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)

Human immunodeficiency virus infection is often followed by neurodegeneration, the cause of motor and cognitive impairment in some patients affected by acquired immunodeficiency. Several in vitro data indicate glycoprotein (gp) 120 as one of the substances responsible for the neurodegenerative event that takes place only if non-neuronal cells (glial cells) are present. Our purpose was to investigate the molecular mechanisms through which glial cells could affect neuron viability after exposure to gp120 protein. We used a sandwich co-culture of primary hippocampal neurons and primary glial cells, where the two cell populations face each other but are separable. Exposure of 1-week-old rat hippocampal neurons in co-culture with glia to 600 pM gp120 protein resulted in the death of 30% of neurons after 6 days of treatment. A significant increase of intracellular calcium ([Ca2+]i), evident 72 h after gp120 exposure (control 45.8+/-7.6 nM, gp120 176.5+/-43.6 nM), preceded neuron death. The gp120 protein affected neither the viability nor the morphology or [Ca2+]i of glial cells. However, a significant amount of reactive oxygen species as well as of interleukin-1beta was produced. Treatment of the co-culture with an antibody against interleukin-1beta prevented neuron increase of [Ca2+]i and cell death but not glial production of reactive oxygen species, whereas prior incubation of glial cells with Trolox, an antioxidant analog of vitamin E, down-regulated interleukin-1beta expression and completely prevented neuron cell death. Our results indicate that reactive oxygen species produced in glial cells by gp120 exposure cause neurodegeneration by inducing the synthesis of interleukin-1beta.
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PMID:Reactive oxygen species generated by glia are responsible for neuron death induced by human immunodeficiency virus-glycoprotein 120 in vitro. 1174 46

Injection of human immunodeficiency virus type 1 (HIV-1)-infected human monocyte-derived macrophages (MDMs) into the basal ganglia of severe combined immunodeficient mice recapitulates histopathologic features of HIV-1 encephalitis (HIVE). Here, we show that the neural damage in HIVE mice extends beyond the basal ganglia and is associated with cognitive impairment. Morris water maze tests showed impaired spatial learning 8 d after MDM injection. Moreover, impaired synaptic potentiation in the hippocampal CA1 subregion was demonstrated at 8 and 15 d. By day 15, post-tetanic, short-term, and long-term potentiation were reduced by 14.1, 29.5, and 45.3% in HIVE mice compared with sham-injected or control animals. Neurofilament (NF) and synaptophysin (SP) antigens were decreased significantly in the CA2 hippocampal subregion of HIVE mice with limited neuronal apoptosis. By day 15, the CA2 region of HIVE mice expressed 3.8- and 2.6-fold less NF and SP than shams. These findings support the notion that HIV-1-infected and immune-competent brain macrophages can cause neuronal damage at distant anatomic sites. Importantly, the findings demonstrate the value of the model in exploring the physiological basis and therapeutic potential for HIV-1-associated dementia.
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PMID:Impaired spatial cognition and synaptic potentiation in a murine model of human immunodeficiency virus type 1 encephalitis. 1189 49

Infection of the central nervous system with human immunodeficiency virus type-1 (HIV) is associated with cognitive impairments that range from mild cognitive and motor difficulties to dementia. Structural neuroimaging abnormalities are also common in HIV-infected patients both with and without cognitive disturbances. The most common abnormalities include high signal intensities in the white matter and atrophy. Research over the past 12 years has helped define the relationship between these neuroimaging abnormalities and the manifestation of cognitive disturbance in HIV. In the present paper, we provide a synopsis of these studies and report the current state of the literature. Our review revealed that atrophy of the caudate nucleus is most consistently associated with cognitive impairment in HIV. The current literature does not support a strong relationship between cortical atrophy or white matter abnormalities and cognitive dysfunction in this population, though methodological issues may have influenced the results. Suggestions for study design and new research directions are provided.
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PMID:Relationships between cognition and structural neuroimaging findings in adults with human immunodeficiency virus type-1. 1203 35

Injection drug users represent a major vector of human immunodeficiency virus (HIV) infection in the nation's inner cities, and are an important population for harm reduction treatment interventions to target. However, there has been relatively little research examining the specific contribution of the multiple factors contributing to cognitive functioning among injection drug users that may affect engagement in, and response to, addiction and HIV-related interventions. The current study examined the independent contributions to neuropsychological (NP) test performance of premorbid educational attainment, medical and psychiatric history, long- and short-term drug use, assessed by laboratory, observation, and self-report measures, and HIV disease, assessed by plasma HIV-1 RNA viral load and CD4+ count, in a sample of 90 HIV-positive injection drug users dually addicted to heroin and cocaine. Fully 88% of the sample showed evidence of impairment (>1 standard deviation below the population mean) on an NP test battery selected to assess processes associated with successful engagement in the treatment of substance abuse and HIV, such as learning and memory of verbal information, capacity to solve new problems and deal with more than one stimulus at a time, visual-motor coordination, and visual tracking and cognitive flexibility. In addition to drug use, independent predictors of NP test performance were HIV viral load, educational attainment, and premorbid medical and psychiatric problems. Findings underscore the multiplicity of factors that contribute to cognitive impairment in HIV-positive drug-abusing individuals in addition to drug use. Clinical implications are discussed.
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PMID:Factors affecting cognitive functioning in a sample of human immunodeficiency virus-positive injection drug users. 1213 61

The effects of human immunodeficiency virus (HIV) infection on central nervous system function were studied with the P3a and P3b event-related brain potentials (ERPs) in patients with HIV compared to unaffected matched controls (n = 14/group). All patients were on anti-viral medication for at least 2 months before testing. Auditory stimuli were employed in an easy 2-stimulus oddball discrimination task to obtain a typical P3b (P300) subcomponent. A 3-stimulus distractor paradigm also was employed in which the target/standard discrimination was very difficult, and an infrequent high-pitched tone non-target was presented to elicit the P3a subcomponent. Subjects responded only to the target stimulus in each task. P3a amplitude was significantly smaller for HIV compared to control subjects. No reliable P3b effects were obtained. The findings suggest that P3a rather than P3b may be a more sensitive measure of cognitive impairment in HIV patients on anti-viral medication.
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PMID:P3a and P3b auditory ERPs in HIV patients receiving anti-viral medication. 1219 63

Human immunodeficiency virus (HIV) infection is associated with psychiatric complications, including cognitive impairment, affective disorders, and psychosis. These psychiatric complications impair quality of life, affect disease prognosis, and impede treatment by compromising medication adherence. They also increase the likelihood of HIV transmission, either directly or via their high prevalence rate among drug abusers. In this article, the authors provide a brief overview of the most common psychiatric complications associated with HIV infection and discuss the role of dopamine as a link between psychiatric manifestations and the progression of immunodeficiency infection.
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PMID:Psychiatric complications in human immunodeficiency virus infection. 1249 Nov 64

Alterations in hippocampal physiology affect cognition in human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD). The mechanism for how this occurs is not well understood. To address this, we investigated how changes in synaptic transmission and plasticity are affected by viral infection and macrophage activation using a severe combined immunodeficiency mouse model of human HIV-1 encephalitis (HIVE). HIVE was induced in mice by stereotactic injection of HIV-1-infected human monocyte-derived macrophages (MDM) into the striatum. Animals were sacrificed after 3, 7 and 15 days. Hippocampal slices were prepared from HIV-1, MDM- and sham-injected animals. Electrically evoked field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus. Neuronal physiology was assessed by input-output and by long-term potentiation (LTP) assays. We observed that a higher stimulation intensity (mA) was required to induce a 1-mV response in the HIVE mice (0.32+/-0.06) compared with shams (0.17+/-0.01) at day 7. The stimulation intensities at day 15 were 0.44+/-0.07 and 0.23+/-0.05 in the HIVE and shams, respectively. An impairment of synaptic function was detected through measuring synaptic responses induced by stimuli with different intensities. Paired-pulse facilitation (PPF) showed deficits in HIVE mice at days 3, 7, and 15. At day 3, PPF ratios were 1.13+/-0.02 and 1.24+/-0.04 in HIVE and sham. The induction and maintenance of LTP was also impaired in HIVE mice. The average magnitude of LTP was 131.23+/-15.26% of basal in HIVE as compared with sham animals of 232.63+/-24.18%. MDM-injected mice showed an intermediate response. Taken together, the results show a range of neuronal synaptic transmission and plasticity changes in HIVE mice that may reflect the mechanisms of cognitive dysfunction in human HAD.
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PMID:Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis. 1269 72

Brain impairment is a distressing manifestation of human immunodeficiency virus (HIV) disease characterized by progressive cognitive impairment leading eventually to dementia and death. Patients with advanced brain impairment are clinically difficult to manage and usually require residential care. In 1997, a brain impairment unit opened at the Mildmay Hospital UK in London to meet the needs of this patient group. It began as a nurse-led unit, has adopted an interdisciplinary approach to care and aims to maximize the quality of life until death. In a study of patients admitted during its first year, it emerged that while the condition of many patients declined resulting in death, some patients improved sufficiently with rehabilitation and ongoing medical treatment to return to independent living. The possible reasons for this are discussed in this article. Study findings have not only affected the approach to care but have also highlighted some unexpected problems; the importance of adopting an interdisciplinary approach in caring for the group of patients becomes evident.
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PMID:HIV-related brain impairment from palliative care to rehabilitation. 1281 63

We examined the impact of neuropsychological (NP) impairment on activities of daily living (ADLs) and quality of life in human immunodeficiency virus type-1 (HIV-1)-infected persons of low socioeconomic status (SES). Thirty-nine patients were stratified into one of three groups: cognitively normal (n = 13), mild cognitive impairment (n = 15), and moderate/severe impairment (n = 11). Quality of life was assessed with the Sickness Impact Profile and ADLs were evaluated via structured interview performed in the patient's residence. While there were no significant differences across groups on disease stage, drug use, depression, or estimated premorbid IQ, cognitively impaired patients were more likely to be unemployed and fail social planning and medication management tasks. Our study confirms a previously reported association between NP impairment and unemployment among HIV-1-infected patients. The data also extend this relationship to a low-SES sample with a high base rate of unemployment, and to instrumental activities of daily living other than work.
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PMID:Impact of human immunodeficiency virus type-1-associated cognitive dysfunction on activities of daily living and quality of life. 1459 Feb 7

The emergence of a subset of circulating monocytes during human immunodeficiency virus type 1 (HIV-1) disease has been shown to correlate with cognitive impairment. Thus, it is hypothesized that diagnostic protein profiles may be obtained from these cells from patients with or at risk for HIV-1-associated dementia (HAD). To address this possibility, we used ProteinChip assays to define a unique monocyte-derived macrophage (MDM) protein fingerprint during HAD and whether it is affected by highly active antiretroviral therapy (HAART). The study included five Hispanic women, one with HAD, two HIV-1-infected without cognitive impairment, and two seronegative controls. All patients were matched by age and immune status. Monocytes were recovered from the peripheral blood leukocytes by Percoll gradient centrifugation and allowed to differentiate in vitro for 7 days. Cell lysates and supernatants were collected from the MDM and analyzed by surface enhanced laser desorption/ionization-time of flight ProteinChip assays. Seven unique protein peaks between 3.0 and 20.0 kDa were found in the HAD MDM sample. Each of these proteins were abrogated after HAART. Additional studies extending this one time point determination would serve to confirm the general utility of MDM protein profiling for the diagnosis and monitoring of HAD.
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PMID:Proteomic fingerprinting of human immunodeficiency virus type 1-associated dementia from patient monocyte-derived macrophages: A case study. 1498 43


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