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O Kosunen

Publications and source records attributed to O Kosunen.

11 recordsLinked to original sources
PubMed1995

A severe loss of choline acetyltransferase in the frontal cortex of Alzheimer patients carrying apolipoprotein epsilon 4 allele.

We measured the activities of choline acetyltransferase (ChAT) in the post mortem frontal cortex in 32 Alzheimer's disease (AD) patients with different apolipoprotein E (apoE) genotypes. The ChAT values were significantly lower for the AD patients with 2 epsilon 4 alleles than for those with 0 epsilon 4 (ANOVA, P < 0.05). The ChAT activities of AD patients carrying 2 or 1 epsilon 4 alleles and those without the epsilon 4 allele also differed significantly: 16.3 +/- 15.2 versus 30.5 +/- 20.6 pmol/mg protein per min, ANOVA, P < 0.05. However, the AD patients carrying the epsilon 4 allele were significantly younger than those with 0 epsilon 4 allele. The study indicates that AD patients carrying the epsilon 4 allele have a more severe cholinergic deficit than the AD patients without the epsilon 4 allele.

Aged↗
PubMed1995

Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer's disease.

We studied a synatophysin-like immunoreactivity in the hippocampal formation of patients with definite Alzheimer's disease, multi-infarct dementia, patients with no evidence of clinical dementia with neuropathological findings fulfilling the criteria of possible Alzheimer's disease, and age-matched nondemented controls. Possible Alzheimer's disease cases were of special interest because they were considered to represent early Alzheimer's disease. We also studied the spatial relationship of synaptophysin-like immunopositivity with amyloid-beta-protein immunopositive senile plaques and anti-paired helical filament immunopositive degenerating neurons locally as well as considering the intrinsic circuits in the hippocampal formation. The synaptophysin-like immunoreactivity was decreased in the hippocampus and the entorhinal cortex in patients with definite and possible Alzheimer's disease but not in multi-infarct dementia patients compared to controls. Equal loss of synapses in possible and definite Alzheimer's disease patients supports the hypothesis that synaptic loss is an early phenomenon in Alzheimer's disease. Unchanged synaptophysin-like immunopositivity in patients with multi-infarct dementia suggests that the loss of synapses is centrally involved in the pathogenesis of Alzheimer's disease and not dementia per se. There was no spatial correlation between loss of synapses and amyloid-beta-protein positive senile plaques. Moreover, we could not find a strict spatial relationship between senile plaques and degenerating neurons. Our results do not support the amyloid cascade hypothesis of Alzheimer's disease that local accumulation of amyloid-beta-protein leads to the loss of synapses.

Aged↗
PubMed1995

Relation of coronary atherosclerosis and apolipoprotein E genotypes in Alzheimer patients.

BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) epsilon 4 allele has been associated with a high risk for coronary heart disease. Increased frequency of the epsilon 4 allele has also been reported in patients with late-onset familial and sporadic Alzheimer's disease (AD). The aim of this study was to investigate the degree of coronary and cerebral atherosclerosis in a neuropathologically verified series of AD patients with different apoE genotypes. In addition, we studied the relationship between the degree of coronary and cerebral atherosclerosis and the extent of beta-amyloid (A beta) accumulation. METHODS: We studied 38 subjects (32 patients with definite AD and 6 age-matched control subjects) for whom postmortem autopsy delay was less than 8 hours. ApoE genotypes were identified through Hha I digestion of the polymerase chain reaction-amplified samples. We used A beta immunohistochemistry to detect diffuse and neuritic plaques as well as cerebrovascular amyloid. The degree of coronary and cerebral atherosclerosis was rated as none, mild, moderate, or severe. RESULTS: The apoE genotypes of the AD patients were epsilon 4/4 2, epsilon 3/4 19, epsilon 3/3 9, and epsilon 3/2 2. We found more severe atherosclerosis of the coronary vessels among AD patients with the apoE epsilon 4 allele compared with those AD patients without the epsilon 4 allele (chi 2 = 4.1, df = 1, P < .05). The extent of cerebral atherosclerosis did not differ among AD subgroups with and without the epsilon 4 allele. The degree of coronary or cerebral atherosclerosis was not related to the amount of amyloid accumulation in the frontal and temporal cortices or in the hippocampal structures. CONCLUSIONS: This study confirms the association of apoE epsilon 4 allele with coronary atherosclerosis in AD patients.

Aged↗
PubMed1994

beta-Amyloid protein immunoreactivity in skin is not a reliable marker of Alzheimer's disease. An autopsy-controlled study.

OBJECTIVES: As a possible diagnostic marker for Alzheimer's disease (AD), we investigated beta-amyloid protein (beta/A4) immunoreactivity in skin. Furthermore, we studied the presence of beta-amyloid precursor protein 695 immunoreactivity in skin. DESIGN: Lifetime skin biopsy specimens were stained for beta/A4 and beta-amyloid precursor protein 695. The follow-up period was 12 months. We determined the correlation between beta/A4 immunoreactivity in skin and brain in patients with a neuropathologic diagnosis. SETTING: All patients with dementia were hospitalized; most of them had moderate to severe dementia. Aged nondemented controls were residents of a nursing home. The Down's syndrome (DS) group included both hospitalized and ambulatory patients. Young nondemented controls were medical students or staff members who volunteered for the study. PATIENTS AND OTHER PARTICIPANTS: The study included a total of 111 subjects. Thirty-five patients had probable AD, nine had possible AD, 15 had multi-infarct dementia, one had idiopathic Parkinson's disease, and one had Parkinson's disease and possible AD. There were also 19 elderly nondemented controls, 23 patients with DS, and eight young nondemented controls. MAIN OUTCOME MEASURES: Immunohistochemical detection of beta/A4 in skin and correlation to the diagnosis of AD. RESULTS: Immunopositivity for beta/A4 antibody was present in and around the endothelium of dermal blood vessels in a proportion of patients with AD and multi-infarct dementia as well as elderly controls. The patients with sporadic AD displayed beta/A4 immunoreactivity significantly more frequently than did patients with familial AD, patients with multi-infarct dementia, and controls. The beta/A4 immunopositivity in skin was rare in the patients with DS and not present in young controls. Instead, 48% of patients with DS but none of other groups had beta-amyloid precursor protein 695 immunoreactivity in skin. Only four (31%) of 13 patients with neuropathologically confirmed AD had shown endothelial beta/A4 immunopositivity in skin biopsy specimens while alive. CONCLUSION: Our results do not support beta/A4 as a diagnostic marker for AD.

Aged↗
PubMed1992

Squamous cell carcinoma of the conjunctiva. Failure to demonstrate HPV DNA by in situ hybridization and polymerase chain reaction.

Squamous cell carcinoma of the conjunctiva is a distinct rarity, often arising at the corneoscleral limbus and initially resembling pterygium or chronic keratoconjunctivitis. In this paper we report 4 patients with conjunctival squamous cell carcinoma/carcinoma in situ, which comprise all the cases found in the files of Kuopio University Hospital during 1959-1991. The clinical appearance, diagnosis and treatment of the lesions are described. All biopsies were studied for the presence of Human papillomavirus (HPV) DNA (recently demonstrated in conjunctival squamous cell papillomas, precancer lesions and carcinomas) by using in situ DNA hybridization (ISH) and polymerase chain reaction (PCR). Both techniques failed to demonstrate the DNA of any of the following HPV types: HPV 6, 11, 16 and 18 in any of the lesions. The results are discussed in the light of the recently proposed HPV etiology of these lesions.

Adolescent↗
PubMed1990

Verrucous carcinoma of the anus containing human papillomavirus type 16 DNA detected by in situ hybridisation: a case report.

Verrucous carcinoma of the anus is a distinct and rare variant of well-differentiated squamous cell carcinoma. A case of anal verrucous carcinoma in a 35 year old man was studied by light microscopy and in situ DNA hybridization. Human papillomavirus (HPV) type 16 DNA sequences were demonstrated in the tumour cells, as well as in cells showing koilocytotic and dyskeratotic changes. The possible viral (HPV) aetiology of verrucous carcinoma is considered with a review of the previous literature.

Adult↗
PubMed1990

Potential of nuclear morphometry and volume-corrected mitotic index in grading transitional cell carcinoma of the urinary bladder.

The potential of nuclear morphometry and volume-corrected mitotic index (M/V index) in grading cases of transitional cell carcinoma of the urinary bladder was studied. 30 cases of bladder cancer including all three WHO grades were evaluated. Four investigators selected independently the most atypical field from paraffin sections, and one investigator measured the nuclear areas from these fields using the IBAS 1&2 image analyzer system. Following the same sampling rule, four investigators counted the mitotic figures per area of neoplastic tissue in the microscopic image at an objective magnification of X40. The mean nuclear areas covered values from 28.1 to 139.0 microns 2 (mean +/- SD 57.2 +/- 18.9). The total variance of measurements was 359.1 and the mean variance between corresponding fields 110.2 (about 30% of the total variation). The efficiency was evaluated by estimating the fraction of falsely classified cases. Instrumental morphometry of nuclear area in a three-grade system gave an efficiency of 79% and of 90%, in a two-grade system. The M/V index varied from 0 to 54 (mean +/- SD 12.3 +/- 10.9). The total variance was 119.8 and the methodological variance 15.5 (about 13% of total variance). In a three-grade system this would correspond to an efficiency of about 75%; in a two-grade system the efficiency would be 88%. The results suggest that nuclear area and M/V index estimates constitute efficient grading systems in bladder carcinoma.

Carcinoma, Transitional Cell↗
PubMed1990

Ultrasonographic detection of metastatic axillary lymph nodes in breast cancer.

Metastatic involvement of the axillary lymph nodes is the most important prognostic factor in breast cancer. Preoperative knowledge of lymph node status would be useful in planning the therapy for breast cancer. The aim of our study was to find how accurately metastatic lymph nodes can be detected with ultrasonography (US). Our study consisted of 63 breast cancer patients having 65 breast cancers. Their axillae were examined preoperatively with US (with a 7.5 Mhz linear-array transducer). 27.7% of these patients had metastatic axillary lymph nodes. With US we could detect 12 of these 18 axillary metastases. In 2 of our 6 false negative results only micrometastases were found on histological examination. In our study the sensitivity of US was 66.6%. There was only one axilla, in which nodes were detected with US, but on histological examination no metastases were found, thus giving a specificity of 97.9%. Our study indicates that in the axilla normal nodes are not visible with US.

Adult↗
PubMed1987

Sampling in diagnostic morphometry: the influence of variation sources.

The variation sources relevant to a diagnostic morphometric study were analysed. The influence of each source was estimated in two experiments, performed in systems applying computer assisted interactive morphometry. In the first experiment one observer measured the areas of a large number of nuclei in a section from a grade II transitional cell carcinoma of the bladder. In the second experiment two groups of researchers, from Ancona and Kuopio, measured one field from five different samples of transitional cell tumours (including the case of grade II carcinoma). It turned out that pure interobserver variation was responsible for about a half of the total variation present in the diagnostic system. When the variation characteristics of the diagnostic system had been determined, the number of nuclei that had to be measured to reach a defined level of accuracy could be estimated. Such an estimate was also dependent on the predefined expectancy probability of reaching a correct estimate. The study showed that group morphometry (statistical, investigative morphometry) and diagnostic morphometry must be understood as two different approaches in histopathology. By applying group morphometry, good research results can be gathered with cruder measurements than in diagnostic morphometry. Because investigations in group morphometry are more standardized than in diagnostic morphometry, a larger number of structures has to be measured in diagnostic histopathology for the same level of accuracy.

Analysis of Variance↗
PubMed1986

Observer variation in interactive computerized morphometry.

The validity of a test system in morphometric histopathology depends on the variation sources involved. Biological variation is one of the variation sources, but is also the object to be studied with morphometry. We studied the variation sources in interactive computerized morphometry in two test systems involving two different commercially available image analyzers. The measurements were made on nuclei in a microscopic field of 5 transitional cell tumors (papilloma and WHO grade I-III carcinomas) of the urinary bladder. It turned out that different observers selected a variable number of nuclei for measurements, the coefficient of variation (CV) in the number of nuclei being 11-11.5%. Mean CV in nuclear perimeter measurements was 4.4-4.8%, and in nuclear area measurements 8.2-8.6%. The variation in measurements by 1 observer was smaller, the CV values being 2.8% for the number of nuclei, 1.2% for nuclear perimeter, and 2.4% for nuclear area. The results showed that interobserver variation can be considerable in these systems. It is suggested that special sampling rules should be tested with the idea of finding the relevant approach with the smallest interobserver variation.

Carcinoma, Transitional Cell↗