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)

The inbred mouse strain CWD/Agl has a high incidence of spontaneous B-cell lymphomas characterized by gross splenomegaly and lymph node enlargement. The endogenous ecotropic retrovirus of CWD/Agl mice is expressed in the spleen within the first 2 weeks of age and in the thymus by 1 month of age. Endogenous xenotropic virus is expressed in the spleen and bone marrow of the earliest age group examined (4 months). Restriction enzyme analysis of DNA extracted from tumorous tissues suggests that mink cell focus-forming viruses are not required for B-cell lymphomagenesis in CWD/Agl mice. CWD/Agl mice provide an important new experimental model for the study of B-cell lymphoma.
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PMID:Expression of murine leukemia viruses in B-cell lymphomas of CWD/Agl mice. 609 92

Unintegrated viral DNA was isolated via the Hirt procedure from mouse fibroblasts newly infected with Friend murine leukemia virus (F-MuLV) clone 201, a biologically cloned helper virus isolated from stocks of F-MuLV complex. A physical map of the unintegrated in vivo linear viral DNA was generated for several restriction endonucleases. The supercoiled viral DNA was digested with EcoRI, which cleaved the viral DNA at a unique site. The linearized viral DNA was then inserted into lambda gtWES.lambda B at the EcoRI site and cloned in an approved EK2 host. Eight independent lambda-mouse recombinants were identified as containing F-MuLV DNA inserts by hybridization with F-MuLV 32P-labeled complementary DNA. One of the F-MuLV DNA inserts was 9.1 kilobases (kb) and had the same restriction enzyme sites as the unintegrated linear F-MuLV DNA. Six inserts were 8.5 kb; each lacked a single copy of the terminally redundant sequences of the unintegrated linear viral DNA. One insert was 8.2 kb and contained a 0.9-kb deletion. After digestion with EcoRI, one recombinant DNA preparation containing an 8.5-kb insert was infectious for NIH 3T3 cells. Undigested recombinant DNA was not infectious. The infectivity of the EcoRI-digested DNA followed multihit kinetics, indicating that more than one molecule was required to register as an infectious unit. The virus isolated from this transfection (F-MuLV-57) was NB-ecotropic, helper-independent, and formed XC plaques. Inoculation of this virus into newborn NIH Swiss mice induced leukemia and splenomegaly in greater than 90% of animals within 3 to 4 weeks. The gross and microscopic abnormalities induced by F-MuLV clone 57 were identical to those seen with the original parent stocks of F-MuLV clone 201. These results indicate that this helper-independent F-MuLV can induce a rapid nonthymic leukemia in the absence of the spleen focus-forming virus.
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PMID:Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus. 624 44

Friend murine leukemia virus (G-MuLV) is a helper-independent, type C retrovirus isolated from stocks of Friend virus complex (spleen focus-forming virus plus MuLV). In cell culture, F-MuLV has an ecotropic and NB-tropic host range and causes XC cells to fuse. When injected into newborn NIH Swiss mice, F-MuLV produces hepatosplenomegaly, severe anemia, and numerous circulating hematopoietic precursors in the peripheral blood with normal thymus and lymph nodes after 3 to 6 weeks. Recently, we molecularly cloned an 8.5-kilobase pair (kbp) form of F-MuLV DNA from which we could recover the pathogenic F-MuLV virus by DNA transfection of NIH 3T3 cells. From this molecularly cloned F-MuLV DNA, we have now subcloned in pBR322 a 4.1-kbp HindIII fragment which contains in continuity 3.0 kbp from the 3' terminus (env and c region), 0.6 kbp of the terminal repeat sequences, and 0.5 kbp from the 5'terminus of the viral RNA (genome). NIH 3T3 fibroblasts were transfected with this DNA fragment an then infected with the wild mouse amphotropic retrovirus (cl 1504-A). In cell culture, 1504-A is a helper-independent type C virus which has an N-tropic host range and does not cause fusion of XC cells. When injected into newborn NIH Swiss mice, 1504-A does not produce splenomegaly or thymic enlargement in mice held for up to 8 months. The transfection with the F-MuLV fragment and the infection with 1504-A consistently yielded virus preparations that were XC positive. From such virus stocks we were able to isolate both helper-independent and replication-defective XC-positive viruses. The helper-independent virus was shown to be a recombinant virus since it contains a gp70 molecule derived at least in part from F-MuLV and a specific gag precursor derived from 1504-A as determined by radioactive immune precipitation assays. When injected into newborn Swiss mice, the recombinant helper-independent virus caused hepatosplenomegaly in approximately 50% of the mice in 6 to 8 weeks. The histology of the diseased splenic tissue was indistinguishable from that seen in the disease caused by the whole F-MuLV. The replication-defective virus could be pseudotyped with new 1504-A virus, and this viral complex also caused the F-MuLV disease picture when the complex was injected into newborn Swiss mice. We conclude that the genetic information responsible for the pathogenicity of F-MuLV is contained within the 4.1-kbp DNA fragment, which includes env gene sequences, the terminal repeat sequences, and the c region sequences of the F-MuLV genome.
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PMID:Subgenomic fragment of molecular cloned Friend murine leukemia virus DNA contains the gene(s) responsible for Friend murine leukemia virus-induced disease. 625 47

The integrated proviral DNA of the polycythemia-inducing isolate of Friend spleen focus-forming virus (SFFVp) has been identified in rat cell clones nonproductively infected with this replication-defective erythroleukemia virus and cloned in phage lambda vectors. These lambda SFFVp recombinants, lambda SFFVp502 and lambda SFFVp542, contain endonuclease EcoRI inserts of size 7.4 and 8.2 kilobases, respectively, and include full copies of the SFFVp genome, along with host flanking sequences. Infectivity of the cloned SFFVp genomes was tested by a two-step DNA transfer procedure involving transfection of the cloned DNA into 3T3 mouse fibroblasts or cotransfer of the cloned DNA into thymidine kinase-deficient 3T3 cells together with the cloned thymidine kinase gene of herpes simplex virus, followed by rescue of the transferred DNA by superinfection with a helper virus. Inoculation of the rescued virus into adult mice resulted in the appearance of spleen foci, rapid splenomegaly, and polycythemia. Early after infection, spleen cell populations contained large numbers of cells capable of forming small erythroid colonies in vitro (CFU-E) in the absence of erythropoietin. Late after infection, these mice contained cells capable of forming macroscopic colonies (CFU-FV) in vitro. These data indicate that molecular clones of SFFVp, in conjunction with a helper virus, induce the appearance of hemopoietic colony-forming cells characteristic of both the early and late stages of Friend leukemia.
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PMID:Clonal analysis of early and late stages of erythroleukemia induced by molecular clones of integrated spleen focus-forming virus. 627 94

Previously, we have molecularly cloned proviral DNA of a polycythemia-inducing strain of the spleen focus-forming virus (SFFVp). In this paper, we report that unintegrated proviral DNA of the anemia-inducing strain of SFFV (SFFVA) has been molecularly cloned into pBR322. This molecularly cloned DNA retains the biological activity of SFFVA, as infectious SFFV can be recovered from the DNA clone by marker rescue using a previously described two-stage cotransfection assay (Linemeyer et al., J. Virol. 35:710-721, 1980). The recovered SFFV retains an important property of the initial SFFVA which distinguishes SFFVA from SFFVP, namely, the ability of SFFVA to cause proliferation of erythroid cells in which hemoglobin synthesis is erythropoietin dependent. By utilizing a marker rescue technique, the splenomegaly and anemia characteristic of SFFVA-induced disease have been traced to a DNA fragment of SFFVA containing sequences coding for the env gene product. gp52. The results suggest that the differences in pathogenicity between SFFVP disease and SFFVA disease are an intrinsic property of the env gene products of these two variants of Friend virus, and future studies with the molecular clones of each strain should allow us to map regions of each env gene responsible for common and distinctive features of the erythroproliferative diseases induced by each virus.
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PMID:Molecular cloning of biologically active proviral DNA of the anemia-inducing strain of spleen focus-forming virus. 629 39

Recombinant murine retroviruses containing the src gene of the avian retrovirus Rous sarcoma virus were isolated. Such viruses were isolated from cells after transfection with DNAs in which the src gene was inserted into the genome of the amphotropic murine retrovirus 4070A. The isolated viruses had functional gag and pol genes, but they were all env defective since the src gene was inserted in the middle of the env gene coding region. Infectious transforming virus could be isolated only from cells transfected with DNA constructions in which the src gene was in the same polarity as that of a long terminal repeat of the amphotropic viral genome. These recombinant viruses encoded a pp60src protein with a molecular weight similar to that of the Schmidt-Ruppin strain of Rous sarcoma virus. In addition, the src protein(s) of these recombinant viruses was as active as protein kinases in the immune complex protein kinase assay. Intravenous injection of helper-independent Moloney and Friend murine leukemia virus pseudotypes of the src recombinant viruses into 6-week-old NIH Swiss mice resulted in the appearance of splenic foci within 2 weeks, splenomegaly and, later after infection (8 to 10 weeks), anemia. Infectious transforming virus could be recovered from the spleens of diseased animals. Such viruses encoded pp60src but not p21ras or mink cell focus-forming virus-related glycoproteins.
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PMID:Construction and isolation of a transforming murine retrovirus containing the src gene of Rous sarcoma virus. 630 22

Lipoprotein prepared from the outer membrane of Salmonella typhimurium is a polyclonal activator of murine B-lymphocytes. It was shown to be mitogenic for splenic cultures, stimulating increased incorporation of [3H]thymidine into DNA. When injected intravenously into mice, the lipoprotein induced splenomegaly and polyclonal B-cell activation. The latter was evident from an increase in the number of plaque-forming cells against trinitrophenylated sheep erythrocytes. Similar results were obtained with Escherichia coli lipoprotein.
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PMID:Polyclonal activation of B-lymphocytes in vivo by Salmonella typhimurium lipoprotein. 634 Dec 38

One of the hallmarks of the hyperglycemic-hyperinsulinemic infant of the diabetic mother (IDM) is macrosomia and selective organomegaly. Primary hyperinsulinemia, with insulin levels similar to those observed in human IDMs at delivery, was produced in the fetal rhesus monkey during the last third of gestation. The effects of this physiologically relevant hyperinsulinemia, in the absence of hyperglycemia, on fetal growth were studied. Fetal macrosomia, with a 23% increase in total body weight, was observed in physiologically hyperinsulinemic fetuses. A similar 27% increase in weight was produced by fetal insulin levels that were 10 times higher. A logarithmic correlation was observed between fetal birth weight ratio and fetal plasma insulin concentration. In contrast to this increase in weight, skeletal growth, as measured by crown-heel length and head circumference, was not affected by hyperinsulinemia. Only cardiomegaly was found in the low-dose hyperinsulinemic fetuses, whereas cardiomegaly, hepatomegaly, and splenomegaly were produced by hyperinsulinemia in which insulin levels were in the highest range. Compositional analysis of heart and skeletal muscle indicated no differences in the protein, RNA and DNA concentration, or in the protein-to-DNA ratio in hyperinsulinemic fetuses. We interpret these data as indicating that fetal insulin plays the predominant role in controlling the normal, as well as the augmented, fetal weight characteristic of the human infant of the diabetic mother.
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PMID:Chronic hyperinsulinemia in the fetal rhesus monkey. Effects of physiologic hyperinsulinemia on fetal growth and composition. 637 21

Therapeutic trials with mizoribine (MZR), an imidazole nucleoside immunosuppressant, on experimental lupus nephropathy of NZB/W F1 mice resulted in the following. The MZR treatment, 20 mg per kilogram of body weight every other day, starting at 14 weeks of age, caused a significantly prolonged survival time of mice with a mean life span of 54.3 +/- 4.2 weeks, compared with the untreated controls, who had a mean survival time of 38.1 +/- 2.9 weeks (P less than 0.01). In addition, MZR suppressed the elevation of serum anti-DNA antibody titers, the spontaneous development of splenomegaly, and the histological development and progression of glomerulonephritis observed in untreated animals. Although no definite explanation is available at present to explain how MZR caused decreased anti-DNA antibody production and delay in the development of glomerulonephritis in these animals, it is suggested that it acts by directly suppressing the hyperfunctioning B cells of lupus mice. MZR may prove to be a promising immunosuppressant for the treatment of human lupus, in view of its lesser side effects such as bone marrow suppression or hepatotoxicity.
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PMID:Effect of mizoribine on lupus nephropathy of New Zealand black/white F1 hybrid mice. 647 55

The trypanocidal drug suramin causes glycosaminoglycan and sphingolipid accumulation in the rat, thus simulating a mucopolysaccharidosis (Constantopoulos et al. 1980). In this paper we report on the extent and nature of the morphological changes that occur in the liver, kidneys, spleen, heart, lung and brain as a result of short or long term suramin administration. The first group of rats received a single intravenous injection of suramin (500 mg/kg) and was sacrificed 3-9 days after the injection. The second group received low doses of suramin (50-90 mg/kg) at 2-3 weekly intervals over 3 months. Samples of the above mentioned organs were processed for light and electronmicroscopy and the remainder of the tissue weighed and assayed for total protein, DNA and RNA content. In both groups of rats, suramin caused an abnormal enlargement of the spleen, kidney, lung and liver, splenomegaly being the most pronounced. The total protein, and DNA content did not alter in the treated rats, however, the RNA content of the spleen increased 100%, 9 days after injection and there was a small but consistent increase in RNA content of the liver, kidney and lung. Significant pathological changes were observed in these organs and also in the brain and heart. The changes were similar in many respects to the pathology seen in the lysosomal storage disorder, mucopolysaccharidosis and further support the proposition that the suramin treated rat might be a useful experimental animal model of the disease. Several mechanisms by which suramin might produce organomegaly in the rat are discussed.
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PMID:Organomegaly and histopathology in an animal model of mucopolysaccharidosis induced by suramin. 681 Jan 85


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