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Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP: However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens. [ABSTRACT FROM AUTHOR]

Pheochromocytoma diagnosis in dogs is challenging because biochemical tests are not always available. In humans, urinary vanillylmandelic acid (VMA) is part of a pheochromocytoma biochemical diagnostic profile, whereas its diagnostic accuracy is currently unknown in dogs with pheochromocytoma. Prospectively, VMA was determined by HPLC and expressed as the ratio with respect to urinary creatinine (VMA:C). The diagnostic accuracy of the VMA:C ratio was evaluated by analyzing the receiver operating characteristic (ROC) curve in 10 healthy dogs, 8 dogs with pituitary-dependent hypercortisolism, 8 dogs with adrenal-dependent hypercortisolism, and 7 dogs with pheochromocytoma. The pheochromocytoma diagnosis was confirmed by histology and immunohistochemistry in all tumors. The VMA:C ratio was significantly higher in dogs with pheochromocytoma (158 [53.4 to 230.8] × 10 -3 ) than in dogs with adrenal-dependent hypercortisolism (48.1 [24.3 to 144.9] × 10 -3 ; P < 0.05), dogs with pituitary-dependent hypercortisolism (37.5 [32 to 47.1] × 10 -3 ; P < 0.001), and healthy dogs (33.8 [13.3 to 87.9] × 10 -3 ; P < 0.001). When using a VMA:C ratio >58.2 × 10 -3 for pheochromocytoma diagnosis, a sensitivity of 85.7% and a specificity of 88.4% were obtained. Nevertheless, when using a cut-off ratio of 4 times the median VMA:C ratio determined in healthy dogs, there was no overlap (100% specificity). The area under the ROC curve indicated that the VMA:C ratio test could be used to discriminate between dogs with and without pheochromocytoma, what leads to the conclusion that it is useful for pheochromocytoma diagnosis in dogs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It has been described that mitochondrial antibodies can be detected in the serum of primary biliary cirrhosis patients (over 90%) and that these antibodies are directed specifically against a component of the mitochondrial inner membrane. In the present study whole mitochondria isolated from rat liver were exposed to mitochondrial antibodies from patients with primary biliary cirrhosis, and to antibodies induced experimentally in rabbits to mitochondrial antigens of rat liver. This was an attempt to study the action of these antibodies and complement on mitochondrial functions. By studying respiratory control and oxidative phosphorylation of mitochondria, no significant, nor specific effect on mitochondrial membranes functions could be detected, after the incubation of suspensions of mitochdondria with normal or immune gamma-globulin (neither from rabbits nor from human) nor with the addition of complement. Furthermore, the respiration of fragmental mitochondria using succinate and NADH substrates was unaffected by the antibodies and complement. Similarly, mitochondrial APT-ase activity and swelling and contraction were not affected by antibody. Experiments are in progress to study the hypothesis of a lymphocyte dependent antibody mediated cytotoxicity in this system. In order to demonstrate that this autoimmune phenomenon might be associated with cellular immunity to a mitochondrial component, we have in a previous report demonstrated impairment of mitochondrial respiratory control by lymphocytes from rabbits sensitized in vivo with mitochondrial antigens. Subsequently we have recently shown evidence of sensitization. In-vivo of lymphocytes from patients with primary biliary cirrhosis as demonstrated by an injurious effect on rat liver mitochondria by lymphocytes from patients with this disease. Further studies are necessary to clarify the involvement of this phenomena in the possible mechanisms responsible for the pathogenesis of the lesions.

The antitumor antibiotic Adriamycin is a potent inhibitor of the sodium-potassium-activated adenosine triphosphatase of native heart microsomes. Adriamycin also inhibits potassium transport (although not sodium transport) in slices of kidney cortex. The effects on both the adenosine triphosphatase and ion transport are markedly reduced by Ca2+, probably by chelation of this metal by Adriamycin. These effects could provide a basis for explaining the Adriamycin cardiotoxicity as a digitalis-type toxicity.

Mitochondria isolated from rat livers were used as a source of antigens capable of producing in vitro activation of lymphocytes that had previously been sensitized in vivo with the same antigen. Such lymphocytes were shown to have an injurious effect on target mitochondria, as was demonstrated by a new biochemical approach based on the study of the inhibition by these cells of mitochondrial respiratory control. A somewhat milder injurious capacity was also observed in normal and sensitized lymphocytes activated in vitro with the mitogen PHA. The lateration of the respiratory control of mitochondria by lymphocytes correlated with an increase in DNA synthesis in these cells.