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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 433 records · Page 24Linked to original sources

Extraneural cholinergic markers in Alzheimer's and Parkinson's disease.

Muscarinic and nicotinic binding sites were analysed in lymphocytes from patients with Alzheimer's disease, Multi-infarct dementia, Parkinson's disease and age- matched controls. A significant decrease in the number of both muscarinic and nicotinic binding sites was obtained in lymphocytes from Alzheimer patients while in Parkinson patients a significant decrease was found only in the nicotinic binding sites. Using butyrylthiocholine as substrate, no change was observed in cholinesterase activity in plasma from Alzheimer patients, whereas a significant decrease in plasma cholinesterase activity was found in Parkinson patients.

Aged↗

Towards a molecular genetic approach to Alzheimer's disease.

The current observations of a familial form of Alzheimer's disease and the alterations in the neurochemistry of Alzheimer tissue including neurotransmitter deficits, paired helical filament and RNA degradation suggest that the modification of specific genes may be responsible for the disease. These genes may be identified with the use of complementary DNA probes synthesized from normal and Alzheimer mRNA. In characterizing the gene expression in demented tissue, we have found that RNA from Alzheimer frontal cortex and hippocampus was partially degraded compared to RNA isolated from control. However, the polyadenylated RNA exhibited no obvious degradation. Similarly, polysome content of the Alzheimer tissue was lower than in control tissues. In addition, the Alzheimer polysomes were much less efficient in protein synthesis.

Alzheimer Disease↗

Regional and subcellular distribution of Thy-1 in human brain assayed by a solid-phase radioimmunoassay.

A solid-phase radioimmunoassay, specific for the monomeric form of human Thy-1, was developed and used for quantitation of the Thy-1 antigen in human brain tissue. Determination of Thy-1 in homogenates of 12 anatomically defined brain regions showed that Thy-1 is present throughout the human brain. However, significant variation was found in the expression of the glycoprotein in different regions. Thy-1 appears to be generally enriched within gray matter: caudate nucleus, cerebral cortex, and putamen were found to contain the highest Thy-1 concentration (approximately 2.5 micrograms Thy-1/mg protein). Interestingly, the cerebellar cortex contained only 25% of the Thy-1 concentration of cerebral gray matter. Cerebral subcortical white matter contained half the amount of Thy-1 compared to cerebral cortex. Determination of Thy-1 in subcellular fractions prepared from human brain biopsy tissue indicated that the highest relative concentration of Thy-1 is associated with synaptosomal membranes and myelin/axonal membrane fractions.

Adult↗

Post-mortem stability of progesterone in rat brain.

Progesterone concentrations in the brains of female rats kept at +20 degrees C or +4 degrees C for 0 to 48 hours after death were investigated. After two hours at +20 degrees C the progesterone concentration in seven studied brain areas were equal to that in control brains (dissected immediately after death). After four hours at +20 degrees C, levels decreased significantly in three brain regions. Intact rats that were placed in a refrigerator (+4 degrees C) after four hours at room temperature (+20 degrees C) showed no further changes in brain progesterone concentration. In the control group, the cerebral cortex, the hypothalamus and the hippocampus contained progesterone levels significantly higher than in all other areas (p less than 0.05). After four hours at room temperature only the hypothalamus showed higher levels (p less than 0.05). In conclusion, time after death and storage temperature affect the post-mortem levels of progesterone. Because of their differences in body masses, the conditions in the rat brain are not comparable to those in the human brain. However, it might be possible to study the regional distribution of progesterone in the human brain if control cases matched with regard to post-mortal time and brain temperature are used.

Animals↗

Comparison between pre- and postovulatory distributions of oestradiol and progesterone in the brain of the PMSG-treated rat.

The pre- and postovulatory levels of oestradiol and progesterone were measured in seven brain areas, peripheral fat, muscle tissue and blood plasma in 49 immature female rats which had been given an injection of 4 IU PMSG (Pregnant Mare Serum Gonadotropin) on the 25th day of life. We observed a uniform decline in oestradiol concentration in all the areas of the postovulatory rat. The highest mean concentrations of oestradiol pre- and postovulatory were found in the hypothalamus and the striatum (260 +/- 26, 110 +/- 11, 200 +/- 39 and 75 +/- 13 pg g-1, respectively). The levels of progesterone showed variable increases in all the areas postovulatory. The highest postovulatory concentration was found in the cerebral cortex (29 +/- 2.0 ng g-1) where the increase was six-fold greater than the increases in any of the other areas compared to preovulatory values. The hypothalamus contained high progesterone levels at both times (3.5 +/- 0.68 ng g-1 and 27 +/- 5.2 ng g-1) compared to other areas. We conclude that the female rat brain exhibits differences in the distribution of oestradiol and progesterone both pre- and postovulatory. Since the levels in different brain areas to a large extent varied independently we suggest different uptake mechanisms and/or different binding capacities in various regions of the rat brain.

Animals↗

Isoelectric focusing and two-dimensional gel electrophoresis in plasma and cerebrospinal fluid from patients with dementia.

IgG profiles of cerebrospinal fluid (CSF) and plasma from patients with Alzheimer's disease/senile dementia of Alzheimer type, multi-infarct dementia and aged nondemented individuals were analyzed using isoelectric focusing (IEF) followed by immunofixation and high resolution two-dimensional polyacrylamide gel electrophoresis (PAGE). The IEF profiles of plasma and CSF in patients with dementia were diffuse and lacked oligoclonal bands and were identical to those of nondemented individuals. The investigation of plasma and CSF by two-dimensional PAGE did not reveal any specific protein pattern in the demented individuals compared to the controls.

Adult↗

Health, disorders, and drug consumption in an elderly population in northern Sweden.

A population study of health state, care, and drug consumption among 187 70-, 75-, and 79-year-old persons in Umeå, Sweden, was performed. It was shown subsequently that women felt less healthy and had a higher drug consumption than men, while concerning definable diseases there was no sex difference. Only 13% of the subjects were considered medically healthy, i.e., without definable diseases. 69% had been hospitalized over the age of 60 years.

Age Factors↗

Single-dose pharmacokinetics of dicloxacillin in healthy subjects of young and old age.

Dicloxacillin was administered as 2 g single intravenous doses to healthy young and old subjects of both sexes aged 19-32 years and 65-76 years, respectively, and the pharmacokinetics were studied. Peak serum concentrations were higher in young than in elderly subjects and in each age group in females than in males. The elimination rate was similar in all groups and the only striking pharmacokinetic differences observed were that the urinary recovery of active dicloxacillin was higher in young subjects and that the non-renal clearance was higher in elderly volunteers. The findings were interpreted to be due to a systemic metabolism of dicloxacillin, compensating for a reduced renal elimination in the elderly subjects. In all subjects dicloxacillin was well tolerated. No increases of serum creatinine were observed.

Adult↗

Alteration of dopamine receptors in the caudate nucleus and the putamen in schizophrenic brain.

Neuroleptic binding to human caudate and putamen was investigated in seven patients with schizophrenia and compared to matched normal controls. [3H]-spiperone was used as a ligand for the binding studies and previous drug treatment was recorded. There was a statistically significant increase in maximal specific binding and in dissociation constants for [3H]-spiperone in the brains of schizophrenics in both brain regions studied. Long term as well as recent neuroleptic treatment both appeared to be associated with increases of Bmax and Kd of [3H]-spiperone.

Adult↗

Age dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved enzyme-linked immunosorbent assay.

A procedure for improving the specificity of enzyme-linked immunosorbent assays (ELISA) was devised, based on addition of antigen-specific or non-immune immunoglobulins to the citrated plasma sample and defining the difference in assay response between these two mixtures as the antigen-specific part of the response. When applied to measurement of tissue plasminogen activator (t-PA; EC 3.4.21.31) antigen in plasma, this procedure resulted in elimination of the overestimates obtained in a large proportion (10-20%) of patients' samples when assayed according to the conventional ELISA technique. Basal t-PA concentrations in plasma were found to be highly age-dependent, normal values being about 3 micrograms/L for adults near 30 years of age and about 10 micrograms/L for those over 60. Patients with gallbladder stone disease had increased mass concentrations of t-PA in plasma, even when corrected for the age effect; patients with multi-infarct dementia did not.

Adult↗

Catecholamine topochemistry in human basal ganglia. Comparison between normal and Alzheimer brains.

Analysis of catecholamine levels in postmortem human control and Alzheimer brains revealed lower mean concentrations of noradrenaline, but not dopamine, in nucleus caudatus, putamen and globus pallidus, but not in hippocampus, of the Alzheimer brains. Generally, noradrenaline levels were higher in the more posterior parts of nucleus caudatus and putamen in the control brains, whereas such gradients were absent in the Alzheimer brains.

Aged↗

Perivascular deposits of serum proteins in cerebral cortex in vascular dementia.

Immunocytochemical techniques were used to study the histopathologic changes in vascular dementia, i. e., both multi-infarct dementia (MID) and MID combined with Alzheimer changes (MID/SDAT). In eight of 13 of the dementia cases strongly immunostained deposits of plasma proteins were observed around numerous capillaries of layers I-IV of frontal grey matter. Each of these deposits contained albumin, prealbumin, IgG, C1q, C3c, and fibrinogen. No such deposits were found in any of the seven non-demented aged controls. In contrast, in white matter in both demented and normal aged control cases only weak immunostaining of serum proteins was observed which gradually decreased with the distance from the vessels. The presence of heavy deposits of serum proteins exclusively around the capillaries of the gray matter in cases with vascular dementia may indicate a defect of the cortical capillary system which might play a role in the clinical symptoms seen in vascular dementia. The enrichment of C1q within the deposits is intriguing as this might occur because of the binding of C1 through its subunit C1q to the antibody-antigen complex and thereby support a possible immunologic involvement in the formation of these deposits.

Aged↗

The uptake of serotonin and dopamine by homogenates of frozen rat and human brain tissue.

A recently described procedure of freezing and thawing, which allows retention of metabolic and functional integrity, has been applied in the study of serotonin and dopamine uptake into frozen rat and post mortem human frozen tissue. The Km and Vmax for the serotonin uptake into human hypothalamus were estimated to be 0.12 microM and 0.03 nmol/g/min respectively. The Km and Vmax for the dopamine uptake into human putamen were estimated to be 0.28 microM and 0.13 nmol/g/min respectively. The results indicate that the freezing procedure does not affect the uptake sites for these transmitters. The storage time before freezing is however of importance for the Vmax value. The Km value for the uptake, on the other hand, seems to be rather resistant to storage time before freezing.

Animals↗

The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue.

Measurement of the frontal cortex and the medulla oblongata pH at autopsy revealed that those brains from individuals who died after long terminal phase had lower pHs than those who died quickly. These low pHs (pH 6.0-6.5) corresponded to lactic acid concentrations (20-25 mM) which are known to be neurotoxic. The cerebrospinal fluid pH and blood pH correlated with the cortical pH. The significance of these observations to the study of the biochemistry and histology on post-mortem human brain tissue and their possible clinical relevance are discussed.

Acidosis↗

Superoxide dismutase isoenzymes in normal brains and in brains from patients with dementia of Alzheimer type.

CuZn superoxide dismutase and Mn superoxide dismutase were analysed in hypothalamus, nucleus caudatus, hippocampus and cortex gyrus cinguli from 14 patients with dementia of Alzheimer type and from 16 controls. Ample amounts of both enzymes were demonstrated in the brains and there was little difference between the various parts of the brain. There were only small differences in the enzymic activities between the two groups indicating that deficiencies of these enzymes are not a very likely cause of brain degeneration in dementias of Alzheimer type.

Age Factors↗

Autoradiographic localization of [3H]neurotensin-binding sites in the hippocampal region of the rat and primate brain.

The distribution of binding sites for the neuropeptide neurotensin was studied in the hippocampal region of the rat, monkey and human brain by using the method of in vitro receptor autoradiography. Biochemical studies of [3H]neurotensin binding to homogenates or sections of the rat hippocampal region showed it to be saturable, reversible and of high specificity. Displacement studies showed that neurotensin-(1-13) and neurotensin-(8-13) were active, while neurotensin-(1-6) and (1-8) were inactive in blocking the specific binding of [3H]neurotensin to hippocampal sections. The autoradiographic studies showed a highly heterogeneous pattern of [3H]neurotensin binding in the hippocampal region: the highest density was present in the entorhinal area while little binding was found in the Ammon's horn. In the rat most of the [3H]neurotensin binding was found in layer II of the medial entorhinal area and in the parasubiculum, while the lateral entorhinal area contained fewer [3H]neurotensin-binding sites. The laminar distribution of binding remained the same throughout the longitudinal axis of the entorhinal area. The pattern of [3H]neurotensin binding in the monkey resembled that seen in the rat inasmuch as the medial was rich and the lateral entorhinal area was poor in [3H]neurotensin-binding sites. In the medial entorhinal area most binding was found in layers I-IV. Unlike in the rat, the hilus of the monkey contained moderate and the molecular layer of the area dentata few [3H]neurotensin-binding sites. In the human brain the outer three layers of both the medial and the lateral entorhinal area contained binding sites for [3H]neurotensin. Binding sites for [3H]neurotensin were found also in the parasubiculum and in the molecular layer of the area dentata of the human brain. The present autoradiographic studies show that the hippocampal region of the rat and primate brain is rich in binding sites for [3H]neurotensin, that a majority of these are situated in the entorhinal area and that despite some differences in the regional distribution of these binding sites within the hippocampal region, some principal similarities may exist between these species.

Animals↗