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Biomedical subjects

B Winblad

Publications and source records attributed to B Winblad.

At least 253 records · Page 14Linked to original sources
PubMed1995

Somatostatinergic phenotype markers in the human neuroblastoma cell-line LA-N-2.

We have characterized somatostatinergic phenotype markers of the human neuroblastoma, LA-N-2. A single mRNA-transcript (approximately 850bp) and two cellular somatostatin immunoreactivity forms, a high molecular weight form (M(r) 15,000) and a fragment corresponding to somatostatin-28 was found, while the somatostatin-14 peptide was absent. Saturation binding experiments demonstrated a single class of high-affinity somatostatin receptors with Kd and Bmax of 0.27 +/- 0.03 nM and 45 +/- 1 fmol/mg protein. Partial G-protein uncoupling (30%) was demonstrated, using GTP gamma S, with an affinity of 9.7 nM. The LA-N-2 cell line, previously shown to be cholinergic, may serve as a simplified system to elucidate heterologous neurotransmittor interactions. Such studies are of interest since dysfunctions of the cholinergic basal forebrain neurons and somatostatin immunoreactive interneurons have been consistently observed in Alzheimer's disease.

Animals↗
PubMed1995

Influence of place learning on somatostatin levels in the rat brain following environmental deprivation.

We have previously reported increased somatostatin levels in the cerebral cortex of rats housed in impoverished environment and subsequently subjected to a behavioural testing procedure, consisting of open-field exposure and spatial learning. The aim of the present study was to evaluate the degree of neurochemical specificity of the activation of somatostatin neurotransmission and to examine whether the altered levels were due to learning stimulation. Adult rats, previously housed individually for 30 days, were exposed to repeated sessions of a spatial learning task (2 days or 14 days) or repeated sessions of free swimming (14 days). The training sessions of the 14 day group consisted in recurrently changed position of the platform in a learning-set paradigm. Our data showed increased somatostatin immunoreactivity, and unchanged substance P immunoreactivity in the posterior part of the cerebral cortex. However, somatostatin levels increased to a similar extent following 14 days of repeated spatial learning sessions as free swimming sessions. We conclude that the activity of the cortical somatostatin system appears to be sensitive to environmentally induced sensorimotor stimulation in general, rather than learning per se. Thus, external stimulation of early clinical dementia patients with preserved sensorimotor receptivity, in an attempt to restore cognitive function, might be associated with altered somatostatin levels.

Analysis of Variance↗
PubMed1995

Effects of long-term ovariectomy and ovarian steroids on somatogenic binding sites in rat brain and liver.

The effects of long-term ovariectomy and replacement with ovarian steroids on the levels of brain and liver somatogenic binding sites as well as plasma and liver growth hormone (GH) were studied in sham-operated (Sham) and ovariectomized female rats receiving either, 17 beta-estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX). Long-term ovariectomy decreased the levels of somatogenic binding sites in the choroid plexus and liver as well as GH in plasma and liver. The levels of these sites in the choroid plexus were partially restored only by estradiol replacement. Moreover, exogenous estradiol but not progesterone restored the levels of plasma and liver GH as well as liver somatogenic binding sites. Our results suggest that estrogens regulate the levels of somatogenic binding sites in the liver and choroid plexus.

Animals↗
PubMed1995

Behavioural deficits in adult rats following long-term adrenalectomy.

Long-term adrenalectomy results in loss of neurones in the hippocampal formation of the adult rat. The effects of long-term adrenalectomy on spatial learning and exploratory behaviour in adrenalectomized (ADX), adrenalectomized normal weight gain (ADXNW), sham operated and naive control male Sprague-Dawley rats were investigated in this study. The ADX rats had significantly longer latencies in the Morris maze task compared to the other groups. In the open-field situation, as a novel finding, the ADX rats showed significantly lower rearing scores compared to other groups. These data indicate that long-term adrenalectomy causes impairment in spatial learning and explorative behaviour in the rat.

Adrenalectomy↗
PubMed1995

Diminished [3H]inositol(1,4,5)P3 but not [3H]inositol(1,3,4,5)P4 binding in Alzheimer's disease brain.

Levels of the calcium mobilising receptors for the phosphoinositide hydrolysis derived second messengers, inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and inositol(1,3,4,5) tetrakis-phosphate [Ins(1,3,4,5)P4] were compared in the cerebellum, superior temporal and superior frontal cortex of a series of Alzheimer's disease and matched control cases. Membrane [3H]Ins(1,4,5)P3 radioligand binding experiments performed under steady state conditions revealed that the number of Ins(1,4,5)P3 recognition sites was significantly decreased in all three brain regions of the Alzheimer's disease cases, compared to controls. In contrast, [3H]Ins(1,3,4,5)P4 binding levels, as assessed in competition analyses, were not significantly different between the groups in any brain region. Moreover, the Hill coefficients for inhibition of [3H]Ins(1,3,4,5)P4 binding by non-radioactive Ins(1,3,4,5)P4 were less than unity in both the control and Alzheimer's disease brains, suggesting that the heterogeneity of these binding sites are also maintained in the disease. It is concluded that disruptions of the phosphoinositide hydrolysis pathway in Alzheimer's disease brain are associated with a selective loss of calcium mobilising Ins(1,4,5)P3, but not Ins(1,3,4,5)P4 receptor sites. These alterations may contribute to an altered calcium homeostasis in Alzheimer's disease, as well as providing one reason for the lack of success of cholinergic replacement therapies aimed at enhancing muscarinic receptor-mediated phosphatidylinositol hydrolysis.

Aged↗
PubMed1995

Reduced nitric oxide responsive soluble guanylyl cyclase activity in the superior temporal cortex of patients with Alzheimer's disease.

Particulate and soluble guanylyl cyclase activities were studied in postmortem temporal cortex from a series of Alzheimer's disease patients and matched control subjects. Particulate guanylyl cyclase activity was not significantly different between groups. In contrast, the Vmax values for basal and sodium nitroprusside-stimulated soluble guanylyl cyclase activities were approximately 50% lower in the Alzheimer's disease cases, compared to controls. This difference between groups was statistically significant for sodium nitroprusside-stimulated, but not for the basal, enzyme activities. These results provide the first evidence for a loss of nitric oxide responsive guanylyl cyclase activity in Alzheimer's disease brain.

Aged↗
PubMed1995

Preservation of kappa 1 opioid receptor recognition site density and regulation by G-proteins in the temporal cortex of patients with Alzheimer's disease.

The pharmacological properties of the kappa 1 opioid receptor were investigated in human post-mortem temporal cortical membranes from control and Alzheimer's disease brains, using the kappa 1-selective radioligand [3H]U69593. [3H]U69593 bound to a single high affinity site population with no significant difference between control (Bmax 31 +/- 4.14 fmol/mg protein, KD 1.01 +/- 0.26 nM) and Alzheimer's disease brains (Bmax 37 +/- 4.63 fmol/mg protein, KD 0.86 +/- 0.08 nM). Competition studies with dynorphin B and alpha-neoendorphin gave flat inhibition curves with Hill coefficients of 0.31 +/- 0.04 and 0.49 +/- 0.09 in the control brains and 0.38 +/- 0.05 and 0.48 +/- 0.08 in the Alzheimer's disease brains, respectively. The pI50 values for dynorphin B and alpha-neoendorphin were 8.73 +/- 0.17 and 8.48 +/- 0.09, respectively, in the control brains and 9.30 +/- 0.22 and 8.70 +/- 0.15 in the Alzheimer's disease brains. The guanine nucleotide analogue Gpp(NH)p inhibited binding by ca. 70% in both the control and Alzheimer's disease brains, the residual binding being sensitive to NaCl in both cases. These results indicate that the pharmacological properties and the functional integrity of G-protein coupling of the kappa 1 receptor recognition site are preserved in Alzheimer's disease temporal cortex.

Aged↗
PubMed1995

Apolipoprotein epsilon 4 allele and disease progression in patients with late-onset Alzheimer's disease.

A random sample of 60 late-onset Alzheimer's disease (AD) cases from a population-based study were apolipoprotein E (apoE) genotyped and clinically examined with a 3-year interval. The epsilon 4 allele carriers had a significantly lower age of disease onset compared to non-epsilon 4 carriers. However, no significant differences were observed between epsilon 4 allele carries and non-carriers for Mini-Mental State Examination (MMSE) test scores at the first examination, in spite of a longer disease duration in the epsilon 4 allele carriers. After 3 years, MMSE test scores were still not significantly different between epsilon 4 carries and non-carriers but more than twice as many non-carriers had died. All other clinical features were similar between epsilon 4 allele carriers and non-carriers. This study indicates that the epsilon 4 allele is associated with a better prognosis of the disease in late-onset AD but that there are probably factors other than the epsilon 4 allele that are important for the AD phenotype.

Age of Onset↗
PubMed1995

Characterization of muscarinic acetylcholine receptors in cultured adult skin fibroblasts: effects of the Swedish Alzheimer's disease APP 670/671 mutation on binding levels.

We have characterised the muscarinic receptor subtypes found in human skin fibroblasts and compared binding levels in cell lines from members of the Alzheimer's disease family with the Swedish amyloid precursor protein (APP) 670/671 mutation. Binding studies with [3H] quinuclidinyl benzilate ([3H]QNB) and the M2/M4 selective antagonist [3H] (+/-)-5,11-dihydro-11-([(2-[(di-propylamino)methyl]-1- piperidinyl]ethyl)amino]carbonyl)-6H-pyrido(2,3-b)(1,4)benzodiazepine-6- one ([3H]AF-DX 384) revealed the presence of a single population of muscarinic receptors on lysed fibroblast membranes. [3H]QNB binding was displaced by a number of selective muscarinic ligands with a rank order of potency: atropine > himbacine > methoctramine > (+/-)-p-fluoro-hexahydro-sila-difenidol hydrochloride > pirenzepine > muscarinic-toxin-3. APP 670/671 mutation carrying cell lines showed 25-35% lower levels of muscarinic receptors labelled with [3H]QNB, [3H]N-methyl scopolamine and [3H]AF-DX 384, compared to controls. This difference was not statistically significant due to large individual variation. It is concluded that muscarinic receptors on adult skin fibroblasts are predominantly of the M2 subtype. Since these cells do not possess M1 and M3 receptor subtypes, they are unlikely to provide a good model for studying muscarinic receptor regulation of APP processing.

Aged↗
PubMed1995

Diminution of preprosomatostatin-mRNA in cerebral cortex of the aged rat.

The aim of the present study was to examine the effect of normal aging on somatostatin neurotransmission. Somatostatin gene expression was analysed in several regions of the cerebral cortex and hippocampus in 3, 7 and 21 month-old Sprague-Dawley rats using quantitative in situ hybridization with a 48mer oligodeoxynucleotide antisense probe. Furthermore the distribution of 125I-Tyr11 somatostatin receptor binding sites was studied using quantitative receptor autoradiography. The results demonstrated a significant reduction of preprosomatostatin-mRNA in the frontal cortex of the aged (21 month) group compared with the young (3 month) and the middle-aged (7 month) groups. The receptor binding densities of the aged (21 month) group tended to be lower, compared to the other groups although no significant region-specific changes were evident. These results indicate neurochemical changes in somatostatin-containing neurons in the frontal cortex during aging.

Aging↗
PubMed1995

No association of JC virus with Alzheimer's disease or astrocytomas.

OBJECTIVES: To investigate if JC virus (JCV) can be involved in the pathogenesis of Alzheimer's disease (AD) and astrocytomas. STUDY DESIGN: A nested polymerase chain reaction (PCR) was used for the detection of JCV DNA in autopsy brain material (cerebral white matter) and cerebrospinal fluid (CSF) specimens from patients with AD and age-matched control patients without neurological diseases, together with biopsies from patients with astrocytomas (grades 3 and 4). Brain autopsy material from AIDS patients with progressive multifocal leukoencephalopathy (PML) was examined as positive control material. RESULTS: JCV DNA was detected by PCR in only one of the 17 brain autopsies from patients with AD, but in none of the 26 control patients without neurological diseases and in none of the 5 astrocytoma biopsies. JCV DNA was, however, detected in the brain material from two patients with PML. CONCLUSION: Our results show that JCV infection does not seem to be directly involved in the pathology of AD or in the development of astrocytomas. In addition, since no viral DNA was detected in CSF specimens from 43 patients without PML (17 with AD and 26 elderly controls), our results suggest that the finding of JCV DNA in CSF correlates to PML.

Journal Article↗
PubMed1995

Estradiol and testosterone in specific regions of the human female brain in different endocrine states.

Post-mortem concentrations of estradiol and testosterone were measured in 17 brain areas, serum and fat in 6 fertile and 5 postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of both steroids. The highest levels of estradiol and testosterone were noted in the hypothalamus, preoptic area and substantia nigra. These findings may assist in the interpretation of functional animal studies where the hypothalamus-preoptic area and the nigrostriatal dopamine system have proved to be target areas for estradiol. When compared to postmenopausal women, estradiol concentrations were significantly higher in the brains of fertile women, which indicates that peripheral serum levels of estradiol are reflected in the brain. This study has yielded information about steroid levels in different endocrine states and could provide a frame of reference for studies of estradiol and testosterone mediated effects on the central nervous system.

Adipose Tissue↗
PubMed1995

Influence of age and gender on skin vessel reactivity to endothelium-dependent and endothelium-independent vasodilators tested with iontophoresis and a laser Doppler perfusion imager.

BACKGROUND: The aim of this study was to evaluate the influence of age and gender on skin vessel reactivity to one endothelium-dependent vasodilator (acetylcholine, ACh), and two endothelium-independent vasodilators with different modes of action (nitroprusside and isoprenaline). METHODS: The substances were iontophoresed into the skin and the results were mapped through a newly developed laser Doppler perfusion imager. Thirty-four healthy, nonsmoking individuals without any medication and without atopic constitution participated in the study. The subjects, 13 men and 21 women, 18 to 80 years of age, were divided into subgroups according to age and gender. RESULTS: A correlation to age for the vascular responses to nitroprusside and, to a lesser extent, ACh was shown for the women (p = .0036 and .0920 respectively). Differences were also observed between the age and gender subgroups with respect to their response to these two substances: young and, to a lesser extent, middle-aged women differed from elderly women and middle-aged and elderly men. The response to isoprenaline was affected neither by age nor gender. CONCLUSIONS: The results of the study suggest that skin vessel reactivity to nitroprusside and, to a lesser extent, ACh is age dependent. This might reflect both functional and structural changes in skin vasculature with aging. Gender differences for these two substances are also suggested, with women exhibiting a greater increase in perfusion after iontophoresis than men. However, higher vasoconstrictor tone among the women may have influenced the results.

Acetylcholine↗
PubMed1995

The role of demographic and life style variables in utilizing cognitive support for episodic remembering among very old adults.

This research investigated the influence of individual difference variables within demographic and life-style domains on episodic recall tasks in which the level of cognitive support increased incrementally. The community-based sample consisted of 253 healthy older adults taken from the Kungsholmen parish in Stockholm, Sweden. Utilizing hierarchical regression procedures, two questions were addressed with regard to the selected individual difference variables: (a) the degree to which they could predict episodic recall and (b) whether they differentially influenced the magnitude of performance gains from the provision of cognitive support in the form of study time, item organizability, and retrieval cues. The results showed that age was negatively related to performance, whereas education and participation in social activities exerted a positive influence on performance. Exercise was also positively related to performance, but only in the least supported tasks. With regard to utilization of cognitive support, education was positively related to performance benefits from more study time and item organizability, age was negatively related to the effect of item organizability, and social activity was positively associated with the ability to benefit from retrieval cues. These results highlight the role of individual difference measures in episodic memory functioning in late adulthood and indicate that these variables are important in predicting the extent to which older adults are able to utilize cognitive support to enhance episodic recall.

Adaptation, Psychological↗
PubMed1995

Family burden in the care of the demented and nondemented elderly--a longitudinal study.

This study describes how the situation will change with time when a close relative cares for a demented or nondemented elderly. The changes over a period of time in cognitive and behavioral deterioration, perceived burden, and social support were examined in a population-based, longitudinal study. Spouses and adult children were interviewed at a 2.5-year interval. Although the support from social services had not increased, the relatives reported less burden and decreased behavioral problems in the demented elderly group. They also reported improved physical health. On the contrary, this long-term follow-up indicated a small increase in social limitation and deteriorated physical health in the group of relatives of mentally healthy elderly. One-third of the demented elderly were admitted to an institution during Time 1 and Time 2, and this may be one reason for the decreased burden.

Activities of Daily Living↗
PubMed1995

The use of medicines with anticholinergic effects in older people: a population study in an urban area of Sweden.

OBJECTIVE: To investigate the use of medicines with anticholinergic properties among older people in an urban population in Sweden. DESIGN: A cross-sectional survey. SETTING: Ordinary homes, sheltered accommodations, nursing homes, and geriatric departments. PARTICIPANTS: All residents aged 75 and older in a district of Stockholm, Sweden. MEASUREMENTS: Structured interviews with older persons, their relatives and/or health care personnel; prescription forms; medical records. RESULTS: The overall use of medicines with anticholinergic effects was comparatively low. Doses of these medicines were also generally low. Concurrent use of several such medicines was uncommon. The most prevalent therapeutic/pharmacological group was neuroleptics. In contrast, antidepressants were used by few older people. The prevalence of medicines with anticholinergic effects was highest at institutions, where neuroleptics were frequent and use of low-potency neuroleptics was not uncommon. CONCLUSION: Our results indicate that the risk of anticholinergic side effects may be quite low in the present population as a whole. However, there may be grounds for revising the therapy in institutions, where the use of neuroleptics was shown to be high and low-potency neuroleptics, known to have a higher incidence of anticholinergic side effects, were not avoided.

Age Factors↗
PubMed1995

Microsatellite D21S210 (GT-12) allele frequencies in sporadic Alzheimer's disease.

Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid precursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups.

Aged↗