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J Grote

Publications and source records attributed to J Grote.

79 records · Page 5Linked to original sources

The effect of propranolol, verapamil and dantrolene treatment on cardiac hypertrophy, enhanced myocardial contractility and tachycardia in the hyperthyroid rat.

Experimentally induced hyperthyroidism is associated with cardiac hypertrophy, tachycardia and elevated myocardial contractility. To investigate the possibility of ameliorating the cardiac changes pharmacologically, hyperthyroid rats were treated with propranolol, verapamil or dantrolene. Cardiac hypertrophy was assessed from the heart mass: body mass ratio and cardiac function was measured in vitro. Both verapamil and propranolol reversed the cardiac hypertrophy of the hyperthyroid animals from 0.92 +/- 0.02 mg.g-1 to 0.70 +/- 0.01 mg.g-1 (P less than 0.001) and 0.72 +/- 0.02 mg.g-1 (P less than 0.001) respectively. Verapamil was effective in reducing the spontaneous heart rate from 331 +/- 8 beats.min-1 to 273 +/- 7 beats.min-1 (P less than 0.001) while propranolol reduced the dP/dtmax of the hyperthyroid hearts from 4089 +/- 87 mmHg.s-1 to 3497 +/- 97 mmHg.s-1 (P less than 0.001). Dantrolene had no effect on any parameter. We conclude from our results that cardiac hypertrophy of the hyperthyroid heart can be reversed by treatment with propranolol and verapamil probably via their inotropic and chronotropic properties.

Animals↗

Synthesis of conjugates for a barbiturate screening assay.

Novel derivatives of barbiturates functionalized with free carboxylic acids were designed and synthesized. Coupling of 5-cyclopentyl-5-carboxycrotylbarbituric acid via its active ester to an aminofluorescein derivative produced a fluorescent tracer. Conjugation of the 5-cyclopentenyl-5-carboxyethylbarbituric acid via its mixed anhydride to thyroglobulin allowed for subsequent development of a polyclonal antibody which was evaluated for binding in a fluorescence polarization immunoassay format with various barbiturates. The binding studies showed good cross-reactivity of a variety of barbiturates containing both aromatic and aliphatic 5-substituents with the tested antisera. The relationship between the immunogen architecture, the chemical structure of the binding analytes, and the characteristics of the antisera is also presented.

Animals↗

Structure-binding relationships for the interaction between a vancomycin monoclonal antibody Fab fragment and a library of vancomycin analogues and tracers.

A series of vancomycin analogues and tracers were synthesized, and their binding interactions with an anti-vancomycin Fab fragment were evaluated under mass transport limiting conditions using surface plasmon resonance detection. Differences observed in binding interactions were utilized to define the vancomycin structural elements critical for antibody recognition. Major structural regions of vancomycin shown to play an important role in anti-vancomycin Fab fragment recognition include two sugar moieties and one chlorinated phenyl ring. The N-methylleucyl residue, the carboxy terminal residue, and residues in the peptide-binding region of vancomycin have minimal impact on the anti-vancomycin Fab fragment/vancomycin binding interaction. The selection of an antibody with such binding properties plays a critical role in the development of a vancomycin immunoassay that employs stable calibrators and controls.

Antibodies, Monoclonal↗

Chemoenzymatic synthesis of 3'-O-(carboxyalkyl)fluorescein labels.

A general and versatile method is described for the synthesis of fluorescent labels. Coupling of the 3'-phenol of fluorescein methyl ester with hydroxyalkyl benzyl esters, followed by benzyl ester hydrolysis, provided a series of fluorescein carboxyalkyl ethers. Use of the Mitsunobu reaction allowed for the introduction of linkers of different lengths onto the 3'-phenol of fluorescein. Chemoenzymatic benzyl ester hydrolysis was achieved with LPL-80 lipase, providing pH-independent labels useful for the preparation of fluorescent conjugates.

Fluoresceins↗

Urinary arsenic excretion as a biomarker of arsenic exposure in children.

Urinary arsenic concentration has been used generally for the determination of exposure, but much concern has been raised over the most appropriate expression for urinary arsenic levels. In this study, we examined the influence of various adjustments of expressing urinary arsenic data. All children who were less than 72 mo of age and who were potty trained were invited to participate in the present study. Urine, soil, and dust samples were collected, and arsenic measurements were made. The geometric mean of speciated urinary arsenic among children who provided first-voided urine samples on 2 consecutive mornings was 8.6 microg/l (geometric standard deviation = 1.7, n = 289). Speciated urinary arsenic was related significantly to soil arsenic in bare areas (p < .0005). Use of a single urine sample versus the average of two first-voided urine samples collected on 2 consecutive mornings did not significantly alter the relationship between environmental arsenic and urinary arsenic levels. Furthermore, none of the adjustments to urinary concentration improved the strength of correlation between urinary arsenic and soil arsenic levels. Concentration adjustments may not be necessary for urinary arsenic levels obtained from young children who provide first-void samples in the morning.

Arsenic↗

A barbiturate screening assay for the Abbott AxSYM analyzer.

A fluorescence polarization immunoassay for barbiturates on the Abbott AxSYM analyzer is described. The assay displayed dilution linearity up to 1200 ng/mL; coefficients of variation varied from 5.96 to 8.61%; recovery varied from 94.9 to 105.3%; and sensitivity was less than 40 ng/mL. Good correlation between the standard six- and factory two-point calibration methods was observed. The Immunoassay demonstrated good cross-reactivity to several commonly prescribed barbiturates; low cross-reactivity with structurally similar compounds; low interference from endogenous substances, dyes, preservatives, and several commonly available adulterants; and good correlation with the TDx Barbiturate Urine assay.

Autoanalysis↗