Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A small proportion of coeliac disease (CD) patients fail to improve after a gluten-free diet (GFD) and may be considered as atypical regarding their outcome (refractory coeliac disease). The aim of this study is to diagnose and manage patients with CD who fail to improve after a GFD. Refractory coeliac disease (RCD) is a malabsorption syndrome defined by persisting villous atrophy with, usually, an increase of intraepithelial lymphocytes (IELs) in the small bowel in spite of a strict GFD and comprises a heterogenous group of diseases. Some of these diseases have to be excluded and can be treated by specific therapies like antibiotics in tropical sprue and giardiasis and immune globulin substitution in common variable immunodeficiency, while other malabsorption syndromes are less well defined and may require immunosuppressive therapy. Standardized treatment, however, has not been evaluated in such patients so far. In a subgroup of patients with RCD, an abnormal intraepithelial lymphocyte (IEL) population may be observed with the lack of surface expression of usual T-cell markers (CD3-CD8 and/or the T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern suggest the presence of an early enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD. This hypothesis has been supported by studies, which revealed progression into overt intestinal T-cell lymphomas in a subgroup of RCD. Steroid treatment has been reported effective even in patients with underlying early EATL. However, long-term results are unsatisfactory in most of these patients with RCD and parenteral nutrition has to be applied in some of these cases. First results with more aggressive chemotherapies and use of cytokines are under way. Due to the difficulty of diagnostic and therapeutic regimens patients should be referred to tertiary centres for coeliac disease.
 ...
PMID:Refractory coeliac disease. 1592 46

Beta-D-2',3'-dideoxy-3'-oxa-5-fluorocytidine (D-FDOC) is an effective inhibitor of human immunodeficiency virus 1 (HIV-1) and HIV-2, simian immunodeficiency virus, and hepatitis B virus (HBV) in vitro. The purpose of this study was to evaluate the intracellular metabolism of d-FDOC in human hepatoma (HepG2), human T-cell lymphoma (CEM), and primary human peripheral blood mononuclear (PBM) cells by using tritiated compound. By 24 h, the levels of D-FDOC-triphosphate (D-FDOC-TP) were 2.8 +/- 0.4, 6.7 +/- 2.3, and 2.0 +/- 0.1 pmol/10(6) cells in HepG2, CEM, and primary human PBM cells, respectively. Intracellular D-FDOC-TP concentrations remained greater than the 50% inhibitory concentration for HIV-1 reverse transcriptase for up to 24 h after removal of the drug from cell cultures. In addition to d-FDOC-monophosphate (D-FDOC-MP), -diphosphate (D-FDOC-DP), and -TP, D-FDOC-DP-ethanolamine and d-FDOC-DP-choline were detected in all cell extracts as major intracellular metabolites. D-FDOC was not a substrate for Escherichia coli thymidine phosphorylase. No toxicity was observed in mice given D-FDOC intraperitoneally for 6 days up to a dose of 100 mg/kg per day. Pharmacokinetic studies in rhesus monkeys indicated that D-FDOC has a t(1/2) of 2.1 h in plasma and an oral bioavailability of 38%. The nucleoside was excreted unchanged primary in the urine, and no metabolites were detected in plasma or urine. These results suggest that further safety and pharmacological studies are warranted to assess the potential of this nucleoside for the treatment of HIV- and HBV-infected individuals.
 ...
PMID:Pharmacology and pharmacokinetics of the antiviral agent beta-D-2',3'-dideoxy-3'-oxa-5-fluorocytidine in cells and rhesus monkeys. 1598 Mar 24

The association of Epstein-Barr virus (EBV) with human immunodeficiency virus-negative T-cell lymphoma was examined in 68 patients using the polymerase chain reaction (PCR) with DNA obtained from formalin-fixed paraffin-embedded tissues and an in situ hybridization technique. EBV-encoded RNA (EBER) was detected in 43 of 68 cases (63%) of peripheral T-cell lymphoma: in 100% (11 of 11 cases) of NK/T-cell lymphomas, 70% (14 of 20 cases) of angioimmunoblastic T-cell lymphomas (AILT) and 49% (18 of 37 cases) of other types of peripheral T-cell lymphoma. A positive band was also detected at high incidence (36 of 65 cases; 55%) in a PCR analysis using primers to detect the Bam HI-W fragment of EBV. In the immunohistochemical analysis using a monoclonal antibody to latent membrane protein 1 (LMP-1) of EBV, one of the EBV-encoded latent gene products, LMP-1, was found to be expressed in 13 of 64 cases (20%), but EBNA-2 was not expressed in all the cases examined (0 of 59 cases; 0%). The 5-yr survival rate was 28% for peripheral T-cell lymphomas overall, 0% for NK/T-cell lymphomas, 38% for AILTs and 28% for other types of peripheral T-cell lymphoma. The difference in the overall survival rate between NK/T-cell lymphoma and non-NK/T-cell lymphoma was significant (P = 0.0498 by Log-rank test). Among peripheral T-cell lymphoma patients overall, the group severely infected with EBV (EBER-ISH ++) had a lower 5-yr survival rate (8%) than the group slightly (EBER-ISH +) or not infected (38%; P = 0.0013).
 ...
PMID:Association of Epstein-Barr virus with human immunodeficiency virus-negative peripheral T-cell lymphomas in Japan. 1640 31

Job's syndrome or hyper-immunoglobulin E syndrome is a primary immunodeficiency characterized by recurrent staphylococcal abscesses and markedly elevated serum immunoglobulin E concentrations. Here we report a case of a woman with hyper-immunoglobulin E syndrome with a diagnosis of peripheral T-cell lymphoma, and we review the pertinent literature.
 ...
PMID:Peripheral T-cell lymphoma and Job's syndrome: a rare association. 1664 41

Ku80 maintains the genome by repairing DNA double-strand breaks (DSBs) through nonhomologous end joining (NHEJ), a pathway that repairs nonspecific DSBs and Rag-1 Rag-2 (Rag)-specific DSBs. As a result, Ku80 deletion results in phenotypes characteristic of defective repair for both nonspecific DSBs (gamma-radiation hypersensitivity and genomic instability) and Rag-specific DSBs (immunodeficiency). ku80(-/-) mice also exhibit neuronal apoptosis, but we do not know the type of DSBs responsible for this response. In spite of genomic instability and immunodeficiency, cancer incidence is not increased in ku80(-/-) mice. However, deletion of the tumor suppressor, p53 greatly increases pro-B-cell lymphoma in ku80(-/-) mice due to IgH/c-Myc translocations suggesting that responses to Rag-specific DNA DSBs suppress cancer. Like suppression of pro-B-cell lymphoma, neuronal apoptosis requires p53 presenting the intriguing possibility that Rag-specific DSBs mediate neuronal development as they do lymphocyte development. Here we delete Rag-1 from ku80(-/-)p53(-/-) mice to differentiate the impact nonspecific vs Rag-specific DSBs have on ku80(-/-) mice. We find that deleting Rag-1 prevents pro-B cell lymphoma confirming Rag-induced DSBs induce this form of cancer. Both the triple mutant mice and the p53(-/-)rag-1(-/-) mice exhibit T-cell lymphoma and medulloblastoma; incidence of T-cell lymphoma is the same for both cohorts whereas incidence of medulloblastoma is higher for the triple-mutant cohort. Thus, p53-mediated neuronal apoptosis likely suppresses medulloblastoma in Ku80-deleted mice and Ku80 likely suppresses medulloblastoma by repairing nonspecific DNA DSBs instead of Rag-specific DSBs. Our observations are the first to show that Ku80 suppresses cancer caused by nonspecific DNA damage and we present a novel mouse model for medulloblastoma.
 ...
PMID:Ku80 and p53 suppress medulloblastoma that arise independent of Rag-1-induced DSBs. 1675 7

Anorectum is a rare location for malignant lymphoma. Involvement of is rare even for the lynphoma associated with acquired immune deficiency syndrome (AIDS), and AIDS has a relatively increased frequency of anorectal lymphoma. Most lymphomas in AIDS patients are of a B-cell origin, and T-cell lymphoma of the gastrointestinal tract is extremely rare. We report here on a case of anorectal and gastric peripheral T-cell lymphoma, unspecified (PTCLu) in a non-AIDS patient. A previously healthy 29-year-old man presented with hematochezia and tenesmus that he had suffered with for the previous 2 months. Sigmoidoscopy showed anal and rectal submucosal tumor. Multiple round-shaped, flat and elevated lesions were noted on the gastric antrum and body as well. He underwent excisional biopsy for the anal mass and the diagnosis was PTCLu. Biopsies of the gastric lesions gave the same diagnosis. There was no lymphoma involved in the bone marrow. At admission, no antibodies against human immunodeficiency virus were detected. He underwent systemic chemotherapy and upfront autologous stem cell transplantation.
 ...
PMID:Anorectal and gastric peripheral T-cell lymphoma, unspecified in a non-AIDS patient. 1724 11

Studies on cellular drug interactions with antiretroviral agents prior to clinical trials are critical to detect possible drug interactions. Herein, we demonstrated that two 2'-deoxycytidine antiretroviral agents, dexelvucitabine (known as beta-d-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, DFC, d-d4FC, or RVT) and lamivudine (3TC), combined in primary human peripheral blood mononuclear (PBM) cells infected with human immunodeficiency virus 1 strain LAI (HIV-1(LAI)), resulted in additive-to-synergistic effects. The cellular metabolism of DFC and 3TC was studied in human T-cell lymphoma (CEM) and in primary human PBM cells to determine whether this combination caused any reduction in active nucleoside triphosphate (NTP) levels, which could decrease with their antiviral potency. Competition studies were conducted by coincubation of either radiolabeled DFC with different concentrations of 3TC or radiolabeled 3TC with different concentrations of DFC. Coincubation of radiolabeled 3TC with DFC at concentrations up to 33.3 microM did not cause any marked reduction in 3TC-triphosphate (TP) or any 3TC metabolites. However, a reduction in the level of DFC metabolites was noted at high concentrations of 3TC with radiolabeled DFC. DFC-TP levels in CEM and primary human PBM cells decreased by 88% and 94%, respectively, when high concentrations of 3TC (33.3 and 100 microM) were added, which may influence the effectiveness of DFC-5'-TP on the HIV-1 polymerase. The NTP levels remained well above the median (50%) inhibitory concentration for HIV-1 reverse transcriptase. These results suggest that both beta-d- and beta-l-2'-deoxycytidine analogs, DFC and 3TC, respectively, substrates of 2'-deoxycytidine kinase, could be used in a combined therapeutic modality. However, it may be necessary to decrease the dose of 3TC for this combination to prove effective.
 ...
PMID:Antiviral and cellular metabolism interactions between Dexelvucitabine and lamivudine. 1740 96

Rheumatoid arthritis (RA) is associated with an increased risk of developing lymphoma. Although the pathogenesis is still unclear, the increased risk appears to be related to the high inflammatory activity of RA, immunosuppressive agents, or Epstein-Barr virus (EBV) infection. We investigated the relationship between EBV latent infection and methotrexate (MTX)-associated lymphoma in RA patients. Nine patients were diagnosed with non-Hodgkin's lymphoma (NHL) during MTX treatment for RA in a multicenter study. The pathologic findings were consistent with diffuse large B-cell lymphoma in 8 patients and peripheral T-cell lymphoma, unspecified in 1. EBV infection was detected in 3 patients by in situ hybridization. Among all 9 patients who were initially treated by MTX withdrawal alone, 2 obtained spontaneous complete response (CR), 1 had partial response, 2 had stable disease (SD), and 4 had progressive disease. Both patients who had a CR and 1 who had SD were positive for EBV. Further examination of the latent EBV infection patterns revealed that 2 patients who obtained a CR had latency Type III, and the other with SD had latency Type II. These results demonstrate that immunodeficiency caused by MTX treatment is associated with the development of EBV-related NHL in RA patients. In patients who were treated by MTX for RA and developed NHL, remission can be observed following MTX withdrawal especially in NHL with latency Type III EBV infection. The analysis of EBV infection, including the latency types, is useful to decide the optimum therapeutic strategy.
 ...
PMID:Remission of lymphoma after withdrawal of methotrexate in rheumatoid arthritis: relationship with type of latent Epstein-Barr virus infection. 1765 84

We describe a case in which a human immunodeficiency virus (HIV)-positive child presented in severe metabolic acidosis secondary to his candidal sepsis and T-cell lymphoma, a rare finding in pediatric AIDS. Significantly elevated levels of Interleukin-10 (IL-10) were found in the patient's serum, which may have played a role in acute demise.
 ...
PMID:Hyper interleukin-10 in an HIV-positive child with t-cell lymphoma and candidal sepsis. 1881 91

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders occur at an increasing frequency in various hereditary and acquired states of immune dysfunction. In a few cases of T-cell lymphoma, especially in angioimmunoblastic T-cell lymphoma (AILT), EBV-associated B-cell lymphoproliferative disorders have been reported. Here, we present two cases of EBV-associated B-cell lymphoma after treatment of T-cell lymphoma (AILT and peripheral T-cell lymphoma, unspecified, PTCL-NOS) with a regimen containing alemtuzumab and fludarabine. Conventional and immunohistological tissue staining showed the typical features of highly proliferating diffuse large B-cell lymphoma in both cases. The monoclonal B-cell population displayed EBV latency type III. At the time of diagnosis the cellular immune status of both patients was severely compromised with an absolute CD4 T-cell count below <120 microl(-1). Our observation supports the notion that combination of cytotoxic drugs and immunosuppressive antibodies in patients with T-cell lymphoma may severely aggravate the already present immunodeficiency. We suggest to monitor the cellular immune status in combination with the EBV load in high risk patients for early detection-and possibly intervention-of EBV-associated lymphoma.
 ...
PMID:Epstein-Barr virus-associated B-cell lymphoma secondary to FCD-C therapy in patients with peripheral T-cell lymphoma. 1883 73


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