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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 397 records · Page 22Linked to original sources
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↗
PubMed1988

Conflicting attitudes toward euthanasia for severely demented patients of health care professionals in Sweden.

This survey study of 1,798 Swedish health care workers in 31 acute and chronic institutional settings found considerable disagreement between staff concerning euthanasia. For example, attitudes of aides and LPNs, were significantly (chi 2 = 42.0, P less than .0001) more favorable toward active euthanasia (38.9% of aides and 28.8% of LPNs were neutral or approved) than were RNs and physicians (20% and 14.9%). This disagreement was most apparent among those staff in institutions with many demented patients. Favorable attitudes were also more frequent among aides experiencing job dissatisfaction and "burnout," younger staff, and those without a relative in long-term care. Possible reasons for favorable attitudes toward active euthanasia and staff attitude polarization are discussed along with implications for patient care.

Adolescent↗
PubMed1988

Acute confusional states in elderly patients treated for femoral neck fracture.

The aims of this study were to estimate the incidence of acute confusional state (ACS), its predisposing factors and consequences in 111 consecutive patients operated for fractured neck of the femur. The incidence of ACS was 61 percent and the predicting factors were old age and dementia. Drugs with anticholinergic effect, depression, and previous stroke were factors that seemed to be associated with the development of ACS. Ninety-two percent of the patients who had severe perioperative blood pressure drops developed ACS. The consequences of ACS were prolonged ward-stay at the orthopedic department, a greater need for long-term care after discharge, and poor walking ability at discharge and six months after surgery. The confused patients also had more complications, such as urinary problems, feeding problems and decubital ulcers, as compared with the nonconfused patients.

Aged↗
PubMed1988

Long-term care of the elderly. A descriptive study of 3600 institutionalized patients in the county of Västerbotten, Sweden.

Probands (n = 3607) living in long-term care institutions in the county of Västerbotten were assessed to estimate whether the prevalence of dementia in different types of institutions had changed since a similar survey was made 7 years before. The probands' motoric functions, vision, hearing, speech, prevalence of behavioral disturbances and psychiatric symptoms, work load and use of psychoactive drugs were also investigated with special emphasis on the differences between the demented and the non-demented. About 40% were demented. This proportion of demented patients had increased in somatic long-stay clinics, nursing homes and homes for the aged since 1975. Further, the mean age of the probands and their length of stay had increased in these institutions. Demented probands were more impaired with regard to motor functions, speech, vision, hearing, ADL-functions, behavioral and psychiatric symptoms, and they also imposed a higher work load on the staff than the non-demented. Demented probands were also prescribed psychoactive drugs, i.e. neuroleptics but not minor tranquilizers or antidepressants, more often than the non-demented in accordance with the increased prevalence of behavioral disturbances and psychiatric symptoms.

Aged↗
PubMed1987

[3H]acetylcholine nicotinic recognition sites in human brain: characterization of agonist binding.

In the presence of a cholinesterase inhibitor to prevent hydrolysis and atropine to block muscarinic cholinergic receptors, [3H]acetylcholine ([3H]ACh) binding to human brain membranes showed highest levels of nicotinic binding sites in the thalamus. [3H]ACh, in the presence of atropine, binds to heterogeneous high-affinity binding sites in human thalamus. Scatchard analysis of the binding gave a Kd of 0.58 nM and a Bmax of 3.3 pmol/g protein for the 'super high-affinity' site and a Kd of 27 nM and a Bmax of 70 pmol/g protein for the 'high-affinity' site. Moreover, in competition studies nicotinic agonists such (-)-nicotine and carbachol displaceable [3H]ACh-specific binding sites consist of both a high- and a low-affinity population of sites. These results indicate that highest levels of [3H]ACh binding in human brain were found in the thalamus. Moreover, the human thalamus was found to have multiple high-affinity nicotinic agonist sites.

Acetylcholine↗
PubMed1987

5-Hydroxytryptamine-sensitive [3H]imipramine binding of protein nature in the human brain. II. Effect of normal aging and dementia disorders.

Recently, a high-affinity [3H]imipramine binding site of protein nature that appeared related to the 5-hydroxytryptamine (5-HT, serotonin) uptake mechanism was demonstrated in the rat brain. In a preceding paper a similar [3H]imipramine binding site of protein nature and displaceable by 5-HT was demonstrated in the human brain. Most previous [3H]imipramine binding studies of the human brain have used desipramine-sensitive binding, which appears to contain a significant amount of additional binding not related to 5-HT neurons. Therefore this study of the human brain in the normal aging, in Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) and in multiinfarction dementia (MID) presents data on 5-HT-sensitive [3H]imipramine binding. The influence of normal aging (17-100 years) was studied in the frontal and cingulate cortices, in the putamen, caudate nucleus, amygdala and in the hippocampus. An age-related change in 5-HT-sensitive [3H]imipramine binding was only noted in the cingulate cortex with a 50% loss in Bmax over the adult age range. In contrast, desipramine-sensitive [3H]imipramine binding studied in the frontal cortex and in the putamen showed marked increases in Bmax with age which correlated with increases in Kd. It is suggested that these increases are related to an increased binding to lipophilic membrane components not related to 5-HT neurons. The 5-HT-sensitive [3H]imipramine binding (Bmax) was reduced to 60% of control in the cingulate cortex and to 50% in the putamen in AD/SDAT. In MID there was a 50% loss of [3H]imipramine binding sites (Bmax) in the putamen, but a 30% loss in the cingulate cortex did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Simultaneous liquid chromatographic determination of seventeen of the major monoamine neurotransmitters, precursors and metabolites. I. Optimization of the mobile phase using factorial designs and a computer program to predict chromatograms.

Utilizing reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection and optimization of the mobile phase using factorial designs and a constructed computer program to predict chromatograms, it has been possible to obtain a satisfactory resolution of seventeen of the major monoamine neurotransmitters, precursors and metabolites. A rapid (less than 25 min) isocratic system for the simultaneous determination of 3,4-dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, normetanephrine, 3,4-dihydroxyphenylethylene glycol, 3-methoxy-4-hydroxyphenylethylene glycol, epinephrine, metanephrine, vanillylmandelic acid, 5-hydroxytryptophan, serotonin, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid in addition to the internal standard isoproterenol is presented. The optimization strategy included selection of variables to optimize by a reduced factorial design a detailed study of these variables by a complete factorial design, theoretical predictions of chromatograms by a constructed computer program and test on the HPLC system. This optimization strategy can easily be applied to any problem of solute separation by liquid chromatography.

Chromatography, High Pressure Liquid↗
PubMed1987

Simultaneous liquid chromatographic determination of seventeen of the major monoamine neurotransmitters, precursors and metabolites. II. Assessment of human brain and cerebrospinal fluid concentrations.

The optimized chromatographic method procedure presented in Part I was employed for the assessment of human brain and cerebrospinal fluid neurotransmitters levels. The optimized sample preparation and chromatographic conditions permitted a rapid (less than 25 min), sensitive and semi-automated high-performance liquid chromatographic analysis which measures all major monoamine neurotransmitters, precursors and metabolites in human brain and cerebrospinal fluid. The brain specimen was deproteinized with perchloric acid (containing Na2EDTA and sodium sulphite), the internal standard and heparin were added and the samples were sonicated, centrifuged, filtered and injected directly into the chromatographic system. Cerebrospinal fluid was handled in a similar manner except that sonication was excluded. The regional distribution of monoamine neurotransmitter concentrations in human brain and cerebrospinal fluid is presented.

Brain Chemistry↗
PubMed1987

A disorder of cortical GABAergic innervation in Alzheimer's disease.

Synaptosomal gamma-aminobutyric acid (GABA) uptake has been used as a biochemical marker for GABAergic terminals in controls and Alzheimer disease brains. Use of this marker suggests a large (ca. 70%) loss of cortical and hippocampal GABA terminals in Alzheimer brain. To explain this observation we suggest that neuron loss in this disorder occurs via a process of cortical retrograde degeneration. This scheme reconciles our findings with previous neurochemical measurements on Alzheimer disease brains and also better reconciles the biochemistry with the histology of the disorder.

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PubMed1987

Region-specific loss of glutamate innervation in Alzheimer's disease.

Synaptosomal D-aspartate has been used as a marker for glutamate neurons in control and in postmortem Alzheimer's disease brains. This technique shows a marked (60%) decrease of the glutamate uptake site in cortical and hippocampal regions. There were no significant changes in subcortical regions. We interpret these results as indicating loss of, or damage to, cortical glutamatergic innervation. These losses probably represent the biochemical correlate of pyramidal neuron damage in Alzheimer's disease.

Alzheimer Disease↗
PubMed1987

Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis.

Autopsied brains from 55 patients with dementia between 59-95 years of age (mean age 77.9 +/- 8.1 years) and 19 non-demented individuals between 46-91 years of age (mean age 74.3 +/- 10.5 years) were examined to establish histopathological criteria for normal ageing, primary degenerative [Alzheimer's disease (AD)/senile dementia of Alzheimer type (SDAT)] and vascular (multi-infarct) dementia (MID) disorders. Senile/neuritic plaques, neurofibrillary tangles, microscopic infarcts and perivascular serum protein deposits were quantified in the frontal lobe (Brodmann area 10) and in the hippocampus. The demented patients were classified according to the DSM-III criteria into AD/SDAT and MID. Operationally defined histopathological criteria for dementias, based on the degree/amount of the histopathological changes seen in aged non-demented patients, were postulated. The demented patients were clearly separable into three histopathological types, namely AD/SDAT, MID and AD-MID, the dementia type where both the degenerative and the vascular changes are coexistent in greater extent than are seen in the non-demented individuals. 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 the AD-MID patients was 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. The clinical diagnosis for AD/SDAT and MID was certain in only half of the AD/SDAT and one third of the MID cases when evaluated histopathologically and by multivariate data analysis. AD/SDAT, MID and AD-MID were histopathologically diagnosed in 49%, 24% and 27%, respectively, of all the dementia cases studied. Opposite correlation between the number of tangles, plaques and the patient age in non-demented and AD/SDAT cases were observed, indicating that the pathogenesis of tangles and plaques in the two groups of patients might be different and that AD/SDAT might not be a form of an exaggerated ageing process.

Aged↗
PubMed1987

Blood-brain barrier in Alzheimer dementia and in non-demented elderly. An immunocytochemical study.

Peroxidase-antiperoxidase staining of formalin-fixed brain was employed to compare the blood-brain barrier (BBB) function in five patients with Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and three patients with AD/SDAT combined with multi-infarct dementia (MID/SDAT) with that of six non-demented aged controls. The diffusion of serum proteins through the BBB was visualized with antisera to albumin, prealbumin, immunoglobulin, C1q, C3c and to fibrinogen. A similar patterns of diffusion was seen in AD/SDAT and non-demented aged individuals. Neuron and glial cells were stained with different antisera in the vicinity of the diffusion. Senile (neuritic) plaques were occasionally visualized with antisera to IgG, C1q and C3c but not with antisera to albumin, prealbumin and fibrinogen in both demented and non-demented aged individuals. Neurofibrillary tangles were not labelled with any of the antisera studied. These results indicate that the BBB is compromised equally in AD/SDAT and in the non-demented elderly.

Aged↗
PubMed1987

Cholinergic topography in Alzheimer brains: a comparison with changes in the monoaminergic profile.

The topographical distribution of the choline acetyltransferase (ChAT) activity and the number of muscarinic binding sites was studied in the anterio-posterior direction of the caudate nucleus, hippocampus, globus pallidus and putamen of four subjects with senile dementia of Alzheimer type (AD/SDAT) and in the same regions in six controls. Intranuclear gradients were observed both for ChAT and muscarinic receptors. The data obtained were compared with data on noradrenaline (NA) concentration. With longer duration of the disease a decrease was found in the noradrenergic and cholinergic systems. One patient died acutely after a rather short duration of the disease. In this patient no change in ChAT activity was found while the NA concentration was decreased in all brain regions. An upregulation of the number of muscarinic receptors was observed in the caudate nucleus and putamen of all cases, except for the case with the shortest duration of the disease.

Aged↗