Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hundred and sixty-two patients (actual number 162) of hematological malignancies were admitted to our department from November 1977 to December 1986. Fourty-three of them (16.4%) were demonstrated to be accompanied with sepsis by blood culture. In acute non-lymphocytic leukemias (AML, APL, AMoL) the rate of sepsis was 33.8% (27 patients), while in lymphocytic malignancies (ML, HD, ATL) it was 11.7% (16 patients), particularly being 3.0% in ATL. Among the detected pathogenic microorganisms, gram-negative bacilli were 86.2% in the former and 50.0% in the latter. Especially, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli occupied 58.6% of the total in the former. Laboratory examination, when sepsis occurred, revealed peripheral neutropenia in acute non-lymphocytic leukemias (mean 831/cmm) but not in lymphocytic malignancy (mean 4,420/cmm). And 20 of the 27 cases showed remarkable neutropenia of below 500/cmm in the former. On the other hand in the latter, out of 16 only one with ATL was the case. Hypogammaglobulinemia was one of the characteristic features in lymphocytic malignancies but not in acute non-lymphocytic leukemias. Hypogammaglobulinemia in lymphocytic malignancies might be affected by long-term immunodepressant therapy. Immunologic skin reaction was demonstrated to be decreased in lymphocytic malignancies on admission. From the findings mentioned above, affecting factors to infections may be mainly neutropenia in acute non-lymphocytic leukemias and immunodeficiency in lymphocytic malignancies. And sepsis can occur frequently under neutropenic condition. In ATL both of humoral- and cellular-immunologic disturbance were detected before therapy. But peripheral neutrophil count was maintained to be normal and this could be the reason for the low septic incidence in ATL despite of total immunodepression.
...
PMID:[Infections in hematological malignancies--clinical analysis of septic patients admitted to the Second Department of Miyazaki Medical College Hospital in the past ten years]. 240 13

The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.
...
PMID:Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines. 249 48

The CD4 molecule functions as a receptor for the binding and infectivity of the human immunodeficiency virus (HIV). It is of interest, therefore, to develop procedures for its down-regulation. In the present study, the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the expression of cell surface antigens of the HL-60 promyelocytic leukemia cell line was analyzed. Exposure of HL-60 cells to 1,25(OH)2D3 resulted in down-regulation of CD4 as assessed by their staining with the Leu-3a monoclonal antibody (MoAb). This treatment increased the staining of HL-60 cells with the monocyte-specific 63D3 MoAb. In contrast to the rapid elimination of cell surface CD4 by exposure of HL-60 to phorbol myristate acetate (PMA), the maximal reduction of CD4 by 1,25(OH)2D3 was attained within 48 h after the beginning of the exposure.
...
PMID:Modulation of the expression of CD4 on HL-60 cells by exposure to 1,25-dihydroxyvitamin D3. 269 87

The human promyelocytic leukemia cell line HL-60 overexpresses the c-myc protooncogene. A calculated secondary structure for c-myc mRNA placed the initiation codon in a bulge of a weakly base-paired region. Treatment of HL-60 cells with 5' d(AACGTTGAGGGGCAT) 3', complementary to the initiation codon and the next four codons of c-myc mRNA, inhibited c-myc protein expression in a dose-dependent manner. However, treatment of HL-60 cells with 5' d(TTGGGATAACACTTA) 3', complementary to nucleotides 17-31 of vesicular stomatitis virus matrix protein mRNA, displayed no such effects. These results agree with analogous studies of normal human T lymphocytes [Heikkila, R., Schwab, G., Wickstrom, E., Loke, S. L., Pluznik, D. H., Watt, R. & Neckers, L. M. (1987) Nature (London) 328, 445-449], except that only one-third as much oligomer was needed for a comparable effect. Proliferation of HL-60 cells in culture was inhibited in a sequence-specific, dose-dependent manner by the c-myc-complementary oligomer, but neither the oligomer complementary to vesicular stomatitis virus matrix protein mRNA nor 5' d(CATTTCTTGCTCTCC) 3', complementary to nucleotides 5399-5413 of human immunodeficiency virus tat gene mRNA, inhibited proliferation. It thus appears that antisense oligodeoxynucleotides added to myc-transformed cells via culture medium are capable of eliciting sequence-specific, dose-dependent inhibition of c-myc protein expression and cell proliferation.
...
PMID:Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. 327 86

Acute myeloid leukemia (AML) is infrequent in patients with human immunodeficiency virus (HIV) infection. Among AML, acute promyelocytic leukemia (APL) has been rarely described in such patients, with only one case being published. We report a 30 years-old intravenous drug abuser HIV-infected male with APL who attained complete clinical, morphological, and molecular remission after differentiation therapy with all-trans-retinoic acid (ATRA) followed by intensive chemotherapy. The results of treatment in this patient and in other AML published cases suggest that therapy for AML should not be modified because of HIV infection if patients have an adequate performance status.
...
PMID:Acute promyelocytic leukemia in a HIV seropositive patient. 938 70

The authors discuss the importance that molecular medicine has assumed in recent years. Molecular methodologies have clearly demonstrated that immunological diversity is based fundamentally on the rearrangement of the genes encoding antigen B and T cell receptors. The importance of oncogenes, and their translocation in tumoral pathologies is emphasized, a case in point being the alterations observed in chronic myeloid leukemia and acute promyelocytic leukemia and their implication for innovative therapy. The importance of prothrombin and factor V genetic-molecular alterations in thromboembolic pathology and of the activation of calcineurin phosphatase or other intracellular signal regulator molecules during cardiac insufficiency genesis is also discussed. Particular attention is paid to progress regarding the socially important Alzheimer's syndrome, and the diagnosis of endocrine tumors. Moreover, the authors believe that the identification of new endocrine nuclear receptors, "orphans" of hormonal ligands, will open up interesting prospects--even therapeutic--in endocrinology. The authors conclude by reviewing the therapeutic prospects for immunodeficiency syndromes and malignant tumors, offered by new gene therapy methodologies. They also discuss recent results of studies on the aging process which, until not many years ago, appeared adventuristic. Today they are opening prospects of great interest.
...
PMID:[Molecular medicine: new tools for better understanding and treatment of diseases in humans]. 1105 61

Inhibitors of the protease of human immunodeficiency virus type 1 (HIV-1) may inhibit cytoplasmic retinoic acid-binding proteins, cytochrome P450 isoforms, as well as P-glycoproteins. These features of the protease inhibitors might enhance the activity of retinoids. To explore this hypothesis, myeloid leukemia cells were cultured with all-trans retinoic acid (ATRA) either alone or in combination with the HIV-1 protease inhibitors indinavir, ritonavir, and saquinavir. Consistent with the hypothesis, the HIV-1 protease inhibitors enhanced the ability of ATRA to inhibit growth and induce differentiation of HL-60 and NB4 myeloid leukemia cells, as measured by expression of CD11b and CD66b cell surface antigens, as well as reduction of nitroblue tetrazolium. Growth of ATRA-resistant UF-1 cells was also inhibited when cultured with the combination of ATRA and indinavir. Moreover, indinavir enhanced the ability of ATRA to induce expression of the myeloid differentiation-related transcription factor C/EBPepsilon messenger RNA in NB4 cells by 9.5-fold. Taken together, the results show that HIV-1 protease inhibitors enhance the antiproliferative and differentiating effects of ATRA on myeloid leukemia cells. An HIV-1 protease inhibitor might be a useful adjuvant with ATRA for patients with acute promyelocytic leukemia and possibly retinoid-resistant cancers.
...
PMID:HIV-1 protease inhibitors decrease proliferation and induce differentiation of human myelocytic leukemia cells. 1107 54

Arsenic has been used as a medicinal for thousands of years. Several reports from China relative to its use mainly in acute promyelocytic leukemia, especially from the Shanghai group, has caused a resurgence in the investigation of the drug in the management of malignancies with focus on malignancies of hematologic origin. Arsenic is eliminated by many routes (urine, feces, sweat, milk, hair, skin, and lungs), although most is ultimately excreted in urine. Multiple myeloma is characterized by the clonal proliferation of malignant plasma cells in the bone marrow associated with bone loss, renal disease, and immunodeficiency. Preclinical evidence suggests an immunologic mechanism behind the therapeutic effects of As2O3 on myeloma cells. This appears to be achieved by a marked increase in lymphokine-activated killers mediated killing and up-modulation of CD38 and Cd54, two molecules involved in cell-cell interactions. Moreover, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoproliferative disorders. Preliminary clinical data in relapsed/refractory multiple myeloma suggest that As2O3 does have a role in the management of multiple myeloma; however, preclinical data show that the addition of ascorbic acid, and using As2O3 in combination with other active chemotherapeutic agents will enhance its role in managing the disease, and this is probably the position the drug will occupy in the armamentarium against myeloma.
...
PMID:Arsenic trioxide: a new immunomodulatory agent in the management of multiple myeloma. 1191 50

Potent drugs such as cyclosporine have provided effective probes of signal transduction pathways and, as well, of human immunodeficiency virus type 1 (HIV-1) replication mechanisms. Recently, it was reported that As(2)O(3), a drug used to treat acute promyelocytic leukemia (PML), stimulates HIV-1 replication. We found that As(2)O(3) accelerates the kinetics of a spreading HIV-1 infection in human T cells and increases the number of cells bearing HIV-1 provirus after a single round of infection. The stimulatory effect occurred after membrane fusion and resulted in increased steady-state levels of newly synthesized viral cDNA. Stimulation was independent of HIV-1 env and most viral accessory genes, and As(2)O(3) had no detectable effects on viral expression postintegration or virion assembly. Murine leukemia virus (MLV) transduction was enhanced by As(2)O(3) to the same extent as HIV-1 transduction, but As(2)O(3) had no additional effect on Fv1 restriction. In contrast, As(2)O(3) largely overcame the specific block to N-tropic MLV reverse transcription posed by human Ref1. As(2)O(3) disrupts PML bodies, nuclear structures named for a major component, the PML protein. We observed no changes in PML bodies in response to HIV-1 infection. Experiments with PML-null target cells indicated that PML has no effect on HIV-1 infectivity and is dispensable for the stimulatory effect of As(2)O(3). As(2)O(3) caused cell death in uninfected cells at the same concentrations which stimulate HIV-1 replication. Among four additional apoptosis-inducing agents, a boost in HIV-1 infectivity was observed only with carbonyl cyanide m-chlorophenylhydrazone, a compound which, like As(2)O(3), disrupts the mitochondrial transmembrane potential. In summary, As(2)O(3) stimulates retroviral reverse transcription, perhaps via effects on mitochondria, and provides a useful tool for characterizing Ref1.
...
PMID:As(2)O(3) enhances retroviral reverse transcription and counteracts Ref1 antiviral activity. 1258 41

Herpes simplex virus type 1 (HSV-1) ICP0 directs the degradation of cellular proteins associated with nuclear structures called ND10, a function thought to be closely associated with its broad transactivating activity. Roscovitine (Rosco), an inhibitor of cyclin-dependent kinases (cdks), inhibits the replication of HSV-1, HSV-2, human cytomegalovirus, varicella-zoster virus, and human immunodeficiency virus type 1 by inhibiting specific steps or activities of viral regulatory proteins, indicating the broad and pleiotropic effects that cdks have on the replication of these viruses. We previously demonstrated that Rosco inhibits the transactivating activity of ICP0. In the present study, we asked whether Rosco also affects the ability of ICP0 to direct the degradation of ND10-associated proteins. For this purpose, WI-38 cells treated with cycloheximide (CHX) were mock infected or infected with wild-type HSV-1 or an ICP0(-) mutant (7134). After release from the CHX block, the infections were allowed to proceed for 2 h in the presence or absence of Rosco at a concentration known to inhibit ICP0's transactivating activity. The cells were then examined for the presence of ICP0 and selected ND10-associated antigens (promyelocytic leukemia antigen [PML], sp100, hDaxx, and NDP55) by immunofluorescence. Staining for the ND10-associated antigens was detected in </=20% of KOS-infected cells in the presence or absence of Rosco, demonstrating that Rosco-sensitive kinases are not required for ICP0's ability to direct the dispersal or degradation of these antigens. In contrast, >90% of 7134- and mock-infected cells stained positive for all ND10-associated antigens in the presence or absence of Rosco. Similar results were obtained with a non-ND10-associated antigen, DNA-PK(cs), a known target of ICP0-directed degradation. The results of the PML and DNA-PK(cs) immunofluorescence studies correlated with a decrease in the levels of these proteins as determined by Western blotting. Thus, the differential requirement for Rosco-sensitive cdk activities distinguishes ICP0's ability to direct the dispersal or degradation of cellular proteins from its transactivating activity.
...
PMID:The differential requirement for cyclin-dependent kinase activities distinguishes two functions of herpes simplex virus type 1 ICP0. 1461 Jan 83


1 2 3 Next >>

---