Cardiac function predicts mortality following thoracoabdominal and descending thoracic aortic aneurysm repair.

OBJECTIVE: Previous studies have identified age, renal failure and aneurysm extent as predictors of mortality following thoracoabdominal and descending thoracic aortic aneurysm (TAA) repair. We studied the impact of coronary artery disease (CAD) and cardiac function on 30-day mortality following TAA repair. METHODS: Between February 1991 and May 2001, we performed 854 TAA repairs. Two hundred ninety-one patients (34%) had a history of coronary artery disease. One hundred forty-one/291 (49%) had undergone coronary artery bypass surgery (CAB) prior to TAA repair. We conducted multivariable analyses of known risk factors along with the left ventricular ejection fraction (EF) and prior CAB to determine the adjusted effect of CAD on outcome. RESULTS: Mortality in patients with CAD was 54/291 (18%) compared to 75/563 (13%) without CAD (P<0.05). In patients who had prior CAB, mortality was 31/141 (22%) compared to 98/713 (14%) patients without prior CAB, (P<0.02). In multivariable analysis, the effects of CAD and CAB on mortality were eliminated by consideration of a low EF (defined as less than 50%). CONCLUSION: Impaired left ventricular function appears to be the strongest cardiac predictor of mortality for TAA repair, independent of the presence of coronary artery disease or coronary artery bypass revascularization.     

Multiple unit activity study of brain stem and limbic structures during environmental habituation and circadian rhythm

Multiple unit activity (MUA) of brain stem, hypothalamic and limbic structures was studied during habituation to a novel environment and circadian rhythm in chronically implanted freely moving rats. MUA was analysed in the mesencephalic reticular formation (MRF), area hypothalami posterior (PH), basal nuclear group of amygdala (AMY), area septalis (SEPT), dorsal hippocampus (HIPP) and area hypothalami anterior (AH). It was found that in the novel environment MUA of all subcortical structures increased to a high level. During habituation MUA in each phase of wakefulness--sleep cycle decreased to stable low level both in brain stem and forebrain structures. Gradual decrease in MUA was characteristic to MRF, and a sharp decrease occured in AH and AMY. The environmental habituation proved to be a long lasting process in rat. During all phases of wakefulness--sleep cycle activity was significantly higher in the light period than in the dark, and MUA base level showed circadian variation both in brainstem and limbic structures. Close correlation was found between the actual MUA level and responsiveness to various sensory modalities both during habituation and circadian rhythm. The higher the MUA level, the higher the responsiveness, and a fall in activity was accompanied by decreased neuronal responsiveness.     

Comparison of antibody repertoires against Staphylococcus aureus in healthy individuals and in acutely infected patients

The management of staphylococcal diseases is increasingly difficult with present medical approaches. Preventive and therapeutic vaccination is considered to be a promising alternative; however, little is known about immune correlates of protection and disease susceptibility. To better understand the immune recognition of Staphylococcus aureus by the human host, we studied the antistaphylococcal humoral responses in healthy people in comparison to those of patients with invasive diseases. In a series of enzyme-linked immunosorbent assay analyses performed using 19 recombinant staphylococcal cell surface and secreted proteins, we measured a wide range of antibody levels, finding a pronounced heterogeneity among individuals in both donor groups. The analysis revealed marked differences in the antibody repertoires of healthy individuals with or without S. aureus carriage, as well as in those of patients in the acute phase of infection. Most importantly, we identified antigenic proteins for which specific antibodies were missing or underrepresented in infected patients. In contrast to the well-described transient nature of disease-induced antistaphylococcal immune response, it was demonstrated that high-titer antistaphylococcal antibodies are stable for years in healthy individuals. In addition, we provide evidence obtained on the basis of opsonophagocytic and neutralizing activity in vitro assays that circulating antistaphylococcal serum antibodies in healthy donors are functional. In light of these data we suggest that proper serological analysis comparing the preexisting antibody repertoires of hospitalized patients with different outcomes for nosocomial staphylococcal infections could be extremely useful for the evaluation of candidate vaccine antigens in addition to protection data generated with animal models.     

Activation of MAP kinases,pp90rsk and pp70-S6 kinases in mouse mast cells by signaling through the c-kit receptor tyrosine kinase or FcϵRI: rapamycin inhibits activation of pp70-S6 kinase and proliferation in mouse mast cells

The high-affinity receptor for IgE, Fc_?RI, represents the major cell surface structure through which mast cells express immunologically specific secretory function. By contrast, the stem cell factor receptor (SCFR), which is encoded by c-kit, is essential for normal mast cell development. The signaling pathways initiated by the stimulation of mast cells through the Fc_?RI, which lacks intrinsic kinase activity, and the SCFR, a member of the receptor tyrosine kinase family, generally have been regarded to be distinct. We report here that mouse mast cells stimulated either with SCF or with IgE and specific antigen exhibit a remarkably similar pattern of activation of mitogen-activated protein kinases (MAPK), 90 kDa-S6 kinases (pp90^rsk), and pp70-S6 kinases (pp70-S6K). These results indicate that all three families of protein kinases are associated with the cell surface receptor-dependent activation of secretion, as well as proliferation, in mast cells. We also show that the immunosuppressant rapamycin, but not FK506, can inhibit both SCF-dependent pp70-S6 kinase activation and SCF-dependent proliferation in mouse mast cells, without suppressing IgE- and antigen-dependent mediator release. These findings suggest that the activation of pp70-S6 kinase represents an important link in the stimulation of cell proliferation by SCF. Our results also indicate that the intracellular signaling pathways initiated by stimulation of mast cells through the Fc_?RI or the SCFR exhibit more overlap than has previously been appreciated.     

Physicochemical model of alginate-poly-L-lysine microcapsules defined at the micrometric/nanometric scale using ATR-FTIR, XPS, and ToF-SIMS

Alginate-poly-L-lysine-alginate (APA) microcapsules are currently being investigated as a means to immuno-isolate transplanted cells, but their biocompatibility is limited. In this study, we verified the hypothesis that poly-L-lysine (PLL), which is immunogenic when unbound, is exposed at the APA microcapsule surface. To do so, we analysed the microcapsule membrane at the micrometric/nanometric scale using attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry. The results indicate that PLL and alginate molecules interact within the membrane. PLL exists in considerable amounts near the surface, contributing to the majority of the carbon within the outermost 100 Angstroms of the membrane. PLL was also detected at the true surface (the outermost monolayer) of the microcapsules. The exposure of PLL does not appear to result from defects in the outer alginate coating. This physicochemical model of APA microcapsules could explain their immunogenicity and will play an important role in the optimization of the microcapsule design.     

Induction of protective immunity to monoclonal-antibody-defined Plasmodium falciparum antigens requires strong adjuvant in Aotus monkeys.

Monoclonal antibodies to the major Plasmodium falciparum merozoite surface coat and rhoptry antigens were produced. A combination of the affinity-purified polypeptides with Freund complete adjuvant which was given three times completely protected an Aotus lemurinus azure (karotype VI) monkey against homologous challenge; however, immunization with the same polypeptides with a muramyl dipeptide derivative [MDP-Lys(L18)] did not protect a second Aotus monkey, even though comparable high antibody titers were induced.     

Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 163–167, August, 2000     

T-lymphocyte activation in IgA nephropathy: Serum-soluble interleukin 2 receptor level,interleukin 2 production,and interleukin 2 receptor expression by cultured lymphocytes

The present study was undertaken to examine the T-lymphocyte activation in IgA nephropathy. Serum-soluble interleukin 2 receptor (sIL2R) levels were studied in 29 IgA nephritic patients, 17 patients with chronic glomerulonephritis (non-IgA nephropathy), and 30 healthy controls during an infection-free period. No difference in serum sIL2R level was demonstrated among these three groups of subjects. However, the serum sIL2R levels of IgA nephritic patient rose significantly during clinical exacerbation with synpharyngitic macroscopic hematuria and the serum sIL2R levels fell when hematuria subsided. Mitogen-stimulated cellular interleukin 2 receptor (IL2R) expression, sIL2R release, and interleukin 2 (IL2) production were also examined in peripheral blood mononuclear cells (PBMC) cultured for 24–48 hr in 21 patients with IgA nephropathy, 17 patients with chronic glomerulonephritides, and 17 healthy controls. The total cellular IL2R expression and sIL2R release did not differ among these three groups of subjects. However, the individual T-cell subsets bearing IL2R were distinctly different between IgA nephritic patients and the other two groups of controls. IgA nephritic patients had increased activated CD4+ lymphocytes and reduced activated CD8+ lymphocytes. Furthermore, IL2 production in response to phytohemagglutinin and pokeweed mitogen stimulation was increased in lymphocytes from patients with IgA nephropathy. The IL2 production did not correlate with the quantities of cellular and sIL2R yet the cellular IL2R expression paralleled the sIL2R released by cultured lymphocytes. Our present study suggests that the T lymphocytes from patients with IgA nephropathy have a defect in overproduction of IL2 and increased activated T helper-cell subset upon mitogenic stimulation. Serum measurement of sIL2R could potentially be useful in monitoring the disease activity.     

Concurrent and consecutive infection and immunisation with yellow fever and UGMP-359 viruses

Concurrent and consecutive infection and immunisation with yellow fever virus and UGMP-359 virus was investigated in mice, using identical doses of both viruses. In double infection it was shown that both viruses could multiply independently of one another, when both were inoculated simultaneously by the intracerebral route. On the other hand, there was mutual exclusion between them when the inoculation of one antedated the other, by the same intracerebral route. Both viruses multiplied to similar titres, in single infection, in the target organ (brain). By the intraperitoneal route, the outcome was influenced byhe relative sensitivity of this route of inoculation to support and sustain the replication of either virus. Thus, because yellow fever virus replicated more than UGMP-359 after intraperitoneal inoculation, the latter is always excluded, even when the inoculation ofUGMP-359 preceded that of yellow fever. In the double immunization studies it was shown that comparative specific antibody titres to both viruses were obtained either when both viruses, as immunogens, were given simultaneously, or when the inoculation of one was alternated, at weekly intervals, with the other.