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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 73 records · Page 4Linked to original sources
PubMed1989

Protein phosphorylation systems in postmortem human brain.

Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders.

Adenosine Triphosphate↗
PubMed1989

Memory improvement at different stages of Alzheimer's disease.

Three groups of patients with dementia of the Alzheimer type (mildly, moderately and severely demented) and two groups of healthy older adults (73 and 82 yr old) were examined on free and cued recall of subject-performed tasks (SPTs) or verbally presented sentences depicting the same verbal information as the SPTs. Results indicated that all groups examined performed better on SPTs than on the verbal task. In addition, for all groups cuing effects were greater in the SPT task than in the verbal task.

Aged↗
PubMed1989

Alzheimer's disease-associated reduction of polysomal mRNA translation.

Polysomes from the frontal cortices of individuals who had histopathologically confirmed Alzheimer's disease were compared with polysomes from individuals who exhibited no neuropathological conditions. The cytosolic polysome yield from Alzheimer's disease frontal cortex was reduced 40% compared with that obtained from control frontal cortex. The translational activity per unit polysome of the Alzheimer's disease polysomes was only 50% of control in a reticulocyte lysate in vitro translation assay in which human polysomes do not undergo reinitiation. These differences exhibited brain region specificity in that polysomes isolated from Alzheimer's disease cerebellum were not different from control cerebellar polysomes. Thus, the disruptions are not due to a secondary and general response of the entire brain to the disease. These reductions were reflected by similar decreases in the translation of the mRNA for high molecular weight neurofilament polypeptide. Thus, the inhibition of polysomal mRNA translation is a mechanism by which gene expression is impaired in pathologically involved brain regions of individuals afflicted by Alzheimer's disease.

Aged↗
PubMed1989

Translational control of gene expression in the human brain.

1. Translational control is the regulation of protein synthesis as an alteration in the efficiency of mRNA translation and is a common mechanism by which cells regulate gene expression. 2. Alternations of total protein synthesis are often the responses of cells to various stress stimuli including starvation, viral infection, and heat shock. 3. Numerous specific genes including ferritin heavy chain, tubulin, vimentin and the lck proto-oncogene have also been shown to be under translational control. 4. Unlike cultured cells or intact organisms, the investigation of translational control in the human brain requires the measurement of components of protein synthesis, especially polysomes. Therefore, we have purified and characterized polysomes from human postmortem brain tissues and compared them to polysomes purified from the adult rat brain. 5. The yield (as A260 units per gram brain tissue), size (as number of ribosomes per message), translational efficiency (as amount protein synthesized per A260 unit), and ability to reinitiate (as amount of protein synthesis prevented by initiation inhibitors) were all significantly lower as exhibited by the human polysomes compared with the rat polysomes. However, the human and rat polysomes synthesized similar polypeptides. 6. Thus, the human polysomes differed from the rat polysomes principally in the efficiency of mRNA translation which is likely due to the greatly reduced ability of the human polysomes to initiate protein synthesis.

Animals↗
PubMed1989

Problems of basic nursing care in acutely confused and non-confused hip-fracture patients.

Thirty-five patients operated on for femoral neck fracture were studied. Fifteen (42.9%) became acutely confused after surgery. Problems in the 14 components of basic nursing care (Henderson 1964), were identified by means of interviews with the patients and their caregivers. The quantitative analysis of the results showed that significantly more of the acutely confused patients had problems in nine out of 14 components of basic nursing care as compared with the non-confused patients. The qualitative analysis showed that the problems of the non-confused patients were mostly caused by the fracture and by hospitalisation. The same problems were also present among the acutely confused patients who, in addition, had problems which arose from the acute confusional state.

Activities of Daily Living↗
PubMed1989

Neurotransmitter deficits in a non-multi-infarct category of vascular dementia.

Brain tissue from 9 severely demented patients cared for in psychiatric long-term wards and with records of stroke episodes, macroscopic signs of brain infarcts and with no clinical evidence of senile dementia of the Alzheimer type was investigated and compared with control material. The mean volume of the brain infarcts in this vascular dementia group was only 6.8 ml. Pronounced disturbances of the serotoninergic and cholingergic systems were found in subcortical and cortical grey matter. These widespread neurotransmitter changes can hardly be explained by the localized brain infarcts per se, but suggest the existence of another category of vascular dementia. Since the neurotransmitter disturbances were found to be similar to those of Alzheimer's disease and senile dementia of the Alzheimer type, it seems more likely that they indicate a common pathway for dementia disorders than that they serve as markers of different dementia categories.

Aged↗
PubMed1989

Multiple actions of THA on cholinergic neurotransmission in Alzheimer brains.

1,2,3,4-tetrahydro-9-aminoacridine (THA) is a cholinesterase inhibitor presently under investigation in clinical trials for treatment of Alzheimer's disease, senile dementia of Alzheimer type (AD/SDAT). To further analyse the underlying mechanisms for its effect in human brain, an in vitro model which allows measurement of acetylcholine (ACh) release from human postmortem brain slices has been used. In control cortical tissue THA induces a decreased release of ACh probably due to negative feedback mechanisms mediated via presynaptic muscarinic autoreceptors. In AD/SDAT cortex THA enhances the release of ACh to control level. This effect is prevented by nicotinic or muscarinic receptor antagonists, which suggest receptor mechanisms involving both nicotinic and muscarinic receptors. Subchronic treatment of rats with THA (10 mg/kg sc twice daily) or physostigmine (0.9 mg/kg sc five times daily) causes a significant increase in the number of high affinity nicotinic receptors in the cortex of THA treated rats whereas no change is found in the physostigmine treated rats. The number of muscarinic receptors are decreased following both THA and physostigmine treatment.

Alzheimer Disease↗
PubMed1989

Histopathological classification of dementias by multivariate data analysis.

Autopsied brains from 55 demented patients, clinically classified according to DSM-III criteria into AD/SDAT and MID and 19 nondemented individuals were available for this study. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in AD-MID patients were not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own.

Aged↗
PubMed1988

Change in nicotinic receptor subtypes in temporal cortex of Alzheimer brains.

Competition experiments using (-)-[3H]nicotine and unlabelled nicotine revealed both high and low affinity nicotinic binding sites in temporal cortex of control and Alzheimer (AD/SDAT) brains. A significant reduction in the proportion of high affinity nicotinic binding sites (-20%) and a parallel increase in the proportion of low affinity nicotinic binding sites was obtained in AD/SDAT brain cortex compared to control brain. Moreover, a marked decrease was observed in the affinity of the low affinity nicotinic binding sites in AD/SDAT.

Aged↗
PubMed1988

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data presented support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged↗
PubMed1988

Distribution of nicotinic receptors in human thalamus as visualized by 3H-nicotine and 3H-acetylcholine receptor autoradiography.

Nicotinic cholinergic receptors in human thalamus were measured using (-)3H-nicotine (20 nM) and 3H-acetylcholine (3H-ACh) (20 nM) as radioligands. The specific binding for 3H-nicotine to homogenates of thalamus was 51.6 +/- 8.3 pmol/g protein and for 3H-ACh 18.6 +/- 1.9 pmol/g protein. Receptor autoradiography indicated a high labelling of both 3H-Nicotine and 3H-ACh in the antero-ventral nucleus of thalamus and dorso-medial nucleus of thalamus, while the labelling was lower in the postero-lateral nucleus of thalamus and in the postero-lateral ventral nucleus of thalamus. Quantitative measurement of the 3H-nicotine autoradiograms showed highest labelling in the anteroventral nucleus of thalamus (17.34 +/- 0.76 pmol/g tissue). This study indicates a heterogeneous distribution of high-affinity nicotinic receptors in the human thalamus.

Acetylcholine↗
PubMed1988

Adrenergic, serotoninergic, histaminergic, and imipramine binding sites in post-mortal human cerebral microvessel preparations.

Cerebral microvessels were prepared from fresh and frozen human brain samples obtained from autopsy cases. Structural integrity and purity of the microvessels were confirmed by light and electron microscopy, and by measurement of the enzymatic marker gamma-glutamyltranspeptidase. Similar morphological and enzymatic characteristics were found for the microvessels prepared from fresh and frozen brain samples. Radioligand binding experiments indicated the presence both in the "fresh" and "frozen" microvessel preparations of specific alpha 1-, alpha 2-, and beta-adrenergic, histamine H1, serotonin S1 and imipramine binding sites, although the density of beta-adrenergic and histamine H1 specific binding sites were lower in the frozen samples than in the fresh samples. Low levels of specific binding to muscarinic, GABAergic and serotonin S2 sites (with respect to the specific binding densities in the crude homogenates) were found in the microvessel preparations.

Adult↗