Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were undertaken in order to determine if NZB mice injected with sheep erythrocyte antigens would respond by showing elevated splenic prostaglandin and cyclic nucleotide levels similar to that observed in normal mice. The results show that young NZB mice can respond to sheep erythrocytes by yielding increased levels of splenic PGF2alpha and cAMP. However, because of increased basal levels of PGF2alpha and cAMP, the net increase observed is lower than that observed with normal mice. In old NZB mice exhibiting signs of disease (splenomegaly) and in which defects in immune competence are known to occur, the injection of SRBC results in in no increase in splenic PGF2alpha levels and a decrease in cAMP levels. These animals also have greatly elevated basal levels of PGF2alpha, cAMP, and cGMP. It is concluded that the cellular immune defect in NZB mice is reflected by their faulty metabolic responses to sRBC. Also, the altered basal levels of PG and cyclic nucleotides may be related to the altered cellular immune competence. The latter conclusion is supported by the reduced capacity of spleen cells from young NZB mice to respond to PGE by increasing cAMP levels and by the lack of an effect of inhibitors of PG synthesis on the immune response to sRBC in both young and old NZB mouse spleen cell cultures.
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PMID:Antigen induced alterations in splenic prostaglandin and cyclic nucleotide levels in NZB mice. 19 Mar 14

Cyclic phosphate derivative of DHPG, 2'-nor-cGMP [9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]-guani ne phosphate-oxide] was evaluated for activity against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo cells and in guinea pigs. By virus yield reduction and plaque reduction assays, 2'-nor-cGMP was demonstrated to be 15- to 20-fold more potent against GPCMV infection than its parental drug DHPG. The selectivity index of 2-nor-cGMP was 110, which was 10-fold higher than that of DHPG. In cultured cells, 2'-nor-cGMP attained maximal antiviral activity when added to the cells within 12 h postinfection. In the studies on GPCMV infection in guinea pigs, 2'-nor-cGMP administered subcutaneously once daily (5 mg/kg per day) for 8 days, starting 24 after virus inoculation, significantly suppressed GPCMV infectivity titers in the blood, spleen, lung, and salivary gland during acute infection (10 days postinfection) as compared with sham-treated infected animals. A greater reduction of GPCMV infectivity titers in the salivary gland was noted during chronic infection (i.e., 24 days postinfection). Clinically, splenomegaly and peripheral lymphocytosis were significantly modified as compared with the sham-treated animals (P less than 0.05). The drug, administered at this dosage, was reasonably tolerated by the guinea pigs and showed clinical benefit.
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PMID:Effect of 2'-nor-cyclic GMP against guinea pig cytomegalovirus infection. 255

A novel compound, LY83583 (6-anilino-5,8-quinolinedione), was found to lower basal levels of cyclic GMP (cGMP) in fragments of guinea-pig lung incubated in vitro. The lowering of cGMP was dose-related reaching a maximum of 72% at 5 X 10(-5) M. Basal levels of cyclic AMP (cAMP) were not lowered by LY83583. cGMP concentrations were also reduced in guinea-pig heart and cerebellum after incubation with LY83583. However, the drug did not alter the levels of this cyclic nucleotide in spleen. Exposure of lung fragments from sensitized guinea pigs to ovalbumin resulted in a marked increase in cGMP and cAMP. LY83583 prevented completely the accumulation of cGMP and attenuated the rise in cAMP. Similar results were obtained in rat cerebellum stimulated with kainic acid. The compound also blocked ovalbumin-induced release of slow reacting substance of anaphylaxis (leukotrienes) from guinea-pig lung. Subcutaneous administration of LY83583 to guinea pigs did not affect cGMP concentrations in vivo in lung, but the total amount of cGMP in spleen was reduced dramatically. This was accompanied by a marked splenomegaly. LY83585 did not inhibit lung guanylate cyclase. In fact, activity was increased in a cell-free preparation from guinea-pig lung. The mechanism by which LY83583 reduced concentrations of cGMP is presently unknown. Nevertheless, our studies suggest that LY83583 will be a valuable pharmacological tool to help elucidate the role of cGMP in biological events.
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PMID:LY83583: an agent that lowers intracellular levels of cyclic guanosine 3',5'-monophosphate. 285 87

A 25-year-old male with a history of recurrent infections presented with fever, severe aplastic anaemia, splenomegaly and retroperitoneal node enlargement. Lympho-histiocytic granulomas were found in spleen, liver and lymph nodes. Granulocyte studies revealed normal morphology, severely impaired random migration and complete absence of directed locomotion. Whereas phagocytosis was slightly reduced, candidacidal activity and nitroblue tetrazolium reduction were normal. Basal granulocyte cyclic GMP levels were within the normal range while a 5-fold increase of cyclic AMP levels was observed. Numerous abnormalities were also found in the patient's lymphocytes: lack of delayed hypersensitivity, reduced response to mitogens, low OKT4/OKT8 ratio, absence of natural killer (NK) activity with normal number of cells recognized by NK-specific monoclonal antibodies. These observations describe a distinct clinico-pathologic entity and suggest the possibility of a common defect in granulocytes and in NK cells.
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PMID:Defective granulocyte chemotaxis and natural killer activity in a patient with recurrent infections. 302 45

To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in the regulation of erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By the age of 10 weeks, cGKI-deficient mice exhibited pronounced anemia and splenomegaly. Compared with control mice, the cGKI mutants had significantly lower red blood cell count, packed cell volume, and hemoglobin concentration. Anemia was associated with a higher reticulocyte number and an increase of plasma erythropoietin concentration. The spleens of cGKI mutant mice were massively enlarged and contained a higher fraction of Ter119(+) erythroid cells, whereas the relative proportion of leukocyte subpopulations was not changed. The Ter119(+) cGKI-deficient splenocytes showed a marked increase in annexin V binding, pointing to phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis. Compared with control erythrocytes, cGKI-deficient erythrocytes exhibited in vitro a higher cytosolic Ca(2+) concentration, a known trigger of eryptosis, and showed increased PS exposure, which was paralleled by a faster clearance in vivo. Together, these results identify a role of cGKI as mediator of erythrocyte survival and extend the emerging concept that cGMP/cGKI signaling has an antiapoptotic/prosurvival function in a number of cell types in vivo.
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PMID:Anemia and splenomegaly in cGKI-deficient mice. 1844 97