The Experts below are selected from a list of 765 Experts worldwide ranked by ideXlab platform

Alan W Flake - One of the best experts on this subject based on the ideXlab platform.

  • complete allogeneic hematopoietic chimerism achieved by in utero hematopoietic cell transplantation and cotransplantation of llme treated mhc sensitized donor lymphocytes
    Experimental Hematology, 2004
    Co-Authors: Satoshi Hayashi, Michael H Hsieh, William H Peranteau, Shuichi Ashizuka, Alan W Flake
    Abstract:

    Abstract Objective In utero hematopoietic cell transplantation (IUHCT) typically achieves low-level mixed hematopoietic chimerism. However, the goal of IUHCT is to achieve therapeutic levels of chimerism. We hypothesized that prenatal adoptive immunotherapy might achieve high-level donor chimerism after IUHCT. Materials and methods BALB/CE15 fetal mice were transplanted with a mixture of C57BL/6 (B6) T-cell–depleted bone marrow (TCD BM) cells and splenocytes from B6 mice presensitized to BALB/C alloantigen. The splenocytes were preincubated in L-leucyl-L-Leucine Methyl Ester (LLME), to minimize graft vs host disease (GVHD). Recipients were followed after birth for donor cell chimerism and GVHD. Results Full donor hematopoietic chimerism following a single prenatal transplant was achieved in seven transplanted animals. Fully chimeric animals were healthy, without evidence of GVHD, and maintained their engraftment for the duration of the study (48 weeks). However, the addition of presensitized LLME-treated cells decreased survival until weaning relative to TCD BM alone, suggesting that some animals were lost to acute GVHD. Surviving chimeric animals demonstrated increased frequencies of T-regulatory cell populations in their spleen and BM, suggesting that they had successfully suppressed GVHD, allowing survival. Conclusions This study represents “proof in principle” that prenatal immunotherapeutic strategies may achieve complete hematopoietic engraftment across full MHC barriers when combined with IUHCT. However, strategies with greater hematopoietic specificity must be developed prior to consideration of clinical application.

Satoshi Hayashi - One of the best experts on this subject based on the ideXlab platform.

  • complete allogeneic hematopoietic chimerism achieved by in utero hematopoietic cell transplantation and cotransplantation of llme treated mhc sensitized donor lymphocytes
    Experimental Hematology, 2004
    Co-Authors: Satoshi Hayashi, Michael H Hsieh, William H Peranteau, Shuichi Ashizuka, Alan W Flake
    Abstract:

    Abstract Objective In utero hematopoietic cell transplantation (IUHCT) typically achieves low-level mixed hematopoietic chimerism. However, the goal of IUHCT is to achieve therapeutic levels of chimerism. We hypothesized that prenatal adoptive immunotherapy might achieve high-level donor chimerism after IUHCT. Materials and methods BALB/CE15 fetal mice were transplanted with a mixture of C57BL/6 (B6) T-cell–depleted bone marrow (TCD BM) cells and splenocytes from B6 mice presensitized to BALB/C alloantigen. The splenocytes were preincubated in L-leucyl-L-Leucine Methyl Ester (LLME), to minimize graft vs host disease (GVHD). Recipients were followed after birth for donor cell chimerism and GVHD. Results Full donor hematopoietic chimerism following a single prenatal transplant was achieved in seven transplanted animals. Fully chimeric animals were healthy, without evidence of GVHD, and maintained their engraftment for the duration of the study (48 weeks). However, the addition of presensitized LLME-treated cells decreased survival until weaning relative to TCD BM alone, suggesting that some animals were lost to acute GVHD. Surviving chimeric animals demonstrated increased frequencies of T-regulatory cell populations in their spleen and BM, suggesting that they had successfully suppressed GVHD, allowing survival. Conclusions This study represents “proof in principle” that prenatal immunotherapeutic strategies may achieve complete hematopoietic engraftment across full MHC barriers when combined with IUHCT. However, strategies with greater hematopoietic specificity must be developed prior to consideration of clinical application.

Gareth Griffiths - One of the best experts on this subject based on the ideXlab platform.

  • l leucyl l Leucine Methyl Ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes
    Journal of Cell Science, 2017
    Co-Authors: Urska Repnik, Marita Borg Distefano, Martin Speth, Cinzia Progida, Bernard Hoflack, Jean Gruenberg, Gareth Griffiths
    Abstract:

    L-leucyl-L-Leucine Methyl Ester (LLOMe) induces apoptosis, which is thought to be mediated by release of lysosomal cysteine cathepsins from permeabilized lysosomes into the cytosol. Here, we demonstrated in HeLa cells that apoptotic as well as sub-apoptotic concentrations of LLOMe caused rapid and complete lysosomal membrane permeabilization (LMP), as evidenced by loss of the proton gradient and release into the cytosol of internalized lysosomal markers below a relative molecular mass of 10,000. However, there was no evidence for the release of cysteine cathepsins B and L into the cytosol; rather they remained within lysosomes, where they were rapidly inactivated and degraded. LLOMe-induced adverse effects, including LMP, loss of cysteine cathepsin activity, caspase activation and cell death could be reduced by inhibition of cathepsin C, but not by inhibiting cathepsins B and L. When incubated with sub-apoptotic LLOMe concentrations, lysosomes transiently lost protons but annealed and re-acidified within hours. Full lysosomal function required new protein synthesis of cysteine cathepsins and other hydrolyses. Our data argue against the release of lysosomal enzymes into the cytosol and their proposed proteolytic signaling during LLOMe-induced apoptosis.

Thomas Reinheckel - One of the best experts on this subject based on the ideXlab platform.

  • intracellular cathepsin c levels determine sensitivity of cells to leucyl Leucine Methyl Ester triggered apoptosis
    FEBS Journal, 2020
    Co-Authors: Nežka Kavcic, Miha Butinar, Barbara Sobotic, Marusa Hafner Cesen, Ana Petelin, Lea Bojic, Tina Zavasnik Bergant, Andreja Bratovs, Thomas Reinheckel
    Abstract:

    L-leucyl-Leucine Methyl Ester (LLOMe) is a lysosomotropic detergent, which was evaluated in clinical trials in graft-vs-host disease because it very efficiently killed monocytic cell lines. It was also shown to efficiently trigger apoptosis in cancer cells, suggesting that the drug might have potential in anticancer therapy. Using U-937 and THP-1 promonocytes as models for monocytic cells, U-87-MG and HeLa cells as models for cancer cells, and noncancerous HEK293 cells, we show that the drug triggers rapid cathepsin C-dependent lysosomal membrane permeabilization, followed by the release of other cysteine cathepsins into the cytosol and subsequent apoptosis. However, monocytes were found to be far more sensitive to the drug than the cancer and noncancer cells, which is most likely a consequence of the much higher intracellular levels of cathepsin C-the most upstream molecule in the pathway-in monocytic cell lines as compared to cancer cells. Overexpression of cathepsin C in HEK293 cells substantially enhances their sensitivity to the drug, consistent with the crucial role of cathepsin C. Major involvement of cysteine cathepsins B, S, and L in the downstream signaling pathway to mitochondrial cell death was confirmed in two gene ablation models, including the ablation of the major cytosolic inhibitor of cysteine cathepsins, stefin B, in primary mouse cancer cells, and simultaneous ablation of two major cathepsins, B and L, in mouse embryonic fibroblasts (MEFs). Deletion of stefin B resulted in sensitizing primary murine breast cancer cells to cell death without affecting the release of cathepsins, whereas simultaneous ablation of cathepsins B and L largely protected MEFs against cell death. However, due to the extreme sensitivity of monocytes to LLOMe, it appears that the drug may not be suitable for anticancer therapy due to risk of systemic toxicity.

Paul S. Robbins - One of the best experts on this subject based on the ideXlab platform.

  • Methyl 2-(Methylthio)benzoate: A sex attractant for the June beetles, Phyllophaga tristis and P. apicata
    2016
    Co-Authors: Paul S. Robbins, Charles E Linn, Glenn A. Salsburyb, Robert E. Woodruffc, Stephen L. Lapointed, Jr. E
    Abstract:

    Male antennae of Phyllophaga tristis (Fabricius) (Coleoptera: Scarabaeidae: Melolonthinae) were tested using a coupled gas chromatograph-electroantennogram detector (GC-EAD) system for electrophysiological responses to five sex pheromones identified from other Phyllophaga species including L-valine Methyl Ester, L-isoLeucine Methyl Ester, L-Leucine Methyl Ester, Methyl 2-(Methylthio)benzoate and Methyl 2-amino benzoate. Male antennae responded only to Methyl 2-(Methylthio)benzoate. In a 2003 field test near Greensburg, Kansas, cross-vane traps baited with rubber septa containing 1 mg of Methyl 2-(Methylthio)benzoate captured 466 male P. tristis. Control traps baited with rubber septa loaded with only hexane captured none. Similarly, in a field test in 2010 in Gainesville, Florida, 265 male P. apicata Reinhard were captured in traps baited with 1 mg of Methyl 2-(Methylthio)benzoate whereas control traps captured only a single male. Resumen Usando un cromatógrafo de gases acoplado a un sistema detector electroantenograma (GC-EAD), antenas de machos de Phyllophaga tristis (Fabricius) (Coleoptera: Scarabaeidae: Melolonthinae

  • Methyl 2 Methylthio benzoate a sex attractant for the june beetles phyllophaga tristis and p apicata
    Journal of Insect Science, 2011
    Co-Authors: Robert E Woodruff, Paul S. Robbins, Glenn A. Salsbury, Stephen L Lapointe, Charles E Linn
    Abstract:

    Male antennae of Phyllophaga tristis (Fabricius) (Coleoptera: Scarabaeidae: Melolonthinae) were tested using a coupled gas chromatograph-electroantennogram detector (GC-EAD) system for electrophysiological responses to five sex pheromones identified from other Phyllophaga species including L-valine Methyl Ester, L-isoLeucine Methyl Ester, L-Leucine Methyl Ester, Methyl 2(Methylthio)benzoate and Methyl 2-amino benzoate. Male antennae responded only to Methyl 2(Methylthio)benzoate. In a 2003 field test near Greensburg, Kansas, cross-vane traps baited with rubber septa containing 1 mg of Methyl 2-(Methylthio)benzoate captured 466 male P. tristis. Control traps baited with rubber septa loaded with only hexane captured none. Similarly, in a field test in 2010 in Gainesville, Florida, 265 male P. apicata Reinhard were captured in traps baited with 1 mg of Methyl 2-(Methylthio)benzoate whereas control traps captured only a single male.

  • l-Leucine Methyl Ester: The Female-Produced Sex Pheromone of the Scarab Beetle, Phyllophaga lanceolata
    Journal of Chemical Ecology, 2003
    Co-Authors: Satoshi Nojima, Paul S. Robbins, Glenn A. Salsbury, Bruce D Morris, Wendell L. Roelofs, Michael G. Villani
    Abstract:

    The female-produced sex pheromone of the scarab beetle Phyllophaga lanceolata was identified as the Methyl Ester of an essential amino acid, l-Leucine. During field testing, 239 male P. lanceolata were caught in traps baited with l-Leucine Methyl Ester. l-IsoLeucine and l-valine Methyl Esters, similar in structure to l-Leucine Methyl Ester and previously identified as female-produced sex pheromone compounds employed by other Phyllophaga species, were also tested. Addition of l-valine or l-isoLeucine Methyl Esters to the l-Leucine Methyl Ester in 1:1 ratios completely inhibited attraction of P. lanceolata males. Males of P. squamipilosa were also captured using l-Leucine Methyl Ester. This is the first record of P. squamipilosa from Kansas.