Alien H-2 Antigens on a Chemically Induced Fibrosarcoma: Further Evidence in Crude Membrane and Soluble Extracts of the Tumor

1979 ◽  
Vol 65 (3) ◽  
pp. 295-308 ◽  
Author(s):  
Marco A. Pierotti ◽  
Silvia Miotti ◽  
Giovanni Invernizzi ◽  
Giorgio Parmiani
Keyword(s):  
Lymphoid Cells ◽  
Specific Inhibition ◽  
Inhibition Assay ◽  
The Public ◽  
Subcutaneous Nodules ◽  
Antigenic Activity ◽  
Chemically Induced ◽  
Mechanical Press ◽  
Private Specificity

Crude membranes (CM) were obtained from in vivo subcutaneous nodules of the methylcholanthrene-incuded BALB/c fibrosarcoma C-1 by forcing tumor fragments through a mechanical press and subsequent differential centrifugation. This immunogenic tumor has been previously shown to express both H-2d and extra H-2k-like antigens. Original H-2d and alien H-2k antigenic activities were present in CM C-1 as judged by the specific inhibition of the C'-dependent cytotoxicity of monospecific H-2 alloantisera on normal 51Cr-labelled lymphoid cells. Both K- and D-end private H-2d antigens (31 and 4), and H-2d public antigens 8, 29, 35 were detected in CM C-1. In addition, the alien H-2Kk.23 private specificity and the public H-2k.1, 5, and 25 were also found in CM C-1. A weak but reproducible activity attributable to the Dk private antigen 32 was also revealed in this material. A hierarchy in the expression of both H-2d and H-2k specificities was evident in CM C-1 which paralleled, although with an overall lower antigenic activity, those of two other BALB/c (H-2d) fibrosarcomas and of a C3Hf (H-2k) lymphoma, respectively. CM from normal BALB/c and C3Hf spleens, while expressing higher amounts of all the tested H-2 antigens, displayed a hierarchy of the different specificities similar to that of neoplastic tissues. Crude soluble (CS) material was obtained from CM C-1 by deoxycholate treatment and was tested in the inhibition assay for the presence of H-2d and alien H-2k antigens. Only specificities with the highest expression in CM were found in CS, i.e. H-2.4 and 29 for H-2d and H-2.25 for H-2*. Both CM and CS from C-1, but not from another control BALB/c sarcoma, were able to significantly inhibit the activity of an oligospecific serum to the Kk-coded antigens.

scholarly journals trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zachary D. Aron ◽  
Atousa Mehrani ◽  
Eric D. Hoffer ◽  
Kristie L. Connolly ◽  
Pooja Srinivas ◽  
...  
Keyword(s):  
Oral Dose ◽  
Neisseria Gonorrhoeae ◽  
Multiple Drug ◽  
Specific Inhibition ◽  
Drug Resistant ◽  
Peptidyl Transfer ◽  
Bacterial Ribosome ◽  
Multiple Drug Resistant ◽  
Unique Site

AbstractBacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.

scholarly journals Catalytic activity and stereoselectivity of engineered phosphotriesterases towards structurally different nerve agents in vitro

2021 ◽  
Author(s):  
Anja Köhler ◽  
Benjamin Escher ◽  
Laura Job ◽  
Marianne Koller ◽  
Horst Thiermann ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Nerve Agents ◽  
Inhibition Assay ◽  
Ache Inhibition ◽  
Catalytic Activities ◽  
Chiral Lc ◽  
Hydrolysis Of ◽  
Medical Countermeasures

AbstractHighly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured kcat/KM values were as high as 6.5 and 1.5 × 108 M−1 min−1 with G- and V-agents, respectively. Furthermore, the stereoselective degradation of VX enantiomers by the PASylated BdPTE-4 and the bispecific BdPTE-7 were investigated by chiral LC–MS/MS, resulting in a several fold faster hydrolysis of the more toxic P(−) VX stereoisomer compared to P(+) VX. In conclusion, the newly developed enzymes BdPTE-4 and BdPTE-7 have shown high catalytic efficacy towards structurally different nerve agents and stereoselectivity towards the toxic P(−) VX enantiomer in vitro and offer promise for use as bioscavengers in vivo.

scholarly journals Cutaneous Hypersensitivity as an Indicator of Visceral Inflammation via C-Nociceptor Axon Bifurcation

2020 ◽  
Author(s):  
Yehong Fang ◽  
Shu Han ◽  
Xiaoxue Li ◽  
Yikuan Xie ◽  
Bing Zhu ◽  
...  
Keyword(s):  
Body Surface ◽  
The Body ◽  
Visceral Organ ◽  
Deep Tissue ◽  
Nociceptive Neurons ◽  
Chemically Induced ◽  
Acute Gastritis ◽  
Cutaneous Hypersensitivity ◽  
Evans Blue Extravasation

Abstract Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure. Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion (DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation (colitis, urocystitis, and acute gastritis) rat models. In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from double-labeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.

Influence of flumequine on in vivo mitogen responses of European eel (Anguilla anguilla L., 1758) lymphoid cells

1995 ◽  
Vol 47 (1-2) ◽  
pp. 143-152 ◽  
Author(s):  
M.H.T. van der Heijden ◽  
G.H.R. Booms ◽  
M.W.T. Tanck ◽  
J.H.W.M. Rombout ◽  
J.H. Boon
Keyword(s):  
Anguilla Anguilla ◽  
Lymphoid Cells ◽  
European Eel

In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 668-670 ◽  
Author(s):  
Manuela Germeshausen ◽  
Karl Welte ◽  
Matthias Ballmaier
Keyword(s):  
Single Cells ◽  
Bone Marrow Failure ◽  
Point Mutations ◽  
Predictive Marker ◽  
Lymphoid Cells ◽  
Lower Percentage ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Bone Marrow Failure Syndrome

Abstract Severe congenital neutropenia (CN) is a rare bone marrow failure syndrome with a high incidence of acute leukemia. In previous studies, we could show that point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R are a highly predictive marker for leukemic development in CN patients. To find out at which stage of hematopoietic development these mutations emerge and how they are propagated during hematopoietic differentiation, we analyzed single cells of different hematopoietic subpopulations from CN patients with CSF3R mutations. We found that CSF3R mutations are not restricted to the myeloid compartment but are also detectable in lymphoid cells, although at a much lower percentage. From our observations, we conclude that CSF3R mutations are acquired in multipotent hematopoietic progenitor cells in CN patients and that they are clonally expanded in myeloid cells expressing the G-CSF receptor due to the growth advantage mediated by the CSF3R mutation.

scholarly journals CELL-MEDIATED CYTOTOXICITY DURING REJECTION AND ENHANCEMENT OF ALLOGENEIC SKIN GRAFTS IN RATS

1972 ◽  
Vol 135 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Hans-Hartmut Peter ◽  
Joseph D. Feldman
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Skin Grafts ◽  
Peak Activity ◽  
Adult Rats ◽  
Background Levels

Cell-mediated cytotoxicity (CMC) in spleens and lymph nodes of allografted rats was determined by release of 51Cr from labeled target cells incubated with aggressor lymphoid cells. CMC was first detected in grafted adult rats on day 5, peaked on days 7 and 8, and declined rapidly to background levels by days 9 to 11. In allografted neonates and in cyclophosphamide-treated or neonatally thymectomized adults CMC was a fraction of that observed in normal adult rats. Enhancing antibodies deferred in vivo peak activity of CMC in allografted neonates for 3–4 days, and blocked in vitro the action of aggressor lymphocytes by binding to target cells. Enhancing antibodies had no effect on the cytotoxicity of aggressor cells, but horse antibodies to rat thoracic duct cells inhibited in vitro CMC of aggressor cells.

scholarly journals Classification of lymphoid neoplasms: the microscope as a tool for disease discovery

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4384-4399 ◽  
Author(s):  
Elaine S. Jaffe ◽  
Nancy Lee Harris ◽  
Harald Stein ◽  
Peter G. Isaacson
Keyword(s):  
Molecular Mechanisms ◽  
Nk Cell ◽  
Clinical Manifestations ◽  
Lymphoid Cells ◽  
World Health ◽  
International Studies ◽  
Lymphocyte Function ◽  
Lymphoid Neoplasms

AbstractIn the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)–cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory.

Effect of Glycyrrhizin and Sappan Wood Extract on Chemically- Induced Oral Mucosal Ulcer: An in vivo Animal Study

2021 ◽  
Vol 13 (4) ◽  
pp. 909-915
Author(s):  
Ariiq Azmi Rofiqi Sulkhan ◽  
Abdul Mun’im ◽  
Sutriyo Sutriyo
Keyword(s):  
Animal Study ◽  
Chemically Induced ◽  
Wood Extract
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