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Biomedical subjects

G Grossman

Publications and source records attributed to G Grossman.

At least 37 records · Page 2Linked to original sources

Influenza virus: an NMR study of mechanisms involved in infection.

High resolution 1H-NMR spectroscopy has been used to study the infection of chicken embryo fibroblasts by influenza virus. Marked changes in the NMR spectrum occur when infectious influenza virus is introduced into the fibroblasts and these changes appear to depend upon the presence of active neuraminidase (EC 3.2.1.18). A crude preparation of neuraminidase from Vibrio cholerae is able to effect similar changes. Only minor spectral changes are observed in the absence of culture medium or when the viral genome material is inactivated by beta-propiolactone. Similarly, little change is seen in the NMR spectrum when amantadine, which is thought to inhibit uncoating of the virus inside the cell, or actinomycin D, which inhibits cellular nucleic acid metabolism, are incubated with fibroblasts prior to the addition of virus. The results suggest that neuraminidase, in co-operation with a factor in the infectious process, initiates a cellular event which can be monitored by NMR. The nature of this cellular mechanism is unknown, but further studies are under way to determine its importance in viral infection.

Amantadine↗

Effect of monoclonal anti-neuraminidase antibodies on the kinetic behavior of influenza virus neuraminidase.

Neuraminidase from the recombinant influenza virus A/NWSHA-Tokyo/3/67NA HON2 has been shown to exhibit non-Michaelis-Menten kinetics. The multiphasic behaviour was demonstrated for both the isolated neuraminidase heads and for the intact virus. Interaction of the enzyme with two monoclonal anti-neuraminidase antibodies (WANA 1 and RANA 1), which recognize separate antigenic determinants on the molecule, resulted in hyperbolic kinetic behaviour. While both antibodies abolished the multiphasic kinetics of the enzymic reaction, only WANA 1 altered the Vmax and Km values, indicating that it may in some way inhibit the interaction of enzyme and substrate.

Antibodies, Monoclonal↗

Characterization of transformed cells and tumors by proton nuclear magnetic resonance spectroscopy.

Cultured acute lymphoblastic leukemic cells give a well-resolved proton nuclear magnetic resonance spectrum characteristic of isolated plasma membranes. We demonstrate that the signals, in the spectrum of whole cells, arise predominantly from the plasma membrane and that cells transformed by pokeweed mitogen have membranes which are significantly less rigid than are normal human peripheral blood lymphocytes. Normal thymus, malignant thymus, and a leukemic T-cell line have been compared by proton nuclear magnetic resonance spin echo experiments, and the normal thymus was found to differ. Cells transformed by the Epstein-Barr virus can also be characterized and shown to differ from the leukemically transformed cells by spin echo experiments. Since no probe molecule was required to obtain these results, this is the first definitive evidence that the structure and fluidity of the plasma membranes change as a result of transformation of lymphocytes. Proton nuclear magnetic resonance spectroscopy can now be used to compare the effect of different mitogens on T- and B-lymphocytes as well as to monitor the effects of drugs, metals, etc., on the plasma membrane of transformed lymphocytes.

B-Lymphocytes↗

Effect of supplementary surfactant on in vivo lung mechanics in the premature rabbit neonate.

Premature newborn rabbits, delivered on day 27 of gestation, were subjected to positive-pressure ventilation, with or without treatment with natural surfactant. The surfactant, obtained by centrifugation of lung wash from adult rabbits, was deposited in the tracheal cannula before the onset of ventilation. Parameters of lung mechanisms, recorded during spontaneous ventilation after 1 h, were significantly improved in animals receiving surfactant. In comparison with littermate controls, surfactant-treated animals also had less prominent bronchiolar epithelial lesions. We conclude that treatment with supplementary surfactant facilitates functional adaptation of the premature lung and prevents the development of epithelial lung lesions during artificial ventilation.

Animals↗

Eastern grey kangaroo muscle creatine kinase.

Creatine kinase has been purified to homogeneity from skeletal muscle of the eastern grey kangaroo, Macropus giganteus. The procedure included ethanol fractionation followed by chromatography on DEAE-cellulose. The enzyme had a molecular weight of approximately 86 000 with two subunits of 43 500. Two sulfhydryl groups were determined for the intact molecule and a further four on unfolding. Under standardized conditions, the metal ion specificity was determined as MgADP- greater than MnADP- greater than CoADP-, CaADP-; and the substrate specificity as MgADP- greater than MgdADP- greater than MgGDP- greater than MgXDP. Initial velocity and product-inhibition studies of the reverse reaction were consistent with a rapid random equilibrium reaction as observed for the rabbit muscle enzyme. However, initial-velocity studies in the forward reaction were consistent with a rapid equilibrium-ordered mechanism with MgATP2- binding before creatine. Preliminary studies on the binding of manganese nucleotides to the enzyme have been carried out using pulsed nuclear magnetic resonance to measure relaxation times of water protons.

Animals↗