Differential long-term subcellular responses in heart and liver to adriamycin stress. Exogenous L-carnitine cardiac and hepatic protection

In order to evaluate the heart and liver responses after adriamycin (ADR) toxic aggression, with and without exogenous L-carnitine (CAR) protection, female Sprague-Dawley rats, body weight 40-60 g, were randomized into four groups: CON, ADR, CAR and CAR-ADR. ADR was injected i.v. at a dose of 15-18 mg/kg body wt (0.1 ml). CAR was administered i.v. at a dose of 20 mg (0.1 ml) before each subdose of ADR, and then orally at 180 mg/kg body wt daily for 12 weeks. Long-term cardiac and hepatic subcellular damage were determined by transmission electron microscopic analysis of ultrathin sections. The ADR-induced long-term cardiac subcellular pathology included loss, disruption and disassembly of myofibrils, and mitochondrial swelling and condensation. On the other hand, the ADR-induced subcellular hepatic alterations consisted of polymorphic mitochondria, cytoplasmic vacuolization and accumulation of lipid droplets. Apparently, cardiac tissue was more affected by ADR toxic aggression than hepatic tissue. However, these alterations were of less severity in protected groups, in both heart and liver, suggesting CAR as a possible hepatoprotector agent against ADR toxicity. Because of the liver-L-carnitine-heart relationship, studying ADR-hepatotoxicity could be helpful in the further understanding of severe ADR-cardiotoxicity.     

Autosomal recessive acrorenal syndrome

We describe two sibs with tetraectrodactyly and oligomeganephronic renal hypoplasia. The parents were unaffected. This syndrome of apparently autosomal recessive origin appears to be the first Mendelian form of the acrorenal developmental field defect identified so far. © 1992 Wiley-Liss, Inc.     

The latent membrane protein-1 in Epstein-Barr virus-transformed lymphoblastoid cells is found with ubiquitin-protein conjugates and heat-shock protein 70 in lysosomes oriented around the microtubule organizing centre.

Immunofluorescence studies on Epstein-Barr virus (EBV)-transformed lymphoblastoid cells have previously shown that the latent membrane transforming protein (LMP-1) is found in patch-like inclusions which also immunostain for vimentin. We now show that EBV transformation causes a major reorganization of intermediate filaments, microtubules, mitochondria, and lysosomal elements, which generally become oriented around the microtubule organizing centre. Immunogold electron microscopy shows that LMP-1 is primarily concentrated in secondary lysosomes together with ubiquitin-protein conjugates and heat-shock protein 70. Intermediate filament inclusion formation with the above characteristics may be a general response triggered by other membrane glycoproteins; as seen, for example, in major human neurodegenerative diseases such as diffuse Lewy body disease.     

Ultrastructural diagnosis in the immotile cilia syndrome

This article reports on the experience with 38 biopsies from nasal mucosa, submitted with the question of immotile cilia syndrome. Fixation in glutaraldehyde with MgSO4 is preferable. At least 50 cilia should be scrutinized in the electron microscope, and dynein arms, radial spokes, sheaths, nexin links and orientation should be tabulated. Six cases displayed virtual absence of inner and outer dynein arms. The orientation of these cilia was random. Two of the patients had situs inversus. In biopsies considered not to represent the immotile cilia syndrome, about four inner and seven outer dynein arms were found per cilium.     

Hypothermia and infection in Wernicke's encephalopathy

Two cases of acute Wernicke's encephalopathy with severe hypothermia as the major presenting feature are reported. Treatment with thiamine was rapidly introduced, but hypothermia nevertheless persisted for several weeks, at times masked by intercurrent infections.     

Clonal heterogeneity of HLA-B27 cellular allorecognition. Delineation of immunodominant sites

The fine specificity of nine cytolytic T lymphocyte (CTL) clones obtained after stimulation of HLA-B27- responder lymphocytes with B27.1+ lymphoblastoid cell lines has been analyzed. These clones defined three different reaction patterns when tested against a panel of target cells including those expressing all known HLA-B27 subtypes: (a) specific recognition of HLA-B27.1, B27.2 and B27d, (b) selective reactivity with B27.1, B27d and HLA-B40 and (c) selective recognition of B27.1, B27.2, B27d, B27f and B40. Representative clones within each group were analyzed in detail. Differences in lytic ability of the various susceptible targets within each group were established by cold target inhibition analyses and by blocking experiments with anti-CD3 and anti-CD8 monoclonal antibodies. When correlated with the known structure of the HLA-B27 subtypes, these results demonstrate the critical relevance of amino acid changes within residues 77-81 and at position 152 in modulating allospecific CTL recognition of HLA-B27.1 and suggest that these residues could be involved in the structure of immunodominant regions of this antigen. The observed cross-reactions with HLA-B40, differing from B27.1 in 16 amino acid residues, suggest that the simultaneous occurrence of multiple amino acid changes could have mutually compensatory effects, so that a cross-reactive epitope might result from various combinations of polymorphic residues.     

Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function

Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients.     

Application of antigens fromTaenia hydatigena cyst fluid for the immunodiagnosis of human hydatidosis

Fluid was collected from cysts ofTaenia hydatigena in 60 adult sheep and fluid from each animal pooled separately. By double diffusion antigen 5 was demonstrated in all pools but one. The criteria are described for selection and standardization of these preparations for use as antigens for the immunodiagnosis of human hydatid disease. Sera from 50 persons harbouring hydatid cysts and from 50 patients with other disease conditions were examined by the arc-5 double-diffusion test, using two antigens prepared fromEchinococcus granulosus andT. hydatigena cyst fluids, respectively. The results showed that a higher diagnostic sensitivity was obtained with the hydatid antigen. The significance of the findings is discussed in terms of their application to human immunodiagnosis in areas where hydatidosis, but not cysticercosis, is rare in livestock.     

Experimental Escherichia coli ascending pyelonephritis in rats: changes in bacterial properties and the immune response to surface antigens.

Systemic and urinary antibody responses were examined in rats with experimental ascending pyelonephritis caused by Escherichia coli O6K13H1. During 12-month follow-up of the infections, bacterial characteristics of the urinary and renal isolates were followed: O and K antigenicity, sensitivity to the bactericidal effect of normal human serum, capacity to attach to urinary tract epithelial cells, hemolytic activity, biochemical pattern, and virulence. During the long-term infection, the urinary and renal bacterial isolates changed in O and K antigenicity, serum sensitivity, and virulence. The adhesive capacity of the bacterial isolates did not change, possibly explaining the persistence of the bacteria in the urinary tract. The serum anti-O6 antibody levels remained high during the entire 1-year observation period, especially in the rats with renal involvement. Urinary anti-O6 antibodies were also found. The serum and urinary antibodies could have played a role in bringing about the observed changes in bacterial characteristics. Antibodies to lipid A were recorded in 9 of 16 rats with pyelonephritis and renal scarring and in 1 of 9 rats not having pyelonephritis or renal bacterial growth.