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 24-year-old Japanese man presented with dyskeratosis congenita (DC, Zinsser-Cole-Engman syndrome) complicated by non-cirrhotic portal hypertension, signet ring carcinoma of the rectum and Pneumocystis carinii pneumonia. At the age of 9 years, he was diagnosed as having DC on the basis of typical clinical manifestations including atrophic lingual papillae, hyperpigmentation of the skin, thrombocytopenia, and ophthalmological abnormalities. A few years later pancytopenia and splenomegaly developed. At 24 years, signet ring carcinoma of the rectum was detected but could not be resected because of the severity of the pancytopenia. Death was due to respiratory failure from P. carinii pneumonia. At autopsy the case illustrated several unique findings for DC, including non-cirrhotic portal hypertension, atrophy of frontal lobe and markedly slender folia of the cerebellum and superimposed infections with herpes zoster virus and P. carinii. Striking lymphocyte depletion and atrophy of lymphoid parenchyma in lymph nodes, tonsils, spleen, gastrointestinal tract, or thymus were seen histologically. The morphological picture supports the suggestion that there is a defect in the cell-mediated immune system in patients with DC, although immunoglobulin levels in the blood are normal. The cell-immune deficiency is a major factor in the poor prognosis.
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PMID:Dyskeratosis congenita (Zinsser-Cole-Engman syndrome). An autopsy case presenting with rectal carcinoma, non-cirrhotic portal hypertension, and Pneumocystis carinii pneumonia. 216 77

Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers of eosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer's patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. IL-5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production of eosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.
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PMID:Eosinophilia in transgenic mice expressing interleukin 5. 223 Jun 51

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), an inhibitor of glycoprotein processing, has been shown to inhibit the human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured cells. In contrast to reverse transcriptase inhibitors, castanospermine targets host enzymes. We have analyzed castanospermine in murine systems, using cultured cells as well as live animals. Plaque formation by Rauscher murine leukemia virus (RLV) was inhibited with a median inhibitory concentration (IC50) of 2 micrograms/ml. RLV-exposed BALB/c mice treated with a 20 day course of castanospermine starting 4 h postinoculation showed a dose-dependent inhibition of splenomegaly. Oral castanospermine therapy given to chronically RLV-infected mice prolonged median survival from 36 to 94 days when compared to untreated controls (p = 0.007). Castanospermine was better tolerated orally than intraperitoneally at the same dose. Toxic effects included weight loss, lethargy, and dose-dependent thrombocytopenia. At the highest intraperitoneal dose, lymphoid depletion occurred in thymus, spleen, and lymph nodes. We conclude that castanospermine is an active antiviral agent in animals and that prolonged oral administration is tolerable; however, when compared to 3'-azido-3'-deoxythymidine in the same murine system, castanospermine was less active and more toxic.
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PMID:In vivo analysis of castanospermine, a candidate antiretroviral agent. 249 48

Histiocytosis X (HX) is a rare disorder of histiocytic proliferation characterized by a broad spectrum of clinicopathologic disease. An unusual case of Letterer-Siwe disease (LSD) or subacute disseminated HX in a 71-year-old woman is presented. The patient had a 3-year history of splenomegaly before skin lesions developed. She presented to our clinic at 1.5 years later and the diagnosis of HX was made by skin biopsy. Topical nitrogen mustard (NM) therapy resulted in complete clearing of cutaneous lesions. Her condition was stable over the next 10 months. However, she subsequently suffered a rapid and fatal dissemination of her disease. Systemic treatment with prednisone, vinblastine sulphate, and suppressin A (SA) (a calf thymus derived hormone preparation that specifically induces suppressor T-cells) was ineffective. Characteristic histopathologic, immunohistochemical, and electron microscopic findings of HX are illustrated. A review of the adult cases of LSD and treatment options for HX are presented and discussed.
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PMID:Letterer-Siwe disease in adults. 264 29

Infection of 10-day-old chickens with an avian osteopetrosis virus resulted in a severe regenerative aplastic crisis. Hematopoietic and lymphopoietic tissues of chickens infected with myeloblastosis-associated virus (of subgroup B, inducing osteopetrosis, MAV-2(O] were analyzed for integrated and unintegrated viral DNA sequences, cell population shifts, weight changes, and morphological alterations. By 6 days postinfection (p.i.), DNA from bone marrow cells and peripheral blood leukocytes (PBL) contained between 0.50 and 0.70 copies of viral DNA per haploid genome. Erythrocytes and splenic leukocytes contained less than 0.10 copies/haploid genome. Granulocytes and precursor mesomyelocytes were absent from bone marrow, but numbers of erythrocytes, erythroblasts, and reticulocytes were normal. By 9 days p.i., bone marrow was severely hypoplastic and both granulopoietic and erythropoietic colonies were depleted. By 12 days p.i., erythrocytes and granulocytes were maximally depressed in peripheral blood and the amount of integrated virus in bone marrow and PBL decreased to less than 0.20 copies/haploid genome. In contrast, erythrocytes contained integrated viral DNA of up to 0.30 copies/haploid genome, indicating infection of erythrocyte precursors. At 18 days p.i., viral DNA was detected only in erythrocytes. Unintegrated viral DNA was not detected in any organs. Anemia was accompanied by splenomegaly and erythrophagocytosis. Viral DNA was never detected in thymus or bursa. Differential counting and flow cytometry of cells from bursa, thymus, and spleen, and of blood lymphocytes did not detect significant population shifts. These results suggest that MAV-2(O) infection of immunocompetent chickens occurs primarily in myelopoietic tissues, and tissues are selectively infected.
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PMID:Analysis of hematopoietic and lymphopoietic tissue during a regenerative aplastic crisis induced by avian retrovirus MAV-2(O). 283 18

Transplantation of allogeneic bursal cells into cyclophosphamide-treated, immunodeficient chickens is a useful experimental model for analyzing the mechanisms of transplantation tolerance, especially because transplanted bursal cells do not produce graft-versus-host disease. In this study we have determined B-lymphoid chimerism in various lymphoid organs after transplantation of allogeneic bursal stem cells or postbursal cells, and used a variety of tests to determine presence of immunological tolerance. Transplanted bursal stem cells induced a state of stable chimerism that could easily be detected in peripheral blood and other lymphoid organs. Chimerism induced by postbursal cells was low in peripheral blood, but clearly observable in other lymphoid organs, especially in spleen and thymus. Both bursal and postbursal cells induced specific unresponsiveness to donor-line alloantigens. Bursal cell recipients accepted donor line skin grafts--and their graft-versus-host reactivity, as assayed by embryonal splenomegaly, and mixed lymphocyte reactivity against donor line alloantigens were significantly decreased. Despite differences in chimerism, a strong transplantation tolerance was readily induced with bursal stem cells and with postbursal cells.
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PMID:Lymphoid cell chimerism and transplantation tolerance induced by bursal and postbursal cells. 293 68

Implantation of either major histocompatibility complex (MHC)-disparate thymus to 7-day thymectomized (Tx) Xenopus in late larval life, or allogeneic skin to perimetamorphic controls, routinely induces tolerance towards implant-strain skin grafts applied in adult life. To characterize this allotolerance further, additional in vivo approaches were attempted. Injection of gamma-irradiated (5000 rads) implant-strain splenocytes into frogs bearing tolerant skin grafts revealed (within 3 days) significantly elevated tritiated thymidine uptake by host spleen cells, compared to siblings injected with isogeneic cells. Although this in vivo 'mixed leucocyte reaction' proved to be thymus dependent, the identity of the cells involved awaits clarification. When non-restored Tx Xenopus are injected with live MHC-disparate splenocytes, graft-versus-host (GVH)-induced mortality ensued within 2 weeks. Such GVH disease also occurred (albeit more chronically) when Tx allothymus-implanted animals were given MHC-incompatible splenocytes, but only when these came from the thymus donor strain. Splenocytes from thymus-implanted animals failed to achieve GVH-induced splenomegaly when transferred to appropriate hosts (bearing MHC antigens of the thymus donor strain). Overall, the experiments indicate that alloreactivity against donor cells is impaired but not completely inhibited in Xenopus following perimetamorphic implantation.
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PMID:In vivo studies on allotolerance perimetamorphically induced in control and thymectomized Xenopus. 296 Jun 13

A novel murine retrovirus complex was derived from the in vivo passage of a molecularly cloned Friend ecotropic helper virus. The virus isolate, myeloproliferative leukemia virus (MPLV), causes an acute (2-3 weeks) and generalized myeloproliferative disorder in adult mice. All strains of mice examined, including the C57BL/6J strain, developed the acute syndrome. This syndrome is characterized by a rapid hepatosplenomegaly, no thymus or lymph node involvement, granulocytosis, thrombocytosis, and erythroblastosis leading to polycythemia. The most prominent feature at the terminal phase of the disease is a granulocytic hyperplasia. The MPLV isolate replicates in vitro on NIH 3T3 fibroblasts but does not induce foci of transformed cells. Thus, MPLV exhibits unique biological properties that distinguish it either from the Friend virus complexes or from acutely transforming sarcomatogenic murine retrovirus which also induced a rapid splenomegaly.
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PMID:MPLV: a retrovirus complex inducing an acute myeloproliferative leukemic disorder in adult mice. 300 28

The effects of cytomegalovirus (CMV) infection on the spleen and thymus of neonatal guinea pigs were assessed. Guinea pigs with neonatally acquired CMV infection developed growth retardation, thymic hypoplasia and splenomegaly. Significant depletion of the T lymphocyte population occurred in the thymuses of these animals whereas inflammatory and immune proliferative responses were clearly evident in their spleens. Higher titers of infectious virus were recovered from the spleen than from the thymus. In addition, spleen cells from neonatally infected animals had significantly reduced proliferative responses to both the T-cell mitogen, concanavalin A, and the B-cell mitogen, lipopolysaccharide. Responses to concanavalin A were most severely impaired. These results point to the significant immunodepressive effect of acute CMV infection and to the dissimilar alterations induced by CMV in the spleen and thymus of acutely infected neonates.
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PMID:Thymic hypoplasia, splenomegaly and immune depression in guinea pigs with neonatal cytomegalovirus infection. 304 Apr 85

A better understanding of the mechanisms involved in the proliferation of splenic colony-forming units (CFU-s) during tumor growth is important for the prevention of bone marrow aplasia during chemotherapy. The in vivo growth of EMT6 cells, a colony-stimulating factor-secreting mammary tumor, in BALB/c and nude mice resulted in splenomegaly and an increase in the number of splenic granulocyte/macrophage colony-forming cells (GM-CFC). Proliferation of CFU-s, observed in BALB/c mice but not in nude mice, most likely resulted from combined direct and indirect actions of factors secreted by tumor and host cells (in particular helper T cells). These factors were detectable in the serum immediately following tumor cell injection. Thus, the GM-CFC response to factors secreted by the EMT6 tumors is thymus-independent while the CFU-s response is dependent upon the presence of T cells. Finally, we show that EMT6 tumor growth had no effect on the determination of CFU-s differentiation toward the various myeloid cell lineages.
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PMID:Thymic dependency of the humoral regulation of CFU-s proliferation in mice bearing a CSF-producing tumor. 304 67


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