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Biomedical subjects

D E Grubbs

Publications and source records attributed to D E Grubbs.

4 recordsLinked to original sources

Identification of intraocular lens-adsorbed proteins in mammalian in vitro and in vivo systems.

OBJECTIVE: Mammalian in vitro and in vivo systems were used to study the protein-adsorbing potential of intraocular lenses (IOLs). METHODS: Intraocular lenses composed of polymethyl methacrylate optics with polypropylene haptics were incubated in rabbit plasma for 3 hours (in vitro grouping) or implanted in rabbit eyes for 48 hours (in vivo grouping). Lens-adsorbed proteins from both experimental groupings were eluted with sodium dodecyl sulfate and identified by Western Blot analyses. RESULTS: The adsorbed protein layer was composed of at least six different proteins: albumin, complement C3 fragments, IgG, fibrinogen/fibrin (as a fibrin clot in vivo), fibronectin, and transferrin. Of the identified components, albumin, IgG, fibronectin, and fibrinogen were the predominant protein species on the in vitro IOLs, while fibronectin and fibrin were on the in vivo IOLs. CONCLUSIONS: The composition of the protein layer has the potential to alter the biological property of IOLs.

Adsorption↗

The lung as a metabolic organ.

Recently, the lung has received increasing attention as a metabolic organ. In this role, the lung modulates the composition of the arterial blood by several mechanisms: removing active substances from the plasma, releasing substances into the plasma, temporarily holding substances from circulation, and activating or inactivating substances that pass through the lungs. In this report, the procedures proposed by different investigators for in vivo noninvasive assessment of the lung metabolic functions are reviewed. Most procedures are based on an estimation of the clearance of plasma amines by the lung endothelial cells. This clearance is assessed by measuring the lung uptake or the extraction fraction of an intravenously (IV) injected radiolabeled amine. Our own procedure, which assesses the number of free pulmonary endothelial amine receptors, is discussed in detail. In our procedure, the number of receptors was computed using the number of injected molecules of amine and determining the lung extraction fraction of the amine during its first pass through the lungs. In goats, using N-isopropyl-p-iodoamphetamine labeled with 123I as the radiopharmaceutical, the total number of endothelial lung amine receptors was found to be 1.589 X 10(20). The methods for studying the lung metabolic functions, which are discussed in this report can be applied in humans to evaluate either physiological or pathological conditions.

Amines↗

Smoke inhalation model for lung permeability studies.

The purpose of this project was the development of a small animal model and the use of external gamma imaging for the study of acute post-inhalation permeability changes. New Zealand white rabbits were anesthetized with ketamine and acepromazine IM, intubated, and a catheter placed in an ear artery. Smoke was produced by burning absorbent cotton in a combustion chamber supplied with 10 liters/min of air. Smoke was delivered to a holding chamber, allowed to cool to room temperature, and immediately delivered to the animals via endotracheal tube. Animals were allowed to inhale smoke for 3 sessions of 2 to 3 minutes. Blood samples were collected for the measurement of PO2, PCO2, and COHb. Lungs were removed at 3 to 4 days postinjury and subjected to microscopic histologic analysis. The results of six animal experiments showed a significant inhalation injury. The mean COHb level was 48% (range, 36%-58%). The change in the pre- and post-injury PO2 and PCO2 values were not significant (mean PO2, 66 mm Hg; mean PCO2, 32 mm Hg). Histologic evaluation of the lungs of three animals at 24 hrs postinjury revealed extensive loss of tracheal epithelium extended to many terminal bronchi. Inflammation of surrounding tissue, including edema and increased migration of polymorphonuclear cells, was also present. Analysis of tissue obtained at 10 to 14 days showed reparative reepithelialization of trachea and major bronchi but acute inflammation and loss of intralobar bronchi. Inflammatory exudate extended to adjacent alveoli. In conjunction with the above model we have developed a method for the noninvasive measurement of lung permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A noninvasive procedure for in vivo assay of a lung amine endothelial receptor.

Lung endothelial N-isopropyl-p-iodoamphetamine (IMP) binding sites were assessed applying principles of competitive binding assay adapted for in vivo measurements obtained by digital imaging. Data were acquired following the method published by Rahimian et al., a modification of the dual indicator dilution technique of Chinard and Crone. Iodine-123 (123I) IMP, the test cellular tracer, and technetium-99m (99mTc) dextran, the reference vascular tracer were imaged during their first pass through the superior vena cava, right heart, lungs, and left heart in West African dwarf goats. The lung fractional extraction of IMP diminished progressively from 0.96 to 0.20 as the amount of IMP in the test tracer boluses was gradually increased from 0.6 to 150 mg. This demonstrated that lung extraction of IMP is by way of a saturable binding system, presumably receptors. The dissociation constant of IMP-lung binding sites reaction was calculated by Scatchard plot and found to be 11.7 mg. The amount of IMP bound at saturation (R), was found to be 30 mg. Assuming that a single molecule of IMP bound a single receptor, the total number of free receptors was computed as the Avogadro's number times R, divided by the IMP molecular weight, and found to be 6.04 X 10(19). Using a computer model, it was determined that the 20 mg per bolus isotherm was the most sensitive for measuring the number of total free receptors (binding sites). This is the first time, to our knowledge, that noninvasive in vivo assessment of receptors in lung has been accomplished. Basically, the method used can be applied in humans and, also, to assess receptors in organs other than the lungs.

Amphetamines↗