Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymerase chain reaction (PCR) was prospectively performed with cerebrospinal fluid (CSF) from 51 patients whose CSF was available for analysis and was submitted for viral culture and/or herpes simplex virus (HSV) serology and 20 patients whose CSF was submitted exclusively to the Clinical Biochemistry Laboratory. Primers were used that flanked a 92 bp segment of the HSV DNA polymerase gene (35 cycles). Amplified products were electrophoresed on agarose gel, blotted onto nylon membrane, and probed with a 32P-labelled sequence internal to the primers. For nested PCR, 1 microliter of PCR product was amplified for an additional 35 cycles before electrophoresis and Southern blot analysis. Review of the clinical records revealed that 15 patients had central nervous system (CNS) infections. Specific HSV DNA sequences were detected in CSF specimens of three of the individuals [PCR(2), nested PCR(1)]. Two of these patients had disseminated HSV infection including encephalitis and one patient had aseptic meningitis. The diagnoses of the 12 patients with CNS infection who did not have HSV DNA detected in CSF included encephalitis [varicella-zoster virus (1), cytomegalovirus (1), Mycoplasma pneumoniae (1)], meningitis [Neisseria meningitidis (1), Coccidioides immitis (1), Enterovirus (1), aseptic meningitis (1)], varicella-zoster radiculitis (2), human immunodeficiency virus dementia (2), and transverse myelitis due to Epstein-Barr virus (1). Importantly, HSV DNA was also not detected in the CSF of the 36 patients who did not have CNS infection and 20 samples submitted exclusively to the Clinical Biochemistry Laboratory. Our findings demonstrate the utility of PCR as a rapid, non-invasive method for the routine laboratory diagnosis of CNS infection due to HSV.
Mol Cell Probes 1992 Oct
PMID:A prospective study of the polymerase chain reaction for detection of herpes simplex virus in cerebrospinal fluid submitted to the clinical virology laboratory. 133 47

Cerebrospinal Fluid (CSF) levels of the main metabolites of monoamines (MHPG, 5-HIAA, and HVA) were measured in patients with early onset (AD) and late-onset (SDAT) Alzheimer's disease, vascular dementia (VD), and elderly controls. Psychobehavioral assessment was carried out by means of MMSE and GBS. Mean MHPG levels did not differ from controls; 5-HIAA was lower in VD when compared to both controls and SDAT. HVA was decreased in AD, SDAT, and VD with respect to controls. Significant correlations between HVA and psycho-behavioral parameters were observed in SDAT and VD groups, whereas no relationship was documented in AD. The SDAT group was divided in SDAT-A (age at onset: greater than 65 less than or equal to 80 yr) and SDAT-B (age at onset: greater than 80 yr). SDAT-A had significantly lower CSF HVA values than SDAT-B (165 +/- 64 vs 235.7 +/- 85). SDAT-B HVA levels were similar to those observed in controls. Correlation analysis between HVA and neuropsychological variables was significant in SDAT-A, but not in SDAT-B. These results might support the evidence of SDAT heterogeneity.
Mol Chem Neuropathol
PMID:CSF monoamine metabolites in old age dementias. 138 90

Reduction of the cerebral metabolic rate of glucose is one of the most predominant abnormalities generally found in the Alzheimer brain, whereas the cerebral metabolic rate of oxygen is only slightly diminished or not at all the beginning of this dementive disorder. This metabolic abnormality may induce severe functional disturbances, obviously preceding morphobiological changes. From the cerebral metabolic rates of oxidized glucose and oxygen, the cerebral ATP formation rate was calculated in incipient early-onset, incipient late-onset and stable advanced dementia of Alzheimer type. A reduction of ATP formation was found from at least 7% in incipient early-onset, to around 20% in incipient late-onset DAT, and from 35% to more than 50% in stable advanced dementia. This approximation was adjusted to findings demonstrating diminished activities of enzymes active in glucose metabolism and formation of oxidation equivalents for ATP production from substrates other than glucose. A reduction for energy formation to the same range was found, as was also recently reported, in vivo in Alzheimer patients. From this rather theoretical point of view, a permanent loss of energy by at least 7-20% in incipient and progressively advancing dementia of the Alzheimer type may be assumed, with an increasing tendency in stable advanced dementia to around 50% energy loss. This energy deficit may have drastic impacts on brain function.
Mol Chem Neuropathol 1992 Jun
PMID:Oxidative energy metabolism in Alzheimer brain. Studies in early-onset and late-onset cases. 141 18

Platelet MAO-B activity, serum vitamin B12 levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B12 levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B12 levels (Group I: less than 200 pg/mL; Group II: greater than or equal to 200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B12 and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type.
Mol Chem Neuropathol
PMID:Platelet MAO-B activity and vitamin B12 in old age dementias. 152 Apr 4

This paper examines inhibition of acetylcholinesterase (AchE) and butyrylcholinesterase (BuchE) by tetrahydroaminoacridine (THA), an acridine analog under consideration for palliative treatment of Alzheimer's dementia. THA causes linear mixed inhibition of AchE hydrolysis of acetylthiocholine, a cationic substrate (KI = 3.8 x 10(-9) M), and linear competitive inhibition of AchE hydrolysis of 7-acetoxy-4-methylcoumarin, an uncharged substrate (KI = 6.8 x 10(-9) M), and N-methyl-7-dimethylcarbamoxyquinolinium, a cationic carbamate (KI = 1.5 x 10(-8) M). Propidium association with AchE in the presence of saturating concentrations of THA is characterized by a dissociation constant of 7.7 +/- 0.7 x 10(-6) M, a value within 2-fold of the dissociation constant in the absence of THA. Association of THA with AchE is, therefore, not mutually exclusive with association of propidium at the peripheral anionic site. Moreover, THA causes dissociation of decidium complexes with AchE at concentrations compatible with a dissociation constant of 7.0 +/- 0.4 x 10(-9) M. Similar relationships were observed for THA inhibition of BuchE hydrolysis of butyrylthiocholine (KI = 2.5 x 10(-8) M) and dissociation of decidium complexes with BuchE (KD = 1.9 +/- 0.1 x 10(-8) M). These kinetic and equilibrium data uniformly indicate that THA associates with AchE and BuchE with high affinity and that the subsequent inhibition comes about through ligand association at the active center rather than at a peripheral site. The noncompetitive component of inhibition reflects association of THA with the acyl-enzyme intermediate, with subsequent effects on the rate of deacylation.
Mol Pharmacol 1992 Feb
PMID:Interaction of tetrahydroaminoacridine with acetylcholinesterase and butyrylcholinesterase. 153 17

Alzheimer's Disease (AD), a disorder of unknown etiology, is the most common form of adult-onset dementia and is characterized by severe intellectual deterioration. The definitive diagnosis of AD is made by postmortem examination of the brain, which reveals large quantities of neurofibrillary tangles (NFT) and senile plaques within the parenchyma. The NFT are composed of paired helical filaments associated with several cytoskeletal proteins. The primary protein component of senile plaques is beta/A4 amyloid, a 42-43 amino acid peptide derived from a much larger molecule, the amyloid precursor protein (APP). Vascular beta/A4 amyloidosis is also prevalent in the disease. The mechanism by which beta/A4 amyloid accumulates in the AD brain is unknown. Recent research has demonstrated that the precursor molecule, APP, is a transmembrane protein with a large extracytoplasmic domain, a membrane spanning region that includes the portion that gives rise to beta/A4 amyloid, and a short intracytoplasmic domain. The precursor has multiple forms among which are those that differ by a variable length insert within the extracytoplasmic domain. The insert has sequence homology to the family of Kunitz protease inhibitor proteins. Cellular and animal models have been developed to study the nature of APP processing and the biological and behavioral consequences of beta/A4 amyloidosis. The results of such studies indicate that the normal processing of APP involves enzymatic cleavage of the molecule within the beta/A4 amyloid region, thus preventing the accumulation of beta/A4 in the normal brain. The factors leading to abnormal processing of APP, and consequent beta/A4 amyloid accumulation within the AD brain, have yet to be identified. In cell culture, the biological effects associated with beta/A4 amyloid include neurotrophic and neurotoxic activities, while the peptide has also been shown to have dramatic behavioral effects in animal models.
J Mol Neurosci 1992
PMID:Molecular and cellular biology of Alzheimer amyloid. 162 58

The most characteristic cellular change in Alzheimer's disease is the accumulation of aberrant filaments, the paired helical filaments (PHF), in the affected neurons. There is growing evidence from a number of laboratories that dementia correlates better with the accumulation of PHF than of the extracellular amyloid, the second major lesion of Alzheimer's disease. PHF are both morphologically and biochemically unlike any of the normal neurofibrils. The major polypeptides in isolated PHF are microtubule-associated protein tau. Tau in PHF is phosphorylated differently from tau in microtubules. This abnormal phosphorylation of tau in PHF occurs at several sites. The accumulation of abnormally phosphorylated tau in the affected neurons in Alzheimer's disease brain precedes both the formation and the ubiquitination of the neurofibrillary tangles. In Alzheimer's disease brain, tubulin is assembly competent, but the in vitro assembly of microtubules is not observed. In vitro, the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. The in vitro dephosphorylated PHF polypeptides stimulate microtubule assembly from bovine tubulin. It is hypothesized that a defect in the protein phosphorylation/dephosphorylation system is one of the earliest events in the cytoskeletal pathology in Alzheimer's disease. Production of nonfunctional tau by its phosphorylation and its polymerization into PHF most probably contributes to a microtubule assembly defect, and consequently, to a compromise in both axoplasmic flow and neuronal function. Index Entries: Alzheimer's disease; mechanisms of neuronal degeneration; neurofibrillary changes; paired helical filaments: biochemistry; microtubule-associated protein tau; abnormal phosphorylation; ubiquitination; microtubule assembly; axoplasmic flow; protein phosphorylation/dephosphorylation.
Mol Neurobiol 1991
PMID:Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer's disease. 172 45

Adrenoleukodystrophy (ALD) is a progressive X-linked disorder that produces pathological changes, mainly in the adrenal cortex and the white matter of the central nervous system. The main biochemical abnormality is the accumulation of saturated unbranched fatty acids with a chain length of 24 or more, referred to as very-long-chain fatty acids (VLCFA). Affected children develop large zones of demyelination associated with perivascular lymphoctyic infiltrations resembling those seen in multiple sclerosis. Adults show a more chronic form of the disease, referred to as adrenomyeloneuropathy (AMN). AMN mainly involves the spinal cord ad peripheral nerves, although the cerebral hemispheres may also be affected. Approximately 15% of female carriers have nervous-system involvement that resembles AMN. It is well known that ALD may initially appear as a psychiatric disorder. In the present study, we have assessed the prevalence of cognitive impairment in a group of AMN patients and neurologically symptomatic ALD heterozygotes initially presenting primarily physical complaints. Sixty percent of these patients demonstrated significant neuropsychological impairment, most commonly a pattern of spared and impaired functions typical of a subcortical dementia. We suggest that this progressive cognitive impairment may underlie other behavioral deficits, affirming the significance of the psychological features of this genetically determined disorder.
Mol Chem Neuropathol 1990 Jun
PMID:Cognitive impairment in adult-onset adrenoleukodystrophy. 209 65

Huntington's disease (HD) is an inherited neuropsychiatric degenerative process characterized by movement disorder, dementia, and, often, affective disorder (AfD) (seen in 38% of patients). Depression in HD is not just an understandable reaction to fatal illness: 10% of HD patients develop mania; AfD can occur 20 yr before neurological signs; and mood disorders are not randomly distributed, but occur in a subset of HD families. This evidence suggests that AfD in HD relates to brain pathophysiology. With its clear neuropathology, HD is proposed as one model for biological underpinnings of idiopathic AfD. There is striking atrophy and neuronal loss in HD neostriatum, particularly caudate. Caudate has rich connections to the limbic system. It is hypothesized that AfD in HD relates to dysfunction of the part of the neostriatum damaged earliest, dorsal medial caudate. Preliminary studies on neuropathological differences between HD patients with and without AfD are discussed. HD neurochemistry is reviewed, emphasizing the excitotoxin hypothesis, which involves dysfunction of the glutamate neurotransmitter system in HD (especially the NMDA receptor, which contains a channel with a phencyclidine (PCP) binding site). Based on the HD model, it is suggested that the glutamate system (particularly NMDA receptors) be examined in idiopathic AfD.
Mol Chem Neuropathol 1990 Mar
PMID:Huntington's disease as a model for mood disorders. Clues from neuropathology and neurochemistry. 214 28

Aging of the brain is characterized, in part, by the appearance of protein anomalies. The proteins deposited within the nervous system structures are hardly soluble. This physiological phenomenon turns out to be pathological, quantitatively at least, and perhaps even qualitatively, in dementia of the Alzheimer's type (DAT). One might wonder whether the brain protein anomalies are related to a general process and, thus, could generate anomalies of the serum proteins. Therefore, we examined, with two-dimensional electrophoresis (2DE), 120 serum samples collected from different neurological patients and 24 serum samples from a control group, and we reached the following conclusion: a protein spot, normally not found and named 10M, corresponding to a molecular weight of 30 kDa with an isoelectric point of +/- 8, is seen in 31% of the patients affected with a neurological disease and in 90% of patients affected with DAT. The frequency of the appearance of this spot, seen after 2DE, increases with age. We wonder whether this protein is playing a role in the formation of the neuropathological lesions observed in DAT.
Mol Chem Neuropathol 1989 Dec
PMID:A serum protein involved in aging? 248 32


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