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)

This is a presentation of the hypothesis of a pathogenetic mechanism common to the dementia seen in Alzheimer's disease (AD), Down's Syndrome (DS) and the acquired immunodeficiency syndrome (AIDS). As there is experimental evidence of defective DNA repair capacity in AD and DS, unrepaired damage to DNA occurs in these diseases and may lead to complete breakdown of cellular function and ultimate cell death. Cobalamin and folate are coordinated in a vulnerable key position in the synthesis of DNA and S-adenosylmethionine (SAM). Cobalamin/folate deficiency, a significant feature in senile dementia of Alzheimer type and in AIDS-related dementia complex, will result in concomitant slowed synthesis of DNA and SAM. The enzyme cystathionine-beta-synthetase (CBS) has been localized to the chromosome band 21q22.3. Owing to gene dosage, CBS activity is increased in trisomy 21. As a consequence, cobalamin/folate metabolism is inhibited, which leads to slowing of DNA and SAM synthesis in DS patients. Amyloidosis is a hallmark of AD and DS brain neuropathology and recent experimental findings support the view that amyloid or amyloid precursors stimulate DNA synthesis, which is in agreement with the hypothesis presented in this paper. In summary, demented patients with cobalamin/folate deficiency, trisomy 21 and human immunodeficiency virus (HIV) infection display a simultaneous downregulation of DNA and SAM synthesis, which may indicate a pathway common to the dementia seen in AD, DS and AIDS.
 ...
PMID:Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease? 1629 95

A total of 181 human immunodeficiency virus (HIV)-seropositive hemophiliacs and 28 hemophilic controls were evaluated by psychometric tests and by electroencephalogram (EEG). Patients were classified from stages 1-6 according to the immunological criteria of the Walter Reed staging system. Statistical analysis of psychometric data showed an effect of the stage of the disease on test performances, indicating a decline in attention, accumulation of perceptual interferences, decline in visuoperceptual speed and visuomotor response speed and reduced verbal memory performance, especially in stage 6 patients. Comparison of performance levels with normative test data already revealed cognitive deficits in about 20-30% of the patients in stages 2-5. As regards verbal memory, especially learning and recognition of new verbal information were impaired. In contrast, there was no significant deficit for nonverbal memory processing. Compared with the controls, patients exhibited an increasing number of abnormal EEG findings in stages 2-6. As a conclusion, in the stages before acquired immunodeficiency syndrome (AIDS) develops, EEG findings as well as psychometric findings indicate central nervous system involvement of AIDS in about 20-30% of cases, whereas in full-blown AIDS there is a marked increase to 80%. Besides a more general deficit of attention and psychomotor speed as is seen in subcortical dementia, there is evidence for a particular verbal learning disorder, suggesting additional selective impairment of the brain.
 ...
PMID:Early signs of cognitive deficits among human immunodeficiency virus-positive hemophiliacs. 159 65

To investigate the epidemiology of human immunodeficiency virus (HIV) encephalopathy, we analyzed cases of acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control (CDC) from September 1, 1987, through August 31, 1991. Of 144,184 persons with AIDS (PWAs), 10,553 (7.3%) were reported to have HIV encephalopathy. The proportion of PWAs with HIV encephalopathy was highest at the extremes of age: in PWAs less than 15 years old the proportion was 13%, and in PWAs greater than or equal to 15 years old the proportion progressively increased with age, from 6% in PWAs 15 to 34 years old to 19% in PWAs greater than or equal to 75 years old (p = 0.00001, chi 2 test for linear trend in proportions). The reported annual incidence of HIV encephalopathy per 100,000 population aged 20 to 59 years was 1.4 in 1988, 1.5 in 1989, and 1.9 in 1990. This analysis best provides estimates for HIV encephalopathy as the initial manifestation of AIDS because the CDC AIDS reporting system often does not ascertain diagnoses after the initial AIDS report. These data suggest that age (very young or old) is associated with the development of HIV encephalopathy and that HIV encephalopathy is a common cause of dementia in adults less than 60 years old in the United States.
 ...
PMID:Epidemiology of human immunodeficiency virus encephalopathy in the United States. 164 Nov 38

Recent evidence in vitro has suggested that neuronal injury observed in the acquired immunodeficiency syndrome dementia complex may depend, at least in part, on toxic effects of the human immunodeficiency virus type 1 envelope protein, gp120. This laboratory previously reported that members of the dihydropyridine class of calcium channel antagonists, nimodipine and nifedipine, greatly attenuate the rise in intracellular calcium engendered by gp120 and prevent subsequent neuronal injury. The relatively low (nanomolar) concentrations of dihydropyridines that were effective suggested that their action might be exerted at the level of the L-type of voltage-dependent calcium channels. In the present study, I tested members of the three other major classes of Ca2+ channel antagonist drugs to determine if they too could prevent neurotoxicity induced by gp120. At the maximal dose that did not cause neuronal damage in and of itself, a diphenylalkylamine piperazine derivative (flunarizine, 10 microM) was the most effective, a phenylalkylamine (verapamil, 100 microM) was possibly effective, whereas a benzothiazepine (diltiazem, 1 microM) was ineffectual in protecting rat retinal ganglion cells from gp120-induced toxicity in vitro. To explain these results, previous work has shown that the various classes of Ca2+ channel antagonists may exhibit differential potency in blocking voltage-dependent Ca2+ current in neurons, with dihydropyridines and flunarizine being the most potent at neuronal calcium channels. Moreover, these channels on mammalian central neurons are relatively insensitive to agents such as verapamil and diltiazem compared with other cell types like muscle. The low micromolar concentrations necessary for potency of flunarizine is in keeping with that predicted by binding and electrophysiological studies for block of voltage-dependent calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Calcium channel antagonists and human immunodeficiency virus coat protein-mediated neuronal injury. 165 45

We studied ocular motor performance in 47 subjects with human immunodeficiency virus (HIV) infection and 25 normal control subjects. Saccade accuracy was the most sensitive measure, being significantly poorer for all four HIV-positive groups (asymptomatic, acquired immunodeficiency syndrome [AIDS] without dementia, and AIDS with dementia, and AIDS-related complex) than for control subjects. While saccade duration and peak velocity were not significantly different across groups, the scatter of saccade duration was increased in all HIV-positive groups. Saccade latency was not significantly affected. In both simple and complex antisaccade tasks, the asymptomatic, AIDS, and AIDS dementia groups made significantly fewer correct-way antisaccades than did control subjects. Latencies of correct-way antisaccades were increased for AIDS and AIDS dementia groups in the simple antisaccade trials, and for all HIV-positive groups in the complex trials. Fixation stability was significantly worse in the AIDS dementia group than in control subjects. Smooth pursuit gain was decreased in the asymptomatic, AIDS, and AIDS dementia groups for the least demanding trial. One or more ocular motor abnormalities were present in 15 (88%) asymptomatic subjects, 11 (69%) with AIDS-related complex, and 14 (100%) AIDS patients without or with dementia.
 ...
PMID:Ocular motor abnormalities in human immunodeficiency virus infection. 168 Mar 2

The first part of this article addresses the neuropsychiatric aspects of human immunodeficiency virus (HIV) infection in children and adolescents, including developmental delay, depression, and dementia. The specific clinical issues of disclosure of diagnosis and discussion of death with a child are examined. The second part presents aspects of the impact of AIDS on families, approaches to HIV antibody testing, and therapeutic interventions for the family.
 ...
PMID:Psychosocial aspects of AIDS in children and adolescents. 170 86

Tryptophan (Trp) is an indispensable amino acid required for biosynthesis of proteins, serotonin and niacin. Indoleamine 2,3-dioxygenase (IDO) is induced by infections, viruses, lipopolysaccharides, or interferons (IFNs) and this results in significant catabolism of Trp along the kynurenine (Kyn) pathway. Intracellular growth of Toxoplasma gondii and Chlamydia psittaci in human fibroblasts in vitro is inhibited by IFN-gamma and this inhibition is negated by extra Trp in the medium. Similarly, growth of a number of human cell lines in vitro is inhibited by IFN-gamma and addition of extra Trp restores growth. Thus, in some in vitro systems, antiproliferative effects of IFN-gamma are mediated by induced depletion of Trp. We find that cancer patients given Type I or Type II IFNs can induce IDO which results in decreased serum Trp levels (20-50% of pretreatment) and increased urinary metabolites of the Kyn pathway (5 to 500 fold of pretreatment). We speculate that in vivo antineoplastic effects of IFNs and clinical side effects are mediated, at least in part, by a general or localized depletion of Trp. In view of reported increases of IFNs in autoimmune diseases and our earlier findings of elevated urinary Trp metabolites in autoimmune diseases, it seems likely that systemic or local depletion of Trp occurs in autoimmune diseases and may relate to degeneration, wasting and other symptoms in such diseases. We find high levels of IDO in cells isolated from synovia of arthritic joints. IFNs are also elevated in human immunodeficiency virus (HIV) patients and increasing IFN levels are associated with a worsening prognosis. We propose that IDO is induced chronically by HIV infection, is further increased by opportunistic infections, and that this chronic loss of Trp initiates mechanisms responsible for the cachexia, dementia, diarrhea and possibly immunosuppression of AIDS patients. In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin. In preliminary studies, others report low levels of Trp and serotonin, and elevated levels of Kyn and quinolinic acid in AIDS patients. The implications of these data in cancer, autoimmune diseases and AIDS are discussed.
 ...
PMID:Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 172 46

Although the human immunodeficiency virus type 1 (HIV-1) is frequently isolated from the cerebrospinal fluid of infected patients, only a small percentage of patients are found to have clinical dementia or neuropathies (or both). The reasons for this remain unclear. In our study, serum neutralizing antibody titers against the human T cell leukemia virus-IIIB isolate of HIV-1 were tested in 10 patients with acquired immunodeficiency syndrome (AIDS) with neurologic complications and 20 patients with HIV infection without neurologic complications. Titers were significantly lower in the neuro-AIDS group, suggesting that impaired neutralizing antibody responses in this subpopulation of patients may be involved in the immunopathogenesis of AIDS encephalopathy.
 ...
PMID:Neutralizing antibody responses in patients with AIDS with neurologic complications. 174 7

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.
 ...
PMID:Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. 182 18

Human immunodeficiency virus infection is frequently complicated by a syndrome of central nervous system dysfunction known as the acquired immunodeficiency syndrome dementia complex (ADC). The ADC is characterized by abnormalities in cognition, motor performance, and behavior, and it produces serious morbidity in a significant number of patients with acquired immunodeficiency syndrome. The pathogenesis of ADC is unclear, but appears to be caused by the human immunodeficiency virus itself, rather than by a secondary opportunistic process. Herein, we review the data regarding the pathogenesis of ADC and hypothesize a mechanism involving excitotoxicity and dopaminergic dysfunction. N-methyl-D-aspartate receptor antagonists may be of therapeutic benefit, as these agents may both limit glutamate-mediated neuronal dysfunction and improve dopaminergic neuronal function.
 ...
PMID:Excitotoxicity and dopaminergic dysfunction in the acquired immunodeficiency syndrome dementia complex. Therapeutic implications. 184 34


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