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)

Twenty patients with anemia and massive splenomegaly were studied in order to elucidate the mechanism by which splenomegaly results in plasma volume expansion. In 18 patients, increased plasma volume accounted for most of the anemia. Fourteen patients had an exaggerated renin response to standing, mean 1967 +/- 613 (SE) ng angiotensin ll/100 ml plasma (p less than 0.05). The mean resting forearm blood flow was increased 3.47 +/- 0.32 (SE) ml/100 ml forearm tissue (p less than 0.001). The venous capacitance was normal, as contrasted to a marked decrease in venous capacitance in patients with anemia of comparable degree without splenomegaly. Cardiac indices were increased in 10 of 11 patients (range 4.1-8.1 liters/min/sq m). In nine of ten patients oxygen consumption was increased (range 147-231 ml/min/sq m). Splenectomy was performed on 14 patients. Splenic blood flow was elevated in four of four patients (range 750-2000 ml/min). Splenic A-V oxygen difference was exaggerated in seven of seven patients and in three of three patients splenic indocyanine-green dye dilution curve failed to show an early peak suggestive of A-V shunting in the spleen. Free portal pressure was elevated in 12 of 12 patients and decreased immediately after splenectomy. The intravascular albumin mass decreased in ten patients, was unchanged in three at 2-4 mo after splenectomy, and was accompanied by a rise in the plasma albumin concentration in nine. These data suggest that a flow-induced portal hypertension with expansion of the portal vascular space is an important early hemodynamic change. This finding, together with a decreased peripheral resistance, probably results in a decrease in effective intravascular volume, resulting in stimulation of the renin-angiotensin-aldosterone system and other renal hemodynamic changes necessary for salt and water retention. Splenectomy usually accomplishes a complete reversal of these abnormalities and correction of the anemia.
 ...
PMID:Mechanism of dilutional anemia in massive splenomegaly. 126 Jan 26

The effects of dietary phosphate binder on deoxycorticosterone (DOC)-salt-hypertensive rats were examined. DOC-treated and non-DOC-treated rats were fed the diet either with or without phosphate binder, dihydroxyaluminum aminoacetate. All rats drank 1% NaCl. DOC-salt-treated rats without binder demonstrated marked glomerular hypertrophy, many globally sclerosed glomeruli, severe proteinuria, focal cardiac fibrosis, and splenomegaly. A significant reduction of glomerular hypertrophy, glomerulosclerosis, severity of proteinuria, splenomegaly, and the myocardial lesion took place when the DOC-salt-treated rats were given phosphate binder. The globally sclerosed glomeruli exhibited remarkable hypertrophy while structurally preserved glomeruli showed little evidence of enlargement. The plasma phosphate level was low in rats with dietary phosphate binder. In conclusion, the dietary phosphate binder ameliorated glomerular hypertrophy, glomerulosclerosis, proteinuria, myocardial fibrosis, and splenomegaly occurring in DOC-salt-treated rats. The data indicated that there was an association between glomerular hypertrophy and glomerulosclerosis in this model. The exact mechanisms of action of the phosphate binder, however, remain far from clear.
 ...
PMID:Prevention of 11-deoxycorticosterone-salt-induced glomerular hypertrophy and glomerulosclerosis by dietary phosphate binder. 231 24

A study was conducted to determine whether the covalent chemical modification of Brucella abortus 19 salt-extractable proteins (BCSP) and BCSP derivatives would modulate the immune responses in BALB/c mice. Salt-extractable proteins BCSP 0-70 and BCSP 70-100 were modified with acetoacetic anhydride, and recombinant proteins rBCSP20 (20 kDa), rBCSP31 (31 kDa), and rBCSP45 (45 kDa) were modified with succinic and dodecanoyl anhydrides. Four weeks after mice were vaccinated with the different preparations, principal and control mice were challenge exposed with a virulent culture of B. abortus 2308, and mice were necropsied 2 weeks later. Serum samples were obtained immediately before mice were challenge exposed and at necropsy. Sera were tested for specific immunoglobulin M (IgM) and G (IgG) antibodies by using an enzyme-linked immunosorbent assay. Acylation decreased the immune responses (increased IgG antibodies and reduced spleen CFU and splenomegaly) induced by both BCSP 0-70 and BCSP 70-100. Modification of the recombinant proteins by dodecanoyl and succinic anhydrides had no effect on the protection induced; however, the IgG serologic responses to the homologous and heterologous proteins were altered. Monophosphoryl lipid A markedly enhanced the immunogenicity of BCSP 0-70.
 ...
PMID:Alteration of protective and serologic responses in BALB/c mice vaccinated with chemically modified versus nonmodified proteins of Brucella abortus 19. 796 Jan 11

The study compared the immune and protective responses induced in BALB/c mice vaccinated with six salt-extractable periplasmic protein fractions (Brucella cell surface proteins [BCSP]) of Brucella abortus 19 and later challenge exposed with B. abortus 2308. BCSP70 was precipitated with ammonium sulfate at 70% saturation, and BCSP100 was precipitated with ammonium sulfate at 100% saturation by use of supernatant fluid of BCSP70 that had been precipitated with 70% ammonium sulfate. Four subfractions were separated from BCSP100 by anion-exchange high-performance liquid chromatography (HPLC). Monophosphoryl lipid A (MPL) from Salmonella typhimurium Re mutant strain was used as a potential immune response modifier in some vaccines. Reduced or increased numbers of CFU and increased spleen size in the principal groups of mice relative to that of the nonvaccinated control group were considered protectiveness or virulence (survival) criteria. Results indicated that vaccines prepared from BCSP70 and BCSP100 were moderately protective and immunogenic. The subfractions designated BCSP100-A through BCSP100-D purified by anion-exchange HPLC were not protective when MPL was not used as an immune response modifier. However, two subfractions were associated with significant (P < 0.05) increases in CFU per spleen and splenomegaly in vaccinated mice compared with those in nonvaccinated challenge-exposed mice. MPL enhanced protection or was neutral when used with BCSP70, BCSP100, BCSP100-C, and BCSP100-D. Serologic results of an enzyme-linked immunosorbent assay indicated that MPL modulated the immunoglobulin G responses induced by BCSP70, BCSP100, and subfraction BCSP100-B vaccines only. The overall results suggest that certain proteinaceous periplasmic fractions might serve as virulence or survival factors in B. abortus infections.
 ...
PMID:Variation of Brucella abortus 2308 infection in BALB/c mice induced by prior vaccination with salt-extractable periplasmic proteins from Brucella abortus 19. 855 Feb 6

2-Biphenylamine (2-aminobiphenyl) is a chemical intermediate used in the manufacture of C.I. Acid Red 15. It is present as a contaminant in 4-biphenylamine (a rubber antioxidant) and in diphenylamine (a dye intermediate, stabilizer for nitrocellulose explosives, and a topical agent for prevention of screwworm infestation in animals). Single-dose, 14-day, and 13-week studies were conducted using technical-grade 2-biphenylamine (2-aminobiphenyl) containing up to 2.5% of the carcinogenic contaminant, 4-biphenylamine. When the contamination was recognized, analytical development was begun to purify the material. The salt, 2-biphenylamine hydrochloride, was prepared to obtain a more pure test product, which contained 0.006%-0.049% 4-biphenylamine. The prechronic tests were completed by the time purification was accomplished, so data from a second 14-day study with 2-biphenylamine hydrochloride were used to help set dose levels for the chronic study. The results of the comparative 14-day studies showed that technical-grade 2-biphenylamine was more toxic to mice than rats than 2-biphenylamine hydrochloride as evidenced by greater incidence of splenomegaly and greater weight gain depression. The technical-grade 2-biphenylamine caused a dose-related decrease in hemoglobin concentration and a dose-related increase in leukocyte count in male and female mice in the 13-week study. Hemosiderosis, congestion, and extramedullary hematopoiesis were present in the spleens of nearly all rats receiving 3,000 ppm or more of the chemical, and in nearly all mice with 1,000 ppm or more 2-biphenylamine in their diets. The chronic study was conducted with the purified 2-biphenylamine hydrochloride by feeding diets containing 1,000 or 3,000 ppm 2-biphenylamine hydrochloride to groups of 49 or 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 rats and 50 mice of each sex served as controls. Survival of dosed male and female rats and dosed female mice was comparable with that of the corresponding controls. Survival of high-dose male mice was significantly (P<0.010) less than that of low-dose and control male mice. There were little or no differences in body weight changes for rats or mice between dosed and control groups, although there was a slight decrease in body weight gain at the end of the study for high-dose male (-11%) and female (-8%) rats. Inflammatory cells and interstitial fibrosis were found in increased incidence in the kidneys of dosed male rats as compared with controls and were considered to be compound related. In addition to the increase in renal inflammation and fibrosis, dosed male rats had more focal cellular changes of the liver than did the controls. There were no increased or decreased incidences of tumors in rats that could be associated with chemical administration. Myelomonocytic leukemia in male rats (control, 14/50; low-dose, 1/50; high-dose, 4/50) and fibroadenomas of the mammary gland in female rats (22/50, 10/49, 9/50) occurred with significantly (P<0.03) decreasing trends and the incidences in the dosed groups were significantly (P<0.02) lower than that in the controls. There were no increased or decreased incidences of tumors in rats that could be associated with chemical administration. Hemangiosarcomas from all sites occurred in female mice with a statistically significant (P</=0.002) positive trend. The observed incidence of hemangiosarcomas was 0/49, 1/50, and 7/50 in the control, low-dose, and high-dose groups, respectively. The incidence in the high-dose group was significantly (P<0.01) higher than that in controls. The conclusion that this was due to 2-biphenylamine rather than the contaminant, 4-biphenylamine, is supported by the absence of urinary bladder tumors, which are common to 4-biphenylamine. Hemangiosarcomas also occurred in male mice with a statistically significant positive trend (P=0.040 by a life table test), with incidences of 0/50, 2/50, and 3/50. None of the pairwise comparisons were statistically different. The development of hemangiosarcomas may have been curtailedment of hemangiosarcomas may have been curtailed in the high-dose group of male mice, since only 21/50 survived until the termination of the study. The hemangiosarcomas found in female mice are uncommon with only 6/816 (0.7&percnt;) previously seen in controls at the same laboratory. The rate for control male mice is equally low: 7/803 (0.9&percnt;). Alveolar/bronchiolar adenomas of the lung occurred at a significantly (P&lt;0.01) decreased rate in male mice with an incidence in dose groups lower (P&lt;0.05) than that in controls. Under the conditions of the bioassay, 2-biphenylamine hydrochloride was not carcinogenic for F344/N rats of either sex. 2-Biphenylamine hydrochloride was carcinogenic for B6C3F1 female mice, inducing hemangiosarcomas at various sites. The evidence for an association between the administration of 2-biphenylamine hydrochloride and the increased incidence of hemangiosarcomas in male mice was equivocal. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Equivocal Female Mice: Positive
 ...
PMID:Carcinogenesis Bioassay of 2-Biphenylamine Hydrochloride (CAS No. 2185-92-4) in F344/N Rats and B6C3F1 Mice (Feed Study). 1277 3

Two variants (A and B) of the widely employed Walker 256 rat tumor cells are known. When inoculated sc, the A variant produces solid, invasive, highly metastasizing tumors that cause severe systemic effects and death. We have obtained a regressive variant (AR) whose sc growth is slower, resulting in 70-80% regression followed by development of immunity against A and AR variants. Simultaneously with the beginning of tumor regression, a temporary anemia developed (approximately 8 days duration), accompanied by marked splenomegaly (approximately 300%) and changes in red blood cell osmotic fragility, with mean corpuscular fragility increasing from 4.1 to 6.5 g/l NaCl. The possibility was raised that plasma factors associated with the immune response induced these changes. In the present study, we identify and compare the osmotic fragility increasing activity of plasma fractions obtained from A and AR tumor bearers at different stages of tumor development. The results showed that by day 4 compounds precipitating in 60% (NH4)2SO4 and able to increase red blood cell osmotic fragility appeared in the plasma of A and AR tumor bearers. Later, these compounds disappeared from the plasma of A tumor bearers but slightly increased in the plasma of AR tumor bearers. Furthermore, by day 10, compounds precipitating between 60 and 80% (NH4)2SO4 and with similar effects appeared only in plasma of AR tumor bearers. The salt solubility, production kinetics and hemolytic activity of these compounds resemble those of the immunoglobulins. This, together with their preferential increase in rats bearing the AR variant, suggest their association with an immune response against this tumor.
 ...
PMID:Changes in red blood cell osmotic fragility induced by total plasma and plasma fractions obtained from rats bearing progressive and regressive variants of the Walker 256 tumor. 1284 75

The toxicity and immunogenicity of the anthrax and pertussis vaccine combinations used in the 1991 Gulf War was assessed in NIH, A/J and Balb/c mice. Inoculation of pertussis vaccines, vaccine combinations, or aluminium salt caused illness, splenomegaly and significant weight loss. Although some animals recovered eventually, a lethal form of ascites developed in some NIH mice and body weights of A/J and Balb/c mice remained below normal levels. Inoculation of anthrax vaccine produced little effect. Exposure to diluted vaccine combinations produced less serious side effects of shorter duration. Single vaccinations induced specific IgG1 antibodies whereas a mixture of IgG1 and IgG2a was produced after multiple injections. Antigen stimulation of spleen cells from mice exposed to pertussis vaccines induced high levels of NO and IL-6, whereas stimulated spleen cells from mice exposed to anthrax vaccine produced only low levels of IL-6. In mice, pertussis vaccines act as an adjuvant for anthrax vaccine, but these vaccines are also the major cause of toxicity of the vaccine combination. The relatively high vaccine dose used, together with the low sensitivity of mice to anthrax toxin, emphasises that caution should be exercised in applying these results to human recipients of these vaccines.
 ...
PMID:Investigation in a model system of the effects of combinations of anthrax and pertussis vaccines administered to service personnel in the 1991 Gulf War. 1701 79

In this study, we present experimental data on the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and tetraethylammonium salt of salinomycinic acid (Sal) on cadmium-induced spleen dysfunction and altered essential metal balance in mice. Sixty-day-old male mice (ICR line) were randomly divided into four groups: untreated control group (Ctrl)-obtained distilled water for 28 days, toxic control group (Cd)-exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg body weight (BW) for 14 days, Cd + DMSA group-obtained cadmium acetate dihydrate as the toxic control group followed by treatment with 20mg/kg BW DMSA for 2 weeks, and Cd + Sal group-mice exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg BW for 2 weeks followed by administration of Sal at an average daily dose of 20mg/kg BW for 2 weeks. The compounds were administered orally via the drinking water of the animals. We found that cadmium exposure caused splenomegaly and reduced the hemoglobin and hematocrit levels and total red blood cell count compared with untreated controls. Cadmium intoxication of mice induced accumulation of the toxic metal ion in the blood and spleen. Alterations in the endogenous levels of calcium (Ca) and iron (Fe) in the spleen of cadmium-exposed mice compared with those in untreated controls were observed. Treatment of cadmium-exposed mice with DMSA or Sal recovered the spleen weight and hematological parameters to normal control values, decreased cadmium concentration in the blood and spleen, and improved splenic architecture. The results prove that Sal is a potential antidote for treatment of Cd-induced spleen dysfunction.
 ...
PMID:Comparative assessment of the effects of meso-2,3-dimercaptosuccinic acid and salinomycin on spleen function of cadmium-exposed mice. 3152 Mar 84

The increased incidence of systemic lupus erythematosus (SLE) in recent decades might be related to changes in modern dietary habits. Since sodium chloride (NaCl) promotes pathogenic T cell responses, we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases, including SLE. Given the importance of dendritic cells (DCs) in the pathogenesis of SLE, we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model. We used an induced lupus model in which bone marrow-derived dendritic cells (BMDCs) were incubated with activated lymphocyte-derived DNA (ALD-DNA) and transferred into C57BL/6 recipient mice. We observed that a high-salt diet (HSD) markedly exacerbated lupus progression, which was accompanied by increased DC activation. NaCl treatment also stimulated the maturation, activation and antigen-presenting ability of DCs in vitro. Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus. These mice had increased production of autoantibodies and proinflammatory cytokines, more pronounced splenomegaly and lymphadenopathy, and enhanced pathological renal lesions. The p38 MAPK-STAT1 pathway played an important role in NaCl-induced DC immune activities. Taken together, our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK-STAT1 signaling pathway and exacerbates the features of SLE. Thus, changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.
 ...
PMID:High salt diet accelerates the progression of murine lupus through dendritic cells via the p38 MAPK and STAT1 signaling pathways. 3229 43

Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic Bacteroides fragilis (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the Bacteroides fragilis toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.
 ...
PMID:Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation. 3312 15


1