Inducible macrophage cytotoxins. II. Tumor lysis mechanism involving target cell-binding proteases.

Thioglycollate-elicited C57BL/6 peritoneal exudate macrophage monolayers (PEMM) stimulated with poly I . poly C or LPS released a macrophage cytotoxin (MCT) that rapidly bound to syngeneic (EL 4) or allogeneic (NS-1, YAC-1) tumor cells but did not bind to normal splenocytes. No binding to human (K562) tumor cells was observed. PEMM stimulated with poly I . poly C destroyed allogeneic tumor cells (NS-1) when separated by cell-impermeable Millipore filters in vitro; in contrast, PEMM not stimulated with poly I . poly C were incapable of lysing targets when separated by membranes. The reversible inhibitors N alpha-p-tosyl-L-arginine methyl ester and soybean trypsin inhibitor and the irreversible inhibitors N alpha-p-tosyl-L-lysine chloromethyl ketone and phenylmethylsulfonyl fluoride, of trypsin-like proteases, significantly or totally inhibited MCT cell-lytic activity for L-929 cells in vitro. Furthermore, modification of MCT-associated arginine residues by 1,2-cyclohexanedione completely blocked lytic activity. MCT was concluded to be an inducible nonspecific cell-lytic effector molecule elaborated by activated macrophages, which could bind to potential target cells, and was itself or was associated with a protease

Surgical management of myelopathy caused by a solitary spinal osteochondroma in a young cat

Case summary A 10-month-old, male castrated, domestic shorthair cat was presented with fast-progressing ataxia of the pelvic limbs. MRI and CT were performed, revealing a bony proliferation at T11, with mass effect and laterodorsal compression of the spinal cord. After hemilaminectomy and the removal of the bony mass, the cat recovered uneventfully. At the 1 year follow-up, the cat did not show any neurological deficits or signs of recurrence. Relevance and novel information Solitary osteochondroma as a cause of neurological deficits in the pelvic limb has been described in dogs and humans, but, to the best of our knowledge, there are no reported feline cases described in the literature, in which CT and MRI were performed in combination with the successful removal of the lesion and an excellent outcome for the patient

Inducible macrophage cytotoxins. I. Biokinetics of activation and release in vitro.

Peritoneal exudate macrophage monolayers (PEMM) from C57BL/6 and DBA/2 mice inoculated ip with tumor allografts were induced to release in vitro labile cell toxin(s), herein called "macrophage cytotoxin(s)" (MCT). Macrophages released MCT spontaneously for a short interval when initially established as monolayers, and they were reinduced to secrete MCT by exposure to allogeneic and syngeneic tumor cells (but not to normal cells) and by exposure to polyinosinic-polycytidylic acid (poly I . poly C) and lipopolysaccharide (LPS). PEMM from normal mice treated ip 3 days previously with thioglycollate were also induced to release toxins in vitro. These cells did not release MCT spontaneously before or after treatment with neoplastic cells but were induced to release MCT by exposure to poly I . poly C or LPS. Resident peritoneal macrophages did not release MCT either spontaneously or after treatment with tumor cells, poly I . poly C, or LPS. MCT released from alloimmune mice stimulated with syngeneic or allogeneic tumor cells were resolved by molecular sieving into a major peak at 140,000--160,000 daltons, called "alpha-MCT," and into a minor peak at 60,000 daltons, called "beta-MCT." However, supernatants from thioglycollate-induced PEMM, stimulated with poly I . poly C or LPS, appeared to be composed entirely of the alpha-class. alpha-MCT from poly I . poly C-stimulated PEMM caused 31--56% lysis of syngeneic EL-4 and allogeneic L-929, NS-1, and YAC-1 tumor cells in vitro but was not cytotoxic for normal cells. Secretion of the MCT by PEMM derived from thioglycollate-treated animals stimulated with poly I . poly C was inhibited by colchicine, emetine, iodoacetic acid, trypan blue, and cytochalasin B

Inducible macrophage cytotoxins. I. Biokinetics of activation and release in vitro.

Peritoneal exudate macrophage monolayers (PEMM) from C57BL/6 and DBA/2 mice inoculated ip with tumor allografts were induced to release in vitro labile cell toxin(s), herein called "macrophage cytotoxin(s)" (MCT). Macrophages released MCT spontaneously for a short interval when initially established as monolayers, and they were reinduced to secrete MCT by exposure to allogeneic and syngeneic tumor cells (but not to normal cells) and by exposure to polyinosinic-polycytidylic acid (poly I . poly C) and lipopolysaccharide (LPS). PEMM from normal mice treated ip 3 days previously with thioglycollate were also induced to release toxins in vitro. These cells did not release MCT spontaneously before or after treatment with neoplastic cells but were induced to release MCT by exposure to poly I . poly C or LPS. Resident peritoneal macrophages did not release MCT either spontaneously or after treatment with tumor cells, poly I . poly C, or LPS. MCT released from alloimmune mice stimulated with syngeneic or allogeneic tumor cells were resolved by molecular sieving into a major peak at 140,000--160,000 daltons, called "alpha-MCT," and into a minor peak at 60,000 daltons, called "beta-MCT." However, supernatants from thioglycollate-induced PEMM, stimulated with poly I . poly C or LPS, appeared to be composed entirely of the alpha-class. alpha-MCT from poly I . poly C-stimulated PEMM caused 31--56% lysis of syngeneic EL-4 and allogeneic L-929, NS-1, and YAC-1 tumor cells in vitro but was not cytotoxic for normal cells. Secretion of the MCT by PEMM derived from thioglycollate-treated animals stimulated with poly I . poly C was inhibited by colchicine, emetine, iodoacetic acid, trypan blue, and cytochalasin B

A simultaneous diagnosis and genotyping method for global surveillance of cetacean morbillivirus

Referenciado en La Provincia. Día 20 de septiembre de 2016, p. 44. "La ULPGC diseña una técnica para detectar un virus letal en cetáceos"Cetacean morbillivirus (CeMV) is considered one of the most important viral pathogens in cetaceans. CeMV outbreaks of lethal disease have repeatedly been observed in Europe, the Americas, and Australia, while large herds of gregarious species were found to be the likely reservoirs and sources of CeMV infection to susceptible species in the Atlantic and Pacific Oceans.1,6254,259Q1Q1SCI