Two cases of "scombroid syndrome" with severe cardiovascular compromise

Two cases of severe intoxication after ingestion of cooked tuna fish were observed. Symptoms and clinical signs were consistent with the scombroid syndrome. Cardiovascular shock was observed in both patients and was associated with subendocardial myocardial infarction in 1 case and acute pulmonary edema with myocardial ischemia in the other. The importance of ECG monitoring in the Intensive Coronary Care Unit is stressed.     

Voltage-dependent activation of frog eggs by a sperm surface disintegrin peptide

No single dose of MR contrast agent is optimal or adequate for the evaluation of all types of CNS lesions. This article discusses the fundamental principles and various background suppression techniques for lesion detection and delineation. An understanding of all factors influencing lesion conspicuity is important in deciding the optimal dose, if any, of contrast agent and the technique necessary for the procedure.     

Stringent allele/epitope requirements for MART-1/Melan A immunodominance: implications for peptide-based immunotherapy

The exclusiveness of the relationship between peptide and HLA alleles, combined with their extensive polymorphism, emphasizes the need for immunization strategies based on endogenous processing of full length proteins (containing multiple epitopic determinants) for presentation to T cells. This could allow vaccination regardless of the patient's HLA phenotype, assuming that individual molecules can be efficient T cell Ags in association with various HLA alleles. An endogenous system of Ag presentation was developed using dendritic cells infected with recombinant viral vectors expressing the melanoma-associated Ag MART-1/Melan A. CD8+ T cells from melanoma patients were activated in vitro by coincubation with infected dendritic cells and tested for recognition of HLA-A-matched melanoma targets. This allowed the analysis of T cell induction in association with any HLA-A allele of a given patient's phenotype. In this system, MART-1/Melan A could not efficiently immunize in association with HLA-A alleles other than A*0201, including the one residue variant from A*0201: HLA-A*0226. Clonal analysis of MART-1/Melan A-specific CTL confirmed that MART-1/Melan A immunodominance is strongly restricted to the AAGIGILTV/HLA-A*0201 combination. The stringent epitope/allele requirements for MART-1/Melan A/TCR interactions were not associated with limitations in the TCR repertoire. In conclusion, autologous induction of MART-1/Melan A CTL by whole Ag processing and presentation is restricted to a unique allele/ligand combination and is excluded by minimal changes in HLA structure. Thus, whole protein vaccination for small m.w. Ags may provide no further advantage over a peptide-based approach.     

Exoantigens from trypanosoma cruzi contain cruzipain

This paper shows that human antibodies specific for exoantigens of pI 4.5 (Eas 4.5), released by the blood forms of the parasite, obtained from chagasic patients sera by immunoabsorption react with cruzipain, the major cysteinyl proteinase of Trypanosoma cruzi. Sera from mice immunized with Eas 4.5 also recognize cruzipain. In addition, mouse antisera to cruzipain were reactive with Eas 4.5 as well as with total antigens excreted by culture-trypomastigotes. This reactivity was inhibited by cruzipain as revealed by enzyme-linked immunosorbent assay (ELISA). Furthermore, it was observed by immunoblot that the exoantigens recognized by mouse antisera to cruzipain have molecular weights between 50 and 60 kDa and human antibodies specific for Eas 4.5 recognize cruzipain with apparent molecular weight of 50 kDa. These findings suggest the presence of cruzipain in Eas and the subsequent release of this enzyme by the parasite.     

Role of adhesion molecule cytoplasmic domains in mediating interactions with the cytoskeleton

The past ten years have seen significant progress in cell biology research aimed at understanding how cytoskeletal filaments interact with the plasma membrane. Considerable evidence suggests that both actin microfilaments and intermediate filaments attach to the membrane via the cytoplasmic domains of various membrane proteins including adhesion molecules. Interactions between the cytoskeleton and adhesion molecules appear to be essential for a variety of cellular functions, including cell-cell and cell-extracellular matrix (ECM) interactions, cell motility, receptor-ligand interactions, and receptor internalization. Recently, many of the detailed molecular mechanisms which mediate the associations between actin filaments and adhesion molecules have been identified. Among adhesion molecules that support the attachment of cytoskeletal filaments to their cytoplasmic domains are members of the integrin and cadherin families, the intracellular adhesion molecule-1 (ICAM-1, an immunoglobulin family member), and the glycoprotein Ib/IX complex in platelets. A general conclusion emerging from these studies is that physical associations between cytoskeletal filaments and transmembrane glycoproteins do not occur directly between the filaments and the cytoplasmic tails of adhesion molecules. Instead, these interactions appear to be indirect and involve a complex ensemble of intermediary linker proteins. The severe effects of cytoplasmic domain deletion and mutagenesis on adhesion-dependent functions support the view that receptor cytoplasmic domains play a vital role in regulating receptor function and in mediating communication across the membrane. Transfection studies with mutant and chimeric adhesion molecules, along with protein-binding studies, are clarifying the mechanisms which physically link the cytoskeleton to transmembrane proteins, regulate cytoskeletal organization, mediate signaling across the cell membrane, and regulate the ligand specificity and binding affinity of surface receptors.     

Hemodynamic characteristics in hypertension

Recent studies have outlined both the importance and limitations of hemodynamic studies in hypertension. Characterization of any type of hypertension cannot be established in terms of cardiac output or total peripheral resistance alone. It depends more on the way in which various factors (hemodynamics, volume, humoral and neural) interrelate than on disturbances of one factor alone. More studies are needed, not so much of each variable alone as of correlations among those variables, e.g. correlations between humoral factors and hemodynamic characteristics. Further, hemodynamic analyses must be extended beyond calculations of TPR to evaluation of other variables such as magnitude and distribution of intravascular volume, indices of aortic distensibility, of velocity of ventricular ejection and of cardiac performance. Interpretation of the results must also take into account factors such as hemodynamic setting, age of patient, neurogenic stimulation and structural changes amongst others. Careful attention to these variables will allow more accurate conclusions regarding characteristics of different types of hypertension, and patterns of response to therapy. Accurate hemodynamic characterization may help orient diagnosis and a rational choice of treatment in initial stages but specially for evaluation of resistant cases.     

The state of several indices of non-specific immunity in rats with nephrotoxic glomerulonephritis

Changes in the interferon reaction of leukocytes, bactericidal property of the blood serum against the E. coli and streptococcus, the activity of beta-lysins in experimental nephrotoxic glomerulonephritis reproducible with the aid of heterogenous nephrotoxic serum in mongrel male rats were studied. This model permitted to trace the changes in the nonspecific protection mechanisms depending on the pathological process in the kidneys. In nephrotoxic glomerulonephritis the most pronounced changes were seen in the interferon reaction of leukocytes: it decreased up to 90% in comparison with the normal depending on the duration of the disease. In difference from this the changes in the anti-bacterial immunity indices were observed at the period of marked nephrotic process activity.     

Metabolites influence control of lysine transfer ribonucleic acid synthetase formation in Escherichia coli K-12

A mutant of E. coli K-12 has been isolated which has only 1-3% of the wild-type lysyl-tRNA synthetase activity [L-lysine:tRNA ligase (AMP forming), EC 6.1.1.6]. Additions of 20 mM L-alanine or 6 mM leucine dipeptides to the culture medium can restore the activity of lysyl-tRNA synthetase in the mutant strain to the wild-type level. Experiments on the in vivo charging of lysine tRNA in the mutant show that in the absence of the metabolites lysine tRNA is charged 15-23%. Upon the addition of 3 mM L-leucyl-L-alanine to the medium the lysyl tRNA synthetase activity increases 25-fold and the in vivo charging of lysine tRNA returns to the wild-type level. Experiments with antibody against lysyl-tRNA synthetase show that the stimulation of lysyl-tRNA synthetase activity by the metabolites is the result of new protein synthesis.