Antibodies to the ADP/ATP carrier, an autoantigen in myocarditis and dilated cardiomyopathy, penetrate into myocardial cells and disturb energy metabolism in vivo

We identified the ADP/ATP carrier, located within the inner mitochondrial membrane, to be an organ- and conformation-specific autoantigen in myocarditis and dilated cardiomyopathy. We also showed that autoantibodies to the ADP/ATP carrier inhibit the nucleotide transport in vitro. Specific binding of the autoantibodies to the carrier was demonstrated by radioimmunoassay and the immunoblot technique; the inhibition of the nucleotide transport was determined by the inhibitor stop method. To establish if these autoantibodies might also affect cardiac energy metabolism in vivo, we measured whether they are capable of penetrating into myocytes and whether subcellular ATP/ADP ratios and phosphorylation potentials of ATP change in hearts of guinea pigs that have been immunized with the isolated ADP/ATP carrier. An intracellular deposition of autoantibodies was observed by direct immunofluorescence and by immunoperoxidase staining on cryosections of the myocardial tissue of animals immunized with the ADP/ATP carrier. Furthermore, binding of autoantibodies to mitochondrial membrane structures was shown by immunoelectron-microscopic methods. The cytosolic and intramitochondrial distribution of adenine nucleotides in stimulated, isolated perfused hearts of guinea pigs immunized with the ADP/ATP carrier was measured by nonaqueous fractionation. Compared with controls performing equal external heart work, the cytosolic ATP decreased in the immunized animals, whereas the mitochondrial ATP increased strongly; ADP concentrations showed an opposite change. Thus, a resultant cytosolic decrease and a marked mitochondrial increase of the ATP/ADP ratio was established. As a consequence, the cytosolic-mitochondrial phosphorylation potential of ATP was diminished. These findings demonstrate that antibodies against intracellular antigens are able to penetrate into living cells, and that autoimmunity to the ADP/ATP carrier may contribute to the pathophysiology of myocarditis and dilated cardiomyopathy by causing an autoantibody-mediated imbalance between intracellular energy delivery and demand.     

Subacute cutaneous lupus erythematosus during PUVA therapy for psoriasis: case report and review of the literature

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.     

C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.     

Laboratory diagnosis of pulmonary embolism: value of increased levels of plasma D-dimer and thrombin--antithrombin III complexes

Plasma D-dimer (DD) and thrombin--antithrombin III complex (TAT) were measured with ELISAs in 99 patients investigated by 102 ventilation--perfusion lung scintigraphy because of suspected pulmonary embolism. High-probability lung scan was associated with increased DD (more than 500 ng/ml) and TAT (more than 4.1 ng/ml) levels (sensitivity of 100 and 70%, respectively). The corresponding figures of specificity were 81 and 42%. In the 56 patients with low-probability or indeterminate probability scans, 31 (55%) had DD concentrations of less than 500 ng/ml. These preliminary data suggest that a plasma DD concentration of less than 500 ng/ml might rule out the diagnosis of pulmonary embolism in suspected patients with an inconclusive lung scanning.     

Intestinal infarction caused by carcinoid associated elastic vascular sclerosis: early presentation of a small ileal carcinoid tumour.

We describe a patient with extensive ischaemic necrosis of the ileum as a result of elastic vascular sclerosis (EVS). A 2 cm carcinoid tumour was located nearby with microscopic evidence of spread to regional lymph nodes. Severe intestinal ischaemia caused by carcinoid associated EVS may be the presenting feature of small carcinoid tumours resulting in their early diagnosis.     

Randomized trial of Codetron for pain control in osteoarthritis of the hip/knee

Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial, saphenous, popliteal and sciatic nerves, and tender points. Seventy-four percent of patients in the real Codetron (Group A) and 28% of the patients in sham Codetron (Group B) improved their pain level more than 25% as measured by visual analogue scale. The difference in pain improvement in the two groups was statistically significant (p less than 0.02 using Fisher's exact probability ratio). Other functional parameters proved to be insensitive to change in this study. This is highly suggestive of beneficial effect of nonhabituating Codetron as a complementary modality in the therapy of chronic pain conditions such as osteoarthritis.