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)

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.
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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 distinctive feature of Alzheimer's disease (AD) is the presence of dystrophic neurites that immunoreact with antibodies to amyloid precursor protein (APP) and ubiquitin (Ub). The authors examined dystrophic axons (DA) present in other chronic conditions such as familial infantile neuroaxonal dystrophy (INAD), aging, cystic fibrosis, and biliary obstruction as well as in conditions of shorter duration such as human immunodeficiency virus (HIV) leucoencephalopathy, infarction and radiation therapy to determine whether APP and Ub immunoreactivity was unique to the DA of AD. A large number of DA immunoreacted with antibodies to the A4, C- and N-terminal regions of APP as well as to Ub. Ub and APP immunoreactivities often, but not always, colocalized. "Acute" DA generally reacted more intensely and in larger number with antibodies to APP than to Ub, whereas the reverse was true for "chronic" DA. Structureless DA immunostained diffusely. In DA with cores or granules, the Ub immunoreaction was occasionally limited to these structures, whereas reaction with antibodies to APP was more diffuse. In view of the contention that impairment of proteolysis is the common pathogenetic step in the formation of DA, Ub immunoreactivity in all DA may indicate a vicarious attempt to degrade accumulated components through an activation of the Ub system. The role of APP in the formation of DA remains to be determined.
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PMID:Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease. 171 43

We show here for the first time that actin, troponin C, Alzheimer amyloid precursor protein (AAP), and pro-interleukin 1 beta (pro-IL-1 beta), are substrates of the protease encoded by the human immunodeficiency virus (HIV) type-1. As has been seen in other non-viral protein substrates of the HIV protease, the presence of Glu residues in the P2' position appears to play an important role in substrate recognition. Three of the four bonds cleaved in actin, two of the three in troponin C, and all of the bonds hydrolyzed in AAP and pro-IL-1 beta have a P2' Glu residue. In fact, Glu residues are accommodated in all positions from P4 to P4' surrounding the scissile bond in substrates of the HIV proteases, and as many as 4 adjacent Glu residues were seen in one of the bonds cleaved in AAP. This study of non-viral protein substrates has also revealed unexpected amino acids such as Gly, Arg, and Glu in the scissile bond itself rather than the more conventional hydrophobic amino acids. The HIV-2 protease hydrolyzed actin in a manner similar to that of the HIV-1 enzyme, but its cleavage of troponin C was distinct in that it split a bond adjacent to a triplet of Glu residues in P2, P3, and P4 that was refractory to the HIV-1 enzyme. Documentation of cleavage sites in the several important cellular proteins noted above has extended our understanding of the features in a substrate that are recognized by these multi sub-site proteases of retroviral maturation. Moreover, the present work adds to an accumulating body of evidence which demonstrates that these enzymes can damage crucial structural and regulatory cellular proteins if ever their activity is expressed outside the viral particle itself.
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PMID:Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus. 190 79

To evaluate the possible role of lentiviruses in Alzheimer's disease we searched for cross-reactive antibodies to human immunodeficiency virus type 1, caprine arthritis encephalitis virus, and equine infectious anemia virus in Alzheimer's disease, Down's syndrome, and related dementing illnesses in serum samples and cerebrospinal fluid samples and in healthy age-matched control subjects. No cross-reactive antibodies were detected.
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PMID:The viral hypothesis of Alzheimer's disease. Absence of antibodies to lentiviruses. 230 89

Sixty-eight human fibroblast cell strains were assayed for radioresistant DNA synthesis (RDS), which is defined here as the absence of a steep component of inhibition of DNA synthesis in a dose-response curve when rate of DNA synthesis is plotted against radiation doses from 0 to 20 Gy or more. Twenty-seven strains from patients who were previously diagnosed to have ataxia-telangiectasia (AT) were positive for this feature. Among the cell strains that did not show RDS were two from AT obligate heterozygotes (i.e., the parents of AT patients), two from patients with Alzheimer disease, two from patients with Friedreich ataxia, one from a patient with Bloom syndrome, one from a patient with Down syndrome, and six from patients with various immunodeficiencies. Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients. RDS therefore is not a necessary trait of human genetic diseases that involve radiosensitivity or immunodeficiency. Although recent reports suggest that some AT patients do not exhibit RDS, we found RDS in all the AT cells we tested.
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PMID:Radioresistant DNA synthesis and human genetic diseases. 272 85

Patients with human immunodeficiency virus (HIV) have often progressive dementia. Human T cell lymphotropic virus Type I (HTLV-I) infection has not been reported to cause dementia. We tested antibodies to HTLV-I and HIV in serum and cerebrospinal fluid in 69 Finnish patients referred because of dementia to an outpatient department of neurology. No antibodies to HTLV-I and HIV were detected in patients with the clinical diagnosis of Alzheimer's disease, vascular dementia, secondary dementia due to a specific cause, or in cases of atypical dementia.
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PMID:No antibodies to HTLV-I and HIV in patients with dementia in Finland. 289 Feb 55

PHA stimulation assay was the first in vitro method for evaluating the T-cell function, and this T-cell proliferative response has been routinely used to discriminate between normal subjects and patients with deficiency in cell-mediated immunity. However, [3H]thymidine incorporation into lymphocyte DNA can be studied by using additional in vitro assay methods since they measure different lymphocyte activation pathways. In the present study we selected three different tests to investigate the reliability of this single approach: PHA induced lymphocyte DNA synthesis; T lymphocyte DNA synthesis to anti-T3 monoclonal antibody (OKT3); autologous mixed lymphocyte reaction (AMLR). In addition, IL-2 receptor expression on the membrane of T-cell stimulated in AMLR both with PHA and anti-T3 was evaluated. This study was performed in various groups of subjects: normal young controls, aged healthy individuals, and patients with Alzheimer's disease (AD), Retinitis Pigmentosa (RP), and with cell-mediated immunodeficiency and clinical evidence of recurrent viral infections (ID). The data reported herein show heterogeneity of results in each group studied and demonstrate the necessity of employing more than one laboratory test for the routine evaluation of T-cell-mediated immunity.
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PMID:Does normal lymphocyte DNA synthesis in response to PHA exclude cell-mediated immunodepression? 294 81

Mental disturbances associated with acquired immunodeficiency syndrome (AIDS) are related not only to profound psychosocial stress, systemic diseases, and neoplasms or opportunistic infections within the central nervous system (CNS); they are also related to the direct neurotoxicity of the etiologic human immunodeficiency virus (HIV), producing an array of both insidious and acute affective, cognitive, and behavioral dysfunction that can mimic many neuropsychiatric disorders. The precise mechanism of this direct neurotoxicity is not known, nor have the frequency, clinical course, or methods of early diagnosis been clearly established; however, a critique of 56 clinical reviews or case reports regarding approximately 800 subjects suggest that at some point following infection an HIV-induced dementia is extremely common, as are marked histopathological changes throughout the CNS. Treatment strategies are discussed.
Alzheimer Dis Assoc Disord 1987
PMID:AIDS dementia: a review of the literature. 333 Nov 19

Using infrared oculography, we recorded the eye movements in a group of patients with acquired immunodeficiency syndrome (AIDS), with or without the AIDS dementia complex (ADC). Our aim was to determine whether the severity of dementia could be correlated with abnormalities of eye movement and whether eye movement abnormalities could be detected prior to the onset of clinical dementia. Abnormalities of eye movement were present in seven of seven patients with mild, moderate, or severe ADC and in six of seven AIDS or asymptomatic human immunodeficiency virus-seropositive patients without clinical dementia, but at risk for ADC. The eye movement abnormalities detected included disturbances of both saccadic and smooth-pursuit function, and their severity correlated strongly with the severity of dementia. The abnormalities were qualitatively similar to those that occur in Alzheimer's disease but quantitatively less severe. Recording of eye movements may be a valuable, noninvasive technique for the early detection of neurologic dysfunction in asymptomatic patients who are seropositive for human immunodeficiency virus or in patients with AIDS, even prior to other clinical evidence of ADC. In particular, it may be of use in selecting high-risk patients requiring antiviral therapy and in monitoring the neurologic response to such treatment.
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PMID:Eye movement abnormalities as a predictor of the acquired immunodeficiency syndrome dementia complex. 275 20

Mitogenesis of human peripheral blood lymphocytes as measured by the uptake of [3H]thymidine was stimulated in vitro by pure orosomucoid glycoprotein when used at concentrations that are considerably lower than the physiological plasma level. The lymphocyte cultures stimulated with PHA or PWM were not affected by low concentration (67 micrograms/ml), but they were mildly suppressed by high concentration (1 mg/ml) of this glycoprotein. The stimulatory response was relatively greater with fractionated T cells than the non-T cells (B cells and monocytes). At 50 micrograms/ml concentration of orosomucoid, the lymphocyte activation was found in randomly selected blood donors which included normal healthy volunteers and patients with T cell immunodeficiency or Alzheimer's disease, demonstrating a consistent immunostimulatory action of this glycoprotein.
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PMID:Lymphocyte stimulation in vitro by orosomucoid glycoprotein. 349 44


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