Biomedical subjects

W H Frey

Publications and source records attributed to W H Frey.

79 records · Page 5Linked to original sources

PubMed1975

Structural properties of pyruvate carboxylases from chicken liver and other sources.

Varieties of pyruvate carboxylase [pyruvate: CO2 ligase (ADP-forming), EC 6.4.1.1] obtained from the livers of several species of vertebrates, including humans, all show the same basic structure. They are composed of large polypeptide chains of molecular weights ranging from 1.2 to 1.3 X 10(5) for the different varieties of the enzyme. The native form of the enzyme appears to be a tetramer with a molecular weight of about 5 X 10(5). In the case of pyruvate carboxylase from chicken liver each polypeptide chain contains a biotin moiety, thus supporting the thesis that the tetramer contains four identical polypeptide chains. Pyruvate carboxylase from yeast appears to be basically similar to those from the vertebrate species and has a tetrameric structure. Each protomer contains a single polypeptide chain with a molecular weitht of 1.25 X 10(5). In contrast, pyruvate carboxylase from two bacterial species, Pseudomonas citronellolis and Axotobacter vinelandii, appears to be a dimer with a molecular weight (2.5 X 10(5)) about half that of the animal and yeast species. As a further difference, each of the protomers of the bacterial enzymes contain two polypeptides of 6.5 and 5.4 X 10(5) molecular weight in case of the Pseudomonas enzyme. The larger of the two polypeptides contains the biotin moiety. The functional units of the bacterial enzyme thus appear to contain two polypeptides while that of the liver and yeast enzymes is made up of a single chain. Neither of these arrangements corresponds with those of other biotin enzymes whose structure has been extensively studied (acetyl-CoA carboxylases from liver or Excherichia coli, and transcarboxylase from Propionibacterium).

Animals↗

PubMedDate not supplied

Free D-amino acids in human cerebrospinal fluid of Alzheimer disease, multiple sclerosis, and healthy control subjects.

This is the first report of the presence of free D-amino acids in lumbar and ventricular human cerebrospinal fluid (CSF) of individuals with Alzheimer disease (AD) compared with CSF of normal control subjects and with individuals affected by multiple sclerosis, as an unrelated neurologic disorder. Free D-amino acids are present at significantly higher levels in AD CSF than normal CSF, whereas in the CSF of patients affected by multiple sclerosis, D-amino acids occurs at the same level as in the normal controls. The total D-amino acid content in ventricular CSF was 1.48 times higher in the AD than controls (26.4 vs 17.9 nmol/mL, p = 0.025). The total D-amino acid content was 1.43 times higher in AD lumbar CSF than controls (1.89 vs 1.32 nmol/mL, p = 0.001). D-Aspartate in particular was 2.74 times higher in AD ventricular CSF compared to normal ventricular CSF (3.34 vs 1.22 nmol/mL, p = 0.029). In lumbar CSF, D-aspartate was 1.5 times higher in AD than controls (0.054 vs 0.036 nmol/mL, p = 0.041). Previously we reported that D-amino acids are elevated in AD brain proteins associated with neurofibrillary tangles compared to normal brain proteins (D'Aniello et al., 1992c; Fisher et al., 1992a,b). Thus, the D-amino acids present in CSF may originate from degradation of brain proteins.

Alzheimer Disease↗

PubMedDate not supplied

Ionic regulation of antagonist binding to the human muscarinic cholinergic receptor of caudate nucleus.

In this in vitro study we investigated the effects of a variety of cations on binding of the cholinergic antagonist, (3H)-quinuclidinyl benzilate, to the human caudate. Physiologic sodium concentrations induced a state of positive cooperativity upon the human muscarinic cholinergic receptor (nHill = 1.41). Lithium at therapeutic equivalency (1 mM) was unique in increasing the dissociation constant (KD) for this antagonist from 35.9 to 72.4 pM. This implies a lithium-induced cholinomimetic effect at the human muscarinic receptor consistent with reports of the reversal of mania by physostigmine. These findings are also relevant to previous cholinergic receptor studies in which various cations have been employed.

Caudate Nucleus↗

PubMedDate not supplied

Neuropathologically confirmed Alzheimer's disease: clinical diagnoses in 394 cases.

In the absence of pathognomonic clinical features, the clinical diagnosis of Alzheimer's disease (AD) remains one of exclusion of other dementias. We investigated the clinical diagnoses among 394 neuropathologically confirmed AD cases in a dementia brain bank. Most patients were correctly diagnosed as AD (348 or 88%). Among the misdiagnosed patients, AD was mistaken for a primary depressive disorder in 14, multi-infarct dementia in 13, Parkinson's disease in nine, and alcoholic dementia in four. The number of misdiagnosed AD patients did not differ between physician specialties but was greater among AD patients with agitation, depression, paranoia, or delusions. This retrospective study suggests that the diagnostic sensitivity for AD is high among a cross-section of practicing physicians and that an important factor in mistaking AD for another illness is unfamiliarity with the potential psychiatric symptoms of AD.

Aged↗

PubMedDate not supplied

Clinical characteristics of chronic Creutzfeldt-Jakob disease.

Chronic Creutzfeldt-Jakob disease, presenting in later life, may be difficult to distinguish from other dementing illnesses. Patients with this disease may lack the characteristic myoclonus and electroencephalographic complexes. We report four patients with a slowly progressive dementia who were misdiagnosed during life and had a spongiform encephalopathy at autopsy. All four patients had early extrapyramidal rigidity, primitive reflexes, and other neurologic signs. The presence of these neurologic findings early in the course of a dementia suggests that clinicians should consider chronic Creutzfeldt-Jakob disease, evaluate the patient with electroencephalographic studies, and emphasize universal tissue precautions.

Aged↗

PubMedDate not supplied

Seizures in Alzheimer's disease: clinicopathologic study.

New-onset epileptic seizures occur in patients with Alzheimer's disease (AD), but the nature and underlying reasons for these seizures are unclear. We identified new-onset, nonsymptomatic seizures in 77 (17%) of 446 patients with uncomplicated, definite AD on autopsy. Among these seizure patients, 69 had generalized tonic-clonic seizures, and 55 had less than three total seizures. The seizure patients had a younger age of dementia onset than did the remaining AD patients; however, at seizure onset, they averaged 6.8 years into their AD and had advanced dementia. When further compared to 77 AD controls, matched for age of onset and duration, the seizure patients did not differ on medical illnesses, amount of medications, and degree of focal neuropathology. We conclude that a few unprovoked generalized seizures frequently occur late in the course of AD, and that AD patients with a younger age of dementia onset are particularly susceptible to seizures.

Age of Onset↗

PubMedDate not supplied

Anandamides inhibit binding to the muscarinic acetylcholine receptor.

Loss of memory and cholinergic transmission are associated with both Alzheimer's disease (AD) and marijuana use. The human brain muscarinic acetylcholine receptor (mAChR), which is involved in memory function and is inhibited by arachidonic acid, is also inhibited by anandamides. Two agonists of the cannabinoid receptor derived from arachidonic acid, anandamide (AEA) and R-methanandamide, inhibit ligand binding to the mAChR. Binding of the mAChR antagonist [3H]quinuclidinyl benzilate ([3H]QNB) is inhibited up to 89% by AEA (half-maximal inhibition at 50 microM). Binding of the more polar antagonist [N-methyl-3H]scopolamine ([3H]NMS) is inhibited by AEA up to 76% (half-maximal inhibition at 44 microM). R-methanandamide inhibits more than 90% of both [3H]QNB binding (I50 = 34 microM) and [3H]NMS binding (I50 = 15 microM) to the mAChR. Both AEA and R-methanandamide stimulate mAChR binding of the agonist [3H]oxotremorine-M at low concentrations (25-75 microM), but significantly inhibit agonist binding at higher concentrations (I50 = 150 microM). The cannabinoid antagonist SR141716A did not alter AEA or R-methanandamide inhibition of [3H]NMS binding to the mAChR, even at concentrations as high as 1 microM. Further, the cannabinoid agonist WIN 55212-2 does not alter antagonist binding to the mAChR. This demonstrates that mAChR inhibition by the anandamides is not mediated by the cannabinoid receptor. Since AEA and R-methanandamide are structurally similar to arachidonic acid, they may interact with the mAChR in a similar manner to inhibit receptor function.

Arachidonic Acid↗