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Immunotoxins and neuropeptide-toxin conjugates experimental applications.
Lappi DA, Wiley RG (2004) Immunotoxins and neuropeptide-toxin conjugates experimental applications. Mini Rev Med Chem 4(5):585-595. doi: 10.2174/1389557043403882
Summary: The use of targeted toxins in research is rich and varied; here the authors describe some of the exciting results that researchers have made in the neurosciences.
A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha.
Blasius A, Vermi W, Krug A, Facchetti F, Cella M, Colonna M (2004) A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha. Blood 103(11):4201-4206. doi: 10.1182/blood-2003-09-3108
Objective: To demonstrate the recruitment and function of natural interferon (IFN)-producing cells (IPCs) in murine infection models.
Summary: Incubation of IPCs with the antibody in vitro or administration of the antibody in vivo dramatically reduce secretion of IFN-α in response to deoxycytidylate-phosphatedeoxyguanylate (CpG) DNA without causing IPC depletion. Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-α secretion.
Usage: Biotinylated 440c antibody mixed with Streptavidin-ZAP was applied to bone marrow-derived IPCs. Approximately 70% of CD11c+ B220hi 440c bright IPCs were depleted from culture within 36 hours.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation.
Anton PM, Gay J, Mykoniatis A, Pan A, O’Brien M, Brown D, Karalis K, Pothoulakis C (2004) Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation. Proc Natl Acad Sci U S A 101(22):8503-8508. doi: 10.1073/pnas.0402693101 PMID: 15159534
Related Products: Corticotropin Releasing Hormone Rabbit Polyclonal (Cat. #AB-02)
Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone.
Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ (2004) Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone. Eur J Neurosci 19(10):2741-2752. doi: 10.1111/j.0953-816X.2004.03366.x
Summary: Narcolepsy is linked to the loss of orexin (or hypocretin)-containing neurons in the brain. These neurons are located in the perifornical region of the posterior hypothalamus and innervate the locus coeruleus (LC). To investigate the role of the LC in sleep the authors injected 0.3 µl of 192-Saporin (Cat. IT-01) or anti-DBH-SAP (Cat. #IT-03) at 1 µg/µl. They also used 0.3 µl of orexin-SAP (Cat. #IT-20) at either 90 ng/µl or 60 ng/µl in a separate group of animals. The results indicate that orexin innervation to the pons plays a role in arousal from sleep.
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)
Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus.
Li AJ, Ritter S (2004) Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus. Eur J Neurosci 19(8):2147-2154. doi: 10.1111/j.1460-9568.2004.03287.x
Summary: It is suspected that hypothalamic neuropeptide Y (NPY) innvervation of the hypothalamus contributes to glucoregulatory feeding. Along with mRNA studies, the authors injected 42 ng of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus. Elimination of the hindbrain catecholamine/NPY neurons abolished increases in NPY expression due to glucoprivic conditions. This response suggests that NPY hindbrain neurons play a role in glucoprivic feeding and other glucoregulatory responses.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
CEACAM6 as a novel target for indirect type 1 immunotoxin-based therapy in pancreatic adenocarcinoma.
Duxbury MS, Ito H, Ashley SW, Whang EE (2004) CEACAM6 as a novel target for indirect type 1 immunotoxin-based therapy in pancreatic adenocarcinoma. Biochem Biophys Res Commun 317(3):837-843. doi: 10.1016/j.bbrc.2004.03.128
Summary: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a cell-surface molecule that is overexpressed in a variety of human cancers. Here, the authors investigate the efficacy of a biotinylated antibody that recognizes CEACAM6 bound to streptavidin-ZAP (Cat. #IT-27) in elimination of tumor cells in vitro and in vivo. Treatment of cultured tumor cells induced significant specific cytotoxicity, while tumor growth was suppressed in a mouse xenograft model. These results indicate targeting of CEACAM6 may be a viable therapeutic strategy.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Spinal neurons involved in the generation of at-level pain following spinal injury in the rat.
Yezierski RP, Yu CG, Mantyh PW, Vierck CJ, Lappi DA (2004) Spinal neurons involved in the generation of at-level pain following spinal injury in the rat. Neurosci Lett 361(1-3):232-236. doi: 10.1016/j.neulet.2003.12.035
Summary: The elimination of substance P receptor-expressing neurons in lamina I of the spinal cord using SP-SAP (Cat. #IT-07) has been shown to reduce behavior associated with chronic pain. The authors investigated the effects of 150 or 300 ng SP-SAP treatment during or after intraspinal administration of quisqualic acid in rats. Both treatments resulted in a reduction of pain-associated behavior. These results demonstrate that pain following spinal cord injury involves a population of spinal neurons expressing the substance P receptor.
Related Products: SP-SAP (Cat. #IT-07)
Recurrent paraplegia after remyelination of the spinal cord.
Jasmin L, Ohara PT (2004) Recurrent paraplegia after remyelination of the spinal cord. J Neurosci Res 77(2):277-284. doi: 10.1002/jnr.20143
Summary: Previously, the authors demonstrated that a 3 µg-injection of CTB-SAP (Cat. #IT-14) into the lumbosacral intrathecal space caused a loss of motor function due to spinal demyelination. The motor function was recovered and stable for up to 9 months, after which the rats exhibited a slow deterioration of motor function, loss of spinal white matter, and the appearance of calcium deposits. The results indicate that the CTB-SAP-induced demyelination model is useful for investigating long term effects of axon and motoneuron loss.
Related Products: CTB-SAP (Cat. #IT-14)
Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity.
Mattsson A, Pernold K, Ogren SO, Olson L (2004) Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity. Neuroscience 127(3):579-591. doi: 10.1016/j.neuroscience.2004.05.038
Summary: The authors have recently shown that cholinergic denervation of the basal forebrain in rats leads to an increased motor response to d-amphetamine, a hallmark of schizophrenia. In the present study 192-Saporin (Cat. #IT-01) was injected into the nucleus basalis magnocellularis or the medial septum/diagonal band of Broca, and OX7-SAP (Cat. #IT-02) was injected intracerebroventricularly. The dopaminergic hyper-reactivity was induced by lesions to the cortex cerebri, but not by damage to the cerebellum or hippocampus.
Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02)
Intrathecal application of saporin conjugates leads to development of pituitary adenomas in rats
Margeta M, Ohara PT, Bollen AW, Jasmin L (2004) Intrathecal application of saporin conjugates leads to development of pituitary adenomas in rats. J Neuropathol Exp Neurology 63(5):518.
Objective: To study the recovery from spinal cord demyelination or the effects of decreased central noradrenergic tone on pain behavior.
Summary: The spectrum of findings varied from small, sometimes multifocal nodules to large neoplasms that entirely replaced the normal gland and showed a significant degree of mitotic activity and nuclear pleomorphism. Development of this novel animal model will enable investigation of non-hormonal factors important in the pathogenesis of pituitary adenomas
Usage: Rats were injected intrathecally with CTB-SAP (IT-14) or to the anti-DBH-SAP (IT-03)
Related Products: CTB-SAP (Cat. #IT-14), Anti-DBH-SAP (Cat. #IT-03)
