Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin challenge causes metabolic dysfunction mediated by TNF, and sequestration of leukocytes. NPC 15669, N-carboxy-L-leucine, N-[2,7-dimethylfluoren-9-yl)methyl] ester, inhibits leukocyte recruitment into inflammatory lesions in animals, and inhibits endotoxin-induced neutropenia and lymphopenia in mice. This study was carried out to determine whether the ability of NPC 15669 to inhibit leukocyte sequestration is sufficient to promote survival after endotoxin challenge. To inhibit leukocyte sequestration directly, mice were treated with anti-CD11a (LFA-1) or anti-CD11b (Mac-1) before endotoxin challenge. Anti-CD11b partly inhibited neutropenia and lymphopenia in response to challenge with LPS, but anti--CD11a had little effect on leukopenia. At doses of 100 and 1000 micrograms/kg, anti-CD11b increased survival to endotoxin challenge from 0 to 20 and 40%, respectively, whereas anti-CD11a was without effect. These observations, coupled with the finding that NPC 15669 does not inhibit endotoxin-induced TNF release suggest that inhibition of leukocyte sequestration can increase survival after endotoxin challenge, and that NPC 15669 or antibodies to Mac-1 may represent effective therapies for gram-negative sepsis and shock.
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PMID:Mice treated with a leumedin or antibody to Mac-1 to inhibit leukocyte sequestration survive endotoxin challenge. 846 78

Niemann-Pick type C (NPC) disease is an autosomal recessive neurovisceral lipid storage disorder. The affected genes are NPC1 and NPC2. Mutations in either gene lead to intracellular cholesterol accumulation. There are three forms of the disease, which are categorized based on the onset and severity of the disease: the infantile form, in which the liver and spleen are severely affected, the juvenile form, in which the liver and brain are affected, and the adult form, which affects the brain. In mice, a spontaneous mutation in the Npc1 gene originated in the BALB/c inbred strain mimics the juvenile form of the disease. To study the influence of genetic background on the expression of NPC disease in mice, we transferred the Npc1 mutation from the BALB/c to C57BL/6J inbred background. We found that C57BL/6J-Npc1(-/-) mice present with a much more aggressive form of the disease, including a shorter lifespan than BALB/c-Npc1(-/-) mice. Surprisingly, there was no difference in the amount of cholesterol in the brains of Npc1(-/-) mice of either mouse strain. However, Npc1(-/-) mice with the C57BL/6J genetic background showed striking spleen damage with a marked buildup of cholesterol and phospholipids at an early age, which correlated with large foamy cell clusters. In addition, C57BL/6J Npc1(-/-) mice presented red cell abnormalities and abundant ghost erythrocytes that correlated with a lower hemoglobin concentration. We also found abnormalities in white cells, such as cytoplasmic granulation and neutrophil hypersegmentation that included lymphopenia and atypias. In conclusion, Npc1 deficiency in the C57BL6/J background is associated with spleen, erythrocyte, and immune system abnormalities that lead to a reduced lifespan.
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PMID:Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology. 2191 Sep 75