Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Direct DNA inoculation induces immune responses through the delivery of nonreplicating transcription units that drive the synthesis of specific foreign proteins within the inoculated host. These proteins are processed within host cells and through association with relevant MHC antigens that can become the subject of immune surveillance and elicit immune responses against pathogens. Direct introduction of DNA into mice has been reported to be antigenic as demonstrated by the use of this technique to develop immune responses against human growth hormone, influenza proteins, as well as HIV-1 proteins. Most recently the demonstration of the use of this technology to produce anti-HIV-1 immune responses has been reported in nonhuman primates. Accordingly a more detailed analysis of this technology could generate important insight into the generality of this approach for immune therapy or vaccine design. In this article we further our investigation of direct DNA inoculation as a tool for induction of relevant immune responses against HIV-1 in vivo. We demonstrate expression of HIV-1 antigens in the inoculated muscle of animals. Inoculated animals demonstrate significant cytotoxic T cell responses against HIV-1 antigen-expressing targets. Furthermore, using a novel challenge system, we demonstrate that the majority of immunized animals can reject lethal, HIV-1 antigen-expressing cell challenge in an antigen-specific manner. This technology has relevance for the development of immunization strategies against HIV as it provides for specific antigen production in vivo without the use of infectious agents.
AIDS Res Hum Retroviruses 1994
PMID:DNA inoculation induces protective in vivo immune responses against cellular challenge with HIV-1 antigen-expressing cells. 786 31

Hemophilus influenza, Streptococcus pneumoniae, and Neisseria meningitidis account for over 75% of all cases of bacterial meningitis. S. pneumoniae is the commonest causative organism in many developing countries, particularly in Africa. In developing countries overall case fatality rates of 33-44% have been reported, rising to over 60% in adult groups. S. pneumoniae accounts for the highest mortality worldwide. Sequela rates of 22-26% of survivors have been found in African studies, mostly of a neurological nature. There have been few reports of AIDS-related bacterial meningitis in the USA, and a recent study from Uganda found no association between HIV infection and meningococcal meningitis. Stronger associations have been found between opportunistic infections, both viral (cytomegalovirus, herpes virus) and non-viral (TB, Toxoplasma gondii, Cryptococcus neoformans). A lumbar puncture and analysis of the cerebrospinal fluid should be performed on suspected cases unless there is suspicion of impending coning (decreasing consciousness or focal neurological signs). The intramuscular administration of chloramphenicol alone is comparable with intravenous use, and can be given as a shorter course of therapy (2 or 3 days) followed by an oral course. The use of adjunct therapy with corticosteroids in children is now commonplace in the USA and Europe. It appears reasonable to use dexamethasone, given early and in high dosage (0.15 mg/kg 6 hourly for 4 days), in those patients who are severely ill. Rifampicin is effective for chemoprophylaxis (10 mg/kg twice daily for 2 days for meningococcal contacts, 20 mg/kg once daily for 4 days for hemophilus contacts, maximum 600 mg per dose). The recent development and introduction of conjugate vaccines for H. influenza (HIB) has led to rapid reductions in the incidence of hemophilus meningitis in many European countries. An important step in improving prognosis is to increase awareness in both health workers and the public, to encourage early hospital referral, and early antibiotic therapy.
 ...
PMID:Bacterial meningitis in developing countries. 868 85

GLQ223 is a highly purified single-chain ribosome-inactivating protein with selective effects against a variety of cells, including macrophages infected with human immunodeficiency virus. We evaluated the safety, pharmacokinetics, and immunologic effects of multiple doses of GLQ223 in 22 patients with AIDS or AIDS-related complex; CD4+ T-cell counts were between 100 and 350/mm3. GLQ223 was administered intravenously at doses of 8, 16, 24, 36, and 50 micrograms/kg of body weight; the drug was administered by constant infusion over 3 h to achieve a concentration in serum of 50 ng/ml; this concentration is known to be associated with anti-HIV effects in vitro. All patients reported a flu-like syndrome characterized by muscle and joint aches and an increase in creatinine kinase levels; symptoms were controlled easily. For patients who received 36 and 50 micrograms/kg, target concentrations in serum were achieved and an increase in CD4+ and CD8+ T cells was sustained; this sustained increase persisted for at least 28 days after the last infusion. beta 2-Microglobulin levels increased during the infusions and then declined when the infusions ended. Repeat infusions of GLQ223 were safe and relatively well tolerated. The target concentration of GLQ223 in serum was achieved and sustained. Our results suggest that GLQ223 may have activity in treating patients with human immunodeficiency virus infection.
 ...
PMID:Safety, activity, and pharmacokinetics of GLQ223 in patients with AIDS and AIDS-related complex. 791 Jul 22

Simultaneous measurements of phenotypically defined memory CD4+ cells and in vitro proliferation to three recall antigens (Ags; tetanus toxoid, influenza, and Candida albicans) were performed in 53 HIV-seropositive subjects and 39 HIV-seronegative controls. The results indicate that the low proliferative responses to recall Ags of those who were HIV infected could be partly, but not fully, explained by a decrease of phenotypically defined memory CD4+ cells. This is, to our knowledge, the first report of experiments that simultaneously measured memory CD4+ cell numbers and function and then examined whether the low responses observed in seropositive subjects could be explained by low numbers of phenotypically defined memory CD4+ cells. A central finding of the study, which argues against prevailing dogma, was that within the CD4+ lymphocyte population, the proportion of cells displaying the memory phenotype was not selectively decreased in HIV-seropositive subjects as compared with the proportion of these cells in seronegative homosexual controls. An entirely new finding of the study was that AIDS patients, many of whom were unresponsive to all three recall Ags tested, actually had a significant increase in the proportion of CD4+ cells with the memory phenotype, and this fraction approached 100% in subjects with CD4+ cell numbers that were near zero. A final observation of the study, possible because some patients were on zidovudine (ZDV), was that there was no evidence that ZDV treatment led to an increased proliferative response to recall Ags in vivo. An in vitro study also found no effect of ZDV, dideoxycytidine (ddC), or azido-dideoxyuridine (AZU) on proliferative responses to recall Ags.
 ...
PMID:Phenotypically defined memory CD4+ cells are not selectively decreased in chronic HIV disease. 791 25

Erythropoietin has been shown to be effective both in the reversal of anaemia in patients with end-stage renal failure and to increase the volume of autologous red blood cells donated preoperatively as well as to decrease the units of homologous blood transfused. This review analyzes the side effects of erythropoietin reported in the literature for long-term administration (mainly in patients with end-stage renal failure) as well as for acute/short-term administration (in patients participating in an autologous predeposit programme). The most important adverse events reported for long-term administration are as follows: (a) arterial hypertension; (b) cerebral convulsion/hypertensive encephalopathy; (c) thrombo-embolism; (d) iron deficiency; (e) influenza-like syndrome. The numbers given for these side effects are mainly taken from the first and dose-finding studies in patients with renal failure. These figures differ very much from the data given in controlled studies analyzing adverse events as well. Summarizing the results from controlled, multi-center trials in patients with end-stage renal failure or in AIDS patients, no significant differences have been observed between the control group and the patients treated with erythropoietin. The overall-incidence of side effects occurring in either group of these two studies was of approximately 83% and 95%, respectively. In contrast to these results the data published for the dose finding/treatment studies is approximately 30% for development of arterial hypertension, approximately 5% for occurrence of cerebral convulsion/hypertensive encephalopathy, approximately 10% for thrombo-embolic complications/clotting of vascular access, approximately 50% for development of iron deficiency, and approximately 10% for symptoms summarized as influenza-like syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adverse events of erythropoietin in long-term and in acute/short-term treatment. 795 Jan 71

Although the original opportunistic pathogens described in AIDS were protozoal and fungal organisms, bacterial infections are now recognized with increased prevalence and altered expression in patients with HIV infection. Especially since populations outside of North America and populations of i.v. drug abusers have been studied, bacterial infections have been shown to cause substantially increased morbidity and mortality both early and late in the course of HIV infection. Just as strategies have been developed for primary and secondary prophylaxis of classical HIV-related opportunistic infections, prevention of bacterial complications should be a high priority. Good hygiene and avoidance of unsterile needles in illicit drug use, tattooing, ear-piercing, or other cosmetic or ritual activities should be emphasized in patient education. Patients should be counseled to avoid uncooked or poorly cooked eggs and poultry and to avoid unpasteurized milk products. Pneumococcal vaccine is recommended for all HIV-seropositive patients and should be given as early as possible after recognition of HIV infection for maximal efficacy. Influenza vaccine is also recommended. It may have a role in preventing bacterial pneumonia secondary to influenza. Patient management should include regular dental care and nutritional evaluation. The use of intravenous or central catheters should be limited to essential therapies. When patients present with new febrile illness, a high index of suspicion for invasive bacterial disease is appropriate. The signs of serious bacterial infection in HIV-positive patients are subtle. Diagnostic evaluation should include cultures of blood and other relevant clinical specimens. Empiric antimicrobial therapy based on the clinical presentation may be life saving in patients with invasive bacterial disease complicating HIV infection.
 ...
PMID:Bacterial infections in HIV-infected patients. 808 71

The major topics covered at this conference included the relevance of the SIV-macaque model for HIV vaccine development, an evaluation of the methods for producing inactivated vaccine, and the possibility of developing attenuated retrovirus vaccines. The possibility that there might be a Graft Versus Host Disease component in human AIDS was discussed, and also the recent discovery that the 'original antigenic sin' phenomenon encountered in influenza vaccines may also be seen in AIDS. It was concluded that results from animal models were encouraging in the quest for an HIV-1 vaccine.
 ...
PMID:Challenges and strategies for AIDS vaccine development. 810 Jun 64

We compared the serologic response of 46 human immunodeficiency virus (HIV)-infected children and adolescents and 61 age-matched controls to standard trivalent inactivated influenza vaccine (A/Taiwan (H1N1), A/Shanghai (H3N2), B/Yamagata). Children were immunized according to the package insert recommendations before the 1990 to 1991 influenza season. Serum antibody titers to influenza A were determined before and 1 month after each vaccination and compared for study and control subjects. Serologic responses of HIV-infected participants were correlated with absolute CD4 counts and stage of HIV disease. Regardless of age or HIV status, all groups responded with significant increases in antibody to the influenza A strains (range, 2.1-fold to 11.8-fold), with the exception that antibody to H3N2 rose only 1.5-fold (P = 0.058) among HIV-positive subjects > or = 9 years old. Pre- and postimmunization antibody titers were significantly higher for controls than for HIV-positive subjects. There was no correlation between serologic responses and CD4 counts among HIV-infected subjects, but those with Centers for Disease Control and Prevention-defined acquired immunodeficiency syndrome responded significantly less well to vaccine. We conclude that HIV-infected children and adolescents produce significant antibody rises after inactivated influenza A vaccination but that their absolute antibody concentrations are lower than those seen in age-matched controls.
 ...
PMID:Serologic response to standard inactivated influenza vaccine in human immunodeficiency virus-infected children. 817 29

In Ethiopia during 1960-1962, more than 100,000 people in the Omo and Didessa river valleys acquired yellow fever and 30,000 died. There have been no yellow fever cases since 1966. Some other aboviruses that arise sporadically are Jos virus, dengue fever, Crimean-Congo hemorrhagic fever, and group A arboviruses. By age 15, all people in surveyed regions were positive for hepatitis A virus. Prevalence of hepatitis B virus increases with age ( 75% of adults in urban areas and many rural areas). The frequency of carriers of hepatitis Bs antigen is greatest in areas where people practice ceremonial tattooing. During 1988-1989, 93% of jaundiced patients in a military camp in Ethiopia had antibodies to hepatitis E virus as a result of a waterborne outbreak. Other hepatitis viruses in Ethiopia are delta and C viruses. All 3 serotypes of poliovirus exist, especially type III. 93% of 1-year-olds have already acquired immunity to it. Peak frequency of onset among paralytic cases is 2 cases. Measles epidemics are common in children. An outbreak in southwestern Ethiopia had a mortality rate of 20%. Immunity to rubella is around 85% for 14-year-olds. It increases with age. Rotavirus causes diarrhea in many children, especially among 7-12 month old infants and in June and November. Most children have been exposed to Epstein-Barr virus, which is responsible for mononucleosis and maybe for Burkitt's lymphoma. Officials do not conduct ongoing surveillance of influenza in Ethiopia. Influenza epidemics have occurred in 1957 and 1963. Rabies is endemic, with dogs being responsible for most cases. In November 1992, there were 3978 AIDS cases. 75% are less than 40 years old, with males more likely to be HIV infected than females. The Falashas of northwest Ethiopia have the world's second highest endemic rate of human T cell leukemia virus-1. Officials do not know the extent of viral diseases because there is no well organized national laboratory. One is needed to conduct surveillance and to evaluate the effectiveness of vaccination activities.
 ...
PMID:Viral diseases in Ethiopia: a review. 818 57

The envelope (Env) protein from HIV-1 is the focus of several vaccine trials in humans. It could be considered for the optimization of Env vaccinal preparations to add within the molecule defined epitopes, for instance epitopes conserved among viral isolates from HIV-1, such as from Gag or Nef proteins. As a first step to this approach, we have constructed by in vitro mutagenesis HIV-1(LAI) Env gp120 molecules in which a 12-amino acid sequence in the first (V1) or the third (V3) hypervariable region was substituted by the hemagglutinin (HA) 307-318 peptide from the influenza virus, a dominant T helper cell epitope in humans. The proteins were produced by recombinant vaccinia viruses. They had kept their structural properties in terms of serological recognition and binding to CD4. Of note, we observed that the gp120 protein substituted in the V1 domain elicited a stronger serological immune response in mice compared to native or V3 substituted gp120. This indicates that gp120 can accommodate large substitutions without major structural perturbations and that, on the contrary, some of them could prove beneficial in terms of immunogenicity.
AIDS Res Hum Retroviruses 1993 Aug
PMID:A peptide substitution in HIV-1 gp120 first hypervariable domain enhances its immunogenicity in mice. 821 46


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