The Journal of clinical investigation
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To study the value of 4-aminopyridine as an antidote to verapamil intoxication, we subjected 12 adult cats to verapamil poisoning by administering doses of 4.0-25.0 mg/kg verapamil by intravenous infusion. Six animals were given 4-aminopyridine 2 X 0.5 mg/kg i.v. after the verapamil infusion was stopped and the other six animals (the control group) were not. ⋯ The six animals that received 4-aminopyridine survived the verapamil intoxication, whereas four of the six animals in the control group died. The results suggest that 4-aminopyridine may be useful in the treatment of verapamil intoxication.
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Previously we reported that chronic renal failure in rats leads to preferential disaggregation of liver membrane-bound polysomes associated with a decrease in albumin synthesis. To determine whether reduced albumin synthesis results from reduced cellular levels of albumin messenger RNA (mRNA) or some other molecular mechanism, we have employed mRNA-DNA hybridization in conjunction with cell-free protein synthesis to determine albumin mRNA sequence content and biological activity in subcellular fractions from control and uremic rat liver. Using high specific activity albumin [3H]-complementary DNA prepared from purified-albumin mRNA, we found that total liver polysomes and albumin mRNA sequence content are increased in uremic animals. ⋯ Evaluation of albumin mRNA size by hybridization analysis revealed a reduced content of intact albumin mRNA molecules per microgram of RNA in the liver of uremic animals. This was associated with increased ribonuclease activity in uremic cytosol. The diminished albumin synthesis by membrane-bound polysomes of uremic rat liver can, therefore, be explained by enhanced degradation of albumin mRNA.
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The contribution of peripheral vascular factors to the high output state in thyrotoxicosis was examined in 11 calves treated with daily intramuscular injections of L-thyroxine (200 micrograms/kg) for 12-14 d. Thyroxine treatment increased cardiac output from 14.1 +/- 1.4 to 24.7 +/- 1.4 liters/min (P less than 0.001) and decreased systemic vascular resistance from 562 +/- 65 to 386 +/- 30 dyn-s/cm5 (P less than 0.01). Blood volume was increased from 65 +/- 4 ml/kg in the euthyroid state to 81 +/- 6 ml/kg when the animals were thyrotoxic (P less than 0.05). ⋯ Mean circulatory filling pressure increased from 10 +/- 1 mmHg in the euthyroid state to 16 +/- 2 mmHg (P less than 0.01) during thyrotoxicosis, while pressure gradient for venous return increased from 10 +/- 1 to 14 +/- 2 mmHg (P less than 0.02). These changes in venous return curves were not affected significantly by ganglionic blockade with trimethapan (2.0 mg/kg per min) before cardiac arrest. Thus, the high output state associated with thyrotoxicosis is not dependent upon a low systemic vascular resistance, but is associated with increases in blood volume, mean circulatory filling pressure, and pressure gradient for venous return.
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We have developed a new, specific, and highly sensitive enzyme-linked immunosorbent assay (ELISA) which quantitates activation of the alternative pathway in human serum, plasma, or on the surface of activators. The ELISA detects the third component of complement (C3b), proteolytic fragment of complement Factor B (Bb), and properdin (P) complex or its derivative product, C3b,P. In the method, activator-plasma mixtures, plasma containing an activated alternative pathway, or other samples are added to the wells of microtitration plates precoated with antibody to P. ⋯ Normal human sera (20) contained low levels (5-20 ng/ml) of ELISA-reactive complexes. A proportion of sera from individuals with the adult respiratory distress syndrome (9-10), typhoid fever (8-10), malaria (3-5), gram-negative sepsis (9 of 47), acute trauma and shock (6 f 25), and systemic lupus erythematosus (3 of 29) showed elevated levels of complexes reactive in the alternative pathway ELISA. In contrast, nine sera from patients with circulating C3 nephritic factor were not reactive in the ELISA.
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Two fractions of sarcoplasmic reticulum, one light (LSR) and one heavy (HSR), were isolated from gracilis muscle of control and malignant hyperthermia (MH)-susceptible pigs. Part of the gracilis muscle biopsy was used to compare the contracture sensitivity of the muscle to the calcium-releasing effects of caffeine on isolated SR membranes. Gracilis muscle of MH pigs was more sensitive to the contracture-producing effects of caffeine than control pig muscle. ⋯ Ruthenium red increased the threshold calcium concentration for calcium-induced calcium release while it reduced the amount of calcium released. Increasing concentrations of Mg2+ increased the Ca2+ threshold for release and the amount of Ca2+ released but did not significantly affect rate of Ca2+ release. Results of the study suggest a defect in the mechanisms causing calcium release from SR in MH-affected muscle.