PubMed Health⌕ Search

Biomedical subjects

John B Williams

Publications and source records attributed to John B Williams.

5 recordsLinked to original sources

In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI.

In vivo cell tracking by MRI can provide means to observe biological processes and monitor cell therapy directly. Immune cells, e.g., macrophages, play crucial roles in many pathophysiological processes, including organ rejection, inflammation, autoimmune diseases, cancer, atherosclerotic plaque formation, numerous neurological disorders, etc. The current gold standard for diagnosing and staging rejection after organ transplantation is biopsy, which is not only invasive, but also prone to sampling errors. Here, we report a noninvasive approach using MRI to detect graft rejection after solid organ transplantation. In addition, we present the feasibility of imaging individual macrophages in vivo by MRI in a rodent heterotopic working-heart transplantation model using a more sensitive contrast agent, the micrometer-sized paramagnetic iron oxide particle, as a methodology to detect acute cardiac rejection.

Animals↗

Matrix-assisted laser desorption/ionization mass spectrometry of discrete mass poly(butylene glutarate) oligomers.

The mass dependency of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) response has been studied using equimolar mixtures of synthetic discrete mass poly(butylene glutarate) (PBG) oligomers of known structure having degrees of polymerization of 8, 16, 32, and 64. Mass discrimination observed was attributed to choice of matrix and detector saturation caused by higher laser intensity and inclusion of matrix ions in the MALDI spectra. Optimization of sample preparation and instrumental parameters provided uniform response over the mass ranged spanned by these four oligomers. The oligomer mixture was shown to serve as a model of more complex polymer distributions in the mass range 780-6000 Da, and application of the discrete mass oligomers as internal and calibration standards was demonstrated. Inclusion of PBG discrete mass oligomers as an internal standard in a quasi-equimolar mixture with polydispersed poly(butylene adipate) (PBA) indicated that some diminution of response occurred during the analysis of this mixture of materials. Reasons for differences in the corrected molecular weight averages of the polydispersed PBA obtained from measurements using MALDI and GPC were studied using individual discrete mass oligomers as calibration standards for GPC. The data indicated that differences in hydrodynamic volumes of PBG oligomers and PEG standards at similar masses resulted in an overestimation by GPC of the molecular weight averages of the PBA distribution.

Calibration↗

Hemodynamic response profile predicts susceptibility to cocaine-induced toxicity.

Cocaine evokes pressor responses due either to a large increase in systemic vascular resistance despite a decrease (>8%) in cardiac output (vascular responders) or to small increases in both cardiac output and vascular resistance (mixed responders) in conscious rats. These studies were designed to determine (1) if the hemodynamic response pattern to cocaine correlates with relative sensitivity to toxicity and (2) if altering the hemodynamic response pattern to cocaine using propranolol enhances toxicity. Rats were instrumented for determination of cardiac output and arterial pressure. After recovery, rats were classified as vascular or mixed responders to cocaine (5 mg/kg, i.v., four to six trials). Two weeks later, cocaine was infused (1.5 mg/kg/min) until death after pretreatment with saline or propranolol (1 mg/kg). Saline-pretreated mixed responders (n=6) had greater tolerance to cocaine toxicity compared to vascular responders (n=11). Furthermore, saline-pretreated vascular responders were less sensitive than propranolol-pretreated vascular responders (n=9) to cocaine toxicity. Therefore, we propose that the initial hemodynamic response pattern to cocaine predicts sensitivity to cocaine toxicity. In addition, propranolol, a drug that enhances the increase in vascular resistance to cocaine, also increases toxicity to cocaine in vascular responders.

Animals↗