Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Avian erythroblastosis virus (AEV) is a replication-defective retrovirus that transforms erythroid and fibroblast cells in vitro and in vivo. The transforming ability of AEV is due primarily to the oncogene v-erb-B. A recombinant murine retrovirus has been constructed by inserting a chimeric gag-v-erb-B gene into a Moloney murine leukemia virus based vector. This retrovirus was used to examine v-erb-B-induced transformation of murine hematopoietic cells. Infection of murine primary fetal liver, adult bone marrow or adult spleen cells with the recombinant virus generated large hemoglobinized erythroid colonies in the absence of exogenous growth factors. Generation of such colonies usually requires the presence of erythropoietin (Epo) and interleukin-3 (IL-3). These growth-factor independent colonies were shown to be derived from early (BFU-E) and not late (CFU-E) erythroid progenitor cells, and the effect was not attributable to growth factors elicited by the virus-producing cell lines. In order to confirm that the recombinant virus was responsible for this transformation of BFU-E to growth factor independence, bone marrow cells from post 5-fluorouracil treated mice were infected and used to repopulate lethally-irradiated mice. Growth factor-independent BFU-E were obtained in up to 30% of day-13 spleen colonies and it was shown by DNA analysis that cells from these colonies contained integrated provirus. Our results indicate that v-erb-B transforms early erythroid progenitors to growth factor independent growth and subsequent differentiation to erythrocytes -a process that normally requires Epo plus either IL-3 or granulocyte-macrophage colony stimulating factor (GM-CSF).
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PMID:Transformation of early erythroid precursor cells (BFU-E) by a recombinant murine retrovirus containing v-erb-B. 216 27

Epstein-Barr virus and HTLV-1 are both lymphotropic viruses, capable of immortalizing lymphocytes in vitro (Fig. 1). Both viruses have been sequenced and subjected to intense molecular biologic scrutiny, and in both cases genes believed to be important in lymphocyte immortalization have been identified. These viral genes are not homologues of cellular oncogenes, nor is there any evidence to suggest insertional mutagenesis. Rather, these genes alter the expression of a variety of cellular genes and, in so doing, alter the growth characteristics of the host cell. Infection with either virus is most likely to be asymptomatic, associated with a benign self-limited lymphoproliferation, or both, but in a small fraction of instances these benign lymphoproliferations give rise to a lymphoma or leukemia. In the case of the Epstein-Barr virus, a variety of cofactors have been identified that are important to the evolution of malignancy. These cofactors include immunosuppression in transplant recipients, cogenital immunodeficiency in the X-linked lymphoproliferative syndrome, human immunodeficiency virus infection in AIDS patients, and malaria in patients with endemic Burkitt's lymphoma. In the case of HTLV-1, cofactors have not been identified. Nonetheless, the importance of cofactors is suggested by the small fraction of the population infected by the virus who actually develop lymphoproliferative disease, and the long latency period between infection and the development of frank lymphoproliferative disease. In organ transplant recipients with lymphomas associated with Epstein-Barr virus infection, the EBV immortalizing/transforming genes are expressed in the malignant tissue. But in Burkitt's lymphoma and in adult T-cell leukemia/lymphoma, the EBV and HTLV-1 immortalizing/transforming genes are not detectably expressed. In Burkitt's lymphoma, it is suggested that the dysregulated myc gene renders the growth effects of Epstein-Barr virus latency genes superfluous. No comparable proto-oncogene translocation or activation has yet been identified in HTLV-1 lymphoma/leukemia.
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PMID:Human lymphotropic viruses associated with lymphoid malignancy: Epstein-Barr and HTLV-1. 217 3

Debilitating disorders of the nervous system have a relatively high prevalence in the tropics, a geographic region that is often deficient in specialists in the fields of neurology and epidemiology. During World War II, attention was called to a possible nutritional origin for most of these diseases. Recently, however, human T lymphotropic virus type I (HTLV-I), formerly linked only to a rare form of leukemia (adult T cell leukemia), has been associated with a spastic paraplegia observed mostly in tropical areas and referred to as tropical spastic paraparesis. This entity is also observed in nontropical areas endemic for HTLV-I, including Japan, South America, and the southern United States. Viruses of the HTLV family are being associated increasingly with pathology in humans. The pathogenesis of HTLV-I-associated tropical spastic paraparesis remains to be understood. However, future research is expected to favor a multidisciplinary approach, with exciting potential insights derived from the fields of neurology, immunology, and infectious diseases. The aim of this review is to summarize contemporary research related to the viral etiology of this clinical entity.
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PMID:Tropical neuromyelopathies and retroviruses: a review. 217 97

The effects of inserting cellular regulatory sequences from the murine transthyretin (TTR) gene into the Moloney murine leukemia virus (M-MuLV) long terminal repeat (LTR) were investigated. Transthyretin is expressed predominantly in the liver and choroid plexus in adult mice, and TTR upstream regulatory elements were previously shown to potentiate transcription in liver-derived cells. The effects of inserting the TTR distal enhancer and/or promoter-proximal sequences into an M-MuLV LTR lacking its enhancers were measured in three ways. (i) Chimeric LTRs were fused to the bacterial chloramphenicol acetyltransferase gene (cat) and tested for transient gene expression by transfection into liver-derived cells or NIH 3T3 fibroblasts. (ii) Infectious M-MuLV containing an altered LTR [delta Mo + TTR(PD) MuLV) was generated, and infectivity in culture on hepatocyte lines and NIH 3T3 cells was tested. (iii) Infection of delta Mo + TTR(PD) MuLV in vivo was tested by inoculating NFS/N mice and performing in situ hybridization of whole animal sections. Chimeric LTR-cat constructs showed higher levels of cat gene expression in liver-derived cell lines than in NIH 3T3 cells, indicating increased LTR activity in these cells. However, in vitro infection did not show significantly higher infectivity in hepatocytes for delta Mo + TTR(PD) M-MuLV than did wild-type M-MuLV. In vivo, delta Mo + TTR(PD) MuLV showed expression in the same tissues as with wild-type M-MuLV-inoculated mice, i.e., lymphoid organs and the intestines and, additionally, two novel sites not seen in wild-type M-MuLV-inoculated animals. Of 10 mice, 8 showed viral expression in the brain and 3 showed expression in the liver. Thus, insertion of TTR elements into the M-MuLV LTR altered LTR activity both in vitro and in vivo.
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PMID:Substitution of murine transthyretin (prealbumin) regulatory sequences into the Moloney murine leukemia virus long terminal repeat yields infectious virus with altered biological properties. 217 84

This study showed several accumulated data through ten years from our experience in hematopoietic disorders and associated infections, which has been analyzed by the Hanshin Study Group of Hematopoietic Disorders and Infections. Since 1979 to 1988, our group had evaluated the sorts of causative organisms and the efficacy of various antibiotics therapy in 2119 cases of infectious diseases associated with hematopoietic disorders. On behalf of evaluating the changes of disease profile for ten years, we divided the accumulated data into three phases; former phase the first three years, middle phase the second three years and late phase the last four years. There was no significant difference in the frequency of various hematopoietic disorders among the three phases. Each leukemia patients occupied 77% of all cases. Sepsis suspected is the most frequent infectious disease accounting for 68.8%. The other infectious diseases were 8.4% of the sepsis, 14.8% of the respiratory infections and 3.1% of the urinary tract infections. Comparing the frequency of infections among the three phases, the respiratory and urinary tract infections inclined to decrease. Of the 532 strains isolated from 2119 cases and identified as causative organisms, gram-negative bacilli occupied 62.8% and gram-positive bacteria 36.5%. In comparing the percentage of gram-negative bacilli among the three phases, it showed a decreasing tendency in order former phase 63.6%, middle phase 76.4% and late phase 43.8%. Pseudomonas, however, had been isolated at almost constant ratio through ten years. On the other hand, the ratio of gram-positive bacteria isolated were 34.5% in former phase, 23.6% in middle phase and 56.3% in late phase, showing increasing a tendency through the period. Twenty-three kinds of antibiotics were administered by intravenous drip infusion. The efficacy rate was 43.9% to 67.2%. In particular, effectiveness of antibiotic therapy often depends on the change of peripheral neutrophil counts from the onset and during the therapy. The efficacy rate, however, was 36% even neutrophil counts have not shown the tendency of increase from less than 100/microliters.
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PMID:[Actual conditions of bacterial infection associated with hematopoietic disorders--changes in 10 years. The Hanshin Study Group of Hematopoietic Disorders and Infections]. 219 67

Eight neutropenic patients with acute lymphocytic or nonlymphocytic leukemia had septicemia due to different strains of Streptococcus mitis (St. mitis), a microorganism not commonly recognized as a special pathogen in leukemic patients. Four of the patients had been treated with high-dose cytosine arabinoside as part of the cytostatic regimen, six had a central venous line and four patients had oral lesions prior to the infection. Selective gut decontamination consisted of co-trimoxazole/colistin in five patients and quinolones in three patients. The first three patients died, either due to interstitial pneumonia with the adult respiratory distress syndrome (ARDS), or due to infection-triggered disseminated intravascular coagulation despite prompt empiric antibiotic therapy including vancomycin. The other patients improved after empiric supplementation of penicillin G (30 Mega/day) to the antibiotic regimen. Beginning ARDS in two of these patients dramatically responded to high-dose steroids. We conclude that St. mitis is a major pathogen in neutropenic leukemic patients. Infection appears to occur independently of acute leukemic cell type, regimen of selective gut decontamination, venous access, visible oral lesions or treatment with high-dose cytosine arabinoside. The clinical course of our patients raises questions about the value of commonly recommended empiric antibiotic regimens, which were clearly ineffective to control infections with St. mitis in this patient group. Our data indicate that immediate antibiotic therapy with penicillin G is indicated and may be life-saving for suspected St. mitis infections in neutropenic leukemic patients.
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PMID:Septicemia due to Streptococcus mitis in neutropenic patients with acute leukemia. 229 85

The retroviral vector N2, which is derived from the Moloney murine leukemia retrovirus, was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells from fetal, neonatal, and adult dogs and cats. Infection of canine and feline bone marrow cells with the N2 vector resulted in resistance of granulocyte-macrophage colony-forming units (CFU-GM) to G418. Approximately 2%-4% of fetal liver, fetal bone marrow, and adult bone marrow day-7 CFU-GM were resistant to 1.75 mg/ml G418, a dose toxic to cells not expressing the NeoR gene, after infection with the N2 retrovirus. In sharp contrast to the low rate of infectivity of both fetal and adult marrow samples, the mean +/- SD of G418-resistant CFU-GM was 11.7% +/- 14.1% and 14.0% +/- 18.1% for neonatal dog and cat marrow samples, respectively. The neomycin phosphotransferase enzyme activity was detected in G418-resistant CFU-GM, confirming that G418-resistant CFU-GM expressed the NeoR gene. The increased efficiency of retroviral vector-mediated gene transfer into neonatal hematopoietic progenitor cells was not due to an increased fraction of actively dividing cells, as determined by tritiated thymidine suicide. Understanding the basis for increased gene transfer into neonatal hematopoietic progenitor cells may be helpful in designing effective retroviral vectors/gene transfer protocols for gene therapy.
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PMID:Increased efficiency of gene transfer with retroviral vectors in neonatal hematopoietic progenitor cells. 230 10

Clostridium septicum is a major cause of spontaneous, nontraumatic gas gangrene. Unlike Clostridium perfringens, C. septicum is relatively aerotolerant and thus appears to be more capable of initiating infection in the absence of obvious damage to tissues. Six cases illustrate the clinical setting and fulminant nature of spontaneous gangrene caused by C. septicum. A lesion in the colon such as carcinoma is often present and is presumed to serve as a portal of entry to the bloodstream. Diabetes and leukopenia are also common predisposing conditions; compromise of vital host responses may facilitate proliferation of those organisms that settle out in the tissues. Acute lymphoma or leukemia during a course of chemotherapy is accompanied by damage to bowel mucosa and granulocytopenia, thus predisposing to spontaneous clostridial gangrene. Infection progresses in a fulminating manner; the majority of patients die within 24 hours of onset. Characteristic symptoms and signs include excruciating pain (although a sense of heaviness may be the only early symptom), swelling of tissues, crepitance, and bulla formation. A hallmark of C. septicum infection is the absence of acute inflammatory cells in involved tissues or in bulla fluid. A series of laboratory investigations demonstrated that fluid obtained from a bulla adversely affected the viability, morphology, and function of polymorphonuclear leukocytes (PMNs), which may explain the paucity of PMNs in involved tissues and may in part contribute to the fulminant progression observed in infection due to this organism.
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PMID:Spontaneous, nontraumatic gangrene due to Clostridium septicum. 233 Apr 82

The incidence of adult leukaemias, their response to therapy and the complications of therapy were studied in 121 cases over seven years (1981-1987). All cases were followed up till recovery or death for periods ranging from seven days to seven years. Adult leukaemias accounted for 2.56% of all admissions due to malignancies. There were 21 cases of acute lymphoblastic leukaemia, 61 of acute myelogenous leukaemia, 36 of chronic myelocytic leukaemia and 3 chronic lymphocytic leukaemia. All received aggressive combination chemotherapy. Remission could be achieved in 57% to 60% of cases. Infection (34%), bleeding (34%), and central nervous system involvement (25%) were the complications during therapy. The cause of death was ascertained in 87 of 90 deaths by a detailed postmortem. Haemorrhage (34.5%), infection (31%) and uncontrolled leukaemia (22%) were the leading causes, either singly or in combination. Some of the uncommon causes of death were fulminant hepatic failure, coronary artery disease, gangrene of the colon and disseminated tuberculosis.
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PMID:A clinical study of adult leukaemias. 188 Jan 6

Infection is the major cause of death in neutropenic patients. Prevention and therapy of infection are an important, dynamic component of the care of the neutropenic patient with leukemia. Nurses caring for these patients must have a current knowledge of immunosuppression, the usual sites and causative organisms, the clinical presentation, and the treatment of infection. This knowledge then needs to be applied clinically in the care of the neutropenic patient.
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PMID:Infection in the neutropenic patient. 240 29


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