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

Both AIDS and cancer are linked to immune dysfunctions of the body which are characterized by the persistence of disease-afflicted cells. To effect a cure with novel gene therapy approaches, these diseased cells must be eliminated either directly or indirectly using cytotoxic or suicide genes, or via activation of specific immune functional cells. Retroviral vectors are useful tools for long-term genome modification owing to their ability to integrate into host chromosomes. However, most oncoretroviruses, including murine leukemia virus (MLV), require cell division to facilitate nuclear entry; this has restricted the application of murine oncoretroviral vectors to cell targets that are actively dividing. Accordingly, gene transfer into hematopoietic stem cells (HSCs) and terminally differentiated cells such as muscles, neurons and dendritic cells (DCs) has been limited with the conventional oncoretroviral vectors. The lentiviral family of retroviruses, including human immunodeficiency virus type 1 (HIV-1), has been developed into useful gene transfer tools. Lentiviral vectors carry several nuclear entry viral proteins, and therefore can target slowly-dividing and non-dividing cells. To activate immune response against cancer or HIV infection, long-term marking of the target cells is not necessary. However, to establish intracellular defense to prevent HIV infection, prolonged genetic modification of target cells such as HSCs will be required. Due to the poor transduction efficiency and the problem of transgene silencing over time with oncoretroviral vectors, most gene therapy studies for AIDS and cancer using oncoretroviral vectors remain proof-of-concept studies. Here we will discuss recent developments in the use of retroviral vectors, including HIV-1-derived lentiviral vectors, for the treatment of AIDS and cancer, and their future therapeutic potential.
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PMID:Retroviral vectors for gene therapy of AIDS and cancer. 1169 91

Photo-comics are an ideal format for education of South African youth about acquired immunodeficiency syndrome (AIDS) given their low literacy rate and the widespread popularity of comic books. An example of the success of this strategy is "Roxy: Life, Love, and Sex in the Nineties," a comic produced as part of a school-based AIDS prevention program run by the National AIDS Research Program. The comic tells the story of an adolescent girl who learns her friend committed suicide because she was infected with the human immunodeficiency virus (HIV). Roxy learns about AIDS and discusses the risk factors with her friends. Focus group discussions were used to generate story ideas and pretesting of the comic book took place among several student groups. By July 1993, 30,000 copies of "Roxy" had been distributed to students, churches, youth groups, civic associations, and organizations working with street children. In addition, the comic was reproduced in a magazine, "Upbeat," that is popular among out-of-school youth. Qualitative evaluation through 8 student focus groups revealed that young people from various cultural backgrounds strongly identify with the themes, characters, and situations depicted in "Roxy." Of particular significance were the realistic portrayals of romantic and sexual relationships, relationships with parents, and dilemmas posed by pressures to use drugs and alcohol. The comic includes a sex education chart with concise condom use instructions.
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PMID:Country watch: South Africa. 1228 65

This testimonial of a male youth describes the psychosocial factors influencing his sex behavior at age 17. After dropping out of school, he moved to his maternal village where he came under the influence of 4 sexually experienced boys. This peer group would take the boy to places in the evening where drinking and heterosexual promiscuity were encouraged. The boy, who was too shy, was subjected to derision by the group when he did not comply with their wishes. He lost his friends, and his self esteem suffered. In order to regain the friendship of the group, the boy had his first intercourse. This affair was fleeting and was followed by another that lasted 2 months. After returning to his paternal family, the boy began having health problems that were unresponsive to drug treatment. The boy read a copy of the pamphlet "Know the Facts about AIDS" and contacted his former girlfriends. One had died 6 months before. The boy went to a hospital clinic for screening. Pre-test counseling was conducted by TASO. The boy tested positive for human immunodeficiency virus (HIV) and immediately thought his death was imminent. This led to thoughts of suicide and denial. The counselor advised the boy that he could prolong his life more than 7 years by treating infections, eating well, getting enough rest, keeping busy to avoid thinking about approaching death, refraining from alcohol and smoking, and getting regular exercise. TASO and the Post-Test Club provide extensive support to the boy. His feelings have turned from anger and denial to hope and acceptance. He has joined the Philly Lutaaya Initiative, a PWA project which aims to change risk behavior and to destigmatize AIDS.
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PMID:Living with HIV / AIDS: a personal testimony. 1228 8

Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. This report covers data during February-December 2001. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults; these behaviors contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 34 state surveys, and 18 local surveys conducted among students in grades 9-12 during February-December 2001. In the United States, approximately three-fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2001 national Youth Risk Behavior Survey demonstrated that numerous high school students engage in behaviors that increase their likelihood of death from these four causes: 14.1% had rarely or never worn a seat belt during the 30 days preceding the survey; 30.7% had ridden with a driver who had been drinking alcohol; 17.4% had carried a weapon during the 30 days preceding the survey; 47.1% had drunk alcohol during the 30 days preceding the survey; 23.9% had used marijuana during the 30 days preceding the survey; and 8.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 2001, 45.6% of high school students had ever had sexual intercourse; 42.1% of sexually active students had not used a condom at last sexual intercourse; and 2.3% had ever injected an illegal drug. Two-thirds of all deaths among persons aged > or = 25 years result from only two causes: cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 2001, 28.5% of high school students had smoked cigarettes during the 30 days preceding the survey; 78.6% had not eaten > or = 5 servings per day of fruits and vegetables during the 7 days preceding the survey; 10.5% were overweight; and 67.8% did not attend physical education class daily. Health and education officials at national, state, and local levels are using these YRBSS data to analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators.
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PMID:Youth risk behavior surveillance--United States, 2001. 1238 72

Lentiviral-mediated gene delivery holds significant promise for sustained gene expression within living systems. Vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 1-based lentiviral vectors can be used to introduce transgenes in a broad spectrum of dividing as well as nondividing cells. In the current study, we construct a lentiviral vector carrying two reporter genes separated by an internal ribosomal entry site and utilize that virus in delivering both genes into neuroblastoma cells in cell culture and into cells implanted in living mice. We utilize two reporter genes, a mutant herpes simplex virus type 1 (HSV1) sr39tk as a reporter gene compatible with positron emission tomography (PET) and a bioluminescent optical reporter gene, firefly luciferase (Fluc), to image expression in living mice by an optical charge-coupled device (CCD) camera. By using this lentivirus, neuroblastoma (N2a) cells are stably transfected and a high correlation (R(2) = 0.91) between expressions of the two reporter genes in cell culture is established. Imaging of both reporter genes using microPET and optical CCD camera in living mice is feasible, with the optical approach being more sensitive, and a high correlation (R(2) = 0.86) between gene expressions is again observed in lentiviral-infected N2a tumor xenografts. Indirect imaging of HSV1-sr39tk suicide gene therapy utilizing Fluc is also feasible and can be detected with increased sensitivity by using the optical CCD. These preliminary results validate the use of lentiviral vectors carrying reporter genes for multimodality imaging of gene expression and should have many applications, including imaging of xenografts, metastasis, and cell trafficking as well as noninvasive monitoring of lentiviral-mediated gene delivery and expression.
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PMID:Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice. 1271 11

Despite the tremendous success of highly active antiretroviral treatment (HAART) introduced nearly 8 years ago for the treatment of human immunodeficiency virus (HIV), innovative therapies, including gene transfer approaches, are still required for nearly half of the general patient population. A number of potential gene therapeutic targets for HIV have been identified and include both viral and cellular genes essential for viral replication. The diverse methods used to inhibit viral replication comprise RNA-based strategies such as ribozymes, RNA decoys, antisense messenger RNAs and small interfering RNA (siRNA) molecules. Other potential anti-HIV genes include dominant negative viral proteins, intracellular antibodies, intrakines and suicide genes, all of which have had a modicum of success in vitro. Cellular targets include CD4+ T cells, macrophages and their progenitors. The greatest gene transfer efficiency has been achieved using retroviral or, more recently, lentiviral vectors. A limited number of Phase I clinical trials suggest that the general method is safe. It is proposed that a national network for HIV gene therapy (similar to the AIDS Clinical Trial Groups) may be the best way to determine which approaches should proceed clinically.
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PMID:Genetic therapy for HIV/AIDS. 1294 54

Human immunodeficiency virus (HIV) infection has become a pandemic concern for many nations. When this disease first presented itself in a global manner in the early 1980s, it was accompanied by fear, denial, misunderstanding, social stigma, and a paucity of available support services. The U.S. Army was becoming increasingly aware of the potential impact HIV could have on the active forces. A tragic event involving the suicide of a young HIV-infected soldier resulted in the development of a comprehensive medical/psychosocial assessment and treatment program for HIV-infected service members and their families at the Walter Reed Army Medical Center. Social work services played an integral role in the development of this program as this profession has done historically in meeting other emerging needs of the military. Special attention is given to the unique psychosocial issues and needs of the HIV-infected service member and the comprehensive and compassionate response of the military medical team with its significant social work contribution.
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PMID:Human immunodeficiency virus social work program at the Walter Reed Army Medical Center: a historical perspective. 1452 41

Apoptosis is a physiological cell suicide program that is critical for the development and maintenance of healthy tissues. Regulation of programmed cell death allows the organism to control the cell number and the tissue size, and to protect itself from rogue cells that threaten homeostasis. The changed activity of numerous genes influences switching of cells to a self-destruction program. Apoptosis requires co-ordinated action and fine tuning of a set of proteins that are either regulators or executors of the process. Cancer, autoimmune diseases, immunodeficiency disease, reperfusion injury and neurodegenerative disorders are characterised by disregulation of apoptosis. Modulation of the expression and activation of the key molecular components of the apoptotic process has emerged as an attractive therapeutic strategy for many diseases.
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PMID:Biochemistry of apoptotic cell death. 1476 39

During the immunodeficiency that follows hemopoietic stem cell transplant or solid organ transplant, lymphoproliferation can develop due to uncontrolled expansion of Epstein-Barr-virus (EBV)-infected B cells that express the full spectrum of EBV latent antigens. As development of post-transplant lymphoproliferative disease (PTLD) in these patients is clearly associated with a deficient EBV-specific cellular immune response, immunotherapy strategies to restore the EBV-specific immune response have been evaluated. In hemopoietic stem cell transplant recipients, adoptively transferred donor-derived EBV-specific T cells have been able to restore immunity and eradicate overt lymphoproliferation. Autologous or closely matched allogeneic EBV-specific cytotoxic T lymphocytes have also shown promise in recipients of solid organ transplant. The use of genetically modified T cells or newer suicide genes may result in improved safety and efficacy. Current challenges are to define indications for immunotherapy or antibody therapy in patients with incipient or overt PTLD.
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PMID:Cellular therapy of Epstein-Barr-virus-associated post-transplant lymphoproliferative disease. 1549 12

Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), kills millions worldwide every year. Vaccines against HIV still seem a distant promise. Pharmaceutical treatments exist, but these are not always effective, and there is increasing prevalence of viral strains with multidrug resistance. Highly active antiretroviral therapy (HAART) consists of inhibitors of viral enzymes (reverse transcriptase (RT) and protease). Gene therapy, first introduced as intracellular immunization, may offer hopes for new treatments to be used alone, or in conjunction with, conventional small molecule drugs. Gene therapy approaches against HIV-1, including suicide genes, RNA-based technology, dominant negative viral proteins, intracellular antibodies, intrakines, and peptides, are the subject of this review.
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PMID:Gene therapy progress and prospects: novel gene therapy approaches for AIDS. 1570 64


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