Cytotoxicity in vitro of preleukaemic lymphoid cells on syngeneic monolayers of embryo or thymus cells

Lymphoid cells from preleukaemic AKR mice were cytotoxic for monolayers of syngeneic embryo and thymus target cells in tissue culture. This reactivity was detectable with cells from mice aged 3–36 weeks but was not present with cells from younger mice. Cytotoxic reactions to syngeneic embryo tissues were also seen with lymphoid cells from high leukaemia strain C3H mice carrying Moloney virus but not with lymphoid cells from normal low leukaemic strain C3H/Bi or DBA/2 mice. Lymphoid or lymphoma cells from leukaemic AKR mice showed reduced reactivity. Phytohaemagglutinin was not necessary for the reaction of preleukaemic AKR cells against AKR monolayers and cytotoxicity was inhibited by preincubation of target cells with an antiserum directed against AKR G+ cells.

The reactivity of preleukaemic AKR and C3H lymphoid cells against syngeneic monolayers may represent some type of allogeneic inhibition due to acquired antigenic differences between aggressor and target cell but the data fit best an interpretation that some lymphoid cells in preleukaemic AKR and C3H mice acquire immunological reactivity to virus-induced G+ or M+ antigens exhibited by the target cells.

     

Granulocyte Stimulating Factor in Patients on Peritoneal Dialysis and LPS Stimulated Peripheral Blood Mononuclear Cells

Dialysate and serum levels of granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF) and leukemia inhibitory factor (LIF) were analyzed in patients with continuous ambulatory peritoneal dialysis (CAPD). Samples from the peritoneal effluent and from serum were obtained during the first months of dialysis and during peritonitis from the first three dialysate bags drained on the day of admittance and from nightbags on days three and ten. Serum samples were drawn on days one and ten. On the first day of infection G-CSF was detected in twelve out of fifteen samples in the dialysate and reached its peak median level, 443 pg/ml, in the first drained bag and thereafter decreased significantly. Also in serum a peak, 190 pg/ml, was observed on the first day. LIF was found in six of ten analyzed dialysate samples, with a peak median level of 77 pg/ml on day one, while only four of ten patients had detectable GM-CSF. Peripheral blood mononuclear cells from non-infected CAPD patients were stimulated with lipopolysacharide and G-CSF levels in the supernatants increased significantly (P < 0.05) after 6 h stimulation. We conclude that G-CSF is produced locally in the dialysate during the acute stage of peritonitis and to a lesser extent also systemically. These findings are in line with G-CSF production after LPS stimulation of peripheral blood mononuclear cells.     

Inhibitory Effect of Glucocorticosteroids on Anti-IgE-Induced Histamine Release from Human Basophilic Leukocytes: Evidence for a Dual Mechanism of Action

Anti-IgE-induced histamine release from human leukocytes is inhibited when the cells before challenge are cultured overnight in the presence of glucocorticoids (GCSs). The present report suggests that the GCSs might exert their effect by at least a dual mechanism of action. Histamine release was induced by a suboptimum concentration of anti-IgE. When the release recorded in the presence of the steroid is plotted against the release recorded in its absence, the data points of several experiments fit a regression line characterized by two parameters: its slope and its intercept with the abscissa. Structure-activity examination with selected GCSs indicates that the orders of potency for affecting these two parameters are not identical. Furthermore, pulse experiments suggest that the cells require different times of contact with the steroid to express inhibition according to the two parameters. The removal of adherent cells or platelets did not markedly affect the degree of leukocyte histamine release or its inhibition by a given GCS, suggesting that the steroid interacts directly with the basophil. Finally, steroid-induced inhibition was not affected by the putative phospholipase A2-inhibitor p-bromophenacylbromide (BPB) or the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA).     

Differential expression of human granzymes A, B, and K in natural killer cells and during CD8+ T cell differentiation in peripheral blood

NK cells and cytotoxic T lymphocytes can induce apoptosis in virus-infected and transformed target cells via the granule exocytosis pathway. The key components of the cytolytic granules are perforin and several serine esterases, termed granzymes. While the cellular distribution of human granzymes A (GrA) and B (GrB) has been well characterized much less is known about the expression pattern of human granzyme K (GrK). In this study GrA, GrB, and GrK expression was analyzed in human peripheral blood lymphocytes using flow cytometry. There was a distinct population of GrK expressing CD8+ T cells with a CD27+/CD28+/CCR5high/CCR7-/perforin-/low/IFN-gamma+ memory-like phenotype, while all CD56bright NK cells were also positive for GrK. In addition, GrK was also expressed in subpopulations of CD56+ T cells, CD4+ T cells, and TCRgammadelta+ T cells. In contrast, GrB was primarily expressed in CD56dim NK cells and differentiated memory CD8+ T cells with the CD27-/low/CD28-/low/CCR5-/low/CCR7-/CD11b+/perforinhigh phenotype. Only few CD8+ T cells expressed both GrB and GrK. GrA was found to be co-expressed in all GrB- and GrK-expressing T cells. Our findings suggest that granzyme expression during the differentiation process of memory CD8+ T cells might be as follows: GrA+/GrB-/GrK+ --> GrA+/GrB+/GrK+ --> GrA+/GrB+/GrK-.     

Acculturation,Discrimination and 24-h Activity in Asian American Immigrant Women

Asian American immigrant (AAI) women may have suboptimal 24-h activity patterns due to traditional gender role and caregiving responsibilities. However, little is known about their objectively-measured activity. We measured AAI women’s 24-h activity patterns using accelerometry and examined cultural correlates of time in sedentary behavior (SB), light intensity physical activity (LIPA), moderate-to-vigorous physical activity (MVPA) and sleep. Seventy-five AAI women completed surveys on acculturation (years of U.S. residency and English proficiency), discrimination, and sleep quality, and 7 days of wrist- and hip-accelerometer monitoring. Linear regression was conducted controlling for age, BMI, and education. We also compared activity patterns across Asian subgroups (East, Southeast, South Asians). On average, AAI women had 33 min of MVPA, 6.1 h of LIPA, 10 h of SB, and 5.3 h of sleep per day. South Asian women had the longest SB and the shortest sleep and MVPA hours. English proficiency was negatively related to MVPA (p?=?0.03) and LIPA (p?<?0.01). Years of U.S. residency was positively related to SB (p?=?0.07). Discrimination was related to shorter (p?=?0.03) and poorer quality sleep (p?=?0.06). Culturally-tailored programs targeting SB and sleep and integrating coping strategies against discrimination could help optimize AAI women’s 24-h activity patterns.

     

Efficacy of vaccination with StroVac for recurrent urinary tract infections in women: a comparative single-centre study

International Urology and Nephrology - To assess the efficacy of prophylaxis for urinary tract infections (UTI) in a two-year follow-up in women with StroVac compared to a therapy with...     

TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.     

Lymphocytes infiltrating the CNS during inflammation display a distinctive phenotype and bind to VCAM-1 but not to MAdCAM-1

The nature of inflammatory lymphocytes recruited to the CNShas been studied in a model of chronic inflammation. Injectionof killed Corynebacterlum parvum into the cortex of the mousebrain produces a circumscribed inflammatory cellular infiltratearound the injection site, and recruited mononuclear inflammatorycells (IC) can be isolated for flow cytometric analysis. Themajority of IC were T cells. In comparison with the predominantnaive population of mesenteric lymph node T cells, IC T cellsexpress much higher levels of CD44, LFA-1 and ICAM-1, and lowerlevels of CD45RB, features commonly associated with memory (previouslyactivated) cells. In addition, in contrast to the L-selectin⁺6-integrin^low phenotype of naive lymph node T cells, IC T cellslacked L-selectin and were 6-integrin^–. Mac-1, recentlyproposed as another marker of memory T cell differentation,was not displayed by IC T cells, suggesting that Mac-1 expressionmay be heterogeneous among memory T cell subsets. A subset ofmesenteric lymph node (MLN) T cells, probably representing activatedT cells undergoing the naive to memory transition, but not ofIC T cells, expressed high levels of 6-, ß7- and E-integrin.IC and MLN naive T cells expressed comparable levels of 4-integrin,but IC T cells stain poorly with anti-ß7 mAbs andwith mAb DATK 32, specific for the 4ß7 heterodimericlymphocyte homing receptor for the mucosal addressin MAdCAM-1,suggesting that these inflammatory cells express more 4ß1than 4ß7. Consistent with this, in in vitro adhesionassays, brain IC bound better than MLN cells to the 4ß1integrin ligand VCAM-1 and the LFA-1 ligand ICAM-1 but adheredvery poorly to the 4ß7 ligand MAdCAM-1. These findingsare consistent with and extend previous immunohistological studiesof T cells in murine experimental autoimmune encephalomyelitis,and demonstrate a distinctive phenotype for lymphocytes beingpresent in the chronically inflamed brain.