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Biomedical subjects

P Karhunen

Publications and source records attributed to P Karhunen.

18 recordsLinked to original sources

A novel frozen brain tissue array technique: immunohistochemical detection of neuronal paraneoplastic autoantibodies.

We introduce a modification of the tissue microarray technique in which several frozen brain tissue specimens are collected to a single frozen brain array block. In the present application, we use it for the detection of neuronal paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different brain regions were collected according to a standard neuropathological autopsy protocol. Cryostat sections from each block were cut and conventionally stained. From representative areas, cylinder tissue samples from each specimen were punched and then arrayed into a recipient array block. Using the cryostat sections of this brain array, autoantibodies from seven anti-Hu-positive patient sera (confirmed by immunoblotting) were screened by immunohistochemistry. Neuronal architecture was well preserved and immunohistochemical staining was comparable to that of conventional cryostat sections. Because of the variable staining pattern in different brain areas, two anti-Hu-positive sera could be detected immunohistochemically by the one brain array. With the present array technique, it is possible to characterize the variable staining patterns of neuronal paraneoplastic autoantibodies in different locations of the human brain. The frozen brain array also allows the detection of RNA and DNA targets involved in neurological diseases.

Aged↗

Apolipoprotein E epsilon4 allele frequency is increased in Parkinson's disease only with co-existing Alzheimer pathology.

We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson's disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: "O + A", with no or only uncertain histological findings of AD, and "B + C" with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apo epsilon4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apo epsilon4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2-5.2). In the O + A group, the frequency of apo epsilon4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apo epsilon4 allele was not increased (odds ratio 0.94). The PD cases with an apo epsilon4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apo epsilon4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apo epsilon4 allele frequency.

Aged↗

Asbestos exposure among Finnish lung cancer patients: occupational history and fiber concentration in lung tissue.

In a series of 65 surgically treated lung cancer patients, past exposure to asbestos was evaluated by personal interviews, and by scanning electron microscopy analyses of the mineral fibers in lung tissue. Lung tissue samples of 17 autopsied male office workers were analyzed as referents. According to occupational history, 37% of the lung cancer patients had definite or probable, 31% possible, and 32% unlikely exposure to asbestos. The fiber concentration in the lung tissue ranged from < 0.1 to 65 million fibers per gram dry tissue in the lung cancer group, and from < 0.1 to 0.8 million fibers per gram dry tissue in the reference group. In 26% of the lung cancer patients, but in none of the referents, the fiber concentration exceeded 1 million fibers per gram dry tissue. Most of the exposed patients had been employed in various construction jobs, and valuable information about the exposure levels could be obtained by the mineral fiber analyses. In general, there was a good accord between the exposure categorization and the fiber burden measured in the lung.

Adenocarcinoma↗

Relative risk of mesothelioma associated with different levels of exposure to asbestos.

The relative risk of mesothelioma associated with different levels of exposure to asbestos was evaluated. The exposure was assessed from work histories of 51 mesothelioma cases and 51 sarcoidosis referents. The lung fiber concentration of the mesothelioma patients was compared with that of two reference groups (13 random autopsy cases and 43 male lung cancer patients). When the categories definite and probable were used as an estimated probability of occupational exposure, an odds ratio of 17.7 [90% confidence interval (90% CI) 3.4-253] and 3.0 (90% CI 0.9-10.6), respectively, was obtained. A lung fiber concentration of greater than 1 million fibers/g of dry tissue as an indicator of accumulated exposure gave an odds ratio of 14.4 (90% CI 2.5-178) for the men in comparison with the autopsy cases and 3.1 (90% CI, 1.3-7.5) in comparison with the lung cancer patients. Elevated risk of mesothelioma was shown to be associated with a lung fiber concentration of greater than 1 million fibers/g of dry tissue.

Adult↗

Failure of TRH and ORG 2766 hexapeptide to counteract alcoholic inebriation in man.

The actions and interactions of alcohol (1.5 g/kg) and two stimulant peptides were investigated in healthy volunteers. Double blind and cross over studies in 8 subjects, at one-week intervals, revealed that ORG 2766 (5 or 20 mg i.m.) and particularly TRH (10 micrograms/kg i.v.) enhanced rather than antagonized alcohol-induced inebriation. The interactions were associated with elevated breath alcohol concentrations. Similar studies with 8 other subjects showed that peptides given in combination with a non-alcoholic drink tended to impair performance assessed as various psychophysiological variables. However, ORG 2766 5 mg was subjectively rated as producing a feeling of improved performance.

Adrenocorticotropic Hormone↗

Fibroblast markers in labial salivary gland biopsies in progressive systemic sclerosis.

Labial salivary gland (LSG) biopsies from 13 patients were studied. Three were normal glands, five showed fibrosis induced by progressive systemic sclerosis (PSS) and five more had PSS-induced fibrosis combined with and focal sialadenitis compatible with Sjögren's syndrome (SS). Monoclonal antibodies to proline-4-hydroxylase (alpha PH or 5B5-A) and the carboxyterminal domain of human type I procollagen (alpha pC or M-38) were used as fibroblast markers. Immunostaining was done with avidin-biotin-peroxidase complex (ABC). Using various sample controls (including cultured fibroblasts and specimens enriched for lymphocytes, plasma cells, granulocytes, monocytes and dendritic cells) as well as analysis of various LSG resident cells, the specificity of the alpha PH and alpha pC markers for fibroblasts was established. Cross reactions were only seen with plasma cells and acinar cells containing the beta subunit of PH or disulfide isomerase involved in SS-SH interchange reactions in these secretory cells. All fibroblasts in fibroblast monolayer cultures at their logarithmic phase of growth stained with the fibroblast markers studied, but false negative staining was seen with resting, mature fibroblasts in dense connective tissue in LSG sections. Therefore, it can be concluded that proline 4-hydroxylase and the COOH-terminal domain of type-I procollagen both indicate fibroblast involvement in collagen (type l) synthesis and thus identify active but not resting fibroblasts. PH+ fibroblast-like cells and pC+ fibroblasts were both more frequent in PSS LSGs than in normal glands, suggesting active local fibroblast involvement in PSS.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗