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

Five patients with primary immunodeficiency and cancer are presented. Two children with ataxia-telangiectasia developed acute lymphoblastic leukemia and malignant lymphoma of B-like origin with chromosome damage and unusual prevalence of antibodies to E.B.V. early antigen. A bone sarcoma occurred in a patient with common variable hypogammaglobulinemia. At least two infants who died with severe combined immunodeficiency had at autopsy congenital myelomonocytic leukemia and malignant lymphoma. These cases indicate the high risk for development of cancer in patients with primary abnormalities of the immune system and suggest the heterogeneity and complexity of pathogenic mechanisms.
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PMID:[Primary immunologic deficiencies and cancer. 5 anatomo-clinical case reports]. 657 32

Neonatal treatment of female rodents with the synthetic estrogen diethylstilbestrol [(DES) CAS: 56-53-1; alpha, alpha'-diethyl-4,4'-dimethoxystilbene] results in immunodeficiency that persists into adulthood, along with progressive development of genital tract lesions. DES-induced immunosuppression was examined as a possible promoter of genital tract lesion and tumor development in BALB/cCrgl female mice. Secondary suppression of T-cell immunity after neonatal DES treatment failed to increase lesion incidence or to promote genital tract tumor development in 8-month-old mice. Although hyperplastic lesions were present in 70% of the genital tracts from DES-treated mice at 8 months of age, apparently few neoplastic cells are present at this time, since transplantation of genital tracts from these animals into syngeneic hosts did not yield tumors. To reduce the possibility that potential tumors were too immunogenic to survive in the syngeneic hosts, genital tract pieces from 12-month-old DES-treated female mice were transplanted into immunosuppressed hosts; only 1 tumor resulted. The tumor was a mixed adenocarcinoma, squamous cell carcinoma, and sarcoma and was immunogenic. These results suggest that immunosurveillance by T-cells is relatively unimportant in DES-induced genital tract lesion development.
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PMID:Effect of immunosuppression on neonatally diethylstilbestrol-induced genital tract lesion and tumor development in female mice. 659 83

The inhibitory effect of alpha 2-macroglobulin (alpha 2M), a major plasma proteinase inhibitor, on human immunodeficiency virus (HIV) proteinase was investigated. The activity of HIV proteinase toward the Moloney murine sarcoma virus-derived gag protein (a high-molecular-mass substrate) was found to be inhibited by alpha 2M at pH 5.5-7.4. On the other hand, the activity toward the B chain of oxidized insulin (a low-molecular-mass substrate) was scarcely inhibited. The complex of alpha 2M and HIV proteinase was isolated by gel filtration and the enzyme was shown to be significantly protected by the complex formation from autoinactivation under nonreducing conditions. The stoichiometry of the complex formation was found to be 2:1 (enzyme: alpha 2M, mol/mol). These results demonstrate the entrapment and concomitant inhibition of HIV proteinase by alpha 2M.
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PMID:Entrapment and inhibition of human immunodeficiency virus proteinase by alpha 2-macroglobulin and structural changes in the inhibitor. 769 Mar 56

Questionnaires were sent to veterinarians who had submitted a fibrosarcoma from a cat to the surgical pathology services of the veterinary schools of the University of Pennsylvania and Tufts University between Jan 1, 1991 and June 30, 1992. Questionnaire items included signalment, FeLV and feline immunodeficiency virus status, site of sarcoma, vaccination site, vaccines used, treatment, biologic behavior of the tumor, and final outcome. Data were analyzed, using Student's t-test for continuous data, chi 2 test for categoric data, and log-rank test for survival estimates. Comparing results for cats with vaccination-site (VS) tumors and nonvaccination-site (NVS) tumors, we determined that VS tumors developed in younger cats and were larger than NVS tumors. Although VS sarcomas were biologically aggressive and redeveloped more often than NVS sarcomas, metastasis was not detected, and cats with VS tumors survived longer than cats with NVS tumors. Vaccination-site sarcomas developed in cats after injection of many types of vaccines, administered singularly or in combination. Of the cats in the VS group administered a single vaccine, 37% were given rabies, 33% were given feline viral rhinotracheitis/calicivirus/panleukopenia virus, and 30% were given FeLV vaccines. Cats with VS tumors were more likely to have received FeLV vaccine and less likely to have received rabies vaccine than those with NVS tumors. Although vaccines produced by certain manufacturers were used most often in cats with VS and NVS sarcomas, it was believed that this probably represented marketing practices and brand popularity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of fibrosarcomas that developed at vaccination sites and at nonvaccination sites in cats: 239 cases (1991-1992). 769 23

2',3'dideoxyinosine (ddI) has potent activity against human immunodeficiency virus (HIV) but is rapidly metabolized by erythrocytic purine nucleoside phosphorylase (PNP), and therefore has a very short plasma half-life in rodents, monkeys and in patients with acquired immunodeficiency syndrome. It is now reported that 100 microM (2-[2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methyl]-phenyl]ethenyl) - phosphonic acid (MDL 74,428), a very potent inhibitor of PNP blocks the intracellular phosphorolysis of ddI in cultured human red blood cells, in T leukemic CEM lymphoblasts and prolongs ddI plasma effective concentration in mice at a dose of 250 mg/kg body weight given i.p. In MDL 74,428-treated CEM cells, despite marked reduction of ddI catabolism, neither further accumulation of ddATP, the active antiviral metabolite of ddI, nor potentiation of the activity of ddI against HIV cytopathogenicity is observed. MDL 74,428 does not also affect the inhibitory effect of ddI combined with ribavirin on the transformation in vitro of C3H/3T3 cells by Moloney murine sarcoma virus (MSV). In mice, on the contrary, MDL 74,428 (200 mg/kg body weight, i.p.) is effective at potentiating the effect of ribavirin used either alone, or combined with ddI on MSV-induced tumour formation and associated mortality. However, in the absence of ribavirin, co-administration of MDL 74,428 with ddI affords, no chemotherapeutic advantage.
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PMID:Potentiating effect of (2-[2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methyl]-phenyl]ethenyl) -phosphonic acid (MDL 74,428), a potent inhibitor of purine nucleoside phosphorylase, on the antiretroviral activities of 2',3'-dideoxyinosine combined with ribavirin in mice. 805 21

A series of linker scanning and deletion mutations has been constructed in the 5' leader sequence of HIV-1. One virus with a 13-base-linker substitution upstream of the 5' major splice site was as impaired in its ability to replicate as a virus with a large deletion, which included these 13 bases, and was less efficient in packaging its genomic RNA than viruses carrying mutations between the 5' major splice site and the gag translation initiation site. These observations have led to the identification of a conserved pattern of repeated sequence elements associated with sequences experimentally defined as necessary for encapsidation of Moloney murine leukemia virus, spleen necrosis virus, avian leukosis-sarcoma viruses, and human immunodeficiency virus type 1.
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PMID:A short sequence upstream of the 5' major splice site is important for encapsidation of HIV-1 genomic RNA. 825 68

Splenic abscess is an infrequent complication in the immunocompromised patient. Six patients underwent splenectomy for presumed splenic abscess from 1987 to 1991. Chemotherapy altered the immune system of four patients; the human immunodeficiency virus (HIV) rendered the other two vulnerable to infection. Five presented with fever but none had leukocytosis; only one exhibited palpable splenomegaly; three had abdominal pain. Cultures documented systemic infection in all but one, an HIV-positive individual. Respiratory embarrassment was the indication for surgery in one patient. In five cases the decision for surgical intervention was made after computed tomography (CT) indicated the presence of multiple splenic lesions and systemic antibiotics failed to resolve the fevers. CT additionally showed hepatic and/or renal microabscesses in four patients. Signs and symptoms experienced preoperatively resolved with splenectomy in all six patients. No additional surgery was required for the patients with extrasplenic abscesses. Surgical pathology determined that three spleens had fungal and two had mycobacterial abscesses. The other was shown to be a spindle cell sarcoma; no abscess was present. This patient had preoperative blood cultures positive for mycobacteria, and the same organism was recovered from retroperitoneal nodes sampled at the time of splenectomy for the sarcoma. Follow-up indicates that no patients experienced surgical complications or sequelae related to their splenic pathology. Splenectomy is necessary and effective in treating splenic abscesses in immunocompromised patients and is appropriate for diagnosis as well as therapy.
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PMID:Management of splenic abscess in immunocompromised children. 833 12

A simple, sensitive and accurate plaque assay was developed using HPB-Ma, a variant of the human T-cell line HPB-ALL, which becomes adherent to the substratum after infection with an amphotropic murine sarcoma virus (MSVa). The simplicity of this novel plaque assay allowed us to examine a large number of serum samples from patients with HIV infection for neutralizing antibody activity against two human immunodeficiency virus type-1 (HIV-1) strains. During the progression of clinical disease, the neutralizing activity in the sera from two individual patients remained unchanged or increased. A patient with a known time of HIV infection produced cross-neutralizing antibody at 25-34 weeks. The neutralizing activity in the sera from 17 asymptomatic carriers, four patients with AIDS-related complex and four AIDS patients was also examined and was found to be unrelated to the clinical stage.
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PMID:New HIV plaque titration; application to the assay of neutralizing antibody. 843 63

The (S)- and (R)-enantiomers of acyclic purine nucleoside phosphonate analogs (i.e., 3-hydroxy-2-phosphonomethoxypropyl [HPMP] derivatives, 3-fluoro-2-phosphonomethoxypropyl [FPMP] derivatives, and 2-phosphonomethoxypropyl [PMP] derivatives of adenine [A], 2-aminopurine, 2,6-diaminopurine [DAP], and guanine [G]) have been synthesized and evaluated for antiviral activity. As a rule, the HPMP derivatives proved effective against DNA viruses but not RNA viruses or retroviruses. In particular, (S)-HPMPA, (S)-HPMPDAP, and (R)- and (S)-HPMPG were exquisitely inhibitory to herpes simplex virus type 1 (50% effective concentrations, 0.63, 0.22, 0.10, and 0.66 microM, respectively). The FPMP and PMP derivatives showed marked inhibitory activities against retroviruses but not DNA viruses. The (S)-enantiomer of FPMPA and the (R)-enantiomer of PMPA were approximately 30- to 100-fold more effective against human immunodeficiency virus and Moloney murine sarcoma virus (MSV) than their enantiomeric counterparts. In contrast, both (S)- and (R)-enantiomers of the DAP and G derivatives proved equally effective against retroviruses, except for (R)-PMPDAP, which was 15- to 40-fold more inhibitory than (S)-PMPDAP. (R)-PMPDAP emerged as the most potent and selective inhibitor of MSV-induced transformation of murine C3H/3T3 cells and human immunodeficiency virus-induced cytopathicity in MT-4 and CEM cells (50% effective concentration, approximately 0.1 to 0.6 microM). When administered intraperitoneally at a single dose as low as 2 mg/kg, (R)-PMPDAP efficiently decreased MSV-induced tumor formation in newborn NMRI mice and significantly increased the survival time of MSV-infected mice. In addition, upon oral administration to MSV-infected mice, (R)-PMPDAP showed marked antiretroviral efficacy.
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PMID:Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. 845 66

In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.
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PMID:Sarcomas in organ allograft recipients. 854 79


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