Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—A possible role of increased oxygen radicals generated by the neutrophils

Neutrophils from the synovial fluid (SFN) of 10 patients with active rheumatoid arthritis (RA) were investigated to determine the generation of oxygen intermediates (OI) (O2-, H2O2, OH .), chemiluminescence, and lysosomal enzymes (lysozyme and beta-glucuronidase). Lymphocytes from healthy individuals were cocultured at 37 degrees C for 17 hr with SFN from the patients and the number of OKT4+, OKT8+, and OKT3+ cells and the response to mitogens were determined. A markedly increased OI and slightly elevated lysosomal enzyme levels were observed in SFN from patients. Coculture of lymphocytes with SFN resulted in a decreased number of OKT4+ and OKT8+ cells and a greatly reduced response to Con A and mildly diminished response to PHA, while OKT3+ cells were not affected. The simultaneous addition of superoxide dismutase and catalase restored the impairment of monoclonal antibody reaction and lymphocyte responsiveness almost to control levels. It is suggested that the disturbed immunoreactivity of synovial fluid lymphocytes from RA patients may be due to increased OI generated by stimulated neutrophils.     

Effect of Azelastine Hydrochloride on Macrophage Chemotaxis and Phagocytosis in Vitro

Azelastine, a newly synthesized anti-allergic agent, was tested for its effects on guinea pig macrophage chemotaxis and phagocytosis. As specific macrophage chemo-attractants, we used macrophage chemotactic factors a and c; separated and highly purified from inflamed skin sites. Macrophage chemotaxis induced by skin extract or chemotactic factors was significantly suppressed by a low concentration of the agent (1 microgram/ml); the effect was dose-dependent. The inhibition of chemotaxis was reversible, because chemotactic activity was restored when the agents was removed by washing cells before chemotactic assay. Inactivation of chemotactic factors was not detected by mixing azelastine and factors a and c. Azelastine may directly interact with macrophages to decrease their chemotactic responsiveness. beta-Glucuronidase activity in the medium and macrophages after phagocytosis of polystyrene latex particles was not affected by this agent at concentrations ranging from 1 to 10 micrograms/ml. The phagocytosis of latex particles or sheep red blood cells opsonized with IgG antibodies (EA) and anchoring of macrophages to substrate were not inhibited and azelastine did not damage the macrophages as determined by lactate dehydrogenase (LDH) release assay.     

REACTIVITY OF LYMPHOCYTE SUBPOPULATIONS IN HUMAN MIXED LYMPHOCYTE CULTURE

Loss of antigenicity in the mixed lymphocyte culture (MLC) reaction of lymphocytes precultured at 22°C for 7–10 days was accompanied by a decrease in bone-marrow-derived lymphocytes (B cells) from 22 ± 1% to 13 ± 1%, and an increase in thymus-derived lymphocytes (T cells) from 65 ± 2% to 83 ± 1% (P < 0.001). Depletion of B cells from a fresh lymphocyte suspension by either antihuman immunoglobulin-coated column fractionation or by sheep red blood cell (SRBC) rosette formation resulted in a significant reduction of the cell's ability to stimulate in MLC (P < 0.001). Coating of lymphocytes with rabbit antihuman brain serum abrogated their ability to respond but not the ability to stimulate in MLC.     

Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture

Sodium arsenite and sodium arsenate were observed to inducemorphological transformation of Syrian hamster embryo cellsin a dose-dependent manner. A linear dose-dependence with aslope of 1 was observed with both compounds when the data wereplotted on a log-log graph. The trivalent sodium arsenite was> 10-fold more potent than the pentavalent sodium arsenate.The compounds also exhibited toxicity; however, transformationwas observed at non-toxic as well as toxic doses. At low doses,enhanced colony-forming efficiency of the cells was observed.To understand the mechanism of arsenic-induced transformation,the genetic effects of the two arsenicals were examined overthe same doses that induced transformation. No arsenic-inducedgene mutations were detected at two genetic loci. However, celltransformation and cytogenetic effects, including endoreduplication,chromosome aberrations, and sister chromatid exchanges wereinduced by the arsenicals with similar dose-responses. Theseresults support a possible role for chromosomal changes in arsenic-inducedtransformation.     

Persistent effect of a low dose of preadministered diethylnitrosamine on the induction of enzyme-altered foci in rat liver

The effect of a low dose of preadministered diethylnitrosamine(DEN) on the induction of enzyme-altered foci in the liversof male full-grown Fischer 344 rats was studied. As a pretreatment,DEN at a dose of 10 mg/kg body wt was injected i.p. At varioustimes after DEN pretreatment a complete initiation, consistingof administration of the same dose of DEN by the same routein rats subjected to partial hepatectomy (PH), was performed,followed by application of selection pressure. Enzyme-alteredfoci stained with -glutamyltrans-peptidase (-GTP) and glutathioneS-transferase placental form (GST-P) were then assayed. Decreasesin the numbers and areas of foci in the rats which receivedsaline + PH 14 or 28 days after DEN pretreatment were observedin comparison with rats which received saline + PH immediatelyafter DEN. On the other hand, the numbers and areas of fociwere not decreased in rats which received the complete initiation,consisting of DEN + PH, at various times after DEN pretreatmentwhen compared with rats which received these at the same timeas the DEN pretreatment. This persistent effect of DEN pretreatmenton the complete initiation lasted up to 182 days after the timeof DEN pretreatment. In this experiment, GST-P was found tobe a more sensitive marker for the detection of putative preneoplasticliver-cell foci than -GTP.     

Abdominal angiography is associated with reduced in-hospital mortality among pediatric patients with blunt splenic and hepatic injury: A propensity-score-matching study from the national trauma registry in Japan

PurposeThe aim of this study was to assess the association between the implementation of abdominal angiography and outcome among pediatric patients with blunt splenic or hepatic injury.MethodsThis was a retrospective observational study, with a study period of 14 years, from January 2004 to December 2017. Blunt-trauma patients with splenic or hepatic injury who were less than 19 years old were included in this study. We used propensity-score-(PS) matching analysis to assess the relationship between abdominal angiography and in-hospital mortality.ResultsIn total, 639 patients were eligible for analysis, with 257 patients included in the abdominal-angiography group and 382 patients in the no-abdominal-angiography group. After PS matching, 224 patients from each group were selected. In the PS matched patients, in-hospital mortality was lower in the abdominal-angiography group than in the no-abdominal-angiography group (4.9% vs. 11.2%, odds ratio 0.416, 95% confidence interval 0.177–0.903).ConclusionIn this population, the implementation of abdominal angiography was significantly associated with lower in-hospital mortality among pediatric patients with blunt splenic or hepatic injury compared with nonimplementation of abdominal angiography.Type of studyPrognosis study.Level of evidenceIII     

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II,randomized, double-blind,placebo-controlled clinical study

Clinical and Experimental Nephrology - The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be...     

Recombinant Sendai viruses with L1618V mutation in their L polymerase protein establish persistent infection, but not temperature sensitivity

The Sendai virus pi strain (SeVpi) isolated from cells persistently infected with SeV shows mainly two phenotypes: (1) temperature sensitivity and (2) an ability of establishing persistent infection (steady state). Three amino acid substitutions are found in the Lpi protein and are located at aa 1088, 1618, and 1664. Recombinant SeV(Lpi) (rSeV(Lpi)) having all these substitutions is temperature sensitive and is capable of establishing persistent infection (steady state). rSeVs carrying the fragment containing L1618V show both phenotypes. rSeV(L1618V), in which leucine at aa 1618 is replaced with valine, has the ability of establishing persistent infection, but is not a temperature-sensitive mutant, indicating that the ability of a virus to establish persistent infection can be separated from temperature sensitivity. The amino acid change at 1618(L-->V) coexisting with aa 1169 threonine is required for acquirement of a temperature-sensitive phenotype. Three amino acid substitutions are also found in the Ppi protein, but rSeV(Ppi) does not show these phenotypes.     

Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts

Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4°C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511±216 vs 417±333 g/dl and 114.1±12.2 vs 91.4±12.2 mg/dl, respectively; P<0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.