Therapeutic evaluation of interleukin-1 for stimulation of hematopoiesis in primates after autologous bone marrow transplantation

A multiple dose IL-1 therapy was evaluated for its capability to stimulate hematopoiesis in normal primates and to restore hematopoiesis after autologous bone marrow transplantation. The administration of IL-1 to normal animals over a dose range of 0.5 to 10 ug/kg/d led to a 7-12 fold increase in peripheral blood neutrophil and monocyte counts after 24 hours. This increase in the mature peripheral blood myeloid cells was followed by changes in the myeloid composition of the bone marrow, where the percentage of myeloid elements increased along with a transient increase in myeloid progenitor cell activity. IL-1 treatment also led to an initial decrease in platelet counts of 10-30% during the first 3 days of treatment. However, a striking finding was a significant and long lasting stimulation of increased platelet production with platelet counts increasing to 77% of baseline 3 days after cessation of treatment and remaining elevated for the next 10 days. The therapeutic potential of the IL-1 regimen to restore hematopoiesis was further evaluated in an established autologous bone marrow transplantation model. In monkeys receiving IL-1 doses, 1.0 and 5.0 ug/kg/d, neutrophil counts recovered to >0.5 x 10e9/1 on day 16, one day earlier than control, but the recovery to baseline neutrophil counts occurred 5 days sooner than control. IL-1 therapy had its greatest effect on the restoration of platelet counts after transplantation, reaching >100 x 10e9/l by day 21, two weeks earlier than control. This work demonstrates that IL-1 therapy stimulates myelopoiesis but its most promising clinical application is the stimulation of platelet production.Views presented in this paper are those of the authors: no endorsement by the Department of the Navy or the Defense Nuclear Agency has been given or should be inferred. This work was supported by the Naval Medical Research and Development Command, Research Task No. 63706N MM095.003.1007 and the Defense Nuclear Agency Work Unit No. 132082.     

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death

Background

The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail.

First report of L1014F kdr mutation in Culex quinquefasciatus in Mexico

The L1014F mutation in the voltage‐sodium channel gene has been associated with resistance to DDT and pyrethroids in various arthropod species including mosquitoes. We determined the frequency of the L1014F kdr mutation in 16 field populations of Culex quinquefasciatus from Northeastern Mexico collected between 2008 and 2013. The L1014F was present in all populations analyzed with the lowest frequency (3.33%) corresponding to the population from Monclova collected in 2012, and the highest frequency (63.63%) from the Monterrey population collected in 2012. The presence of a kdr mutation in populations of Cx. quinquefasciatus from northeastern Mexico provides evidence of pyrethroid resistance. This requires a special attention, considering that pyrethroid‐based insecticides are commonly used in vector‐control campaigns, especially against Aedes aegypti (L.).     

Studies on the differentiation of egg envelopes. I. The starfish, Astropecten aurantiacus

We have studied the differentiation of the oocyte vitelline coat (VC) and jelly coat (JC) of the starfish, Astropecten aurantiacus. The precursor material of both envelopes is secreted by the oocyte while the follicle cells do not appear to participate in the secretory process. The first indication of differentiation of the VC is the deposition of a fine fibrillar material between the microvilli which emerge from the oocyte surface. External to this, a more loosely organized material becomes the precursor of the JC. At this time both layers are periodic acid-Schiff (PAS)-positive. In a later stage, the material between the microvilli acquires a more compact organization, looses its PAS-positivity while acquiring fucose binding protein (FBP) affinity. On the contrary, the JC remains PAS-positive and FBP-negative. In the full grown oocytes the VC is made up of densely packed fibrils oriented tangentially to the oocyte surface and is tightly bound to the microvilli. The observations are discussed in connection with the problem of the role of the egg envelopes in sperm-egg recognition and in the induction of the acrosome reaction.     

Sulle capacità di sviluppo della placca midollare in condizioni di espianto

Zusammenfassung Durch Anwendung der Explantationsmethode vonMangold wird der Rumpfschwanzteil der Medullarplatte in vitro explantiert, um die Evolutionsfähigkeiten der isolierten Medullaranlage und die Entwicklungskorrelationen zwischen dem Chorda-Mesodermkomplex und der Morphohistogenese des Rückenmarks zu studieren.Es wird vor allem festgestellt, daß der Neuralstrang, der sich aus der explantierten Neuralplatte bildet, auch ohne Mitwirkung der Chorda oder irgendeines Stützorgans verlängerungsfähig ist.Von großer Bedeutung für die Morphohistogenese des Neuralstranges scheint die Chorda zu sein, und gewissermaßen auch das Mesoderm.Fehlt das Mesoderm, so schmelzen die Ganglien zu einer einzigen Masse zusammen, ventral zum Neuralstrang; die Struktur des Neuralstranges erleidet aber dadurch keine Veränderung.Fehlt die Chorda dagegen, so treten sehr wichtige Veränderungen im Neuralstrang ein, d. h. übermäßige große der Neuralröhre oder mehrfache Röhrenbildung, Zerstörung der Zellen- und Fasernanordnung, Neuroblastenabsonderung aus dem Rumpfteil des Neuralstranges.Wenn aber, auch bei fehlender Chorda, der Neuralstrang von Mesodermmassen begleitet wird, ist seine Struktur viel regelmäßiger.Es scheint also, daß das Mesoderm, außer die Wirkung auf die Zerteilung der Ganglienanlagen, auch gewissermaßen die ausgebliebene Wirkung der Chorda ersetzen kann.     

Nematospiroides dubius: passive transfer of protective immunity to mice with monoclonal antibodies

Nine hybridoma cell lines secreting monoclonal antibodies specific for Nematospiroides dubius were produced by fusion of the mouse myeloma cell line NS-1 to either spleen cells or mesenteric lymph node cells from mice repeatedly infected with N. dubius. Seven of the antibodies were identified as IgM and two as IgG1. Each monoclonal antibody bound to polypeptide epitopes on both infective larvae (L3) and adult worms. However, five antibodies bound preferentially to L3 and three to adult worms. All nine antibodies reacted with high molecular weight protein antigens. Passive protective immunity in Balb/c mice was demonstrated with monoclonal antibodies Nd2 and Nd3 in ascites fluid which stunted both male and female worms and reduced parasite fecundity.     

Entamoeba histolytica: Differential gene expression during programmed cell death and identification of early pro- and anti-apoptotic signals

We have demonstrated that programmed cell death (PCD) in Entamoeba histolytica is induced in vitro by G418 aminoglycoside antibiotic. To ascertain if biochemical and morphological changes previously observed are paired to molecular changes that reflect a genetic program, we looked here for early differential gene expression during the induction of PCD.Using cDNA-amplified fragment length polymorphisms (AFLPs) and in silico derived analysis we showed in E. histolytica a differential gene expression during PCD induced by G418. The genes identified encoded for proteins homologous to Glutaminyl-tRNA synthase, Ribosomal Subunit Proteins 40S and 18S, Saposin-like, Silent Information Regulator-2 (Sir-2), and Grainins 1 and 2. Using real-time quantitative PCR (RT Q-PCR), we found that glutaminyl-tRNA synthetase, sir-2, grainins and saposin-like genes were strongly overexpressed after 30 min of PCD induction, while its expression dramatically decreased up to 60 min. On the other hand, overexpression of ribosomal genes increased only 7-fold of basal expression, showing a progressive down-regulation up to 90 min. glutaminyl-tRNA synthetase, sir-2 and grainins could act as negative regulators of PCD, trying to control the biochemical changes related to PCD activation. Overexpression of saposin-like gene could act as up-regulator of some cell death pathways. Our results give evidence of the first genes identified during the early stage of PCD in E. histolytica that could be implicated in regulation of apoptotic pathways.