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)

A sarcomatoid renal cell carcinoma has been isolated from a patient with Stauffer's syndrome. The tumor, designated BA1119, has been established in tissue culture over 80 passages. Subcutaneous deposition of BA1119 in athymic mice induced splenomegaly and hepatic dysfunction which became fatal within four weeks without metastasis. Suramin is a synthetic polyanionic compound which is capable of altering the function of a number of biologic systems and inhibiting the activity of a variety of protein and growth factors. In this study we attempted to study the effect of suramin on growth of BA1119 in culture and in nude mice. Suramin, at 300 micrograms/ml., had a profound inhibitory effect on cell growth during a six-day culture period. Suramin given i.p. weekly to nude mice at clinically relevant doses (200 mg./kg.) caused significant shrinkage of subcapsular tumor deposits. Splenic hypertrophy secondary to BA1119-induced Stauffer's syndrome was inhibited by suramin. Synergistic effect with enhanced cytotoxicity on BA1119 cells was observed when suramin (100 micrograms/ml.) was used in combination with lymphokines, such as gamma interferon (500 units/ml.) and alpha tumor necrosis factor (300 ng./ml.). These results may suggest a therapeutic efficacy of suramin in renal cell carcinoma patients with Stauffer's syndrome.
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PMID:Inhibitory effects of suramin on a human renal cell carcinoma line, causing nephrogenic hepatic dysfunction. 155 13

We have investigated the involvement of nitric oxide (NO) in intestinal graft-vs.-host reaction (GvHR) in mice. Treatment of mice with L-NG-monomethyl arginine (L-NMMA), a specific inhibitor of NO synthesis, abolished the mucosal pathology of intestinal GvHR and reduced the associated lymphocytic infiltration of the epithelium. L-NMMA had no effect on splenomegaly in GvHR, nor did it interfere with the growth of an undifferentiated crypt stem cell line, or the production of tumor necrosis factor-alpha by activated macrophages in vitro. In contrast, L-NMMA inhibited the enhanced activity of natural killer (NK) cells which occurs in GvHR. We conclude that a NO-dependent mechanism is essential for intestinal immunopathology in GvHR and that this may reflect a role for NO in NK cell function.
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PMID:Nitric oxide mediates intestinal pathology in graft-vs.-host disease. 163 8

Leukocytosis associated with malignant disease has been known as a paraneoplastic syndrome and occurs occasionally in patients with oral malignancies. In this study, mechanisms underlying leukocytosis associated with malignancy was investigated, using a squamous cell carcinoma of the maxilla from a patient who manifested marked leukocytosis. When the patient's tumor was inoculated into nude mice, it formed squamous cell carcinoma (MH85) and induced leukocytosis and splenomegaly. Leukocytosis and splenomegaly paralleled tumor growth. Surgical excision of MH85 tumor resulted in a dramatic reduction of leukocyte count and spleen weight, indicating an involvement of humoral mediators released by MH85. MH85 cells conditioned medium (MH85CM) were shown to contain granulocyte-colony stimulating factor (G-CSF) activity, which is a potent growth factor specific for granulocytes. These results suggest G-CSF or G-CSF like substance secreted by MH85 cells is responsible for leukocytosis in MH85 bearing nude mice (MH85 mice) and in the patient. MH85 cell growth was stimulated by G-CSF and inhibited by anti-G-CSF antibody, thus suggesting that G-CSF like substance is a autocrine growth factor for MH85 cells. Splenectomized MH85 mice developed less severe leukocytosis than did non-splenectomized mice. This finding indicated that not only G-CSF like substance secreted by MH85 cells but other humoral factors released by the hyperplastic spleen contribute to the development of leukocytosis. Splenic monocytes derived from MH85 mice and MH85CM-stimulated splenic monocytes showed increased secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), both of which have been reported to induce neutrophilia in animals. Moreover, injection of anti-TNF-antibody into neutrophilic MH85 mice significantly, although not completely, decreased leukocyte count. Thus, it seemed likely that increased secretion of TNF and IL-1 by spleen cells that are stimulated by humoral factors released from MH85 also contributes to the progression of leukocytosis. In splenectomized mice, enlargement of MH85 tumor was retarded and metastases were impaired compared these in nonsplenectomized mice. Coculture of splenocytes from MH85 mice with normal spleen cells, inhibited blastogenesis in response to mitogen. The result suggests that splenocytes from MH85 mice played as immune suppressive cells. MH85CM conferred immune suppressive activity on normal spleen cells. This suppressor cell-inducing factor (SCIF) in MH85CM was found to have an apparent molecular weight of approximately 25kd, and its biological activity was neutralized by anti-G-CSF antibody. Therefore, SCIF secreted by MH85 cells was likely to be G-CSF like substance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on the pathophysiology of paraneoplastic syndromes: both cancer cells and host immune cells are responsible for the pathophysiology of leukocytosis associated with oral cancer]. 172 87

The toxic effects of endotoxin-free human recombinant tumor necrosis factor (rH-TNF), shown to contain less than 50 pg endotoxin/mg rH-TNF, were investigated and compared with those of rH-TNF and endotoxin coadministered at 4-400 ng endotoxin/mg rH-TNF in female Sprague-Dawley rats. The mean lethal dose of 5.9 mg/kg rH-TNF found for the endotoxin-free rH-TNF was far higher than that attributed to rH-TNF by other investigators. Coadministration with endotoxin derived from E. Coli. Salmonella abortus equi, or Serratia marcescens reduced the apparent mean lethal dose of rH-TNF in correspondence to the endotoxin concentration, with a value of 0.7 mg/kg rH-TNF observed at 1600 ng, 757 ng, and 5260 ng endotoxin/mg rH-TNF, respectively. Coadministration also resulted in more severe histopathologic and physicochemical effects than rH-TNF alone. Histopathologic abnormalities observed only in coadministration included interlobular edema and hemorrhage of the pancreas and, most remarkably, splenomegaly, which was not observed with rH-TNF alone even at lethal doses. The results indicate that particular care in determining endotoxin contamination is essential in any consideration of TNF toxicity.
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PMID:Exacerbation of toxic effects by endotoxin contamination of recombinant human tumor necrosis factor. 252 55

The influence of antibodies to recombinant murine tumor necrosis factor-alpha (anti-rMuTNF-alpha) on the development of the graft-versus-host reaction in vivo was investigated. This was done by evaluating the degree of splenomegaly in newborn BDF1 (B6xDBA/2) mice 10-11 days after injection of autologous BDF1 (controls) or semiallogeneic B6 (test) spleen cells. Splenomegaly, as reflected by the spleen index, among test BDF1 mice was 3-4-fold greater than the SI of control BDF1 mice. However, the treatment of test BDF1 mice with multiple injections of rabbit anti-rMuTNF-alpha antiserum resulted in a significant reduction in the SIs. In additional experiments, hamster monoclonal antibodies to rMuTNF-alpha were also shown to be effective in preventing the GVHR in vivo. Neither normal rabbit serum nor normal hamster IgG affected the GVHR in test BDF1 mice. These results indicate that TNF-alpha plays an important role in the development of the GVHR in vivo and suggest that antibodies, or other antagonists, to TNF-alpha may have potential use for the management of organ or tissue transplants.
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PMID:Prevention of the graft-versus-host reaction in newborn mice by antibodies to tumor necrosis factor-alpha. 252 89

Murine retrovirus infection induces loss of vitamin E and immune dysfunction with loss of cytokine production by T-helper cells. Therefore interferon-gamma (IFN-gamma) was given during dietary vitamin E supplementation to effectively prevent murine retrovirus-induced immunosuppression, cytokine dysregulation, and development of murine AIDS. Administration of IFN-gamma during vitamin E supplementation significantly prevented development of retrovirus-induced suppression of splenic natural killer cell activity and T cell proliferation. It also significantly slowed retrovirus-induced elevation of T helper (Th) 2 cytokine [interleukin (IL)-4, IL-5, and IL-10] production and monokine (IL-6 and tumor necrosis factor-alpha) secretion by splenocytes. The treatment also prevented loss of Th1 cytokine (IL-2 and IFN-gamma) secretion by splenocytes from retrovirus-infected mice alleviating splenomegaly and hypergammaglobulinemia. The combined therapy had an additive therapeutic impact. It was more effective than IFN-gamma treatment or vitamin E supplementation alone in delaying the development of retrovirus-induced immunosuppression with its cytokine dysregulation.
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PMID:Vitamin E supplementation with interferon-gamma administration retards immune dysfunction during murine retrovirus infection. 749 68

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in a liquid diet, significantly restored levels of interleukin-2 (IL) and interferon-gamma produced by splenocytes, which were suppressed by retrovirus infection. Retrovirus infection elevated levels of IL-6 and IL-10 produced by splenocytes, which were significantly normalized by all levels of vitamin E supplementation, respectively. Increased levels of IL-6 and tumor necrosis factor-alpha, produced by splenocytes during progression to murine AIDS, were also significantly normalized by all levels of vitamin E supplementation. Vitamin E supplementation restored retrovirus-suppressed splenocyte proliferation and natural killer cell cytotoxicity. Vitamin E supplementation also alleviated the AIDS symptoms: splenomegaly and hypergammaglobulinemia. These data indicate that dietary vitamin E supplementation at extremely high levels was not immunotoxic, and can modulate cytokine release and normalize immune dysfunctions during progression to murine AIDS. It should favorably affect host resistance and thereby retard the development of AIDS.
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PMID:Modulation of immune function and cytokine production by various levels of vitamin E supplementation during murine AIDS. 762 53

Four B-CLL patients, treated with verapamil for cardiac problems, showed substantial reduction of lymphadenopathy in one, a 3- and 5-year stabilization of B-CLL in two patients, and a dramatic decrease in lymphocyte count, lymphadenopathy and splenomegaly in one stage IV patient. We therefore studied the effects of verapamil on B-CLL cells in vitro. In 13 samples we observed that verapamil strongly inhibited in vitro proliferation of pokeweed mitogen (PWM) stimulated and unstimulated cells. Using a cytotoxic bioassay, we found that verapamil markedly inhibited the spontaneous and PMW-induced release of tumor necrosis factor (TNF) by B-CLL cells. These findings suggest that verapamil may block B-CLL cell proliferation through inhibition of TNF release and thereby may contribute to the management of B-CLL.
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PMID:Verapamil inhibits B-cell proliferation and tumor necrosis factor release and induces a clinical response in B-cell chronic lymphocytic leukemia. 780 9

Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor necrosis factor (TNF) alpha were measured in 42 patients with primary hypogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 congenital hypogammaglobulinemia (CH), 7 X-linked agammaglobulinemia (XLA), and in 21 healthy controls. The cytokine levels were correlated to other immunological parameters including serum levels of neopterin and soluble CD8 (sCD8) antigen. IL-6 was detectable in 48% and IL-4 in 36% of the CVI patients, but in none of the controls. Seventy-five percent of the CVI patients with elevated IL-4 levels had detectable IL-6. In contrast, no patients in the XLA group and only three CH patients had detectable IL-4 or IL-6 levels. TNF alpha and IL-1 alpha were detected in only a few serum samples with no significant differences between patients and controls. In the CVI group elevated IL-6 levels were significantly associated to reduced numbers of CD4+ and CD19+ lymphocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis. The raised IL-6 levels were confirmed in longitudinal testing, probably reflecting a characteristic immunological dysregulation in these patients. Cytokine alterations may play a role in the pathogenesis of the immunodeficiency and for the clinical manifestations in CVI patients. Alternatively, elevated cytokine levels may be only a marker of chronic immune activation, particularly in monocytes, possibly delineating a distinct subgroup of patients within the heterogeneous CVI group.
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PMID:Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. 790 14

Mice with skin tumors induced either by 7,12-dimethylbenz[a]anthracene complete carcinogenesis or subcutaneous injection of a carcinogenic keratinocyte cell line showed moderate to severe splenomegaly as a result of an increase in splenic granulocyte-macrophage and erythroid (erythroid burst-forming unit) progenitors. To test whether the observed alterations involve the release of soluble factors by the epidermal component of skin tumors, we used an in vitro approach. A series of mouse keratinocyte cell lines resembling progressive stages of skin carcinogenesis and carrying either normal or activated Ha-ras genes were assayed for their ability to produce the factors required for colony growth of hematopoietic-committed progenitors. Only the conditioned media of keratinocytes harboring activated Ha-ras genes were able to support the growth of granulocyte-macrophage colony-forming units. In addition, preincubation of normal bone-marrow cells with conditioned media from the transformed epidermal cell lines stimulated in vitro amplification of the hematopoietic granulocyte-macrophage progenitor compartment. To identify the possible factors responsible for the activities detected in the keratinocyte-conditioned media, we performed northern blot analysis using the cytokine probes granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, stem cell factor, interleukin-1 alpha, interleukin-3, and tumor necrosis factor-alpha. The cell lines expressed different cytokine mRNA combinations that positively correlated with the colony-stimulating activity detected in the corresponding conditioned medium. These results suggest that transformed epidermal tumor cells in vivo may alter normal hematopoiesis as a consequence of the production of cytokines that act in autocrine or paracrine loops probably related to tumor growth.
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PMID:Augmented expression of cytokines in mouse epidermal tumor cells and its possible involvement in the induction of hematopoietic alterations. 794 4


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