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)

Retinitis pigmentosa (RP) is the most common inherited retinal disease, in which photoreceptor cells degenerate, leading to blindness. Mutations in the rod photoreceptor cGMP phosphodiesterase beta subunit (PDEbeta) gene are found in patients with autosomal recessive RP as well as in the rd mouse. We have recently shown that lentivirus vectors based on human immunodeficiency virus (HIV) type 1 achieve stable and efficient gene transfer into retinal cells. In this study, we evaluated the potential of HIV vector-mediated gene therapy for RP in the rd mouse. HIV vectors containing a gene encoding a hemagglutinin (HA)-tagged PDEbeta were injected into the subretinal spaces of newborn rd mouse eyes. One to three rows of photoreceptor nuclei were observed in the eyes for at least 24 weeks postinjection, whereas no photoreceptor cells remained in the eyes of control animals at 6 weeks postinjection. Expression of HA-tagged PDEbeta in the rescued photoreceptor cells was confirmed by two-color confocal immunofluorescence analysis using anti-HA and anti-opsin antibodies. HIV vector-mediated gene therapy appears to be a promising means for the treatment of recessive forms of inherited retinal degeneration.
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PMID:Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. 1043 72

Ocular manifestations have been reported in up to 60% of individuals infected with human immunodeficiency virus (HIV) in the United States, and it is becoming increasing apparent that these ocular manifestations almost invariably reflect extent of progression of the disease. The prevalence of ocular abnormalities among acquired immunodeficiency syndrome (AIDS) patients in Taiwan has not been reported. In the present study, we examined and followed up the ophthalmic conditions of a total of 274 HIV-infected patients during the period from March 1993 to May 1999. The results show that cotton-wool spots was the most common ocular finding in this series of patients with AIDS, occurring in 22 (32.8%) of 67 AIDS patients. Cytomegalovirus (CMV) retinitis was the most commonly seen opportunistic ocular infection, occurring in 14 (20.8%) of 67 AIDS patients. These findings suggest that AIDS patients should be closely followed for signs of opportunistic ocular disease which may initially be asymptomatic. Close co-operation between the ophthalmologist and the internist is essential to ensure timely therapeutic intervention, which can decrease the risk of further complications including visual impairment and blindness.
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PMID:Ophthalmic findings in patients with acquired immunodeficiency syndrome. 1080 64

Glaucoma, a group of optic neuropathies, is the leading cause of irreversible blindness. Neuronal apoptosis in glaucoma is primarily associated with high intraocular pressure caused by chronically impaired outflow of aqueous humor through the trabecular meshwork, a reticulum of mitotically inactive endothelial-like cells located in the angle of the anterior chamber. Anatomic, genetic, and expression profiling data suggest the possibility of using gene transfer to treat glaucomatous intraocular pressure dysregulation, but this approach will require stable genetic modification of the differentiated aqueous outflow tract. We injected transducing unit-normalized preparations of either of two lentiviral vectors or an oncoretroviral vector as a single bolus into the aqueous circulation of cultured human donor eyes, under perfusion conditions that mimicked natural anterior chamber flow and maintained viability ex vivo. Reporter gene expression was assessed in trabecular meshwork from 3 to 16 days after infusion of 1.0 x 10(8) transducing units of each vector. The oncoretroviral vector failed to transduce the trabecular meshwork. In contrast, feline immunodeficiency virus and human immunodeficiency virus vectors produced efficient, localized transduction of the trabecular meshwork in situ. The results demonstrate that lentiviral vectors permit efficient genetic modification of the human trabecular meshwork when delivered via the afferent aqueous circulation, a clinically accessible route. In addition, controlled comparisons in this study establish that feline and human immunodeficiency virus vectors are equivalently efficacious in delivering genes to this terminally differentiated human tissue.
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PMID:Genetic modification of human trabecular meshwork with lentiviral vectors. 1174

Around 70% of female infertility in developing countries is caused by sexually transmitted diseases (STDs) that can be traced back to husbands or partners. STDs and reproductive tract infections cause 750,000 deaths and 75 million illnesses among women each year worldwide, and these deaths may more than double by the year 2000. Death rates are rising fastest in Africa, followed by Asia and Latin America. About 450,000 cases of potentially fatal reproductive tract cancers are diagnosed annually: an estimated 354,000 occur in Third World women, virtually all of whom die. Worldwide, roughly 250 million new infections of chlamydia, gonorrhea, and the human papillomavirus are sexually transmitted each year. Chlamydia and the human papillomavirus account for 50 million and 30 million new cases per year, respectively. The human immunodeficiency virus (HIV) infected 1 million people worldwide between April and December 1991, according to the World Health Organization. A study in the Indian state of Maharashtra revealed that 92% of the 650 rural women examined had an average of 3.6 infections of gynecological type or sexually transmitted type per women. Another study in 2 rural Egyptian villages found that half of 509 nonpregnant women aged 20 to 60 years had infections. Only 2 facilities for the diagnosis and treatment of STDs exist in all of Kenya. In Ibadan, Nigeria, with a population of 2 million, there is only 1 recognized STD clinic. The physical consequences of several STDs have been linked to increased risks of AIDS transmission. Early recognition and treatment of STDs in pregnant women would cut infant mortality. Maternal infections with chlamydia, gonorrhea, or herpes are transferred to infants at birth 25% to 50% of the time. In Africa, infant blindness caused by gonorrhea infection is 50 times more common than in industrial countries. The International Women's Health Coalition's March 1992 meeting of more than 50 Third World scientists, health advocates, and policymakers made suggestions to make universally available simple, inexpensive, rapid diagnostic tests for STDs and to develop vaginal microbicides that protect women against STDs.
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PMID:The other epidemics. Sexually transmitted diseases. 1215 77

Cytomegalovirus (CMV) retinitis is an important ocular complication in human immunodeficiency virus-infected individuals and the leading cause of blindness in those not undergoing highly active antiretroviral therapy. Murine CMV (MCMV) infection of mice has been shown to be a useful small-animal model for the study of CMV pathogenesis in the eye. The purpose of this study was to evaluate CMV persistence in ocular tissue and to determine the potential for reactivation. Following subretinal inoculation of immunocompetent BALB/c mice, tissues were tested for infectious virus by plaque assay and for the presence of viral DNA and RNA by PCR. The latent phase of the infection in mouse tissues was analyzed by plaque assay, PCR, and explantation cocultivation in both immunocompetent and cyclophosphamide-treated mice. The acute phase of the infection was resolved by 2 to 3 weeks postinfection, while viral DNA persisted beyond 12 months. Immediate-early 1 transcripts were detected in 100% of the ocular samples tested, and glycoprotein H transcripts were detected in 86% of the samples, but no difference in viral DNA or RNA levels between immunocompetent and immunosuppressed animals was measured. Irrespective of immune status, no in vivo reactivation was detected; however, reactivated virus was observed in 76 to 82% of the eyes following explantation onto a permissive cell layer. The transcriptional activity and relatively high frequency of explantation-induced reactivation in both immunocompetent and immunosuppressed mice suggest that control of MCMV latency in ocular tissue might involve other regulatory events that are not entirely dependent on intact specific immunity.
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PMID:Persisting murine cytomegalovirus can reactivate and has unique transcriptional activity in ocular tissue. 1218

At present, about 250 million new cases of sexually transmitted diseases (STDs) occur in the world each year. This statistics includes 120 million cases of trichomoniasis, 50 million cases of chlamydia, 30 million cases of genital warts, 25 million gonorrhea cases, 20 million cases of genital herpes, 3.5 million syphilis cases, 2.5 million case of hepatitis B virus, 2 million cases of chancroid, and 1 million infections with human immunodeficiency virus (HIV). Among the adverse health sequelae the STDs are sterility, infertility, stillbirth, miscarriage, blindness, brain damage, and cancer. The greatest incidence of STDs is in the 20-24-year age group, followed by persons 15-19 years of age. The finding that lesions caused by some STDs can increase the risk of HIV infection by more than 300% has led governments concerned with control of acquired immunodeficiency syndrome (AIDS) to take a more aggressive stance toward the prevention and treatment of STDs. There are many obstacles to STD prevention, however, including the development of treatment-resistant strains, inadequate infrastructure for diagnostic testing and penicillin treatment, resistance to changing sexual behavior, increased travel and migration, and the practice of exchanging sex for drugs. Even in some developed countries where the rate of STD infection has finally stabilized, the level remains unacceptably high and STDs cannot be considered as under control. In developing countries, STDs have reached epidemic levels and the number of new infections reported annually shows a pattern of steady increase. The World Health Organization is urging governments to intensify STD prevention activities through funding research, health education, and more accessible clinic services.
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PMID:Sexually transmitted infections increasing -- 250 million new infections annually. 1231 65

Patients with sexually transmitted diseases (STDs) in developing countries are often untreated for long periods of time or receive ineffective treatment, producing complications that can lead to infertility, blindness, and even death. In addition, there is growing research evidence that people with bacterial or viral STDs are more likely to acquire--and perhaps transmit--the human immunodeficiency virus (HIV). STD control programs in developing countries must be reorganized to include: 1) good management of patients with STDs and their contacts, 2) case finding for syphilis in the antenatal population, 3) screenings and case findings for gonorrhea in high-risk groups, and 4) systematic prophylaxis for ophthalmia neonatorum in newborns. Since diagnosis before treatment is problematic in rural areas, the World Health Organization recommends simple treatment protocols based on the most common STD symptoms--urethral discharge; gynecological complaints such as vaginal discharge, low abdominal pain, or dysuria; genital ulceration; and inguinal bubo, a swelling of the lymph nodes in the groin. Other components of this approach include standardized treatment, contact tracing and treatment, health education targeted at high-risk groups, follow-up and case referral where necessary, and the collection of simple statistics on treatment efficacy and STD epidemiology. The incidence of STDs in developing countries is steadily increasing as a result of urbanization, increased numbers of young people, and delayed age at marriage. However, this situation can be combatted through application of treatment protocols, technological advances, improvements in the health care delivery system, and awareness on the part of policy makers of the seriousness of the STD problem.
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PMID:Management of sexually transmitted diseases. 1234 18

Human cytomegalovirus (HCMV) is the most common viral opportunistic infection in patients suffering with acquired immunodeficiency virus (AIDS). HCMV is a systemic infection that may infect several sites in the body, including the retina, gastrointestinal tract, lungs, liver, and central nervous system. Retinitis is the most frequent manifestation of HCMV infection, occurring in 15-40% of all patients. HCMV is progressive and destroys the retina, eventually leading to blindness. Although, there are several drugs available to treat this disease, they are often of limited efficacy and have significant side-effects. Antisense oligonucleotides represent a novel alternative to the currently available drugs. Due to their high affinity and specificity to target the HCMV RNAs, interest in antisense technology to treat HCMV infections has been intense during the past few years. Two antisense drugs are currently in clinical trials, ISIS 2922 (Formivirsen) and GEM 132.
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PMID:Antisense approach for the treatment of cytomegalovirus infection. 1599 90

Herpes simplex viruses (HSV) are highly pervasive pathogens in the human host with a seroconversion rate upwards of 60% worldwide. HSV type 1 (HSV-1) is associated with the disease herpetic stromal keratitis, the leading cause of infectious corneal blindness in the industrialized world. Individuals suffering from genital herpes associated with HSV type 2 (HSV-2) are found to be two- to threefold more susceptible in acquiring human immunodeficiency virus (HIV). The morbidity associated with these infections is principally due to the inflammatory response, the development of lesions, and scarring. Chemokines have become an important aspect in understanding the host immune response to microbial pathogens due in part to the timing of expression. In this paper, we will explore the current understanding of chemokine production as it relates to the orchestration of the immune response to HSV infection.
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PMID:Herpes simplex virus and the chemokines that mediate the inflammation. 1657 Aug 56

Pediatric human immunodeficiency virus type 1 (HIV-1) infection is endemic throughout southern Africa. Neurologic complications are described in 20% to 60% of published series, mostly related to HIV-1 encephalopathy. With increasing HIV prevalence, more atypical cases are presenting. We present, as illustrative cases, seven children (three girls) with unusual neurologic sequelae as a consequence of HIV-1 infection. The median age at presentation was 33 months (range 7 months-6 years). Five of the seven children were developmentally normal before presentation. They presented with progressive multifocal leukoencephalopathy, myelopathy, intractable seizures, acute vasculitis and blindness, hemiplegia, peripheral neuropathy, and paraspinal lymphoma. Neuroimaging of the brain was performed in five patients, of whom one had basal ganglia calcification. All children had poor outcome with incomplete recovery or continued deterioration. In conclusion, children with HIV-1 infection who survive beyond the first year of life can present with a wide variety of neurologic complications. A similar spectrum of neurologic manifestations is likely to occur in other sub-Saharan African countries, characterized by high HIV prevalence. The case histories demonstrate that the neurologic features of pediatric HIV infection do not easily fit into a simplified classification system.
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PMID:Specific neurologic complications of human immunodeficiency virus type 1 (HIV-1) infection in children. 1697 Aug 87


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