Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accell particle-mediated gene delivery technology was employed for the intracellular delivery of antigen-encoding expression vectors in epidermal tissues in laboratory animals. Delivery of plasmid DNA-coated gold microparticles using the Accell gene delivery system resulted in de novo antigen expression in epidermal cells that stimulated the induction of antigen-specific humoral and cytotoxic cellular immune responses. Optimal DNA delivery conditions favoring maximal humoral responses required the delivery of 5 x 10(7) micron-sized gold particles containing 300 plasmid copies per particle (80 ng of vector total) into a 4-cm2 area of abdominal skin. Comparison of immune responses between animals that received intramuscular injections of relatively large quantities of vector DNA (100 micrograms) and those that received intracellular deliveries of submicrogram quantities of the same DNA to the epidermis demonstrated that the latter approach was considerably more effective at eliciting strong humoral responses. In addition, cytotoxic cellular immune responses were elicited to HIV-1 gp120 following epidermal delivery of HIV-1 gp160 or gp120 expression constructs. A qualitative shift from predominantly cytotoxic cellular to predominantly humoral immune responses with continued immunization indicated the potential for optimizing delivery conditions to favor specifically one type of response over the other.
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PMID:Accell particle-mediated DNA immunization elicits humoral, cytotoxic, and protective immune responses. 786 32

The approach of providing passive protection to young infants by immunizing pregnant women can bypass the problems of immunological immaturity in the neonate, avoid or delay active immunization of the infant in the first year of life, and prevent transmission of an infection from the mother to the neonate. Optimal vaccines for this approach should induce high immunoglobulin G antibody titers that quickly reach their maximum level after immunization and persist at protective levels for several years, thus providing passive protection in subsequent pregnancies. Specific applications of this approach include the worldwide practice of maternal immunization with tetanus toxoid vaccine and ongoing studies of maternal immunization to prevent Haemophilus influenzae type b, group B streptococcal, pneumococcal, meningococcal, and human immunodeficiency virus infection in the infant. Addressing the cultural, sociological, and legal aspects of maternal immunization will be required to ensure the success of this approach.
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PMID:Maternal immunization to prevent infectious diseases in the neonate or infant. 815 47

In summary, HIV is a retrovirus with devastating consequences for those infected. Primary modes of transmission are through sexual contact and parenteral exposure to infected blood and body fluids. Prevalence of the virus among trauma patients, risk of exposure, and infection of health care workers are variable and to a large extent not known. Existing HIV infection and AIDS have both direct and indirect effects on care and outcome of trauma patients. Caring for these patients presents many challenges. Manifestations and complications of each condition may mask, mimic, or compound the other. Optimal care and outcome depend on knowledge of both diseases, and the specific nuances of their management. As with all trauma patients, a team approach coordinated by an identified team leader is indicated. Finally, to protect both the patient and the care giver, policies that effectively reduce exposure must be formulated, promulgated, and practiced.
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PMID:Human immunodeficiency virus and infectious considerations. 825 42

Optimal conditions for in vitro anti-human immunodeficiency virus type 1 (HIV-1) antibody (Ab) synthesis and detection were re-appraised. Western blot (WB) and radioimmunoassay (RIA) could detect about 1 and 10 ng, respectively, of HIV-1-specific Ab (HIV-Ab), while the sensitivity of an enzyme-linked immunosorbent assay (ELISA) was much lower. Optimal HIV-Ab recovery was obtained by culturing 2.5 x 10(6) peripheral blood mononuclear cells (PBMC)/ml from seropositive subjects for 16 days in the absence of mitogens; at higher cell concentrations, background levels were unacceptably high. The background of non-de novo synthesized HIV-Ab was due to insufficient PBMC washing and/or cytophilic immunoglobulin (Ig); a particular washing procedure, as well as 24 h peripheral blood mononuclear cells (PBMC) pre-culture, might help in limiting this phenomenon. However, results should be compared with those obtained in cultures containing puromycin especially in infants, where a higher CD16 antigen expression in lymphocytes is likely responsible for increased amounts of cytophilic Ig released in culture supernatants, compared to adults.
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PMID:Standardization of in vitro synthesis and detection of HIV-1-specific antibodies. 842 52

The continued spread of penicillin-resistant pneumococci raises therapeutic concerns. Optimal therapy for resistant infections is unknown and it is not clear whether the efficacy of penicillin or equally active beta-lactam agents is compromised in non-meningeal-resistant infections. A prospective nonintervention study was undertaken to compare the clinical response in penicillin-resistant vs. penicillin-susceptible bacteremic pneumococcal infections, excluding meningitis. Of 108 children enrolled, 35 (32%) had penicillin-resistant (one highly resistant) isolates. Seventy-eight children had pneumonia, 21 had occult bacteremia (sepsis) and 9 had peritonitis. Children with resistant infections were more likely to have underlying disorders, especially human immunodeficiency virus infection, and to have received antimicrobial therapy in the previous month. After 48 hours of therapy 64% of penicillin-susceptible infections showed improvement vs. 60% of penicillin-resistant infections (odds ratio, 1.2; 95% confidence intervals, 0.5 to 3.0). In children with pneumonia treated with ampicillin or an equivalent beta-lactam agent, 93% with penicillin-susceptible infections had improved by Day 7 of therapy compared with 88% with resistant infections (odds ratio, 1.9; 95% confidence interval 0.3 to 15.9). The durations of respiratory distress, fever and oxygen requirement were similar in penicillin-susceptible and -resistant infections. These results suggest that intermediate penicillin resistance is of little significance in pneumococcal pneumonia or sepsis and that standard beta-lactam therapy is still highly effective. Further studies of highly penicillin-resistant infections are necessary.
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PMID:Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease. 878 62

The protein coding regions of all retroviral pre-mRNAs are flanked by a direct repeat of R-U5 sequences. In many retroviruses, the R-U5 repeat contains a complete core poly(A) site-composed of a highly conserved AAUAAA hexamer and a GU-rich downstream element. A mechanism that allows for the bypass of the 5' core poly(A) site and the exclusive use of the 3' core poly(A) site must therefore exist. In human immunodeficiency virus type 1 (HIV-1), sequences within the U3 region appear to play a key role in poly(A) site selection. U3 sequences are required for efficient 3' processing at the HIV-1 poly(A) site both in vivo and in vitro. These sequences serve to promote the interaction of cleavage and polyadenylation specificity factor (CPSF) with the core poly(A) site. We have now demonstrated the presence of a functionally analogous 3' processing enhancer within the U3 region of a distantly related lentivirus, equine infectious anemia virus (EIAV). U3 sequences enhanced the processing of the EIAV core poly(A) site sevenfold in vitro. The U3 sequences also enhanced the stability of CPSF binding at the core poly(A) site. Optimal processing required the TAR RNA secondary structure that resides within the R region 28 nucleotides upstream of the AAUAAA hexamer. Disruption of TAR reduced processing, while compensatory changes that restored the RNA structure also restored processing to the wild-type level, suggesting a position dependence of the U3-encoded enhancer sequences. Finally, the reciprocal exchange of the EIAV and HIV U3 regions demonstrated the ability of each of these sequences to enhance both 3' processing and the binding of CPSF in the context of the heterologous core poly(A) site. The impact of U3 sequences upon the interaction of CPSF at the core poly(A) site may therefore represent a common strategy for retroviral poly(A) site selection.
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PMID:A common mechanism for the enhancement of mRNA 3' processing by U3 sequences in two distantly related lentiviruses. 862 81

There has been a slight change in the total number of TB cases notified since 1985, when the first case of HIV was reported. Although there has been an increase in the incidence of TB in HIV-infected cases, the percentage of multidrug-resistant tuberculosis (MDRTB) in this group is the same as in the HIV-negative group (2.7%). The multidrug-resistant (MDR) rate in 1988 was nearly 2% in Thailand, increasing to 5% in 1994. The factors that promote MDRTB in Thailand include irregular drug taking, high initial drug resistance, the prescription of inappropriate regimens, and drug intolerance. The percentages of total initial drug resistance, four-drug resistance, and MDRTB have increased to 22.4%, 1.4%, and 4.8%, respectively. Comparable figures for acquired resistance are up to 2.5-, 10-, and 6-fold, respectively. Duration of treatment for 24-30 months depends on severity, previous therapy, and the number of drug resistances. Surgery is suggested for persistent positive case with localized lesions and good cardiopulmonary reserve. Quinolones are among the most promising drugs for second-line therapy against MDRTB. Quinolone and ofloxacin are promising drugs for MDRTB, achieving a sputum conversion rate of 59-79%. A prospective study showed a success rate of 67% with no adverse effects. However, when different regimens were examined, it was found that at least four anti-TB drugs are required. In current multicenter, controlled, prospective trials in Bangkok, 600 mg ofloxacin daily is combined with pyrazinamide, p-aminosalicylate, amikacin, and ethambutol, with a treatment duration of 18-24 months with a 2-year follow-up. No adverse effects were reported for the ofloxacin 300 mg/day regimen in several studies done. Optimal MDRTB treatment requires appropriate organization for planning and implementation and directly observed therapy. Guidelines developed in April 1996 call for at least 3-4 culture-sensitive drugs given for either 2-2.5 years or until negative sputum cultures have been present for at least 1 year.
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PMID:Treatment of multidrug-resistant tuberculosis in Thailand. 898 Aug 62

A modified peptide-based indirect ELISA technique for the detection of HIV-1 specific antibodies in the sera of HIV-1 seropositive individuals is described. We found that the reduction of non-specific binding of HIV-1 seropositive sera to the ELISA plate was essential for the reliable detection of serum antibodies in the peptide based indirect ELISA. Optimal results were obtained using Immulon microtitre plates, different concentrations of denatured. purified grade of casein in the blocking (1%) and washing (0.25%) solutions and by diluting HIV-1 seropositive sera 1 in 1600. These conditions reduced non-specific binding and improved assay sensitivity. We show that the inclusion of a control peptide is essential to reducing the incidence of false positive and false negative results. Taken together, the modifications described in this report improve reliability of the peptide-based indirect ELISA without compromising its sensitivity and have particular relevance for those wishing to apply the peptide-based indirect ELISA technique to serum samples which exhibit high levels of non-specific binding. To illustrate this, levels of antibody in the sera of HIV-1 seropositive and seronegative donors that are specific for peptides derived from a conserved region of HIV-1 gp120 sharing homology with the FAS apoptosis antigen were analysed using this technique.
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PMID:Optimisation of a peptide-based indirect ELISA for the detection of antibody in the serum of HIV-1 seropositive patients. 900 46

Optimal stimulation and prevention of anergy in T cells requires signaling through the CD28 molecule. During HIV disease progression, CD28 expression is lost, particularly on CD8+ T cells. Because alterations in cytokine production patterns occur during HIV infection, we determined whether CD8+ T cell phenotype or function was affected by cytokine environment. Treatment of CD8+ T cells with IL-4 decreased levels of both CD28 surface expression and message and increased CD8 expression. Furthermore, CD8+ T cells that had down-regulated CD28 had reduced proliferative capacity. The inhibitory effects of CD28 reduction could be compensated either by increased anti-CD3 or by exogenous IL-2, suggesting that the strength of T cell signaling necessary for the production of IL-2 and subsequent proliferation is negatively regulated by IL-4. CD8+ subpopulations with differential CD28 expression produced different patterns of cytokines, particularly IL-2 and IFN-gamma. Furthermore, CD8+ T cells that had reduced CD28 levels but made their own IL-2 were able to proliferate in response to TCR stimulation. These results suggest that loss of CD28 expression and CD8 T cell function can be regulated by the cytokine environment, which may be altered during HIV disease progression. Whether the dysfunction of CD8+ T cells in HIV infection occurs by such a mechanism is the subject of future investigation.
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PMID:Regulation of CD28 costimulation in human CD8+ T cells. 902 89

The hematologic manifestations of HIV infection and AIDS are common and may cause symptoms that are life-threatening and impair the quality of life of these patients. The most important of these manifestations are cytopenias. Anemia and neutropenia are generally caused by inadequate production because of suppression of the bone marrow by the HIV infection through abnormal cytokine expression and alteration of the bone marrow microenvironment. Thrombocytopenia is caused by immune-mediated destruction of the platelets, in addition to inadequate platelet production. The incidence and severity of cytopenia are generally correlated to the stage of the HIV infection. Other causes of cytopenia in these patients include adverse effects of drug therapy, the secondary effects of opportunistic infections or malignancies, or other preexisting or coexisting medical problems that may be prevalent in the HIV-infected population. Diagnosis of the mechanism and cause of the cytopenia may allow for specific management. Optimal management of the underlying HIV infection is essential, and mild cytopenia in asymptomatic patients may need no specific management. Supportive care for anemia includes the use of erythropoietin in addition to the judicious use of red blood cell transfusions. Therapy for neutropenia includes the use of the myeloid growth factors G-CSF and GM-CSF. Immune-mediated thrombocytopenia may be treated with a combination of zidovudine, corticosteroids, IVGG, and splenectomy. Platelet transfusions are sometimes needed for the treatment of thrombocytopenia caused by decreased production. Other hematologic manifestations such as hypergammaglobulinemia and lupus anticoagulants are commonly asymptomatic and usually require no specific therapy, but they can rarely cause morbidity and require specific interventions.
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PMID:Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 909 37


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