Biology subjects

Johnson, S. P.

Publications and source records attributed to Johnson, S. P..

4 recordsLinked to original sources

bioRxiv2023

The Symptomatology and Diagnosis of Domoic Acid Toxicosis in Stranded California Sea Lions (Zalophus californianus): A Review and Evaluation of 20 Years of Cases to Guide Prognosis

Domoic acid (DA) is a glutaminergic excitatory neurotoxin that causes morbidity and mortality of California sea lions (Zalophus californianus; CSL) and other marine mammals due to a suite of effects mostly on the nervous and cardiac systems. Between 1998 and 2019, 11,737 live-stranded CSL were admitted to The Marine Mammal Center (TMMC; Sausalito, CA, USA), over 2,000 of which were intoxicated by DA. A plethora of clinical research has been performed over the past 20 years to characterize the range of toxic effects of DA exposure on CSLs, generating the largest dataset on the effects of natural exposure to this toxin in wildlife. Here we review published methods for diagnosing DA intoxication, clinical presentation and treatment of DA-intoxicated CSL, and present a practical, reproducible scoring system called the neuroscore (NS) to help assess whether a DA-affected CSL is fit for release to the wild following rehabilitation. The largest proportion of DA-intoxicated CSL were adult females (58.6%). The proportions of acute and chronic cases were 63.5% and 36.5%, respectively, with 44% of affected CSL released and 56% either dying naturally or euthanized. The average time in rehabilitation was 15.9 days (range 0-169) for all outcomes. Logistic regression models were used to assess the relationships between outcome (released vs. euthanized or died) and multiple variables to predict the outcome for a subset of 92 stranded CSLs. The best performing model (85% prediction accuracy; area under the curve = 0.90) consisted of four variables: final NS, change in NS over time, whether the animal began eating in rehabilitation, and the state of nutrition on admission. These results suggest that a behavioral scoring system is a useful tool to assess the fitness for release of stranded DA-intoxicated CSL.

zoology↗

bioRxiv2021

Xenotransplantation of porcine progenitor cells in an epileptic California sea lion (Zalophus californianus)

BackgroundDomoic acid (DA) is a naturally occurring neurotoxin harmful to marine animals and humans. California sea lions exposed to DA in prey during algal blooms along the Pacific coast exhibit significant neurological symptoms, including epilepsy with hippocampal atrophy. ObservationsHere we describe a xenotransplantation procedure to deliver interneuron progenitor cells into the damaged hippocampus of an epileptic sea lion with suspected DA toxicosis. The sea lion has had no evidence of seizures following the procedure, and clinical measures of well-being including weight and feeding habits have stabilized. LessonsThese preliminary results suggest xenotransplantation has improved the quality-of-life (QOL) for this animal and holds tremendous therapeutic promise.

neuroscience↗

bioRxiv2017

Investigating low-velocity fluid flow in tumours using convection-MRI

Several distinct fluid flow phenemena occur in solid tumours, including intravascular blood flow and interstitial convection. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we have developed a novel magnetic resonance imaging (MRI) technique named convection-MRI. It uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extra-vascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations and tumor xenograft models to investigate the technical feasibility of convection-MRI. We report a good correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma and show that convection-MRI can provide insights into the growth and response to vascular-targeting therapy in colorectal cancers.

biophysics↗

bioRxiv2017

Development of noninvasive biomarkers of response to proteasome inhibitor therapy (ixazomib) by imaging disrupted protein homeostasis in mouse models of solid tumors

With clinically-approved proteasome inhibitors now a standard of care for multiple myeloma, and increasing interest in their use in solid tumors, methods for monitoring therapeutic response in vivo are critically required. Here, we show that tumor protein homeostasis can be noninvasively monitored, using chemical exchange (CEST) magnetic resonance imaging (MRI) as a surrogate marker for proteasome inhibition, alongside diffusion MRI and relaxometry. We show that the in vivo CEST signal associated with amides and amines increases in proportion to proteasome inhibitor dose (ixazomib) and the magnitude of therapeutic effect in colorectal cancer xenografts. Moreover, we show that SW1222 and LS174T human colorectal cancer cell lines demonstrate differing sensitivities to ixazomib, which was reflected in our MRI measurements. We also found evidence of a mild stimulation in tumor growth at low ixazomib doses. Our results therefore identify CEST MRI as a promising method for safely and noninvasively monitoring changes in tumor protein homeostasis.

biophysics↗