Search PubMed⌕ Search

Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 343 records · Page 19Linked to original sources
PubMed1992

Neurotransmitter-mediated inhibition of post-mortem human brain adenylyl cyclase.

The effects of a range of neurotransmitter agonists showing selectivity for receptor types inhibitorily coupled to adenylyl cyclase were compared in membrane preparations of hippocampus, frontal cortex and caudate nucleus/striatum from previously frozen post-mortem human and rat brain. Agonists were tested against basal and forskolin stimulated activities, forskolin being a potent activator of the catalytic sub-unit of the enzyme. Of those agonists tested, only somatostatin (100 microM) and neuropeptide Y (10 microM) gave consistent inhibitions of basal and forskolin stimulated enzyme activities in all three regions of both human and rat brain. Somatostatin-mediated inhibition of human brain adenylyl cyclase was reduced in the absence of GTP and in the presence of the guanine nucleotide partial agonist, guanosine 5'-O-thiodiposphate, consistent with a G-protein-linked receptor. No such GTP-dependence was found for the neuropeptide Y-mediated adenylyl cyclase inhibition. GTP-dependent somatostatin mediated inhibitions of human brain adenylyl cyclase activity were of highest magnitude in the thalamus, intermediate magnitude in the hippocampus and caudate nucleus and lowest magnitude in the frontal cortex. It is concluded that of a range of neurotransmitter receptor agonists tested, only somatostatin gives robust, GTP-dependent responses that are reproducible enough to be used with post-mortem tissue for the comparison of receptor function in human brain disorders.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Health and social consequences for relatives of demented and non-demented elderly. A population-based study.

A population-based study was performed to investigate the subjective and objective burden due to caring for a demented relative. All the relatives of the subjects with cognitive impairment, detected in a district of Stockholm, living at home, were included in the study. When compared with relatives of elderly, mentally healthy persons living at home in the same district, they had high ORs for subjective burden and for use of psychotropic drugs. Spouses were the most stressed. However, the ORs for use of medical facilities and somatic drugs were close to unity, showing that caring for a demented person did not affect the physical health of the relative. A second comparison between relatives of demented persons living at home and in institutions, showed that the relatives of institutionalized subjects were less frequently spouses and had more problems with their physical health, but both groups had similar subjective feeling of stress.

Adolescent↗
PubMed1992

A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid.

Mutations at codon 717 in exon 17 of the beta-amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co-segregates with the disease in two large (probably related) early-onset Alzheimer's disease families from Sweden. Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript. This mutation occurs at the amino terminal of beta-amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the beta-amyloid sequence.

Alzheimer Disease↗
PubMed1992

Loneliness among elderly people living in stockholm: a population study.

The purpose was to investigate experienced loneliness among the elderly. The material included 1725 people, aged 75 and over. The study describes relationships between loneliness, social network, cognitive function and health. Thirty-five per cent experienced loneliness, and a higher percentage was found among women. A gradual increase in loneliness was found up to the age of 90, after which a levelling was found. Elderly persons living together with a partner experienced less loneliness. There were no significant differences between those with and without children. Ten per cent reported not having any friends and, of these, one out of two experienced loneliness. A high frequency of experienced loneliness was found among elderly people with reduced cognitive function. Subjectively experienced bad health and loneliness were strongly related to each other, i.e. a person who experienced loneliness did usually not feel completely healthy.

Aged↗
PubMed1992

Adenylyl cyclase activity in postmortem human brain: evidence of altered G protein mediation in Alzheimer's disease.

The effects of agonal status, postmortem delay, and age on human brain adenylyl cyclase activity were determined in membrane preparations of frontal cortex from a series of 18 nondemented subjects who had died with no history of neurological or psychiatric disease. Basal and guanosine 5'-O-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were not significantly reduced over an interval from death to postmortem of between 3 and 37 h and were also not significantly different between individuals dying with a long terminal phase of an illness and those dying suddenly. Basal and aluminum fluoride-stimulated enzyme activities showed a negative correlation with increasing age of the individual. In subsequent experiments, basal and guanosine 5'-O-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were compared in five brain regions from a series of eight Alzheimer's disease and seven matched nondemented control subjects. No significant differences were observed between the groups for either basal activity or activities in response to forskolin stimulation of the catalytic subunit of the enzyme. In contrast, enzyme activities in response to stimulation with guanosine 5'-O-(3-thiotriphosphate) and aluminum fluoride were significantly reduced in preparations of neocortex and cerebellum from the Alzheimer's disease cases compared with the nondemented controls. Lower guanosine 5'-O-(3-thiotriphosphate)-, but not aluminum fluoride-, stimulated activity was also observed in preparations of frontal cortex from a group of four disease controls compared with nondemented control values. The disease control group, which contained Parkinson's disease and progressive supranuclear palsy patients, showed increased forskolin-stimulated activity compared with both the nondemented control and the Alzheimer's disease groups. These findings indicate a widespread impairment of G protein-stimulated adenylyl cyclase activity in Alzheimer's disease brain, which occurs in the absence of altered enzyme catalytic activity and which is unlikely to be the result of non-disease-related factors associated with the nature of terminal illness of individuals.

Adenylyl Cyclases↗
PubMed1992

A comparative study of the social conditions of spouses of long term patients cared for either in nursing homes or home care.

In order to study the social conditions of spouses of patients suffering from long term illnesses structured interviews were performed. The interviewees were divided into two groups: spouses of persons with chronic conditions cared for at home and spouses of patients cared for in nursing homes. Each group consisted of 27 spouses and there were no differences in physical health score, Mini mental score or ability to manage primary Activities of Daily Living functions between the groups. Home care spouses paid fewer visits to children, had fewer friends and paid fewer visits to friends and they also had time for hobbies or interests significantly more seldom (reading, visits to church) than nursing home spouses. There were no significant differences between the groups concerning sex, socio-economic class, housing conditions and amount of home health services. Their contact with children and their feelings of loneliness were reported to be the same.

Aged↗
PubMed1992

Clinical staging of dementia in a population survey: comparison of DSM-III-R and the Washington University Clinical Dementia Rating Scale.

In a population survey in Stockholm, 224 dementia cases were staged using two scales: the Washington University Clinical Dementia Rating Scale and DSM III-R. Both scales had to be modified by adding additional specifications and, in the case of DSM III-R, a new category of questionable dementia. After modification, the comparison of the two scales showed good agreement when all stages were analyzed (kappa = 0.60), but moderate agreement on the questionable and mild stages (kappa = 0.47). These results confirm the staging of mild dementia as the most problematic issue. Finally, the scales both showed moderate agreement with the categorized Mini-Mental State Examination (MMSE) (0-17 for severe and moderate forms; 18-23 for mild cases). Our data suggest new cut-off points for the MMSE when used as a staging scale.

Aged↗
PubMed1992

Characterisation of dopamine and serotonin uptake inhibitory effects of tetrahydroaminoacridine in rat brain.

The effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on uptake rates of radioactive 5-hydroxytryptamine (5-HT) and dopamine were investigated in rat diencephalon and striatal homogenates, respectively. Six and eight microM of THA were needed to inhibit 50% of dopamine and 5-HT uptake rates. Kinetic parameters, Km and Vmax, using six different concentrations of dopamine and 5-HT were estimated in the presence or absence of THA. A significant decrease in Vmax without any change in Km values was observed for both dopamine and 5-HT in the presence of THA. The results show that THA is a non-competitive uptake inhibitor of dopamine and 5-HT in the nerve terminals. The re-uptake blocking effect of THA on dopaminergic and serotonergic neurones, following THA treatment, might lead to increased levels of these monoamines in brains of Alzheimer patients and contribute in the therapeutic effects of the drug.

Analysis of Variance↗
PubMed1992

Occurrence of dementia in advanced age: the study design of the Kungsholmen Project.

The Kungsholmen Project is a study on elderly people living in a parish of Stockholm, Sweden. The study uses a longitudinal approach with the principal purpose of determining the natural history of Alzheimer's disease and other dementias. The study population consists of all 2,368 inhabitants of the Kungsholmen area in Stockholm, aged 75 years and above in October, 1987. The study design consists of three phases. Phase I consists of a screening test used in order to identify the 'possible' dementia cases; phase II is a complete clinical examination carried out in order to reach a final diagnosis of dementia; in phase III the whole population is reexamined in order to ascertain new cases of dementia. DSM-IIIR criteria for dementia and different types of dementia are used. The final diagnosis is based on a consensus using two preliminary diagnoses, made separately by different physicians.

Aged↗
PubMed1992

Subjective loneliness--a comparison between elderly and relatives.

The survey was aimed at examining the differences between the elderly's subjectively experienced loneliness and relatives' appraisal of the situation. The interviews contained structured questions about relatives' knowledge of the elderly's loneliness and their social contacts with the elderly. In total, 178 relatives took part in the interviews. The Cognitive-impaired group included 66 pairs elderly/relatives, where the elderly persons were cognitively impaired, and the Cognitive-intact group 112 pairs, where the elderly persons had normal cognitive function. There were differences between relatives' appraisal of loneliness and the elderly's own experience. The elderly with cognitive deficits seemed to feel loneliness more often than persons with intact cognitive ability. Relatives tended to overestimate the elderly's loneliness, especially among persons with cognitive difficulties. These elderly more often had short frequent visits, while persons in the Cognitive-intact group had longer, but not so frequent visits.

Aged↗
PubMed1991

Preservation of 5-hydroxytryptamine1A receptor-G protein interactions in the cerebral cortex of patients with Alzheimer's disease.

The coupling of 5-hydroxytryptamine1A (5-HT1A) receptors to guanine nucleotide binding (G) proteins was investigated in membranes prepared from frontal and parietal cortices of control and Alzheimer's disease brains by characterising the effect of guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) on [3H]8-hydroxy-2-(di-n-propylamino)-tetralin ([3H]8-OH-DPAT) binding parameters. In the absence of guanine nucleotides, [3H]8-OH-DPAT bound to a single high affinity binding site in all membrane types. The number of [3H]8-OH-DPAT binding sites was significantly decreased in the parietal cortex of Alzheimer's disease samples compared with controls, whereas in the frontal cortex the number of binding sites remained unchanged. Gpp[NH]p reduced the [3H]8-OH-DPAT binding affinity and the number of binding sites to the same degree in both regions in control and Alzheimer's disease cases. [3H]8-OH-DPAT binding was inhibited in a concentration dependent manner with an IC50 value of approximately 1 microM in all cases. These results suggest that the 5-HT1A receptor-G protein complex is functionally intact in these regions in Alzheimer's disease brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Coupling of human brain cerebral cortical alpha 2-adrenoceptors to GTP-binding proteins in Alzheimer's disease.

The coupling of alpha 2-adrenoceptors to guanine nucleotide binding G-proteins was investigated in cerebral cortical membranes from control and Alzheimer's disease brain by characterizing the effects of MnCl2 and Gpp[NH]p on [3H]clonidine binding. The manganese induced elevation of [3H]clonidine binding was apparent in both control and Alzheimer's disease samples and the effect showed no significant difference between the two groups in the frontal cortex. However, the MnCl2 concentration dependence curves for control and Alzheimer's disease samples were significantly different from one another in the temporal cortex, whereas the pattern of stimulation by MnCl2 remained the same. The guanine nucleotide analogue, Gpp[NH]p inhibited [3H]clonidine binding in a concentration-dependent manner, the profiles of inhibition showing no significant differences between control and Alzheimer's disease samples. Analysis of the effect of Gpp[NH]p on [3H]clonidine saturation binding curves showed no significant differences between control and Alzheimer's disease samples in either frontal (Kd = 9.68 +/- 1.38, 9.1 +/- 2.6 nM; Bmax = 40.23 +/- 4.33, 44.3 +/- 9.4 fmol/mg, control and Alzheimer's disease values, respectively), or temporal (Kd = 11.61 +/- 4.04, 5.38 +/- 2.5 nM; Bmax = 52.0 +/- 14.0, 31.07 +/- 8.00 fmol/mg control and Alzheimer's disease values, respectively) cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Alzheimer beta/A4 amyloid precursor protein in human brain: aging-associated increases in holoprotein and in a proteolytic fragment.

Alzheimer beta/A4 amyloid precursor protein (APP) has been suggested to play a central role in the pathogenesis of Alzheimer disease. We have measured the content of different species of APP holoprotein and carboxyl-terminal fragments in human brains from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. By using an antibody directed against the cytoplasmic domain of APP, five species were resolved. Three of these, of molecular masses 106, 113, and 133 kDa, represent presumptive immature and mature isoforms of APP holoprotein. Two smaller proteins, of molecular masses 15 and 19 kDa, represent presumptive proteolytic carboxyl-terminal fragments of APP. The 133-, 113-, 106-, and 15-kDa species were found in both grey and white matter, whereas the 19-kDa species was found only in grey matter. Total APP immunoreactivity (sum of all five species) and the levels of the 113-, 106-, and 15-kDa species were not significantly different in brain samples from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. In contrast, the levels of the 133- and 19-kDa species increased 2- to 3-fold with age. A correlation was observed between the levels of the 133- and 19-kDa species, suggesting a possible precursor-product relationship. The size of the 19-kDa fragment indicated that it might have an intact beta/A4 domain and therefore be amyloidogenic. The age-dependent increase either in a mature APP isoform and/or in a putative amyloidogenic fragment could explain why Alzheimer disease is associated with advanced age.

Adolescent↗
PubMed1991

Assay of a phosphatidylinositol bisphosphate phospholipase C activity in postmortem human brain.

The activity of a phospholipase C which hydrolyses exogenous phosphatidylinositol-4,5-bisphosphate [( 3H]PtdIns(4,5)P2) in membranes prepared from frozen postmortem human brain and rat brain was investigated. Enzyme characteristics were essentially similar in membranes prepared from frozen postmortem brain and fresh or frozen rat brain. The [3H]PtdIns(4,5)P2 solubilization and assay procedure employed resulted in an efficient availability of the substrate for the enzyme. The non-hydrolysable guanosine triphosphate analogue guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) stimulated hydrolysis rapidly with a half maximum activity of approximately 25 microM. This stimulation was not specific for guanine nucleotides as ATP, imidodiphosphate and pyrophosphate also caused enzyme activation. However these activation effects could be distinguished by the polyanion spermine. The non-hydrolysable guanine dinucleotide analogue guanosine 5'-[beta-thio]diphosphate acted as a partial agonist thereby inhibiting the stimulatory effect of Gpp[NH]p. Gpp[NH]p-stimulated enzyme activity showed a maximum response in the presence of 1 mM deoxycholate and displayed a pH optima in the range 7.0-7.5. PtdIns(4,5)P2 hydrolysis was observed in the absence of added calcium, but hydrolytic cleavage was inhibited in the presence of divalent ion chelators. Magnesium inhibited PtdIns(4,5)P2 hydrolysis in a concentration-dependent manner. Elucidation of these aspects of the phosphatidylinositol cycle in normal human postmortem brain will permit comparative studies in CNS disease states.

Aged↗
PubMed1991

Alzheimer's disease: paired helical filament immunoreactivity in cerebrospinal fluid.

A competitive enzyme-linked immunosorbent assay with high sensitivity has been developed for measuring ubiquitin reactivity of paired helical filaments (PHF). Using the assay, ubiquitin immunoreactivity was estimated in the cerebrospinal fluid (CSF) of 44 patients who had been clinically diagnosed as having Alzheimer's disease (AD) and of 38 control patients, including 20 neurological cases. Monoclonal antibody (mAb) 5-25 to isolated paired helical filaments was used. This mAb recognizes amino acids 64-76 of ubiquitin. The levels of ubiquitin immunoreactivity measured in CSF (twice diluted) were significantly higher in the AD (p less than 0.001) than in the control group. In only a minority of instances were values for ubiquitin levels the same in AD and control groups: on PHF-coated plates, immunoreactivity values for 77% of the AD CSF specimens were higher than those for 92% of the controls, and on ubiquitin-coated plates, values for 85% of the AD CSF specimens were higher than those for 88% of the controls. On immunoblots of both AD and control CSF, mAb 5-25 stained a series of protein bands. The free ubiquitin that is also present in the CSF was not labeled. No striking differences were detected in the immunoblot pattern of AD and control CSF. This study demonstrates the presence of quantitative differences in the conjugated ubiquitin in AD and control CSF.

Adult↗
PubMed1991

Wish to transfer to other jobs among long-term care workers.

This study is based on questionnaires that were sent to the homes of health care personnel working in geriatric care (N = 583) and acute care (N = 328). The purpose was to investigate differences between these groups of personnel regarding job assignment, intention to transfer to another job, attitudes towards demented patients, and the experience of burnout. The results showed that more persons working in acute care were self-assigned to their jobs than those working in geriatric care. More persons in geriatric care stated a wish to transfer to another job in the health care field than those in acute care. The personnel who constantly work with demented patients showed the most positive attitudes towards this group of patients. A larger proportion of personnel with high burnout scores wanted to transfer to another job, compared to those with low burnout scores.

Aged↗