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C Jespersen

Publications and source records attributed to C Jespersen.

8 recordsLinked to original sources
PubMed1995

Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme.

We have used expression of human medium chain acyl-CoA dehydrogenase (MCAD) in Escherichia coli as a model system for dissecting the molecular effects of two mutations detected in patients with MCAD deficiency. We demonstrate that the R28C mutation predominantly affects polypeptide folding. The amounts of active R28C mutant enzyme produced could be modulated between undetectable to 100% of the wild-type control by manipulating the level of available chaperonins and the growth temperature. For the prevalent K304E mutation, however, the amounts of active mutant enzyme could be modulated only in a range from undetectable to approximately 50% of the wild-type, and the assembled mutant enzyme displayed a decreased thermal stability. Two artificially constructed mutants (K304Q and K304E/D346K) yielded clearly higher amounts of active MCAD enzyme than the K304E mutant but were also responsive to chaperonin co-overexpression and growth at low temperature. The thermal stability profile of the K304E/D346K double mutant was shifted to even lower temperatures than that of the K304E mutant, whereas that of the K304Q mutant was closely similar to the wild-type. Taken together, the results show that the K304E mutation affects (i) polypeptide folding due to elimination of the positively charged lysine and (ii) oligomer assembly and stability due to replacement of lysine 304 with the negatively charged glutamic acid.

Acyl-CoA Dehydrogenase↗
PubMed1995

[Post-infarction, myocardial ischemia: clinical importance and risk factor].

The myocardial scar, left behind by an infarct, makes up a potential substrate for complex ventricular arrhythmias due to the presence in such tissue of electrical inhomogeneity, altered refractoriness, and abnormal conduction properties, which facilitate the induction of reentrant arrhythmias and the release of abnormal automatic responses of the partially repolarised cells. The mechanism(s) by which complex ventricular arrhythmias is/are transformed into malignant arrhythmias has/have not yet been definitely proven. The observation that coronary revascularization - in patients with ischaemic heart disease surviving out of hospital cardiac arrest - improves the prognosis, indicates that transient ischaemic attacks might be the trigger of malignant ventricular arrhythmias in patients with prior myocardial infarction. Patients with large infarct scars (heart failure) have an increased incidence of complex ventricular arrhythmias, death, and ischaemic events. Antiarrhythmic medical intervention does not improve the prognosis in these patients. Intervention with ACE-inhibitors reduces the prevalence of complex ventricular arrhythmias, the incidence of death, and reinfarction, but not arrhythmic death, indicating that residual ischaemia might be the major risk variable in patients with heart failure. Ischaemia is one of several risk markers for transient supraventricular arrhythmias in patients recovering from an acute myocardial infarction (AMI). In addition, anti-ischaemic intervention in patients recovering from AMI suppresses residual myocardial ischaemia and thereby reduces major events.

Arrhythmias, Cardiac↗
PubMed1988

Prenalterol in severe congestive heart failure. I. The immediate haemodynamic effects as compared to nitroglycerine.

The immediate haemodynamic effects of prenalterol and nitroglycerine were examined in 15 patients, with severe chronic heart failure. Prenalterol was given intravenously in increasing doses of 2, 4, and 8 mg. Cardiac index increased significantly by 16%, 24%, and 32%, respectively. Heart rate increased by 16%, 19%, and 24%. Stroke volume index, systemic artery pressure, pulmonary artery pressure, and right atrial pressure did not change. Prenalterol reduced systemic vascular resistance by 15%, 17%, and 24%, respectively. Forearm blood flow and forearm vascular resistance was unchanged. Cardiac index and heart rate were not changed by 0.5 mg nitroglycerine, administered sublingually. Systolic and diastolic blood pressure were on average reduced by 14% and 12%, respectively. Systolic and diastolic pulmonary artery pressure and right atrial pressure were similarly reduced by 17%, 31%, and 39%, respectively. Nitroglycerine lowered calculated systemic vascular resistance by 11%, whereas forearm blood flow and forearm vascular resistance was unchanged. The conclusion is that prenalterol acutely increased cardiac index and improved haemodynamics in 14 out of 15 patients, mainly due to an increased heart rate. Nitroglycerine did not change cardiac index in the same group of patients.

Aged↗
PubMed1988

Prenalterol in severe congestive heart failure. II. Long-term oral treatment. Results with comments on the methods for evaluation of drugs in congestive heart failure.

Nine patients with severe congestive heart failure were treated with a partial beta-1-agonist prenalterol for 9.6 months on average. Five of the nine patients improved with an increase in NYHA-functional capacity of one class. In four of these patients, the improvement was maintained for 12 months. Upon discontinuation, deterioration occurred only in one case; in the latter, improvement reoccurred on reinstitution of prenalterol treatment. Significant improvement on exercise testing, however, occurred only in two patients. Prediction as to which patients would benefit from oral prenalterol was not possible from the pretreatment haemodynamic variables; similarly, the effect of oral prenalterol treatment could not be predicted from the response to prenalterol given intravenously. A critical review of the methods for evaluation of therapeutic intervention in congestive heart failure concludes the article.

Administration, Oral↗