McArdle's disease: a study on the molecular basis of two different etiologies of myophosphorylase deficiency.

Three patients with myophosphorylase deficiency were investigated. Two had no detectable activity, while one had 1% residual activity. The patient with 1% residual activity had 40% of the normal amount of myophosphorylase protein. No myophosphorylase protein could be detected in the other two cases. A precipitin band in the Ouchterlony double immunodiffusion test was not present in any case. This study showed that modifying the normal enzyme (without changing the molecular weight) changed the immunoprecipitin activity of the phosphorylase protein. Therefore, immunoprecipitation is not a valid technique for differentiation of the variants of myophosphorylase deficiency, and another method, for example SDS-electrophoresis, should be applied.     

Selective inhibition of sulfate conjugation in the rat: Pharmacokinetics and characterization of the inhibitory effect of 2,6-dichloro-4-nitrophenol

The pharmacokinetics of 2,6-dichloro-4-nitrophenol (DCNP) have been studied in the rat. Upon i.v. injection the plasma decay curve of DCNP showed a rapid distribution phase. After 30 min the plasma concentration reached a value that was constant for at least 90 min, indicating very slow elimination of DCNP. The volume of distribution was 88 ml/kg and a high degree of binding (over 99%) of DCNP in vitro to bovine serum albumin was found. The concentration of DCNP in the liver was between 30 and 50% of the plasma values. While in vivo the effect of DCNP persisted for a long time, its action was readily reversible in the single-pass perfused rat liver. In vivo, the effect of the dose of DCNP on the inhibition of sulfation of the phenolic compound harmol was investigated. Upon the i.v. injection of 26 μmole DCNP/kg an instantaneous and complete inhibition of sulfation of harmol was found. Using this property of DCNP, the rate of sulfation of harmol in vivo was evaluated in relation to the dose and the time after injection of the substrate. Saturation of sulfation apparently occurred because the consumption of inorganic sulfate was extremely small.     

Physico-chemical and immunological properties of acid alpha-glucosidase from various human tissues in relation to glycogenosis type II (Pompe's disease).

The physico-chemical and immunological properties of acid alpha-glucosidase from various human tissues have been studied. Heat stability of acid alpha-glucosidase from heart, liver and skeletal muscle is identical, but for kidney some different results are obtained. Identical isoelectrofocussing patterns are found for heart, liver and skeletal muscle. Furthermore, the effect of antiserum against human liver acid alpha-glucosidase on the activity of acid alpha-glucosidase from various tissues is studied. The results are discussed in relation to glycogenosis type II (Pompe's disease).     

Symptomatic mucocele of the appendix diagnosed preoperatively

An unusual case of preoperatively diagnosed mucocele of the appendix is presented. The correct preoperative diagnosis was based on the following: (1) a long history of pain, (2) a palpable mass, (3) suspicious calcifications on plain film of the abdomen, and (4) characteristic appearance on a preoperative barium enema.     

Quinidine-induced ventricular flutter and fibrillation without digitalis therapy

Three cases are described with documented ventricular flutter and fibrillation during quinidine medication without concomitant digitalis therapy. In all three patients the arrhythmia developed while they were receiving moderate doses of quinidine. Although no changes in QRS width were observed after administration of quinidine, there was marked prolongation of the Q-T interval. The mechanism of development of ventricular flutter and fibrillation in patients taking quinidine may be similar to that in patients with the Q-T prolongation syndrome.     

Continuous hypothermic arrest versus intermittent ischemia for myocardial protection during coronary revascularization.

To assess the safety of two commonly used methods of myocardial protection, 144 consecutive patients who underwent coronary artery bypass grafting for chronic disabling or unstable angina were studied. Profound local cardiac hypothermia (LCH) with a single continuous period of ischemic arrest was used in 71 patients and compared with intermittent ischemia with intervening periods of reperfusion in 73 patients. Both groups were similar in age, sex distribution, number of obstructed coronary arteries, and number of coronary arterial bypass grafts performed. The electrocardiogram, serum glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured preoperatively, the day of operation, and for two days postoperatively. The operative mortality was 0.7%. The overall perioperative myocardial infarction rate defined by QRS criteria was 6.3%. In the LCH group the infarction rate was 4.2%, and in the ischemia group, 8.2%. Although mean initial postoperative SGOT and LDH were noticeably lower in the LCH group, other enzyme values, including CPK, did not differ noticeably between the groups. These data indicate that a single continuous period of ischemic arrest with profound local cardiac hypothermia as well as intermittent aortic cross-clamping with moderate systemic hypothermia are safe techniques for protecting the myocardium during coronary revascularization.     

Kinetics of sulfation and glucuronidation of harmol in the perfused rat liver preparation: Disappearance of aberrances in glucuronidation kinetics by inhibition of sulfation

Harmol is conjugated by glucuronidation and sulfation when it is given to the rat in vivo. In the once-through perfused rat liver preparation glucuronidation of harmol shows kinetic aberrances [Pang et al., J. Pharmac. exp. Ther. 219, 134 (1981)]. In order to further delineate the mechanism behind this, sulfation was inhibited to about 10% of control by 2,6-dichloro-4-nitrophenol. The loss of sulfation was compensated by an increase in the rate of glucuronidation, keeping the total clearance by the liver virtually constant in spite of the loss of sulfation. The inhibition of sulfation eliminated the previously observed lag-phase in the kinetics of glucuronidation; the rate of glucuronidation was now almost linear with the input concentration of the substrate harmol. The constant clearance of harmol in spite of inhibition of sulfation, the occurrence of the lag-phase in glucuronidation in the presence of sulfation, and the disappearance of this lag-phase in the absence of sulfation can be explained by either diffusion-limited metabolism of harmol or a heterogeneous sub-lobular distribution of the sulfating and glucuronidating systems. Activation of glucuronidation by harmol at high concentration can be excluded.