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Biomedical subjects

G Hanson

Publications and source records attributed to G Hanson.

At least 91 records · Page 5Linked to original sources

Hydrolysis of peptides by carboxypeptidase A: equilibrium trapping of the ES2 intermediate.

The cobalt absorption and electron paramagnetic resonance (EPR) spectra of cobalt carboxypeptidase undergo unique variations on formation of catalytic peptide and ester intermediates as previously recorded in cryoenzymologic experiments employing rapid-scanning spectroscopy and cryotrapping [Geoghegan, K. F., Galdes, A., Martinelli, R. A., Holmquist, B., Auld, D.S., & Vallee, B. L. (1983) Biochemistry 22, 2255-2262]. We here describe a means of stabilizing these intermediates, which we have termed "equilibrium trapping". It allows peptide intermediates to be observed for longer periods (much greater than 1 min) at ambient as well as subzero temperatures. The reaction intermediate with the rapidly turned over peptide substrate Dns-Ala-Ala-Phe is trapped when the cobalt enzyme (greater than 10 microM) has catalyzed the attainment of chemical equilibrium between high concentrations of the hydrolysis products Dns-Ala-Ala, 10 mM, and L-phenylalanine, 50 mM, and the product of their coupling Dns-Ala-Ala-Phe. Under these conditions, Dns-Ala-Ala-Phe is present in the equilibrated substrate-product reaction mixture at a level that exceeds the one predicted on the basis of K'eq for hydrolysis of this substrate and is close to the enzyme concentration. Other pairs of peptide hydrolysis products yield similar results. Visible absorption and EPR spectra of the cobalt enzyme show that the synthesized peptide binds to the active site in the mode previously recognized as the ES2 catalytic intermediate in peptide hydrolysis. Equilibrium trapping of the ES2 intermediate allows analysis of its physicochemical properties by methods that could not be employed readily under cryoenzymological conditions, e.g., circular dichroic and magnetic circular dichroic spectra.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboxypeptidases↗

Rapid high-efficiency hemodialysis.

Reductions in treatment time are attractive for patients and dialysis centers. However, there are concerns related to treatment adequacy and increased intradialytic symptoms. Treatment times were progressively reduced in 12 stable patients on standard 4-h acetate hemodialysis, solute clearances being increased proportionately, until the tolerance limit manifested by increased complications or 2.5 h of treatment was reached. Once shortened schedules (mean reduction approximately 31%) were achieved, a 2-month surveillance period was initiated, followed by 2 additional months of bicarbonate therapy, treatment time being unchanged. Rapid bicarbonate hemodialysis was associated with a significantly lower incidence of hypotension, nausea, and vomiting than rapid acetate or standard acetate therapies. Fluid removal was comparable with that of standard treatment, and serum chemistry levels remained stable. Based on the success of these studies treatment times have been reduced in greater than 200 patients with high-efficiency bicarbonate therapy for long-term evaluations.

Acetates↗

Aleukemic leukemia cutis.

A 46-year-old man presented with nodular skin lesions, a biopsy specimen of which demonstrated a poorly differentiated malignancy. Touch preparations with histochemical staining and electron microscopy confirmed leukemia cutis. Results from a bone marrow aspirate disclosed focal areas of increased myeloblasts, and cytogenetic analysis revealed an abnormal karyotype as follows 46,XY, t(1;2) (q44p13). Antileukemic therapy resulted in prompt disappearance of the skin nodules, and a return of the patient's bone marrow to normal was noted, but after six months of intensive chemotherapy leukemia cutis recurred without morphologically identifiable leukemia in the bone marrow. The patient underwent successful bone marrow transplantation from an HLA-identical sibling but died 70 days after the transplant from disseminated aspergillosis.

Acute Disease↗