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Biomedical subjects

S A Robicsek

Publications and source records attributed to S A Robicsek.

9 recordsLinked to original sources

Multiple high-affinity cAMP-phosphodiesterases in human T-lymphocytes.

Cyclic nucleotide phosphodiesterases (PDEs) are the only enzymes that inactivate intracellular cyclic AMP (cAMP). Because the functions of T-lymphocytes are modulated by cAMP levels, the isozymes of PDE in these cells are potential targets for new drugs designed to modify the body's immunity through selective alteration of T-lymphocyte PDE activity. Cyclic GMP and 3(2H)-pyridazinone-4,5- dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-5-methyl-monohydrochloride (CI-930) selectively inhibit the catalytic activity of one of the two high affinity cAMP-PDE isozyme families known to occur in mammals, whereas d,l-1,4-[3-butoxy-4-methoxybenzyl]-2-imidazolidinone (Ro 20-1724) selectively inhibits the other. The objectives of this investigation were: (1) to determine whether human T-lymphocytes contain one or both of these pharmacologically distinguishable high-affinity cAMP-PDEs, and (2) to determine the effects of selective inhibitors of these PDEs on lymphocyte blastogenesis. High-affinity cAMP-PDE was found in both the soluble and particulate fractions of T-lymphocyte sonicates. Cyclic GMP and CI-930 inhibited PDE in the particulate fraction better than in the soluble fraction, but the converse was found for Ro 20-1724. CI-930 or Ro 20-1724, used alone, attenuated T-lymphocyte blastogenesis, but neither suppressed it completely. In combination, the same PDE inhibitors caused greater suppression of blastogenesis than either produced alone. The results indicate that human T-lymphocytes contain both CI-930- and Ro 20-1724-inhibitable isozymes. Either of the isozymes can modulate human T-lymphocyte blastogenesis, but inhibition of both isozymes produces synergistic antiblastogenic effects.

3',5'-Cyclic-AMP Phosphodiesterases

Prevention of retrovirus infection after injury with contaminated instruments: an experimental study.

Owing to similarities between human immunodeficiency virus and feline retroviruses, the feline model was chosen for the study to investigate the efficacy of timely topical treatment of accidental human immunodeficiency virus infection in the operating room. Cats were subcutaneously inoculated with either feline leukemia virus or feline immunodeficiency virus. An effort was made to neutralize the virus in loco either by infiltration of the inoculation site with povidone-iodine or with monoclonal antibodies, or by cauterization and excision. The animals were periodically monitored for feline leukemia virus antigens or for feline immunodeficiency virus antibodies. The results indicated that in the feline model, the development of generalized virus infection may be prevented by local measures if applied immediately.

Animals

Can AIDS be prevented after injury with contaminated instruments?

Particulate matter comparable in size with that of human immunodeficiency virus was subcutaneously injected into experimental animals. Such matter remained at the inoculation site long enough to suggest the possibility that human immunodeficiency virus can be destroyed in loco before it invades the host's circulation. These findings may be useful in developing a method to prevent acquired immunodeficiency syndrome after accidental injury with human immunodeficiency virus-contaminated instruments.

Acquired Immunodeficiency Syndrome

Biological thresholds of cold-induced phrenic nerve injury.

The effects of controlled cooling on phrenic nerve signal conduction were investigated by cooling an isolated segment of the phrenic nerve with a constant but variable temperature probe. The conduction of a standard electrical stimulus applied to the nerve proximal to the cooled section was measured by detector electrodes sutured to the diaphragm. Nerve conduction of the applied stimulus ceased between 10 degrees and 12 degrees C but returned within seconds after the probe was removed. The delay in the return of conduction increased as nerve temperature decreased until at a temperature of 4 degrees C the ability to conduct did not return after 4 hours. The amount of fat surrounding the nerve and the blood flow rate along the cooled portion of the nerve were observed to ameliorate the effects of low temperature on stimulus conduction. Total body cooling also appears to offer some protection against loss of conduction.

Animals

High pressure liquid chromatography of cyclic nucleotide phosphodiesterase from purified human T-lymphocytes.

The cyclic nucleotide phosphodiesterase (EC 3.1.4.17) in extracts of purified human peripheral blood T-lymphocytes was examined by ion exchange high pressure liquid chromatography. Four peaks of activity were isolated. The first peak of activity selectively hydrolyzed cyclic GMP. The following 3 peaks of activity (Ia, IIa and IIIa) were selective for cyclic AMP. The selective low Km cyclic AMP-phosphodiesterase inhibitor, Ro 20-1724 (d,1-1,4-[3-butoxy-4-methoxybenzyl]-2-imidazolidinone), did not inhibit the activity in Ia whereas it did inhibit the activity in IIa and IIIa (IC50 = 17 microM). The authors conclude that ion exchange high pressure liquid chromatography described in this communication is a useful method for the isolation of different forms of cyclic nucleotide phosphodiesterase activity from human T-lymphocytes.

3',5'-Cyclic-AMP Phosphodiesterases

Experiments with a bowl of saline: the hidden risk of hypothermic-osmotic damage during topical cardiac cooling.

Some of the misconceptions in the application of cardiac hypothermia are that the temperature of cold normal saline solution is necessarily above 0 degrees C, cold saline solution and slush are relatively safe for living tissues, and normal saline will retain normal osmolality even if partially frozen. These postulates were examined in thermodynamic experiments that demonstrated three points: (1) The temperature of unfrozen saline solution may drop way below the freezing point. (2) When liquids and solid components of saline solution are separated, the components will become hypo-osmolar or hyperosmolar. (3) Ice chips and slush ice produced in the operating rooms may reach temperatures as low as -36 degrees C. We recommend that the possibility of these events should be taken into consideration whenever topical cardiac hypothermia is clinically applied.

Cold Temperature

A new temporary pacing electrode.

A simple method for the positioning of a temporary pacemaker electrode in the course of open-heart operation is presented. Instead of using "back-stitching," we recommend that after the wire electrode is passed through the myocardium, it should be driven through a small pledget of Silastic rubber material to hold it in position.

Cardiac Pacing, Artificial