A voltage-gated cation conductance channel from fragmented sarcoplasmic reticulum. Effects of transition metal ions.
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Biomedical subjects
Publications and source records attributed to C Miller.
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We have shown that the function of the effector cells in antibody mediated cell dependent cytotoxicity (ADCC) can be reduced by the use of a number of drugs and prostaglandins. Both polymorphonuclear leucocyte and mononuclear effector cells were studied. Aminophylline and isoproterenol markedly reduced this activity. All the prostaglandins tested--PGA1, A2, E1 and E2 had a similar but more profound effect. At a dose of 100 mg/ml hydrocortisone had relatively little influence and neither ASA nor indomethacin had any effect on the effector cells tested. It is suggested that the effect of PGE1 in stimulating a recrudescent herpes simplex infection may be by reducing the efficacy of ADCC in host defence.
AK+ -selective membrane conductance channel from rabbit sarcoplasmic reticulum (SR) is studied in an artificial planar phospholipid bilayer. Membranes containing many such channels display voltage-dependent conductance, which is well described by a two-state conformational equilibrium with a free energy term linearly dependent on applied voltage. Pronase-derived alkaline proteinase b (APb), when added to the side of the membrane opposite to the SR vesicles (trans side), reduces the voltage dependence of the K+ conductance. Single-channel fluctuation experiments show that after APb treatment, the channel is still able to undergo transitions between its open and closed states, but that the probability of forming the open state is only slightly voltage-dependent. In terms of the conformational model, the enzyme's primary effect is to reduce the effective gating charge of the opening process by over 80%; a second effect of APb is to reduce the internal free energy of opening from +1.2 to +0.4 kcal/mol. The kinetics of APb action are strongly voltage-dependent, so as to indicate that the enzyme can react only with the channel's open state. The results imply that the channel contains a highly charged polypeptide region which moves in the direction perpendicular to the membrane plane when transitions between the open and closed states occur. A lysine or arginine residue in this region becomes exposed to the trans aqueous solution when the channel is in its open conformation.
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The interaction of fragmented sarcoplasmic reticulum (SR) with an artificial planar phospholipid membrane under conditions known to induce fusion of phospholipid vesicles raises the conductance of the planar bilayer by several orders of magnitude. Measurements of steady-state electrical properties of bilayers thus modified by SR show that two types of conductance pathways are present. One is a voltage-independent pathway which may be somewhat anion-selective. The other is a voltage-gated ionophore showing selectivity to small monovalent cations. This latter ionophore is fully oriented within the artificial bilayer and is inhibited asymmetrically by divalent cations. It is also inhibited below pH6. The ionophore displays single-channel conductance fluctuations between two states. "open" and "closed", with an open-state conductance of 1.4 x 10-10 mho in 0.1 M K+. The physiological function of this ionophore is unknown.
Administration of thymosin fraction V to NZB/NZW F1 mice, an animal model for human SLE, accelerated the appearance of proteinuria and anti-nDNA antibodies, increased deposition of immunoglobulins in kidneys, and significantly shortened survivals. Although the addition of thymosin to in vitro cultures of spleen and lymph node cells from thymosin-treated mice increased DNA synthesis in response to stimulation with Con A, in vivo treatment with thymosin did not affect the Con A response. There was no effect on in vitro responses to PHA or LPS, or on IgM antibody formation to SRBC (T cell dependent) or SSS III (T cell independent) immunizations. Antibodies to thymosin or contamination of our thymosin preparations with nucleic acids could not be demonstrated. The acceleration of autoimmune disease produced by thymosin treatment could not be explained by alteration of the T and B cell functions studied.
The findings of McCurley et al. are generally replicated by this study. Community rates are usually lower than those of comparable institutional residents, except for convalescent hospitals used for the care of the profoundly retarded in the United States. Attention is drawn to the sharp mortality difference between ambulatory and non-ambulatory retarded individuals and the affect of the ability to walk can have on the estimation of mortality rates. The ambulation factor should be considered more routinely in future studies. Finally, a revision of the usual method of estimation of age at death was attempted. The utility of the method, similar to standardisation procedures widely used in demography, provides estimates which are more directly comparable between studies.
A convergence of 20 degrees for full crowns is the most likely to be seen clinically, as determined by random measurements taken at a dental laboratory. Castings did not seat without cement, by an average of 215 micron at 10 degrees of convergence, or by 99 micron at 20 degrees of convergence. Biting forces will seat a casting approximately 150 micron, but will cause random concentrations of force against tooth structure, thus compressing it. All castings tend to rebound from this position. Zinc phosphate and polycarboxylate cemented crowns seated to 33 micron and 20 micron respectively when relieved, but each were elevated to 112 micron when not relieved. A silicophosphate cement displaced crowns with 20 degrees of convergence 122 micron under "ideal" clinical conditions, even when relieved; and with CBA 9080 cement, more than 500 micron. A die relief method was found to be the most suitable of the three casting compensation techniques. Casting retention, after cementation, was increased by 25%.
The authors present an unusual case of eosinophilic granuloma arising in the region of the foramen rotundum.
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We have used a 51Cr release assay to demonstrate that human polymorphonuclear leucocytes (PMNL) can damage herpes simplex infected target cells sensitized with antiviral antibody. Effective sensitizing antibodies were found in both serum and saliva of all those persons tested who were subject to recurrent cold sores. PMNL were much less effective as killer cells than peripheral blood mononuclear cells, but as they are the predominant inflammatory cell with the HSV1 lesion they may be, quantitatively, more important. The cytotoxic effects of both PMNL and mononuclear cells were significantly reduced by prostaglandin E1 as well as by several drugs that were tested. It is suggested that antibody dependent PMNL-mediated cytotoxicity may play a role in the human host defences against recrudescent herpes simplex infection.
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Dopamine (da) concentrations in rat adrenals, plasma and brain were variably elevated 1 h after a large parenteral dose of morphine. In adrenals, unlabelled DA increased 2-fold and labelled DA, synthesized from 3H-tyrosine, increased more than 4-fold. The increases could be prevented by inhibition of DA-synthesizing enzymes and spinal cord transection, respectively. Labelled DA in plasma increased 2.7-fold after morphine in intact rats but did not increase in those with spinal cord transection. It is concluded that: (1) morphine stimulates the adrenal by increasing nerve impulse flow, (2) increased nerve impulse flow increases DA synthesis and levels, and (3) the increased DA levels result in increased release of DA into the bloodstream.
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