Harold Baum

Serology of Primary Biliary Cirrhosis

The aetiology of primary biliary cirrhosis (PBC) still remains unknown. Many features point towards an autoimmune disorder [25]: the female preponderance, the familial aggregation, the association with other autoimmune conditions, the protracted course, the presence of various types of antibodies (smooth muscle (SMA), nuclear (ANA), and especially mitochondrial antibodies (AMA)), and the histological lesions (showing granuloma formation and infiltration of bile ducts by lymphocytes). In addition in a high percentage of patients circulating cryoglobulins have been detected [91] and there is a striking abnormality of the complement system [45] and impairment of cell mediated immunity [62]. Also cellular immunity against biliary antigens [64] and mitochondria [18] has been described, and patients’ lymphocytes also seem to interfere in vitro with some mitochondrial functions [16, 24]. AMA apparently play no role in the pathogenesis of PBC but their incidence in almost 90% of all PBC patients led to the speculation that these antibodies could be related to the aetiology of the disease.

Studies on the nature of adenosine diphosphatase activity from rat liver mitochondria

Adenosine diphosphatase (ADPase) activity was studied in rat liver with [beta-32P]ADP as a substrate. Mitochondria and outer mitochondrial membrane fractions were isolated and assayed for ADPase and various marker enzymes. ADPase activity was strikingly reduced when the outer membranes were removed from the mitochondria whether by digitonin treatment or osmotic shock. Addition of the inter-membrane space subfraction to the purified outer membranes resulted in enhanced ADPase activity. Addition of the inter-mitochondrial membrane enzyme adenylate kinase to outer membranes also produced a large stimulation of activity. The ADPase activity could also be reconstituted in vitro with adenylate kinase and either mitoplast ATPase or ouabain-sensitive (Na+ + K+ + Mg2+)-ATPase. Chloroform-released ATPase, however, was not capable of producing an ADPase activity when combined with adenylate kinase. Gel permeation chromatography of Triton-solubilised outer mitochondrial membranes was unable to resolve ADPase activity from contaminating ATPase. These results suggest that the majority of ADPase activity in rat liver mitochondria consists of the coupled activity of adenylate kinase and ATPase.

Mitochondrial respiration and the thrombin-induced release reaction of platelets

Abstract Respiration has been monitored polarographically in suspensions of washed platelets isolated from pig blood. Induction of the release reaction by addition of thrombin to such suspensions resulted in a stimulation of respiration. A respiratory stimulation of similar magnitude was achieved by adding 2 deoxy-D-glucose or uncouplers of oxidative phosphorylation. Oligomycin caused a pronounced inhibition of respiration which could be reversed by adding uncouplers but not thrombin or deoxyglucose. Antimycin A caused a total inhibition of oxygen uptake and prevented the respiratory stimulation otherwise observed on addition of thrombin. It is concluded that the stimulation of respiration caused by thrombin reflects a response of platelet mitochondria to a change in the intracellular ratio of ATP/ADP, consequential upon ATP breakdown during the release reaction. The nature of the energy-dissipating reactions stimulated by thrombin is discussed.

Characteristics of Ca2+ uptake in mitochondria of brown adipose tissue

Abstract The rate of calcium uptake in brown adipose tissue mitochondria is here shown to be a sensitive parameter of energisation in this tissue, as demonstrated by high susceptibility to purine nucleotides and albumin. Complete uptake of low amounts of calcium generally requires added phosphate. Bicarbonate can at least partially substitute for phosphate, whereas acetate cannot. Calcium transport in brown fat mitochondria is of interest due to recent indications of an important role of this organelle in regulation of cytosolic calcium levels.