Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA

In the search for HLA-linked immune response genes that control susceptibility to tuberculosis, we performed HLA typing and measured antibody titers to well-defined Mycobacterium tuberculosis antigenic determinants in 101 patients with sputum smear-positive pulmonary tuberculosis and 64 healthy controls from Surabaya, Indonesia. HLA-DR2 and DQw1 were associated with sputum smear-positive pulmonary tuberculosis (attributable risk = 36% and 39%, respectively), while DQw3 was associated even more strongly with the control group (preventive fraction = 57%). Antibody titers to the TB71 and TB72 epitopes of the 38-kDa protein, present only on tubercle bacilli, were strongly associated with DR2 (Pcorr = .001 and .024, respectively). The association of both the disease and the antibody response to the 38-kDa antigen of M. tuberculosis with Class II HLA genes HLA-DR2 indicates that Ir-gene-mediated regulation of the immune response to this antigen may be of pathogenic significance for the development of sputum smear-positive tuberculosis.     

Metabolism of 3H- and 14C-labeled glutamate, proline, and alanine in normal and adrenalectomized rats using different sites of tracer administration and sampling

Alanine, glutamate and proline labeled with 14C and 3H were infused into fasted normal and adrenalectomized rats. Alanine was administered by the A-V mode (arterial administration-venous sampling), and glutamate and proline by both the A-V and V-A (venous administration-arterial sampling) modes. The kinetics of 14C alanine and 14C glutamate differed markedly from those of the tritium-labeled compounds, but there was little difference in the kinetics of 3H and 14C proline. The replacement rate calculated from the A-V mode for glutamate was about half that obtained in the V-A mode, but there was little difference with proline. The masses of the amino acids (total content of amino acids in the body) were calculated from the washout curves of the tritium-labeled compounds after the infusion of tracer was terminated. The masses for the normal rats were 407 mumol/kg for alanine, 578 mumol/kg for glutamate and 296 mumol/kg for proline. The so-called distribution spaces calculated conventionally from total masses and the amino acid concentrations in plasma are much greater than the volume of the body, reflecting the fact that amino acid concentrations in tissues greatly exceed those in plasma. Adrenalectomy markedly affected the kinetics of the three amino acids, and their replacement rates were greatly reduced. The proline and glutamate masses were reduced by at least one half, while that of alanine was unchanged. Adrenalectomy markedly reduced the conversion of proline to glutamate. The hydrocortisone regimen used in this study restored the metabolism of alanine and glutamate to normal, but had no effect on that of proline.     

Skeletal muscle blood flow and venous capacitance in patients with severe sepsis and systemic hypoperfusion

Alterations in peripheral vascular tone are presumed to contribute to circulatory failure during severe sepsis. Decreased venous tone with venous pooling may decrease effective circulatory blood volume, while decreased arterial tone with redistribution of systemic blood may compromise tissue nutrient flow. We compared forearm arterial and venous tone and forearm blood flow in ten patients with and ten patients without sepsis. The FVT, MVC, and FBF were measured by air plethysmography. In the septic patients, MCV was 1.4 +/- 0.1 ml compared with 3.1 +/- 0.2 ml in nonseptic patients (p less than 0.01). The FVT was 13.4 +/- 1.0 mm Hg/ml in septic patients versus 7.0 +/- 0.5 mm Hg/ml in nonseptic patients (p less than 0.01). The ratio of FBF to cardiac output was 0.28 +/- 0.07 percent in septic patients and 0.31 +/- 0.07 percent in nonseptic patients. These data suggest that increased peripheral venous capacitance and redistribution of skeletal muscle blood flow are not present in patients with sepsis.     

Education of patients with arterial disease. A plan for the use of Expert System in angiology via Minitel

We are presenting a computer program requiring the use of an Expert System accessible by Minitel, intended for patients with arterial disease and their attending physician. The objective is not to make a diagnosis, but to train the patients in applying health measures to the handling and prevention of his/her disease. While remaining anonymous, the patient may consult the program at home, without any time constraint. Only the patient's physician can authorize him/her to have access to the program. The Expert System may adjust the answers to the patients according to the past history and recent data. Contrary to a computer program, new knowledge does not impair the functioning of the system. The physician has access to simplified modules regarding his patient, and specific modules regarding the treatment. Such a system would help general practitioners in following his patient and would facilitate the Doctor-Patient relationship during consultations.     

Life-span development: a review of theory and practice for families with chronically ill members

While the family's primacy in the patient's adaptation to chronic illness increasingly is being recognized by health professionals and social scientists, the reverse side of the coin, that is, the impact of chronicity on the family, has received little attention. A life-span development perspective is used to enrich the more traditional frameworks employed to study family development and also as a unifying framework from which to view the impact of illness on individual family members and the family as a unit. A review of selected literature reveals a profile of families most at risk for serious disruption in situations involving chronic illness. Propositions suggesting interventions directed at patients and families experiencing chronicity are derived.     

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.     

Bilateral rupture of diaphragm with delayed strangulation

A 64-year-old woman presented in shock. The computed tomography (CT) scan confirmed rupture of the left diaphragm with strangulation. Three days after surgery, the patient developed herniation of abdominal contents on the right side with cardiorespiratory collapse. Marlex mesh was used to repair on the right side. Postoperatively, she needed partial gastrectomy for massive duodenal ulcer bleeding. A dual chamber pacemaker was used to correct the complete heart block.     

Ontogeny of serum insulin-like growth factor binding proteins in the rat

Insulin-like growth factors (IGF-I and -II) are peptide growth factors that may be important for neonatal development. Specific high affinity IGF binding proteins (BPs) have been characterized in serum and extracellular fluids. The major serum binding complex in the adult has an apparent Mr of 150 K, while the predominant BP in the neonate is approximately 30 K. In the rat, the transition from the neonatal BP to the adult form occurs during the third postnatal week, concomitant with an increase in serum IGF-I and a decrease in serum IGF-II concentrations. Using specific RIAs and Western ligand blot analyses we have characterized the changes in serum IGF and IGF BPs, respectively, during the early postnatal period. Seven BPs were identified in serum with apparent Mr values of 42, 41, 40, 38, 28, 26, and 22 K. After deglycosylation, the 42, 41, 40, and 38 K BPs were reduced to two bands with apparent Mr values of 35 and 32 K, while the 28, 26, and 22 K BP were unchanged. In the neonate, the 28, 26, and 22 K BPs were present, with the 28 K BP in highest concentration. With increasing age, the 28 K BP decreased and the 42, 41, 40, and 38 K BPs appeared at approximately 19 days of age. Comparison of Western ligand blots of neonatal serum, BRL-3A conditioned media, rat amniotic fluid, and rat cerebrospinal fluid (CSF) demonstrated that all contained a prominent 28 K BP. A polyclonal antibody (alpha Hec 1) developed against the 31 K human IGF-BP (hBP-31) immunoprecipitated the 28 K BP from neonatal rat serum, BRL-3A media, rat amniotic fluid, and rat CSF, but did not react with adult rat serum. These findings suggest that, in the rat, the predominant neonatal serum BP is structurally and immunologically similar to the major BRL-3A, amniotic fluid, and CSF BPs, but distinct from the predominant adult serum BP.     

Canine serum keratan sulfate and hyaluronate concentrations. Relationship to age and osteoarthritis

Elevated serum levels of keratan sulfate (KS) and hyaluronate (HA) in patients with osteoarthritis (OA) have been reported. We measured KS and HA in dogs to determine if there was an elevation of these serum glycosaminoglycans in a canine model of OA. A single intraarticular injection of 1 mg of chymopapain into a shoulder joint increased serum KS by tenfold, and HA by less than twofold, in 24 hours. Serum KS and HA levels were 3-5-fold higher in dogs younger than 2 months of age than in older dogs. Serum KS and HA concentrations and synovial fluid KS concentrations were unrelated to spontaneous cartilage degeneration in 1-year-old dogs. Higher KS levels in synovial fluid correlated with higher KS levels in serum (r = 0.54, P less than 0.025). The mean KS concentration in sera of older dogs (greater than 3 years old) with OA was 37% higher than that in disease-free controls, but the difference between the groups was not statistically significant. Thus, elevated levels of serum KS and HA do not appear to have clinical significance in this model of OA.