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I Alafuzoff

Publications and source records attributed to I Alafuzoff.

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

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PubMed1991

Regional distribution of somatostatin receptor binding and modulation of adenylyl cyclase activity in Alzheimer's disease brain.

We have previously reported a reduction in the inhibitory effect of somatostatin on adenylyl cyclase activity in the superior temporal cortex of a group of Alzheimer's disease cases, compared to a group of matched controls. In the present study, the levels of high affinity 125I-Tyr11-somatostatin-14 binding, its modulation by guanine nucleotides and the effects of somatostatin on adenylyl cyclase activity have been measured in preparations of frontal cortex, hippocampus, caudate nucleus and cerebellum from the same patient and control groups. A significant reduction in 125I-Tyr11-somatostatin-14 binding was observed in the frontal cortex, but not other regions, of the Alzheimer's disease group, compared with control values. The profiles of inhibition of specific 125I-Tyr11-somatostatin-14 binding by Gpp(NH)p were similar in all regions in both groups. No significant differences in basal, forskolin-stimulated, or somatostatin and neuropeptide Y inhibitions of adenylyl cyclase activity were found between the two groups. The pattern of change of somatostatin binding in the Alzheimer's disease cases observed in the present study differs from the reported pattern of loss of somatostatin neurons and may be secondary to the degeneration of somatostatin receptor-bearing cholinergic afferents arising from the nucleus basalis. The results of this study indicate that impaired somatostatin modulation of adenylyl cyclase is not a global phenomenon in Alzheimer's disease brain and also that there are no major disruptions of somatostatin receptor-G-protein coupling or of adenylyl cyclase catalytic activity in this disorder.

Adenylyl Cyclases↗
PubMed1991

Granulomatous peritonitis and appendicitis of food starch origin.

Two patients with food starch granulomatous reactions, one a necrotising granulomatous peritonitis after the perforation of a gastric ulcer and the other a non-necrotising granulomatous appendicitis, are described. The possibility of food starch induced inflammation must be considered in the differential diagnosis of granulomatous diseases of the gastrointestinal tract.

Adult↗
PubMed1990

Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.

The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.

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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.

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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.

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PubMed1988

Nutritional status in patients with acute stroke.

By measuring three anthropometric variables (relative weight, triceps skinfold thickness and arm muscle circumference) and three circulating proteins (albumin, transferrin and prealbumin), nutritional status was assessed in 100 consecutive patients with acute stroke. On admission to hospital, two or more indicators showed subnormal values for 16%; this was associated with the female sex, high age and a history of atrial fibrillation. At discharge, 22% had two or more subnormal indicators. Poor nutritional status during the hospital stay appeared to be related to infections, the male sex, the intake of cardiovascular drugs and high age. Fewer of the patients with two or more subnormal nutritional indicators were able to return home than of the patients with none or one subnormal nutritional indicator. We conclude that undernutrition is not uncommon at the onset of stroke and that certain risk groups for the development of undernutrition during hospital stay can be identified.

Acute Disease↗
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)

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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↗
PubMed1986

Muscarinic receptor subtypes in hippocampus in Alzheimer's disease and mixed dementia type.

The relative proportion of super-high, high and low affinity agonist binding sites was measured in the hippocampus from individuals with dementia of the Alzheimer type (AD/SDAT), mixed (AD-MID) type and controls, using labelled quinuclidinyl benzilate ([3H]QNB) competing with unlabelled carbachol. A significant reduced number of [3H]QNB binding sites was obtained in dementia groups. A significant decrease in the proportion of super-high affinity agonist (V1) binding sites was found in the AD-MID group compared to controls while no change was found in the AD/SDAT group. The affinity constant (K1) for the V1 site was also significantly lower in the AD-MID group compared to controls.

Aged↗
PubMed1986

Defective brain microtubule assembly in Alzheimer's disease.

Brains obtained within 2-4 hours post mortem and histopathologically confirmed for Alzheimer's disease and non-Alzheimer brains from age-matched controls were examined for in-vitro assembly of microtubules and neurofilaments. Microtubule assembly was observed only in control but not in Alzheimer brains, and neurofilaments were obtained from both types of brain. The microtubule-associated protein tau, which stimulates assembly of microtubules from tubulin, was abnormally phosphorylated in Alzheimer but not in control brain microtubule preparations. Alzheimer brains did not show the presence of any inhibitor of microtubule assembly or any abnormality of tubulin. DEAE-dextran, a polycation which mimics tau in stimulating microtubule assembly, induced the assembly of microtubules in Alzheimer brain. Tubulin from both normal and Alzheimer brains was labelled on western blots by a monoclonal antibody to the tyrosinylated carboxy-terminal epitope of alpha tubulin. These studies suggest that in Alzheimer's disease tubulin can be assembled into brain microtubules, but the process is defective, probably because of abnormal phosphorylation of tau. This post-translational alteration of tau might be the cause of the neurofibrillary abnormality in Alzheimer's disease.

Aged↗
PubMed1986

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↗
PubMed1985

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↗