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

Normal and pathologic reticulin networks colored black by silver nitrate can be automatically quantitated by electronic image analysis. By using this technique, different parameters can be obtained, such as the average density, the surface of network meshes, the thickness of the fibers, the complexity of the reticulum, and the heterogeneity of the myelofibrosis distribution. All of these parameters were obtained in 83 osteomedullar biopsies of blood diseases (primary splenomegaly, chronic myeloid leukemia, polycythermia vera, acute leukemia, and aplastic anemia). We have shown that there is no relation between the different parameters obtained and the medullary richness, hematopoietic center, or patient survival. On the other hand, the histomorphometric parameters can be used to distinguish acute leukemia and chronic myeloid leukemia myelofibrosis, while the parameters in primary splenomegaly are shown to be very heterogeneous.
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PMID:[Quantitation of myelofibrosis in blood diseases by electronic image analysis (author's transl)]. 29 Sep 75

Liquid propellant XM46 is being considered as a replacement for solid propellants, both as part of a regenerative injection gun system and as a working fluid in an electrothermal gun system. The XM46 formulation contains hydroxylammonium nitrate, triethanolammonium nitrate, and water. Male and female Sprague-Dawley rats received XM46 in drinking water containing 2.0, 1.0, 0.2, or 0.0 g XM46/liter throughout a 90-day study. Mating occurred following 14 days of treatment. One-half the male rats per group were necropsied after 28 days of treatment; the remaining males and all dams were necropsied following 90 days of treatment. No mortality occurred in any of the parental animals during the study. The study did not demonstrate any adverse effects on reproduction or litter parameters. Hemolytic anemia and methemoglobinemia were common in both sexes of rats. Splenomegaly was found in both sexes; in male rats as early as 28 days. Exposures via drinking water containing XM46 for 90 days did not result in any decrease in reproductive performance in male or female rats, but it did result in clinical signs of hemolytic anemia at doses as low as 17 mg/kg/day.
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PMID:General toxicity and reproductive screen of liquid propellant XM46 administered in the drinking water of Sprague-Dawley rats. 749 35

We investigated whether gamma interferon (IFN-gamma; a Th1 cytokine), tumor necrosis factor alpha (TNF-alpha), and interleukin-4 (IL-4; a Th2 cytokine) modulate nitric oxide (NO) production in vivo during blood stage infection with Plasmodium chabaudi AS. Treatment of resistant C57BL/6 mice, which resolve infection with P. chabaudi AS and produce increased levels of IFN-gamma, TNF-alpha, and NO early during infection, with anti-IFN- gamma plus anti-TNF-alpha monoclonal antibodies (MAbs) resulted in a reduction of both splenic inducible NO synthase mRNA and serum NO3- levels by 50 and 100%, respectively. Treatment with the anti-TNF-alpha MAb alone reduced only serum NO3- levels by 35%, and treatment with the anti-IFN-gamma MAb alone had no effect on NO production by these mice during infection. Susceptible A/J mice, which succumb to infection with P. chabaudi AS and produce increased levels of IL-4 but low levels of IFN-gamma, TNF-alpha, and NO early during infection, were treated with an anti-IL-4 MAb. The latter treatment had no effect on NO production by this mouse strain during infection. In addition, our results also demonstrate that treatment of resistant C57BL/6 mice with anti-IFN-gamma plus anti-TNF-alpha MAbs affects, in addition to NO production, other traits of resistance to P. chabaudi AS malaria such as the peak level of parasitemia and the development of splenomegaly. Furthermore, the change in spleen weight was shown to be an IFN-gamma-independent effect of TNF-alpha. Treatment of susceptible A/J mice during infection with an anti IL-4 MAb had no effect on these markers of resistance. Thus, these results demonstrate that TNF-alpha and IFN-gamma are critical in the regulation of NO production and other traits of resistance during P. chabaudi AS malaria in C57BL/6 mice. These data also indicate that treatment with an anti-IL-4 antibody alone is not able to induce NO production or confer resistance to A/J mice against P. chabaudi AS malaria.
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PMID:In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice. 855 72

Our laboratory has previously shown that after immunization with a strain of Salmonella typhimurium, SL3235, made avirulent by a blockage in the pathway of aromatic synthesis, murine splenocytes were profoundly suppressed in their capacity to mount an in vitro antibody plaque-forming cell (PFC) response to sheep erythrocytes. Evidence indicated that suppression was mediated by nitric oxide (NO), since the in vitro addition of NG-monomethyl-L-arginine blocked suppression. The present studies examined the effect of blocking NO production on Salmonella-induced immunosuppression by in vivo administration of aminoguanidine hemisulfate (AG). AG was administered to C3HeB/FeJ mice in their drinking water (2.5% solution) for 7 days prior to intraperitoneal inoculation with SL3235. AG treatment inhibited the increase in nitrate and nitrite levels in plasma and nitrite levels in the spleen seen in immunized mice. Importantly, AG treatment completely blocked suppression of the splenic PFC response and markedly attenuated the suppression of the response to concanavalin A in immunized mice, providing further evidence that Salmonella-induced immunosuppression is mediated by NO. AG treatment also alleviated the majority of the splenomegaly associated with SL3235 inoculation, which correlated with a blockage of influx of neutrophils and macrophages into spleens, as assessed by flow cytometry. AG treatment unexpectedly resulted in 90% mortality in mice injected with the highly attenuated vaccine strain of Salmonella, SL3235. Increased mortality in AG-treated mice correlated with inability to clear organisms from the spleen by day 15 postinoculation and with persistent bacteremia, compared with control mice. Collectively, these in vivo results underscore the dual biological consequences of NO production following Salmonella infection, with NO being necessary for host defense, but also having the potentially adverse effect of immunosuppression. A unifying hypothesis to explain how these seemingly paradoxical effects could both result from NO production is presented.
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PMID:In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen. 991 5

Antiarthritic effects of two acyclic nucleoside phosphonates, 9-(2-phosphonomethoxyethyl)adenine (PMEA; Adefovir) and 9-(2-phosphonomethoxypropyl)adenine (PMPA), as well as their more bioavailable prodrugs, bis(pivaloyloxymethyl)ester of PMEA [bis(POM)-PMEA; Adefovir Dipivoxil] and bis(isopropyloxycarbonyloxymethyl)ester of PMPA [bis(POC)-PMPA], were investigated in a model of adjuvant-induced arthritis in Lewis rats. The drugs were injected subcutaneously at doses of 5-50 mg/kg. PMEA and its prodrug inhibited by > 80% arthritic paw swelling, splenomegaly and fibroadhesive perisplenitis. Both prophylactic and therapeutic dosing regimens were effective. Neither PMPA nor bis(POC)-PMPA suppressed development of arthritic lesions. Substantially reduced nitrite + nitrate levels were detected in serum and urine of PMEA-treated animals as compared to those of untreated diseased controls. Also, complete suppression of the disease-associated, greatly enhanced systemic levels of the chemokine, RANTES (regulated upon activation, normal T cell expressed and secreted), was observed in rats injected with PMEA. Additional in vitro studies showed that PMEA does not change, PMPA enhances, and both prodrugs inhibit the immune-activated NO production. Under the same conditions PMEA inhibits, while PMPA slightly stimulates, secretion of RANTES. Collectively, these data suggest that the in vivo-inhibited production of nitric oxide (NO) is a consequence rather than a mechanism of antiarthritic action of PMEA. Possible mechanisms for the anti-RANTES activity of PMEA remains to be firmly established.
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PMID:Chemokines, nitric oxide and antiarthritic effects of 9-(2-phosphonomethoxyethyl)adenine (Adefovir). 1044 94

One hundred and five patients with Plasmodium falciparum were included, forty-three with cerebral malaria and sixty-two without cerebral manifestations. The main clinical presentations in cerebral malaria patients were fever (76.4%), pallor (72%), splenomegaly (60.5%), deep coma (39.5%), jaundice (18.6%), pulmonary oedema (13.9%), subconjunctival haemorrhage (13.9%), severe anemia (Hb<5mg/l) (53.5%), hypoglycemia (glucose<40mg/dl) (67.4%) and haemoglobinuria (6.9%) while in non cerebral malaria patients the clinical presentations were fever (83.8%), pallor (67.7%), splenomegaly (66%), jaundice (9.7%), severe anemia (Hb<5gm/dl) (51.6%) and hypoglycemia (glucose<40mg/dl) (3.2%). Nine patients from cerebral malaria group died after admission. Serum level of nitric oxide (nitrite plus nitrate) were assayed for all patients, serum level of nitric oxide were highly significant in patients with cerebral malaria than those without (34.6 +/- 2.3n. mol/ml VS 12.9 +/- 1.3n. mol/ml; P<0.01). In cerebral malaria, nitric oxide levels were highly elevated in patients with deeper coma than those with lighter coma (48.2 +/- 3.1n. mol/ml VS 24.4 +/- 1.3n. mol/ml; P<0.001) and also higher among patients with longer duration of coma (>72 hours) than among patients with shorter duration of coma (<72 hours) (54.5 +/- 2.8 n. mol/ml V.S. 23.6 +/- 3.1n. mol/ml; P<0.001). Also, nitric oxide levels were correlated with clinical outcome, fatal cases (9 patients) having significantly higher nitric oxide levels than survivors (56.2 +/- 3.1 n. mol/ml VS 32.5 +/- 1.3 n. mol/ml; P<0.001). Thus, higher levels of nitric oxide are associated with indices of disease severity and may predict outcome in-patients with cerebral malaria. These data are consistent with the hypothesis that nitric oxide is involved in the pathogenesis of cerebral malaria.
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PMID:Plasma levels of nitric oxide in association with severe Plasmodium falciparum in Yemen. 1256 1

Hydroxylammonium nitrate (HAN) is the main active toxic component of the new HAN-based liquid propellant. It is a moderately toxic and caustic substance to animals, and can be administrated through dermal, oral or respiratory route. HAN causes severe damage to skins, eyes, and red blood cells of the hematologic system. Significant signs of HAN poisoning include hemolytic anemia, methemoglobinemia, splenomegaly, erythrocyte destruction and Heinz body formation. This review summarize the toxicity of hydroxylammonium nitrate, and discuss the primary protection methods.
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PMID:[Proceedings on the toxicity of a new hydroxylammonium nitrate (HAN)-based liquid propellant]. 1500 17

Introduction Patients with chronic liver disease ultimately progress to develop cirrhosis and portal hypertension. Recently it seems well established that nitric oxide disturbances play a key role in the pathogenesis of chronic liver disease and portal hypertension. The aim of this work was to clarify the correlation between chronic liver disease stages, liver function status, esophageal varices presence and nitric oxide disturbances. Subjects and methods All subjects (n = 120) in the present study were classified into; group I which included 15 age and sex matched healthy volunteers (taken as control), group II which included 20 patients with chronic active hepatitis, and group III which included 85 patients with hepatic cirrhosis. All subjects included were subjected to full clinical assessment, routine laboratory investigations, serum nitrate level determination using colorimetric method, abdominal ultrasonography and upper endoscopy. Results Increased serum nitrate level could not be detected in patients with chronic active hepatitis as well as those with early cirrhosis (Child's class A). Progressive and significant increase of serum nitrate levels were detected in more advanced stages of cirrhosis (Child's class B & C). The best non-invasive predictor for the presence of oesophageal varices was a combination of platelet count <150.000/mm(3), splenomegaly >18 cm, Child's class B or C and serum nitrate >/=38 mumol/l, with 93.3% sensitivity and 100% specificity. Conclusion Serum nitrate level can be used as a non-invasive predictor for progression of chronic liver disease as well as for the presence of oesophageal varices.
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PMID:Nitric oxide levels in chronic liver disease patients with and without oesophageal varices. 1966 72

The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats.
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PMID:The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis. 2700 15