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

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

The antiviral nucleoside analogue 2',3'-dideoxycytidine (ddC) is a DNA chain terminator and/or inhibitor of human immunodeficiency virus (HIV) reverse transcriptase. We evaluated the effects of ddC in 36 New Zealand white rabbits. Three/sex were assigned to a control group and 5 treatment groups (10-250 mg/kg/day) for 13 or 18 weeks. Blood samples were taken 1 week prior to treatment and weekly thereafter to termination with the exception of the 2 highest dose groups, where blood sample collection was terminated at week 13. Selected hematological analytes were measured weekly with the exception of prothrombin time (PT) and activated partial thromboplastin time (APTT). PT and APTT and selected biochemical analytes were measured prior to treatment, at 7 weeks, and after 13 weeks of treatment. All rabbits were necropsied. Giemsa and hematoxylin and eosin sections were prepared from methacrylate-embedded marrow. Hematological effects included decreases in red blood cell count, hemoglobin, hematocrit, and white blood cell count and increases in mean corpuscular volume and red cell distribution width. Platelets, platelet volume, PT, APTT, and mean corpuscular hemoglobin concentration values were variable or unchanged. Effects were dose-related, most were seen at 1 week, and they persisted to term. Bone marrow histopathologic changes included megalocytosis, erythroid hypoplasia, bizarre erythroid nuclear morphology, nuclear-cytoplasmic asynchrony, and increased mitotic figures. Lymphopenia caused by ddC plateaued at 2 weeks and persisted until termination. Heteropenia (neutropenia) was sporadic. Biochemical values for serum analytes were unchanged by treatment. The principal hematological effect of ddC upon the erythron was characterized as a nonregenerative macrocytic anemia with erythroid hypoplasia and megaloblastic erythropoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematological effects of 2',3'-dideoxycytidine in rabbits. 133 36

Polysulfated polysaccharides are attractive candidates for antiviral drug development because of their potent in vitro activities against human immunodeficiency virus (HIV), herpesviruses, and other enveloped viruses. To determine the potential anti-HIV activity of a prototypical polysulfated polysaccharide, we administered the maximally tolerated dose of dextran sulfate by continuous intravenous infusion to 10 subjects with symptomatic HIV infection for up to 14 days. Since parenteral dextran sulfate is an anticoagulant, the infusion was adjusted to produce the greatest acceptable increase in activated partial thromboplastin time. Drug concentrations in plasma achieved with this protocol were up to 200-fold greater than the 50% inhibitory concentration for free HIV infectivity in vitro. Despite this, circulating HIV antigen (p24) levels increased in all eight subjects who received the drug for more than 3 days (median proportional increase, 73.5%; range, 32 to 130%); this increase was highly significant when it was compared with that in a large cohort of untreated historical controls (Fisher's exact test, P less than 0.001). Frequent decreases in infusion rate were required in all subjects to maintain a constant activated partial thromboplastin time; plasma dextran sulfate levels did not fall as the infusion rate decreased, suggesting a decline in estimated drug clearance over time. Continuous intravenous dextran sulfate was toxic, producing profound but reversible thrombocytopenia in all eight subjects who received drug for more than 3 days and extensive but reversible alopecia in five of these subjects. Because of its toxicity and lack of beneficial effect on surrogate markers, dextran sulfate is unlikely to have a practical role in the treatment of symptomatic HIV infection.
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PMID:Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection. 181 Jan 88

Four kinds of gangliosides, namely GM1a, GD1a, GD1b and GT1b and their sulfated derivatives were examined for antiviral activities against human immunodeficiency virus type 1 and abilities to modulate CD4 antigen on the cell surface. The infection of human T cells with the virus was markedly inhibited by treatment with the sulfated gangliosides at a concentration of 10 micrograms/ml, while the non-sulfated gangliosides had only weak antiviral activities. The sulfated gangliosides completely inhibited syncytium formation induced by HIV-1 at 30 micrograms/ml. The CD4 antigen on the surface of T cells became hardly detectable after treatment with them. They did not damage cells, nor prolong the activated partial thromboplastin time at concentrations of up to 100 micrograms/ml, suggesting that they may have little side effect in vivo.
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PMID:Inhibition of infection with human immunodeficiency virus type 1 by sulfated gangliosides. 199 95

The term antiphospholipid syndrome is used to characterize a complex of clinical and pathologic findings mediated by a group of antibodies formed against a family of antiphospholipids. These antiphospholipid antibodies were originally found in patients with lupus erythematosus in whom the partial thromboplastin time was prolonged and in patients with other autoimmune diseases; subsequently, they have been observed in association with a variety of other conditions, including infections, reactions to drugs, malignant neoplasms, human immunodeficiency virus disease, and as an isolated finding. In recent years, there has been some clarification of the significance of the various tests for antiphospholipid antibodies, including the lupus anticoagulant test and the anticardiolipin antibody tests, in predicting the antiphospholipid syndrome. The mechanism of disease, however, has not been well defined. The most common cutaneous lesion seen in seven patients with lupus anticoagulant and anticardiolipin antibody who have the antiphospholipid syndrome was ulceration due to thrombosis of dermal veins and arteries. Often there is a reactive vascular proliferation around the thrombosed vessels. The presence of primary thrombosis of both veins and arteries in thrombotic disorders is unusual and may provide insight into the mechanism of thrombosis in antiphospholipid syndrome.
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PMID:Cutaneous histopathologic findings in 'antiphospholipid syndrome'. Correlation with disease, including human immunodeficiency virus disease. 211 49

Expression of tumor necrosis factor (TNF alpha), tissue factor (TF), and interleukin 1-beta (IL-1 beta) mRNA was evaluated in monocytes isolated from patients infected with human immunodeficiency virus (HIV). There was a significant depression (66%) of the induced level of TF mRNA expression in response to lipopolysaccharide. Conversely, the response of TNF alpha and IL-1 beta, following LPS induction, was "normal." TF mRNA reduction was also observed to a lesser degree in AIDS-related complex patients (20%) but not in asymptomatic seropositives. TF is necessary for initiation of the coagulation protease cascade, leading to thrombin production and fibrin deposition, which play a role in inflammatory responses. Its selective reduction may be a factor in the diminished resistance to secondary infections observed in AIDS. Further, since the TF defect increases as patients progress toward AIDS, it may serve as a marker for disease progression.
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PMID:A selective defect in tissue factor mRNA expression in monocytes from AIDS patients. 229 2

Human immunodeficiency virus (HIV) infection is associated to different clinical and laboratory hemostatic alterations. The most important is thrombocytopenia, which very often leads to a picture indistinguishable from idiopathic thrombocytopenic purpura with poor clinical relevance but with possible important problems of differential diagnosis. Thrombotic thrombocytopenic purpura is sometimes associated to HIV infections, although only few reports there exist. Finally, the high incidence of lupus anticoagulant in some phases of HIV infection has not a clinical relevance, but is essentially a laboratory finding which is to be known because it can cause a prolonged partial thromboplastin time.
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PMID:Hemostatic alterations during human immunodeficiency virus infection: a review. 267 75

The hemostatic function of 40 feline immunodeficiency virus (FIV) seropositive and 8 FIV and feline leukemia virus (FeLV) seropositive cats was evaluated and compared with reference values from 30 clinically healthy cats. The FIV-positive cats were divided into 3 groups: group I included asymptomatic carriers; group II comprised sick FIV-infected cats with illnesses not likely to influence the hemostatic system; and group III included FIV-positive cats with diseases potentially associated with coagulopathies. Platelet counts in FIV/FeLV-infected cats were significantly lower than in healthy cats (P < .003), whereas the differences in the 3 groups of FIV-positive cats were variable (group I, P = .009; II, P = .05; III, P = .09). Thrombocytopenia (< 145,000 platelets/microL) was present in 4 FIV-positive and 3 FIV/FeLV-positive cats. Platelet aggregation induced by collagen (0.5 and 0.25 micrograms/mL), adenosine diphosphate (ADP) (1 and 0.6 mumol/L), and thrombin (0.4 and 0.25 IU/mL) was not significantly different from that of healthy cats. The plasma coagulation system was evaluated by measuring one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, coagulation factor assays, fibrinogen and fibrin degradation products (FDP), and plasma exchange test. The OSPT was similar in FIV-seropositive cats and in the healthy control group. Cats with FIV infection, however, had markedly shorter clotting times than healthy cats when using a modified test system (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemostatic disorders in feline immunodeficiency virus-seropositive cats. 783 13

Thromboembolic complications associated with prothrombin complex concentrate treatment may be related to the high levels of factors II and X in these products. We report here results from preclinical safety studies with a human coagulation factor IX product (AlphaNine; Alpha Therapeutic Corp., Los Angeles, Calif.) that contains no detectable factor II or VII and less than 10 units of factor X/100 units of factor IX. This product was manufactured from virally inactivated factor IX complex with a barium citrate adsorption step followed by affinity chromatography yielding factor IX concentrate with a specific activity of about 86 factor IX units/mg protein. Electrophoresis and immunoblot analysis indicated that the factor IX represents about 65% of the protein in this product. The virus inactivation step incorporated into the manufacturing process (incubation with n-heptane at 60 degrees C for 20 hours) was shown to inactivate at least 8.6 logs of type 1 human immunodeficiency virus. The barium citrate adsorption and affinity chromatography steps were found to remove 2.0 logs of the marker virus, vaccinia, and the DEAE ion-exchange chromatography used to produce factor IX complex was found to remove 1.4 logs of the marker virus, Sindbis. Analysis of three separate manufacturing lots with the polymerase chain reaction revealed no evidence of hepatitis C virus. The purified factor IX was nonthrombogenic when tested at doses of 450 units/kilogram in a rabbit stasis (Wessler) model, whereas the prothrombin complex concentrates were found to be thrombogenic at doses of less than 50 units/kg. There was no evidence of DIC in a porcine model after infusion of 200 units/kg of coagulation factor IX, as manifested by negative fibrin monomer tests, the absence of fibrin in blood vessels at autopsy, little or no change in prothrombin times and partial thromboplastin times, and only moderate decreases in platelet levels after infusion.
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PMID:Human coagulation factor IX: assessment of thrombogenicity in animal models and viral safety. 844 88

We identified 100 patients (51 males and 49 females) as having the lupus anticoagulant. The following diagnoses were found in the patient population: human immunodeficiency virus positivity, 20%; systemic lupus erythematosus, 10%; prolonged preoperative activated partial thromboplastin time (APTT), 10%; procainamide hydrochloride-induced inhibitor, 9%; deep vein thrombosis, 6%; seizure disorders/epilepsy, 5%; and miscellaneous conditions, 40%. Identification was based on a prolonged APTT (> 40 seconds) that normalized with increased phospholipid concentrations and/or a prolonged Russell viper venom clotting time patient-control ratio of 1.20 or greater. In 68 cases (group 1), patient plasma prolonged the APTT of normal plasma in a 1:1 mixing study. However, in 32 cases (group 2), no such prolongation was observed. There was a significant difference between presenting APTTs in patients from group 1 (mean +/- SD, 58.29 +/- 13.30 seconds) compared with that in group 2 (mean +/- SD, 47.93 +/- 5.09 seconds). Furthermore, 66% of group 1 patients had elevated anticardiolipin antibody titers compared with only 41% in group 2. Of the 32 patients in group 2, 16 (50%) were positive for human immunodeficiency virus. We concluded that the investigation of a lupus anticoagulant should not be abandoned because patient plasma does not prolong the APTT of normal plasma in a mixing study, especially in a human immunodeficiency virus-positive population.
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PMID:The lupus anticoagulant. High incidence of 'negative' mixing studies in a human immunodeficiency virus-positive population. 850 27

Colominic acid is a homopolymer of N-acetylneuraminic acid (NANA), which has an alpha-2,8 ketosidic linkage between its polymer units. In this study, colominic acids were sulfated under different conditions and their antiviral activities against human immunodeficiency virus type 1 (HIV-1) were examined. Sulfated colominic acids, containing 6-12% sulfur, blocked the expression of HIV-1 antigen in MT-4 cells or C8166 cells following exposure to MOLT-4/HTLV-IIIB or HIV-1[GUN-1]. The compounds inhibited syncytium formation upon co-cultivation of MOLT-4 cells (clone 8) with MOLT-4/HTLV-IIIB cells and abolished the production of HIV-1 p24 antigen in culture medium of peripheral blood lymphocytes (PBLs). HIV-1 reverse transcriptase (RT) activity was not directly affected by the drugs. The compounds did not prolong activated partial thromboplastin time (APTT) at 10 and 1.0 microgram/ml, suggesting that they may not have appreciable side effects in vivo. These agents were still able to block the expression of HIV-1 antigen even when the cells were infected with HIV-1 in RPMI-1640 medium containing high percentages of fetal calf serum (FCS). These properties may be therapeutically advantageous if these compounds were considered for possible clinical use.
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PMID:Sulfated colominic acid: an antiviral agent that inhibits the human immunodeficiency virus type 1 in vitro. 879 13


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