Limitations of the electrocardiographic response to exercise in predicting coronary-artery disease.

The electrocardiographic response to exercise was compared with the results of coronary angiography in 89 patients with Type II hyperlipoproteinemia who had previous myocardial infarction or typical angina or both (43 patients)(Group A), "atypical angina" (16 patients)(Group B)or positive electrocardiographic response to exercise without other evidence of cardiac disease (30 patients)(Group C). Thirty-nine of 43 in Group A had greater than or equal to 50 per cent stenosis, and 26 (67%) of these 39 had negative exercise tests. In Group B, five of the 16 had greater than or equal to 50% stenosis, and three had positive exercise tests (one patient had a false-positive test). In Group C, eleven of 30(37%) had greater than or equal to 50% stenosis; however, nine (30%) had minor stenosis (less than or equal to 50%), and 10(33%) normal coronary arteries. The diagnostic usefulness of exercise electrocardiography is limited. False-negative responses are frequent in patients with clinically suspected coronary disease, and false-positive responses frequent in asymptomatic patients.     

Identification and characterization of linear B-cell epitopes of beta-globulin, a major allergen of sesame seeds

BACKGROUND: The increased consumption of foods containing sesame seeds is paralleled by an increase in reported sesame-induced allergic reactions. OBJECTIVE: This study aimed at identifying and characterizing the linear B-cell epitopes of the 14-kd beta-globulin, the major allergen of sesame seed. METHODS: A peptide containing 71 amino acids (peptide B) was previously identified by us as the IgE-binding region on beta-globulin. To determine the amino acid sequence of the IgE-binding sites on peptide B, we synthesized overlapping peptides 20 and 10 amino acid residues long that span the entire length of peptide B, which were offset from each other by 10 and 2 amino acid residues, respectively. Sera from 20 subjects given diagnoses of allergy to sesame beta-globulin served to identify the epitopes by using the dot-blot test. RESULTS: At least 9 different IgE-recognition sites were identified on peptide B. Three of them, numbers 2, 3, and 13 (corresponding to amino acids 46-55, 48-57, and 76-86, respectively, in the beta-globulin sequence), appeared to be immunodominant IgE-binding epitopes. Also, these peptides were best recognized in terms of intensity of response. There was no obvious sequence motif shared by the 9 different IgE-binding epitopes of beta-globulin. However, approximately 60% of the amino acids represented in the epitopes are hydrophobic residues. CONCLUSION: Identification of the IgE-binding epitopes might provide a better understanding of the functional role the allergens play in the disease and might have implications for immunodiagnosis and probably immunotherapy.     

CD154-CD40-induced reactivation of latent HIV-1 infection

Reservoirs of latent HIV-1 in T cells and macrophages pose one of the major obstacles that hamper final eradication of HIV-1 from infected patients. Targeting costimulatory molecules expressed on cell types harboring latent HIV-1 to achieve reactivation may provide a new approach to overcome this problem. One such molecule is CD40, a member of the tumor necrosis factor (TNF)-receptor family. Using THP89GFP cells as a model for latently infected macrophages, we demonstrate that trimeric forms of recombinant CD154 allow for the direct reactivation of latent HIV-1 infection. Reactivation is augmented by the release of TNF-alpha. The presence of TNF-alpha is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-alpha are sufficiently high to reactivate latent HIV-1 in a latently HIV-1-infected T-cell line (J89GFP). Taken together, our results demonstrate that costimulatory molecules may be attractive targets to reactivate latent HIV-1 in infected patients.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

Myotonic dystrophy, syringomyelia, and 2/13 translocation in the same family.

The present report describes a sibship with 2 individuals affected by myotonic dystrophy and a third with syringomyelia. The mother was affected by myotonic dystrophy. A balanced 2/13 translocation was detected in the individual with syringomyelia, in one affected by myotonic dystrophy and in their clinically normal father. The association between the phenotypic anomalies and the chromosome alteration is coincidental.     

Ultrastructural localization of human HL-A membrane antigens by use of hybrid antibodies

The localization of HL-A histocompatibility antigens at the surface of human lymphocytes in electron microscopy has been studied using hybrid antibodies to bind electron-dense particles (ferritin and plant viruses) to anti-HL-A antibody. A discontinuous distribution of the markers is observed at the cell surface, which is identical with that described for H-2 antigens on mouse lymphocytes with the same technique. Double labelling experiments suggest that the areas of the cell surface where HL-A antigens are detected contain also the heterologous lymphocyte antigens detected by an anti-thymocyte serum and that HL-A antigens are not renewed at a detectable level during the period of the labelling procedure in the areas of the cell surface which are not labelled primarily with ferritin-anti-IgG-anti-HL-A complexes. The interpretation of the discontinuous labelling of HL-A antigens with direct immunoferritin techniques is discussed.     

Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression

1. This study evaluates the associative interactions between inputs that lead to long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG). Previous studies have revealed that when two inputs are coconditioned, the extent of LTP is greater than when each input is conditioned alone. Moreover, for a weak input that does not show LTP when conditioned alone, LTP can be induced in that weak input if it is coconditioned with a strong input. LTD results when one input is silent when another is conditioned. In the present study, we evaluate whether these associative interactions depend on the extent of overlap of the terminal fields of the different inputs. 2. The experiment took advantage of the topographical organization of the temporodentate pathway from the entorhinal cortex (EC) to the DG. Four stimulating electrodes were placed so as to activate ipsilateral and crossed components of the projections from medial and lateral portions of the EC. Recording electrodes were positioned unilaterally in the DG so as to record field potentials. The localization of the synaptic field that was activated by each electrode was determined by current source density (CSD) analysis. The extent of overlap between the terminal fields of ipsi- and contralateral pathways was assessed, and the pathways were divided into groups where the overlap between current sinks was 0-50 or 51-100%. 3. Conditioning stimulation (400-Hz trains of 8 pulses delivered 8 times) was delivered to pathways alone or in combination with other pathways. The extent of LTP was evaluated after coactivation of pathways that overlapped substantially (51-100%) or minimally (0-50%). The extent of LTD was evaluated in pathways that were silent during conditioning of other overlapping or nonoverlapping pathways. 4. The extent of associative LTP or LTD depended on the extent of overlap between the terminal fields of pathways. Coactivation of two pathways that overlapped by 51-100% led to LTP; coactivation of pathways that overlapped by 0-50% did not. Moreover, LTD was induced in a crossed pathway when an ipsilateral pathway that overlapped by 51-100% was activated, but not when a nonoverlapping (0-50% overlap) ipsilateral pathway was activated. The degree of associative LTP or LTD that was induced in crossed pathways was correlated with the percent overlap with the terminal field of the active ipsilateral pathway. 5. Evaluation of whether LTD was induced when one division (medial or lateral) of the ipsilateral pathway was silent when the other division was conditioned revealed similar relationships.(ABSTRACT TRUNCATED AT 400 WORDS)     

Subcellular Localization of Salmonella enteritidis Endotoxin in Liver and Spleen of Mice and Rats

Salmonella enteritidis¹⁴C-endotoxin was recovered predominantly from the nuclear and mitochondrial subcellular fractions of livers and spleens of mice and rats, 3.5 hr and 3 days after intravenous administration. Of the recovered radioactivity, 10 to 20% was present in the liver mitochondrial fraction as high-molecular-weight, biologically active material, suggesting the presence of intact endotoxin. Autoradiographic studies demonstrated nuclear and cytoplasmic labeling in the liver and at least nuclear label in spleen cells. The resistance of rats, as compared to mice, to the induction of amyloidosis does not appear to be based on a difference in subcellular localization of endotoxin within the reticuloendothelial system.     

Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant.

Stabilization of polyriboinosinic-polyribocytidylic acid against enzymatic hydrolysis by addition of poly-1-lysine and carboxymethylcellulose (PICLC) resulted in a compound with marked adjuvanticity. The primary antibody response of rhesus monkeys to formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine was significantly potentiated if the vaccine was combined with PICLC prior to vaccination. The antibody response was maintained at a significantly higher level than controls for 2.5 months postvaccination and paralleled immunological responses reported for live, attenuated (TC-83) vaccine.     

Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis.

Puromycin aminonucleoside--(PAN) treated rats develop acute nephrotic syndrome, mimicking human minimal lesion disease. In PAN nephrosis, podocyte detachment from the glomerular basement membrane (GBM) is the most likely cause of massive proteinuria in this model. To elucidate further the mechanisms of PAN-induced cellular dysfunction, new methods were employed to visualize podocyte cytoskeletal aggregation and to measure fibrillar attachment to the GBM. Adult Sprague-Dawley rats (n = 4/group) received a single tail-vein injection of PAN (75 mg/kg). On days 1, 2, 3, and 5 following injection, 24-hour urine collections were obtained for creatinine clearance, albuminuria, and total proteinuria. Then kidneys from each group were fixed by perfusion. Podocytic cytoskeleton was visualized by scanning electron microscopy. Subepithelial GBM staining and attachment fiber number, observed on digitized images of transmission electron micrographs, were quantitated with computer-based density analysis. A significant reduction in attachment fiber number in the GBM lamina rara externa occurred by day 5. On scanning electron micrographs, the secondary and tertiary podocytic processes were observed to be formed by highly aggregated cytoskeleton, which became partially disaggregated by day 3, was totally absent by day 5, and normalized by day 20. Immunogold staining revealed that actin and vinculin localized to the tertiary podocytic processes in the normal state were dispersed into the cell body following PAN. Podocyte cytoskeletal disaggregation precedes, and detachment from the GBM occurs simultaneously with, the onset of massive proteinuria in the PAN model.