On the trail of Dr. Fifer.

A gift from a patient drew Hope, BC, family physician Gerd Asche irrevocably into the local medical history of the 1858 Fraser River Gold Rush. Because of his interest in Dr. Max William Fifer, Asche undertook research missions in British Columbia, England and the US, converted his computer room to a research and writing centre, and wrote a biography of his predecessor and colleague. He recounts his experience and the growing satisfaction provided by his interest in medical history.     

On the function of sleep.

It is proposed that sleep serves the function of maintaining immobility in animals at times when immobility is an optimum behavioural survival strategem. Sleep is of great evolutionary age and is always carefully tailored to the life-style of each animal; abundant in some species and absent from others. The survival advantages conferred on an animal by the power of sleep to schedule behaviour effectively may justify its existence and persistence in the evolution of species.     

On the mechanism of alpha-amylase.

Two inhibitors, acarbose and cyclodextrins (CD), were used to investigate the active site structure and function of barley alpha-amylase isozymes, AMY1 and AMY2. The hydrolysis of DP 4900-amylose, reduced (r) DP18-maltodextrin and maltoheptaose (catalysed by AMY1 and AMY2) was followed in the absence and in the presence of inhibitor. Without inhibitor, the highest activity was obtained with amylose, kcat/Km decreased 103-fold using rDP18-maltodextrin and 10(5) to 10(6)-fold using maltoheptaose as substrate. Acarbose is an uncompetitive inhibitor with inhibition constant (L1i) for amylose and maltodextrin in the micromolar range. Acarbose did not bind to the active site of the enzyme, but to a secondary site to give an abortive ESI complex. Only AMY2 has a second secondary binding site corresponding to an ESI2 complex. In contrast, acarbose is a mixed noncompetitive inhibitor of maltoheptaose hydrolysis. Consequently, in the presence of this oligosaccharide substrate, acarbose bound both to the active site and to a secondary binding site. alpha-CD inhibited the AMY1 and AMY2 catalysed hydrolysis of amylose, but was a very weak inhibitor compared to acarbose.beta- and gamma-CD are not inhibitors. These results are different from those obtained previously with PPA. However in AMY1, as already shown for amylases of animal and bacterial origin, in addition to the active site, one secondary carbohydrate binding site (s1) was necessary for activity whereas two secondary sites (s1 and s2) were required for the AMY2 activity. The first secondary site in both AMY1 and AMY2 was only functional when substrate was bound in the active site. This appears to be a general feature of the alpha-amylase family.