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)

HIV-1 infection is often complicated by the dysfunction of central nervous system (CNS). Degenerative neuronal changes as well as neuronal loss have been documented in individuals with acquired immunodeficiency syndrome. Feline immunodeficiency virus (FIV) causes similar CNS manifestation and FIV infected cats provide an animal model for human immunodeficiency virus infection in humans. In this study, we examined the brain of FIV-infected cats and controls with immunohistochemical techniques using antibodies to microtubule-associated protein 2 (MAP-2) and glutamic acid decarboxylase (GAD). We found a significant decrease in expression of MAP-2 and GAD in neurons of infected animals compared to controls. In contrast, the expression of neurofilaments and glial fibrillary acidic protein was rather increased. The changes observed in the brain were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases like Alzheimer's disease and other dementing disorders. These changes in the feline brain give insight into the deleterious effects of FIV on the CNS.
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PMID:Decreased expression of MAP-2 and GAD in the brain of cats infected with feline immunodeficiency virus. 1187 47

Social workers provide senior citizens with varied services in diverse settings and are in a position to assume leadership in slowing the spread of AIDS among this age group. Unfortunately older people often do not receive the knowledge needed to protect themselves against infection. Historically, older Americans have been largely ignored by HIV/AIDS prevention programs. The major risk behaviors among senior citizens include sexual activity without using condoms, alcohol and drug use, blood transfusions received before 1985, and misdiagnosed opportunistic illness such as Alzheimer's, Parkinson's, respiratory disease, and sexually transmitted diseases. The article discusses guidelines that can help social workers provide prevention education to older Americans. Social work's primary prevention AIDS education efforts can help older adults safely live out the rest of their lives secure in the understanding that they possess the knowledge to protect themselves from HIV/AIDS infection.
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PMID:Older Americans and AIDS: some guidelines for prevention. 1201 97

Alzheimer's disease, Huntington's disease and prion diseases are part of a growing list of diseases associated with formation of beta-sheet containing fibrils. In a previous publication, we demonstrated that the self-association of the Alzheimer's beta-amyloid (Abeta) peptide is inhibited by peptides homologous to the central core domain of Abeta, but containing N-methyl amino acids at alternate positions. When these inhibitor peptides are arrayed in an extended, beta-strand conformation, the alternating position of N-methyl amino acids gives the peptide two distinct faces, one exhibiting a normal pattern of peptide backbone hydrogen bonds, but the other face having limited hydrogen-bonding capabilities due to the replacement of the amide protons by N-methyl groups. Here, we demonstrate, through two-dimensional NMR and circular dichroic spectroscopy, that a pentapeptide with two N-methyl amino acids, Abeta16-20m or Ac-K(Me)LV(Me)FF-NH2, does indeed have the intended structure of an extended beta-strand. This structure is remarkably stable to changes in solvent conditions and resists denaturation by heating, changes in pH (from 2.5 to 10.5), and addition of denaturants such as urea and guanindine-HCl. We also show that this peptide, despite its hydrophobic composition, is highly water soluble, to concentrations > 30 mm, in contrast to the nonmethylated congener, Abeta16-20 (Ac-KLVFF-NH2). The striking water solubility, in combination with the hydrophobic composition of the peptide, suggested that the peptide might be able to pass spontaneously through cell membranes and model phospholipid bilayers such as unilamellar vesicles. Thus, we also demonstrate that this peptide is indeed able to pass spontaneously through both synthetic phospholipid bilayer vesicles and cell membranes. Characterization of the biophysical properties of the Abeta16-20m peptide may facilitate the application of this strategy to other systems as diverse as the HIV protease and chemokines, in which there is dimerization through beta-strand domains.
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PMID:Design and characterization of a membrane permeable N-methyl amino acid-containing peptide that inhibits Abeta1-40 fibrillogenesis. 1208 25

Alzheimer's disease is characterized by deposition of beta-amyloid peptide (Abeta) into plaques in the brain, leading to neuronal toxicity and dementia. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system can also cause a dementia, and amyloid deposition in the central nervous system is significantly higher in HIV-1-infected individuals compared with uninfected controls. Here we report that Abeta fibrils stimulated, by 5-20-fold, infection of target cells expressing CD4 and an appropriate coreceptor by multiple HIV-1 isolates but did not permit infection of cells lacking these receptors. Abeta enhanced infection at the stage of virus attachment or entry into the cell. Abeta fibrils also stimulated infection by amphotrophic Moloney leukemia virus, herpes simplex virus, and viruses pseudotyped with the envelope glycoprotein of vesicular stomatitis virus. Other synthetic fibril-forming peptides similarly enhanced viral infection and may be useful in gene delivery applications utilizing retroviral vectors. These data suggest that Abeta deposition may increase the vulnerability of the central nervous system to enveloped viral infection and that amyloidogenic peptides could be useful in enhancing gene transfer by enveloped viral vectors.
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PMID:Stimulation of enveloped virus infection by beta-amyloid fibrils. 1211 88

Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and HIV neuroAIDS. In this study, we have investigated an agent, phenylbutyric acid, that ameliorates cell death in murine astrocytes infected with ts1 MoMuLV (ts1). Phenylbutyric acid, an aromatic short chain fatty acid, was shown to prevent the loss of catalase that occurs in ts1 infected astrocytes, and to prevent ts1-mediated cell death. Cell cotransfection studies demonstrated that phenylbutyric acid activates peroxisome proliferator receptors (PPARs) in astrocytes, and binds to the peroxisome proliferator-activated receptors alpha and gamma. This observation suggests that the effects of PBA may be mediated by PPARs in astrocytes. Phenylbutyric acid also maintained catalase protein levels in brain of ts1-infected mice, and delayed the hindlimb paralysis caused by ts1 infection. Because PBA activates peroxisome proliferator-activated receptors and prevents loss of catalase, we suggest that ts1-induced oxidative stress in infected astrocytes that is alleviated by PBA is mediated via PPARalpha and/or PPARgamma.
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PMID:The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidative cell death. 1216 16

Macrophage/microglia (M phi) are the principal immune cells in the central nervous system (CNS) concomitant with inflammatory brain disease and play a significant role in the host defense against invading microorganisms. Astrocytes, as a significant component of the blood-brain barrier, behave as one of the immune effector cells in the CNS as well. However, both cell types may play a dual role, amplifying the effects of inflammation and mediating cellular damage as well as protecting the CNS. Interactions of the immune system, M phi, and astrocytes result in altered production of neurotoxins and neurotrophins by these cells. These effects alter the neuronal structure and function during pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both HAD and MS affect sub-cortical white matter. AD is a cortical disease. The process of M phi and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M phi are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M phis produce these molecules and are activated by beta-amyloid proteins and related oligopeptides. Demyelination in MS involves M phi that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M phi and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M phi and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease.
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PMID:The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. 1222 Jun 87

Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis, transcription and differentiation in addition to functions in the nervous system. Deregulation of CDKs in various diseases has stimulated an intensive search for selective pharmacological inhibitors of these kinases. More than 50 inhibitors have been identified, among which >20 have been co-crystallized with CDK2. These inhibitors all target the ATP-binding pocket of the catalytic site of the kinase. The actual selectivity of most known CDK inhibitors, and thus the underlying mechanism of their cellular effects, is poorly known. Pharmacological inhibitors of CDKs are currently being evaluated for therapeutic use against cancer, alopecia, neurodegenerative disorders (e.g. Alzheimer's disease, amyotrophic lateral sclerosis and stroke), cardiovascular disorders (e.g. atherosclerosis and restenosis), glomerulonephritis, viral infections (e.g. HCMV, HIV and HSV) and parasitic protozoa (Plasmodium sp. and Leishmania sp.).
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PMID:Pharmacological inhibitors of cyclin-dependent kinases. 1223 54

A major factor in the context of evaluating depression in the elderly is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders, including cancer, heart disease, Parkinson's disease, Alzheimer's disease, stroke, and arthritis. In this article, we hope to bring clarity to the definition of comorbidity and then discuss a number of medical disorders as they relate to depression. We evaluate medical comorbidity as a risk factor for depression as well as the converse, that is, depression as a risk factor for medical illness. Most of the disorders that we focus on occur in the elderly, with the exception of HIV infection. This review focuses exclusively on unipolar disorder. The review summarizes the current state of the art and also makes recommendations for future directions.
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PMID:Comorbidity of depression with other medical diseases in the elderly. 1236 69

Oxidative stress plays an important role in many neurodegenerative conditions including Alzheimer's disease and Parkinson's disease. 4-Hydroxynonenal (HNE), a lipid-soluble aldehydic product of membrane peroxidation, has been known to decrease neuronal survival by impairing Na+, K+, and -ATPase activity. HNE also increases neuronal vulnerability to excitotoxic injury and disrupts homeostasis by activating proteases which mediate the destruction of cellular protein and structure. The present study demonstrated that the hydrophobic HIV protease inhibitor, ritonavir inhibited HNE-mediated apoptosis in hippocampal primary neurons. In neurons exposed to oxidative stress induced by HNE (1 microM), ritonavir at 100 pM increased cell survival and completely abolished the apoptotic effects of HNE (P < 0.01). Ritonavir and its analogues might have useful cytoprotective effects for use in limiting the natural course of tissue injury after conditions where oxidative stress plays a role.
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PMID:Ritonavir protects hippocampal neurons against oxidative stress-induced apoptosis. 1238 58

Our current understanding of nitric oxide (NO), cyclic GMP (cGMP) and protein kinase G (PKG) signaling pathways in the nervous systems has its origins in the early studies conducted on vascular tissues during the late 1970s and early to mid-1980s. The pioneering research into the NO/cGMP/PKG pathway in blood vessels conducted by the laboratories of Drs. Ferid Murad, Louis Ignarro and Robert Furchgott ultimately led to the awarding of the 1998 Nobel Prize in Physiology or Medicine to these three scientists. On the basis of further pioneering studies by Drs. John Garthwaite, Solomon Snyder, Steven Vincent and many other neuroscientists during the late 1980s and throughout the 1990s, it became recognized that NO serves as a neurotransmitter/neuromodulator in the central and peripheral nervous systems and that certain neural cells possess a cGMP signaling pathway similar to that in vascular smooth muscle cells. Although NO (at high concentrations) is toxic and thought to participate in neuronal cell death during stroke and neurodegenerative diseases (e.g. amyotrophic lateral sclerosis, Alzheimer's disease, HIV dementia and Parkinson's disease), recent evidence suggests that NO at low physiological concentrations can act as an antiapoptotic/prosurvival factor in certain neural cells (e.g. PC12 cells, motor neurons and neurons of dorsal root ganglia, hippocampus and sympathetic nerves). The antiapoptotic effects of NO are mediated, in part, by cGMP and a downstream target protein, PKG. Other cGMP-elevating factors (e.g. atrial and brain natriuretic peptides) and direct PKG activator (e.g. 8-bromo-cGMP) also have antiapoptotic effects which have been quantified by the new capillary electrophoresis with laser-induced fluorescence detector technology. Inhibition of soluble guanylyl cyclase and lowering of basal cGMP levels cause apoptosis in unstressed neural cells (NG108-15 and N1E-115 cells). The cGMP/PKG pathway appears to play an essential role in preventing activation of a proapoptotic pathway, thus promoting neural cell survival.
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PMID:Involvement of cyclic GMP and protein kinase G in the regulation of apoptosis and survival in neural cells. 1239 44


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