrium in liver, and muscle Se concentrations and grew significantly slower (p < 0.05) at 5- and 9-month exposure. Se-induced deformities were observed in fish fed > or =2.7 mg of Se kg(-1) diets at 5-month and in fish fed > or =0.7 mg of Se kg(-1) diets at 9-month. Fish fed 26.0 and 57.6 mg of Se kg(-1) diets had higher liver lesion scores at 5-month while fish fed 6.6 and 57.6 mg of Se kg(-1) diet had higher liver lesion scores at 9-month. Results indicate that survivals, growth, changes of tissue Se concentrations, and histopathology of juvenile splittail were dose-dependent, but their response thresholds to dietary Se concentrations differed and depended on treatment concentrations and duration of exposure. Chronic exposure to 6.6 mg of Se kg(-1) diet induced deleterious health effects that can potentially impact survival of juvenile splittail.

Animals↗

PubMed2004

The promise of metabolomics in cancer molecular therapeutics.

A systematic elucidation of cancer cell dysfunction and therapeutic mechanisms seems within reach with modern functional genomics and proteomics tools. However, for this potential to be realized, the metabolic consequences of gene expression and protein activity must be understood. 'Metabolomics' is currently a major missing component. It differs from classical metabolic studies by its greater breadth, depth and speed, enabled by the huge advances in analytical instrumentation (especially nuclear magnetic resonance and mass spectrometry) over the past two decades. Multiple metabolic pathways and networks can now be traced by the flow of atoms through metabolites, known as isotopomer analyses. Thus, metabolomics demands both high-throughput and high-information content analyses, and interpretation: the latter is currently a bottleneck. There are currently very few metabolomic studies in cancer therapeutics, despite this great need and potential.

Animals↗

PubMed2002

Selenium biotransformations into proteinaceous forms by foodweb organisms of selenium-laden drainage waters in California.

Selenium contamination represents one of the few clear cases where environmental pollution has led to devastation of wildlife populations, most notably in agricultural drainage evaporation and power plant coal-fly ash receiving ponds. Complex biogeochemistry, in particular extensive biotransformations and foodchain transfer, governs Se ecotoxicology and toxicology, for which the mechanism(s) are still elusive. However, total waterborne Se concentration has been widely used as a criterion for regulating and mitigating Se risk in aquatic ecosystems, which does not account for Se biogeochemistry and its site-dependence. There is a need for more reliable indicator(s) that encompass Se ecotoxicity and/or toxicity. Selenomethionine warrants special attention since it simulates Se toxicosis of wildlife in laboratory feeding studies. While low in free selenomethionine, microphytes isolated from Se-laden agricultural evaporation ponds were abundant in proteinaceous selenomethionine. This prompted a more extensive survey of Se speciation in foodchain organisms including microphytes, macroinvertebrates, fish, and bird embryos residing mainly in the agricultural drainage systems of the San Joaquin Valley, California. Total Se in biomass, water-soluble fractions, and protein-rich fractions were measured along with GC-MS analysis of proteinaceous selenomethionine. In all foodchain organisms, water-soluble Se constituted the major fraction of total biomass Se, while proteinaceous Se was a substantial, if not dominant, fraction of the water-soluble Se. In turn, proteinaceous selenomethionine comprised an important fraction of proteinaceous Se. In terms of total biomass Se, an average 1400-fold of Se biomagnification from water to microphytes was observed while subsequent transfer from microphytes to macroinvertebrates exhibited an average of only 1.9-fold. The latter transfer was more consistent and greater in extent for proteinaceous Se and proteinaceous selenomethionine, which is consistent with their importance in foodchain transfer. Proteinaceous Se in the omnivorous carp (Cyprinus carpio) liver also demonstrated a relation to ovarian lesions, while deformed stilt (Himantopus mexicanus) embryo was more abundant in proteinaceous selenomethionine than were normal embryos. Although limited in the number of organisms surveyed, these findings provide an impetus for further field and laboratory feeding studies to substantiate the hypothesis that proteinaceous selenomethionine underlies Se ecotoxicity, which may in turn prove to be a reliable indicator of Se risk in aquatic ecosystems.

Animals↗

PubMedDate not supplied

An electrophoretic profiling method for thiol-rich phytochelatins and metallothioneins.

Thiol-rich peptides such as phytochelatins (PCs) and metallothioneins (MTs) are important cellular chelating agents which function in metal detoxification and/or homeostasis. The variations in molecular sizes and lack of chromophores of these peptides make their analysis difficult. This paper reports an electrophoresis-based method for a broad screen of thiol-rich peptides and proteins. The method uses the thiol-selective fluorescent tag, monobromobimane, coupled with Tricine--sodium dodecyl sulphate--urea polyacrylamide gel electrophoresis for a sensitive determination of both PCs and MTs. Results for PCs were confirmed by two-dimensional NMR and HPLC-tandem MS analyses. Sample throughput is substantially improved over chromatography-based methods through parallel sample analysis in 1 h of electrophoretic separation. The method is versatile in that peptides ranging from glutathione to large proteins can be analysed by simple modification(s) of the extraction and electrophoretic conditions, and the nature of the method supports serendipitous detection of unexpected or novel thiol metabolites.

Bridged Bicyclo Compounds↗