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Biomedical subjects

I Alafuzoff

Publications and source records attributed to I Alafuzoff.

83 records · Page 5Linked to original sources

Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multi-infarct dementia.

Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from age-matched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.

Brain Chemistry↗

Blood components in an elderly population.

The reference intervals of 18 blood components were established for an elderly population in the 8th decade of life. The most significant findings were a broader range of values for most of the components, lower values of plasma folate and plasma potassium and higher values of erythrocyte sedimentation rate, plasma creatinine and serum cholesterol, the lattermost in women only, compared to younger people.

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Muscarinic receptor compensation in hippocampus of Alzheimer patients.

The activity of the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) (presynaptic marker) and number of muscarine-like receptor binding sites have been measured in the hippocampus from eight individuals with senile dementia of Alzheimer type (SDAT) and ten controls. A negative correlation (r = 0.80; p less than 0.05) was found between the ChAT activity and the number of muscarine-like receptors in the SDAT group but not in the controls. The findings might indicate an ongoing compensatory receptor mechanism as a response to changes in presynaptic cholinergic activity.

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Selegiline treatment and the extent of degenerative changes in brain tissue of patients with Alzheimer's disease.

BACKGROUND: A beneficial effect of selegiline (L-deprenyl) in Alzheimer's disease (AD) has been reported in several clinical studies. METHODS: The brain tissue from 17 deceased patients, members of a double-blind clinical trial to assess the potential benefit of selegiline in AD, were analysed. FINDINGS: In our study, the decrease in the Mini-Mental State Examination (MMSE) scores during the progress of the disease had been significantly influenced by selegiline treatment. Prior to death, the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo. However, according to our results, none of the lesions critical for AD diagnosis, such as counts of senile/neuritic plaques, neurofibrillary tangles or beta-A4 load, were influenced by the selegiline treatment. INTERPRETATION: In conclusion, according to our study, mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment, leading to the functional benefit found in AD.

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Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia.

Plasma and cerebrospinal fluid (CSF) from 20 patients with Alzheimer's dementia or senile dementia of Alzheimer type (AD/SDAT), 23 with multi-infarct dementia (MID) and 16 controls were assayed for their content of immunoglobulins (Ig) and albumin (Alb). The concentrations of IgG and Alb were used to analyze the blood-CSF barrier function in the respective group. MID patients had significantly (P less than 0.001) elevated plasma IgG levels compared to controls and AD/SDAT patients. CSF concentration of Alb was significantly higher in MID (P less than 0.01) and AD/SDAT (P less than 0.05) patients compared to the controls. Concentration of CSF IgG was significantly (P less than 0.05) lower in AD/SDAT patients compared to the MID patients; no significant differences were found when CSF concentrations of IgG of demented patients were compared to controls. These findings may indicate a blood-CSF barrier dysfunction especially in cases with MID with significantly (P less than 0.001) elevated values of transudation. Also these findings indicate a non-specific and/or specific binding of IgG in CNS tissue and/or vessel walls in both forms of dementia on the basis of low IgG ratios compared to proportionally higher Alb ratios. There were no signs of local synthesis of IgG in CNS in either group of demented patients.

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Calpain and calpastatin in normal and Alzheimer-degenerated human brain tissue.

The Ca2(+)-dependent neutral proteases calpain I and II as well as their specific inhibitor, calpastatin, were isolated from normal and Alzheimer-degenerated frozen human brain tissue. In the Alzheimer group calpain I activity was higher in cortex than in mesencephalon. The calpastatin activity was lower in cortex in both groups. This may implicate a higher Ca2(+)-dependent proteolysis in cortex compared to mesencephalon. In the Alzheimer group the cortical calpain II level decreased with an increasing degree of neuropathological changes. In the control group, the level of calpastatin decreased as the number of plaques and tangles increased. Evidence was obtained for a correlation of net calpain activity and the extent of neuropathological changes in cortex.

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Astrogliosis and the ApoE genotype. an immunohistochemical study of postmortem human brain tissue.

Significantly increased glial fibrillary acidic protein (GFAP) expression was seen in postmortem brain tissue from demented patients with Alzheimer's disease (AD) (73 cases, 61 females/12 males, mean age 84 +/- 9 years) compared to controls (22 cases, 10 females/12 males, mean age 78 +/- 9 years). In demented patients, the GFAP expression, counts of AD lesions, senile/neuritic plaques (SP/NP) and neurofibrillary tangles (NFT) were higher in patients carrying the apolipoprotein E (ApoE) epsilon4 allele compared to those without the ApoE epsilon4 allele. The astrogliosis correlated significantly with the counts of NFT in demented patients both with and without the ApoE epsilon4 allele. Furthermore, the astrogliosis correlated significantly with the counts of SP/NP, but this correlation, however, was influenced by the ApoE epsilon4 allele, being significant only in those cases without the ApoE epsilon4 allele. Our results demonstrate that not only the extent of AD lesions and GFAP expression, but also the relationship between AD lesions and the GFAP expression is influenced by the ApoE epsilon4 allele.

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Intact brain serotonin system in vascular dementia.

Pre- and postsynaptic elements of the 5-hydroxytryptamine (5-HT, serotonin) system were studied in a control group and in patients with vascular dementia (VAD). The 5-HT uptake site was used as a presynaptic marker for 5-HT terminals and 5-HT1A and 5HT2 receptors were used as postsynaptic markers. The binding sites were quantified with radioligand binding techniques, where the radioligands used were [3H]paroxetine, [3H]8-OH-DPAT and [3H]ketanserin, respectively. The presynaptic uptake site was studied in frontal and temporal cortices and caudate nucleus. 5-HT1A and 5-HT2 receptors were studied only in frontal and temporal cortices. There were no differences between control and VAD groups in any of the regions investigated with respect to the number of binding sites (Bmax) and binding affinity (Kd). This indicates that both pre- and postsynaptic parts of the 5-HT system are intact in these brain areas in VAD.

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

Rapidly progressive multifocal leukoencephalopathy with substantial cell-mediated inflammatory response and with cognitive decline of non-Alzheimer type in a 75-year-old female patient.

Autopsy findings of rapidly progressive and widespread multifocal leukoencephalopathy (PML) in a 75-year-old woman with no known predisposing disease are demonstrated. Originally she was given a clinical working diagnosis of syndrome of progressive supranuclear palsy (PSP). The neuropathological investigation revealed widespread white and gray matter changes consistent with PML, and the JC virus was verified by EM, in situ hybridization and immunohistochemistry. In contrast to the few chronic inflammatory cells generally seen in PML in this case there was a substantial cell-mediated inflammatory response reflected in numerous T-helper and T-killer cells. The uncommon, widespread distribution of lesions and substantial cell-mediated response reported might indicate that the rearrangement of viral genome, previously suggested of importance for viral growth in the central nervous system (CNS), is also important for viral spread within the CNS, infectivity of glial cells and for the activation of cell-mediated immunity.

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Castleman's disease of the leptomeninges--immunohistochemical findings in 2 cases.

OBJECTIVE: Castleman's disease is an uncommon benign lymphoproliferative disorder that arises in lymph nodes. Few cases of Castleman's disease affecting the central nervous system have been described. CASE HISTORY: We report 2 new cases of Castleman's disease confined solely to the leptomeninges. The patients were referred to neurosurgery with presumptive clinical diagnosis of meningiomas. Histological investigation of the operative specimens taken from the abnormal leptomeninges revealed nodular lymphoid areas with multiple germinal centers surrounded by concentrically layered proliferations of small lymphocytes. Histologically, these 2 cases fulfilled the classification criteria for the mixed and for the hyaline-vascular type of Castleman's disease. The immunohistochemical analysis revealed a polyclonal B cell proliferation in the lesions with perifollicular T cell proliferation with the T helper cell predominance. CONCLUSIONS: The authors conclude that Castleman's disease involving the leptomeninges have a similar immunological pattern reported for the disease in extracranial locations and that, though being rare, Castleman's disease should be considered as a differential diagnosis when dealing with mass lesions of leptomeninges.

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Protein p62 common in invaginations in benign meningiomas--a possible predictor of malignancy.

OBJECTIVE: It is known that p62 is a cytosolic conserved protein that binds non-covalently to ubiquitin. Expression of p62 has been seen in inclusions in neoplasias like hepatocellular and breast carcinomas but also in neuronal inclusions of degenerative brain disorders. Dysfunction of ubiquitin system leads to presence of p53 in cells suggested to be a predictor of future recurrence of meningioma. MATERIAL: The study material included 45 benign meningiomas of postmenopausal women operated in Kuopio University Hospital between 1994 and 2002. METHODS: Patterns of p62 immunopositivity in meningiomas was evaluated and the results were correlated to clinical and histological parameters. RESULTS: Constant p62 labeling in at least each field measuring 1 mm in diameter was detected consisting of 5 different patterns. The most common labeling was seen in nuclear invaginations either as grains or homogenous labeling, followed by Marinesco like nuclear inclusions or rode like inclusions outside the invagination. In some cases cytoplasmic granular staining was seen. No correlation between different p62 patterns or extent of p62 expression, histological subtypes or proliferation marker Ki-67 was noted. CONCLUSION: Our results indicate that in the benign not recurrent meningiomas, signs of functioning proteosomal system, can be detected using the p62 labeling. The function of proteosomal system in malignant and specifically invasive meningiomas needs to be further elucidated.

Adaptor Proteins, Signal Transducing↗