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

The role of the thymus in neurologic disorders induced by the murine retrovirus, ts1, a neuropathogenic and lymphocytopathic mutant of the Moloney murine leukemia virus-TB, was examined using severe combined immune deficiency (SCID) mice. Athymic nude mice are resistant to ts1-induced neurologic disease. All SCID mice inoculated neonatally with ts1 developed neurologic disorders similar to those of inoculated BALB/c mice, albeit after a longer latency period. In some experiments, instead of inoculating ts1 directly, purified thymocytes, CD4+, or CD8+ T cells from ts1-infected BALB/c mice were transferred to neonatal H-2 compatible SCID mice. We found that SCID mice that received infected thymocytes developed the disease faster than those that received infected CD4+ T cells. SCID mice that received infected CD8+ T cells did not develop any disease. Thus, the (rudimentary) thymus of SCID mouse plays a key role in ts1-induced neurologic disease. In addition, flow cytometric analysis of the reconstituted SCID mice showed that CD8+ T cells migrate and preferentially colonize the thymus while CD4+ T cells were found in the spleen and to a lesser extent in the thymus. However, the significance of this organ specific movements of transferred cells in relation to the virus infection remains unclear. In view of the involvement of the thymus and the CD4+ T cells in human immunodeficiency virus infection, which also infects the central nervous system (CNS) in most cases, our findings in this murine model may help us better understand how the thymus may contribute to the damage of the CNS in retrovirus infections.
 ...
PMID:Rudimentary thymus of SCID mouse plays an important role in the development of retrovirus-induced neurologic disorders. 839 Nov 82

Although feline immunodeficiency virus (FIV) and the unrelated retrovirus feline leukemia virus (FeLV) are associated with acquired immune deficiency in cats, experimental and field evidence indicates that coinfection with both viruses may lead to more serious disease syndrome. A third feline retrovirus, feline syncytium-forming virus (FeSFV), which is far more prevalent than either FIV or FeLV and is considered nonpathogenic in nature, is consistently coisolated from sick, FIV-infected cats. To determine the potential role of FeSFV in enhancement of FIV-mediated disease, persistent FeSFV infection was established in 14 of 24 nine-month-old cats. Four months later, half the FeSFV-infected and half the noninfected cats were inoculated with blood obtained from a cat persistently infected with the Petaluma strain of FIV. At postinoculation week 17, 1 male cat infected with only FIV died of bacterial bronchopneumonia that could have been attributed to FIV-induced acquired immune deficiency-like syndrome. However, none of the remaining cats had clinical illness, whether infected with either virus alone or coinfected with both viruses. As early as postinoculation week 6, decreases were observed in the CD4+ to CD8+ T-lymphocyte ratio of both groups of cats inoculated with FIV. Infection with FeSFV had no effect on the CD4+ to CD8+ T-cell ratio. Mitogen stimulation assays and total WBC count were unaffected by FeSFV infection, although an increase in numbers of neutrophils from FeSFV-infected cats was consistent, especially when compared with the decrease observed after FIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Evaluation of cofactor effect of feline syncytium-forming virus on feline immunodeficiency virus infection. 839 Dec 29

Disseminated infection with the rapidly growing mycobacteria Mycobacterium chelonae and Mycobacterium fortuitum is uncommon. Only eight cases were diagnosed at Duke University Medical Center (Durham, NC) over the last 14 years. We identified 46 other cases by review of the medical literature since 1960. We categorized these 54 cases into three groups according to underlying disease and outcome. Group 1 comprised patients with no identified immune defect, a kidney transplant, collagen vascular disease, or chronic renal failure; these patients usually presented with skin involvement and responded well to antimicrobial therapy (survival rate, 90%). Group 2 comprised patients with cell-mediated immune deficiency, lymphoma, or leukemia; they presented with widespread, multiorgan involvement and severe illness. The survival rate in this group was only 10%. Patients in group 3 (who had other underlying diseases) had intermediately severe illnesses and intermediate responses to therapy. These groups provide the basis for an understanding of disseminated infection secondary to rapidly growing mycobacteria and of the profound effect that unresolved immunosuppression has on survival.
 ...
PMID:Disseminated infection with rapidly growing mycobacteria. 851 48

Hodgkin's disease (HD) has been linked to an increase risk of second malignant neoplasms (SMN), especially non-Hodgkin's lymphoma (NHL) and acute nonlymphoblastic leukaemia (ANLL). The mutagenic property of cytotoxic therapy as well as defective immunity have been implicated as playing a major role in the development of SMN in patients previously treated for HD. We report a case of a 14-year-old girl with HD who developed two different second malignancies within a latent period of 28 months following HD diagnosis. The patient presented initially with bilateral cervical and supraclavicular as well as mediastinal and paraaortic lymphadenopathy. She was staged as IIIA, nodular sclerosing type HD, and was given eight alternative cycles of MOPP-ABVD followed by "mantle" field radiotherapy to a total dose of 3.3 Gy plus 0.4 Gy to the upper mediastinum. Within 8 months following the completion of therapy, a period of myelodysplasia and progressive severe immune deficiency, considered as a result of initial treatment, occurred. Eighteen months after HD diagnosis while the patient was continuously neutropenic and heavily immunocompromised, a peripheral T-cell lymphoma of the angiocentric immunoproliferative lesion type (AIL) Grade III, appeared in both lungs within and beyond the radiation field, with no evidence of HD in biopsy specimens. After institution of a new chemotherapy regimen (L17M), a satisfactory response regarding NHL lesions was noted. However, 10 months later the myelodysplastic syndrome (MDS) accompanied by complex chromosomal abnormalities evoluted to frank ANLL with a rapid fatal course. This case supports the hypothesis that combined modality treatment accompanied by severe immunodeficiency may result in the development of multiple second malignancies even within a very short latent period, especially in a subgroup of HD patients who may be particularly increased risk of second cancers.
 ...
PMID:Secondary malignancies in a child with Hodgkin's disease: T-cell lymphoma and myelodysplastic syndrome evolving into acute nonlymphoblastic leukaemia. 861 70

Mice infected with the replication-defective virus (BM5def) in the LP-BM5 murine leukemia virus (MuLV) mixture develop an immune deficiency syndrome and encephalopathy characterized by impaired spatial learning and memory as demonstrated in the Morris water maze. However, the molecular mechanism (or mechanisms) underlying this cognitive deficit remains unknown. Here we report that brain fyn kinase, which has been proposed to be involved in spatial learning and memory, was unresponsive to glutamatergic stimulation in mice with MAIDS. Thus, whereas application of glutamate to hippocampal slices from control mice increased fyn protein tyrosine kinase (PTK) activity more than 2.5-fold, these changes were significantly impaired in LP-BM5 MuLV-infected mice. Moreover, mice with MAIDS exhibited an abnormal histological distribution of fyn PTK in the hippocampus. These findings suggest that virus-associated disruption of fyn kinase-mediated signaling contributes to the cognitive deficits observed in mice with MAIDS and other retrovirus-induced encephalopathies.
 ...
PMID:Altered brain fyn kinase in a murine acquired immunodeficiency syndrome. 864 68

Mice infected with Friend Leukemia Virus (FLV) rapidly develop erythroleukemia and severe immune deficiency which resembles human AIDS. We have reported that mice infected with a lethal dose of FLV can be 100% cured by 150 cGy total body irradiation (TBI). This curative effect was associated with restoration of cellular immunity which was compromised by the virus. This restoration may result from activation of the IFN-gamma system and IL-2 production. Our research work further demonstrated that no spleen focus-forming virus (SFFV) specific mRNAs, no 6.0kb SFFV fragments and SFFV envelope glycoproteins were detectable in FLV-infected mice treated with low dose TBI. Predicated on our report, del Regato has initiated clinical trials to treat AIDS patients with low dose TBI. The preliminary results are encouraging and the study is continuing. We have also studied the effects of low dose TBI on the expression of the P53 gene. The results show loss or inactivation of P53 tumor suppressor genes in FLV-infected mice, but P53 expression was restored in FLV-infected mice treated by low dose TBI. It is intriguing to speculate that in the curative effect of low dose TBI on mice infected with retrovirus, the P53 tumor suppressor gene may play an important role. It would be of interest to see if this type of treatment, which was well tolerated by mice, would be beneficial in other types of virally induced disease, including AIDS.
 ...
PMID:Curative effect of split low dosage total-body irradiation on murine AIDS induced by Friend virus: the results and the possible mechanism. 874

Double-stranded DNA breaks (DSBs) trigger p53-mediated cell cycle arrest or apoptosis pathways that limit the oncogenic consequences of exposure to genotoxic agents, but p53-mediated responses to DSB generated by normal physiologic events have not been documented. "Broken" V(D)J coding ends accumulate in scid lymphocyte precursors as a consequence of a mutation in DNA-dependent protein kinase (DNA-PK). The ensuing failure to rearrange efficiently antigen receptors arrests lymphoid development. Here we show that scid thymocytes express high levels of p53 protein, attributable to recombinase activating gene (RAG)-dependent generation of DSB adjacent to V, D, and J gene segments. To examine the functional importance of p53 expression in vivo, we bred p53-/- scid mice. The absence of p53 facilitated production of in-frame V(D)Jbeta coding joints and developmental progression of scid thymocytes, in addition to a dramatic accumulation of pro-B cells. All mice developed disseminated pro-B or immature T cell lymphoma/leukemia by 7-12 weeks of age. We present evidence that p53 deficiency prolongs the survival of scid lymphocyte precursors harboring broken V(D)J coding ends, allowing the accumulation of aneuploid cells. These results demonstrate that a p53-mediated DNA damage checkpoint contributes to the immune deficiency characteristic of the scid mutation and limits the oncogenic potential of DSBs generated during V(D)J recombination.
 ...
PMID:V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors. 876 47

Following the outbreak of human immune deficiency virus (HIV) infection in the early 1980's, there has been an increase in reported cases of Kaposi's sarcoma, among other childhood malignancies, from the East and Central African region. To assess the status of childhood cancers at Kenyatta National Hospital during the AIDS epidemic period and to compare the findings with those obtained before the outbreak, relevant data were extracted from ward admission registers for all children admitted in the paediatric wards and in whom a diagnosis of a malignant disease was confirmed. The data were summarised in tables and bar charts. The hospital based prevalence for malignant diseases was 1.27% (CI = 1.23,1.31). Lymphoma (51.3%), leukaemia (21.3%), nephroblastoma (8.5%) and rhabdomyosarcoma (5.2%) are the most common childhood cancers. Compared with earlier studies, the frequency of acute lymphoblastic leukaemia, Hodgkin's disease and rhabdomyosarcoma appear to have increased. Despite the AIDS epidemic, there has been no obvious increase in number of cases of Kaposi's sarcoma.
 ...
PMID:Childhood cancers in a referral hospital in Kenya: a review. 899 44

We have assessed the diagnostic efficacy of a novel polyclonal rabbit antiserum directed to the recombinant major capsid protein VP1 of JC virus (JCV). Immunohistochemistry for VP1 was compared to non-radioactive JCV DNA in situ hybridization (ISH) in ten cases of progressive multifocal leukoencephalopathy (PML). Tissue sections from postmortem brains were studied from PML patients suffering from immunodeficient conditions of various causes: immunodeficiency syndrome (AIDS, n = 7), severe combined immune deficiency due to adenosine deaminase deficiency (n = 1), sarcoidosis (n = 1) and leukemia (n = 1). VP1 immunohistochemistry demonstrated the presence of JCV in lesional oligodendrocytes of all PML patients, whereas ISH was able to detect JCV in nine out of ten cases. We conclude that VP1 immunohistochemistry is a specific, sensitive and rapid method for confirming the diagnosis of PML.
 ...
PMID:Detection of JC virus by anti-VP1 immunohistochemistry in brains with progressive multifocal leukoencephalopathy. 929 91

We examined five children who underwent allogeneic peripheral stem cell transplantation (PSCT) using positively selected CD34+ cells from three or two loci-mismatched donors. CD34+ cells mobilized from peripheral blood were separated by immunomagnetic beads. CD34+ cells at 2.2-6.2 x 10(6)/kg were transplanted into three patients with refractory leukemia, a patient with relapsed medulloblastoma and a patient with Fanconi's anemia following a conditioning regimen which included irradiation, alkylating agents and antithymocyte globulin treatment. The number of infused CD3+ cells included in grafts was 2.3-22.7 x 10(4)/kg. Four patients achieved engraftment and hematopoietic reconstitution (> 5 x 10(8)/l of neutrophils on day 10 or 11). Graft rejection was observed in the patient with Fanconi's anemia, but a rapid engraftment was obtained after second PSCT. Although no prophylactic agents other than ATG (included in the conditioning regimen) were used, greater than grade I acute GVHD was not observed, but limited chronic GVHD was observed in two patients. The two patients with leukemia relapsed on days 103 and 210, respectively, and the patient with medulloblastoma died of disease on day 159. The patient with Fanconi's anemia died of fungal infection. CMV and HHV-6 diseases developed in four and two patients, respectively. Thus, although SCT using positively selected peripheral CD34+ cells may be an alternative approach for overcoming graft rejection and GVHD from HLA- mismatched donors, persistent immune deficiency attributing to extremely low numbers of T cells in grafts can potentially lead to reactivation of herpes viruses.
 ...
PMID:Allogeneic peripheral stem cell transplantation using positively selected CD34+ cells from HLA-mismatched donors. 950 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>