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)

Treatment of a 74 year old patient with chronic myelogenous leukemia (CML) with busulphan resulted in an abrupt and pronounced decrease of the white blood cell (WBC) count with restoration of normal peripheral blood cell morphology and regression of splenomegaly. The Philadelphia positive (Ph+) clone was however still detectable. The alterations in the WBC count and morphology were not preceded by marrow hypoplasia but correlated closely with a marked decrease in the serum levels of Transcobalamin I (TC I), a vitamin B12-binding protein derived from immature myeloid precursors and a reciprocal rise in serum TC III, a vitamin B12-binding protein originating from terminally differentiated mature granulocytes. Studies on the HL-60 cell line showed that busulphan is capable of inducing leukemic cells to differentiate into granulocyte-like cells. These observations, taken together, suggest that in addition to its potent myelosuppressive effects, busulphan may induce apparent clinical remissions in some CML patients by promoting terminal cell differentiation.
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PMID:Induction of differentiation of myeloid leukemic cells by busulphan: in vivo and in vitro observations. 826 Sep

Underlying diseases, complications, clinical findings, and laboratory findings were evaluated in 158 cases of septicaemia admitted to Jikei University Hospital from 1975 to 1994, in order to conjectured factors that prescribe for the prognosis. 50% of the patients had underlying diseases. Malignancy including leukaemia (31 cases, 39.2%) was the most common underlying disease, followed by low birth weight infant (17 cases, 21.5%), aplastic anemia (9 case, 11.4%), and congenital heart disease (7 cases, 8.9%). The death rate for patients with underlying disease (27.8%) was significantly greater than the mortality for normal patients with septicaemia (8.9%) (p < 0.05). Meningitis (24.7%) was the most common complication, followed by DIC (19.6%), shock (15.2%), and pneumonia (10.8%). The mortality rate of septicaemia complicated by shock was 66.7% (p < 0.01), and that complicated by DIC was 45.2% (p < 0.01). The mortality rate for patients with the clinical findings of respiratory distress, cough, abdominal distention, cyanosis, splenomegaly, or peripheral coldness was more than 40% and significantly greater (p < 0.01). Mortality rate in patients with granulocyte counts of < 4.000/mm3, platelet counts of < 5 x 10(4)/ mm3, total protein of < 5.0 g/dl, or ESR of < 20 mm/hr were significantly greater (p < 0.01) than those in patients with normal laboratory findings. Coincidence rate of blood and stool cultures was 57.9% for E. coli, and 28.6% for Klebsiella sp., and that of blood and throat cultures was more than 30% for Pseudomonas sp., Haemophilus influenzae, and Staphylococcus aureus. In the study of antimicrobial susceptibility for microorganisms isolated, the number of drug resistant S. aureus had increased in the last 10 years.
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PMID:[Study on septicaemia in infants and children in the past 20 years. Part 2. An analysis of factors that prescribe for the prognosis]. 889 May 45

Using a human melanoma/Scid xenograft model with the C8161, M24-met, LD-1 and other human melanoma lines to investigate spontaneous metastasis, we made the observation of marked splenomegaly (up to five times normal weight and size) in only those xenografts exhibiting high degrees of spontaneous metastasis. Evaluation of this revealed the cause to be massive myelopoiesis due to ectopic granulocyte/ colony-stimulating factor (G-CSF) production by the melanoma cells. Because of these observations linking G-CSF expression with metastasis of human melanoma, we decided to investigate the mechanism of this ectopic production. No gross amplification or rearrangement of the G-CSF gene could be detected as the basis for the increased transcriptional activity in any of these lines. Human-human somatic cell hybridization studies carried out between the metastatic C8161 and several different nonmetastatic non-G-CSF-expressing lines revealed, in addition to metastatic dominance, 3- to 10-fold enhancement of G-CSF transcription and expression in the fusions compared with C8161 itself. The suggestion of a trans-dominant mechanism was further supported by transfection studies with a human G-CSF promoter-CAT-reporter construct, which revealed 3- to 5-fold increased reporter activity in only those melanoma lines and hybrids expressing G-CSF. Furthermore, no obvious autocrine or paracrine effects of this ectopic G-CSF expression on the melanoma lines' growth or metastasis were apparent, as all of the G-CSF-expressing lines lacked the G-CSF receptor and injections of purified recombinant G-CSF exerted no stimulatory effects on their tumorigenicity, latency, growth, or metastasis in Scid mice. Thus, we advance the hypothesis that G-CSF expression is serving as a marker of a more generalized trans-dominant pathway linked to tumor progression and metastasis. This hypothesis has direct relevance to many human cancers where ectopic hormone or growth factor production occurs with no obvious autocrine or paracrine benefit to the tumor.
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PMID:Ectopic G-CSF expression in human melanoma lines marks a trans-dominant pathway of tumor progression. 906 Aug 33

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.
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PMID:HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines. 920 2

Granulocyte colony-stimulating factor (G-CSF) has been used to improve granulocyte count in chronic neutropenia and myelodysplasia, to minimize the incidence and duration of neutropenia during conventional chemotherapy, and to mobilize peripheral blood stem cells prior to leukapheresis for use in autologous and allogeneic marrow transplantation. The most common toxicity is bone pain, and other reactions such as inflammation at the site of injection have also occurred. In patients with chronic neutropenia, splenomegaly has been described with long-term use, and extramedullary hematopoiesis has also been reported. However, thus far, no life-threatening sequelae of these effects are found in the literature. We now describe a case of spontaneous splenic rupture four days following a six-day course of G-CSF therapy in an allogeneic donor of peripheral blood stem cells.
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PMID:Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): occurrence in an allogeneic donor of peripheral blood stem cells. 950 2

We have recently reported that interleukin 18 (IL-18) pretreatment induces immunologically mediated antitumor effects in BALB/c mice injected i.p. with syngeneic Meth A sarcoma. In this study, mice were pretreated with IL-18 before Meth A transplantation, and immunocompetency in pretreated or untreated tumor-bearing mice (TBM) 3, 9, and 15 days after transplantation was compared with that of normal mice. On day 3, pretreated TBM mitogen-stimulated spleen cells produced significantly decreased levels of IL-2 and IFN-gamma during 24-h culture. In contrast, IL-10 and granulocyte macrophage colony-stimulating factor productions were significantly enhanced in pretreated TBM cultures, and natural killer (NK) cell activity was also significantly augmented. Splenomegaly was also observed in the pretreated TBM on day 3, and the proliferating cells were identified as asialo GM1+ cells by flow cytometry. Cytotoxic activity of pretreated TBM spleen cells after a 5-day mixed lymphocyte-tumor cell culture did not differ from that of untreated TBM and normal mice on day 3 but was significantly enhanced on days 9 and 15 compared with that observed in normal mice and untreated TBM. Concurrently, the production of IL-2 and of IL-10 recovered and decreased, respectively, and NK activity dropped to normal levels. The effects of IL-18 on cytokine production and NK activity observed on day 3 treated TBM were also reproduced in normal mice. In conclusion, IL-18 seems to enhance the generation of NK activity early after tumor transplantation and simultaneously induces an increase and a decrease in the production of IL-10 and IL-2, respectively. As NK activity subsides to normal levels and IL-10 synthesis decreases, IL-2 synthesis is restored, and cytolytic cell activity is significantly enhanced. These results provide new insight into the immunologically mediated antitumor effects of IL-18.
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PMID:Interleukin 18 induces the sequential activation of natural killer cells and cytotoxic T lymphocytes to protect syngeneic mice from transplantation with Meth A sarcoma. 937 69

As it is not known what changes to leucocyte homeostasis are mandatory for effective adjuvant action, the biological relevance of systemic changes elicited by different vaccine formulations can only be interpreted in the context of the immunological outcomes. We used flow cytometry to quantify the changes in leucocyte subsets induced in mice intradermally immunized with SAMA4 (adjuvant group), outer membrane proteins (OMP) purified from Actinobacillus pleuropneumoniae (OMP antigen group), SAMA4 adjuvanted OMP (OMP vaccine group), or phosphate-buffered saline (PBS: control group). This approach allowed direct comparisons to be made between the effects of antigen, adjuvant or antigen-adjuvant complexes on immune effector cell populations. Antigens complexed with the liposome-iscom hybrid adjuvant, SAMA4, generated strong antibody responses and cytotoxic T-cell activity in animals immunized intradermally, reflecting remobilization and recruitment of specific cell populations. Splenomegaly, due to granulocytosis, monocytosis and megakaryocytosis, was most prominent in the OMP vaccine group. Histological examination of spleen sections confirmed that these changes were due primarily to splenic haematopoiesis. Circulating numbers of granulocytes and monocytes increased significantly (P < 0.05) in the blood of the OMP vaccine group, as did granulocyte numbers in the lungs (P < 0.05). No changes in T- and B-cell numbers were detected by flow cytometry in the spleens, lungs or blood over the 28-day period in any treatment group. Thymocyte numbers (predominantly CD4+CD8+ cells) in the OMP vaccine group fell by 95% within 3 days of immunization. Identical cellular responses were obtained when an innocuous antigen, ovalbumin, was complexed with SAMA4 instead of OMP, thus demonstrating that the adjuvant effects of SAMA4 were due to synergistic interaction between antigen and adjuvant and not due to the presence of toxic components. The association of strong adaptive immune responses with such complex changes in leucocyte homeostasis induced by complexing adjuvant and antigen suggested that the changes were important for effective vaccination and were not purely circumstantial.
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PMID:Flow cytometric analysis of cellular changes in mice after intradermal inoculation with a liposome-iscom adjuvanted vaccine. 951 63

The administration of a high dose of IL-12 into the mice resulted in the induction of splenomegaly. From the flow cytometry analysis of cellularity in an enlarged spleen, it was demonstrated that Thyl.2-CD45RB-c-Kit + Sca-1 + Lin- hematopoietic progenitor cells markedly increased in IL-12-administered mouse spleen compared with untreated mouse spleen. The IL-12-induced hematopoietic progenitor cells showed a greatly enhanced colony-forming activity in CFU-granulocyte/macrophage (CFU-GM), blast-forming units-erythroid (BFU-E) and CFU-spleen (CFU-S) assay. Moreover, it was initially demonstrated that the transfer of IL-12-induced splenic hematopoietic progenitor cells into immunodeficient RAG2-/- mice caused a complete reconstitution of their immune functions including T- and B-cell-mediated immunity. Thus, the evidence that IL-12 has a capability of inducing hematopoietic progenitor cells possessing stem cell-like activity in vivo, indicated another important immunomodulating activity of IL-12 in immunotherapy.
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PMID:Reconstitution of immune systems in RAG2-/- mice by transfer with interleukin-12-induced splenic hematopoietic progenitor cells. 969 15

Felty's syndrome is a rare disorder characterized as a systemic manifestation of severe rheumatoid arthritis associated with granulocytopenia and splenomegaly. We report a retrospective analysis of a series of seven patients treated successfully with low-dose methotrexate. leading to sustained clinical improvement (number of swollen joints) and normalization of the granulocyte count for an observation period of 1 yr. Our cohort is the largest ever published with methotrexate treatment of this rare condition. Our results confirm earlier single case reports suggesting methotrexate to be the first-choice treatment nowadays in Felty's syndrome.
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PMID:Methotrexate treatment in Felty's syndrome. 973 84

Previously we described activating mutations of hbetac, the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, hbetacFIDelta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the hbetacFIDelta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in hbetac may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic hbetac activation has the potential to contribute to pathological events in the central nervous system.
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PMID:Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice. 983 20


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