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43 records – page 1 of 5.

Aberrant p53 protein expression in cervical intra-epithelial neoplasia.

https://arctichealth.org/en/permalink/ahliterature23877
Source
Histopathology. 1993 Nov;23(5):471-4
Publication Type
Article
Date
Nov-1993
Author
R. Pöllänen
Y. Soini
K. Vähäkangas
P. Pääkkö
V P Lehto
Author Affiliation
Department of Pathology, University of Oulu, Finland.
Source
Histopathology. 1993 Nov;23(5):471-4
Date
Nov-1993
Language
English
Publication Type
Article
Keywords
Cervical Intraepithelial Neoplasia - metabolism - microbiology
DNA, Viral - genetics - isolation & purification
Female
Gene Expression
Genes, p53
Humans
Mutation
Papillomavirus, Human - genetics - isolation & purification
Precancerous Conditions - genetics - metabolism - microbiology
Research Support, Non-U.S. Gov't
Tumor Suppressor Protein p53 - genetics - metabolism
Uterine Cervical Neoplasms - genetics - metabolism - microbiology
Abstract
We investigated aberrant p53 expression in 81 cases of cervical intra-epithelial neoplasias (CIN) using a polyclonal antibody CM-1. The presence of human papillomavirus (HPV) DNA was evaluated by in situ and dot blot hybridization. Significant (more than 1% of cells positive) p53 positivity was found in three cases (4%) of which only one contained HPV DNA. In an additional nine cases, occasional p53 staining was found in basal epithelial cells, frequently associated with epithelial hyperplasia and increased subepithelial inflammation. The results show that aberrant p53 expression is an infrequent finding in CIN lesions. It can be seen in lesions both with and without HPV infection. Most importantly, there was no p53 expression in most cases of HPV-negative CIN, suggesting that p53 inactivation is not an obligatory step in the development of cervical dysplasia. However, our findings do not exclude the possibility that p53 mutations can occur later in the course of cervical carcinogenesis.
PubMed ID
8314222 View in PubMed
Less detail

Absence of p53 mutations in benign and pre-malignant male genital lesions with over-expressed p53 protein.

https://arctichealth.org/en/permalink/ahliterature21534
Source
Int J Cancer. 1998 Aug 31;77(5):674-8
Publication Type
Article
Date
Aug-31-1998
Author
K. Castrén
K. Vähäkangas
E. Heikkinen
A. Ranki
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Int J Cancer. 1998 Aug 31;77(5):674-8
Date
Aug-31-1998
Language
English
Publication Type
Article
Keywords
Biopsy
Bowen's Disease - genetics - pathology
Carcinoma in Situ - genetics - pathology
Carcinoma, Squamous Cell - genetics - pathology
Condylomata Acuminata - genetics - pathology
Exons
Female
Genes, p53
Genital Diseases, Male - genetics - pathology - surgery
Genital Neoplasms, Male - genetics - pathology - surgery
Humans
Male
Mutation
Papillomavirus, Human - isolation & purification
Precancerous Conditions - genetics - pathology - surgery
Research Support, Non-U.S. Gov't
Skin Neoplasms - genetics - pathology
Tumor Suppressor Protein p53 - biosynthesis
Uterine Cervical Neoplasms - genetics
Vulvar Neoplasms - pathology
Abstract
Mutations of the tumor-suppressor gene p53 are common in epithelial tumors. Clonal mutations of p53 have been found in cervical and vulvar carcinomas negative for human papillomavirus (HPV), though at least in cervical cancer HPV infection and p53 mutations are not mutually exclusive. We have previously shown that about 40% of male genital warts and bowenoid papulosis lesions exhibit immunohistochemically detectable aberrant p53 protein, irrespective of the presence of HPV DNA. We studied p53 mutations in exons 4-8 with SSCP and sequencing in 13 male patients with 1 to 3 therapy-resistant genital warts or intra-epithelial neoplasias each and in 4 patients with penile squamous cell carcinoma. Thus, 13 genital warts, 6 bowenoid papulosis, 1 Queyrat's erythroplasia and 1 carcinoma in situ were studied. p53 protein was detected immunohistochemically, and HPV status was analyzed with DNA in situ hybridization and amplification of HPV-specific DNA. There was no correlation between p53 protein expression and HPV status. No mutations in exons 5-8 of the p53 gene were found in any of the lesions, and furthermore, no exon 4 mutations were found in lesions positive in p53 immunohistochemistry. In conclusion, overexpression of p53 does not indicate a p53 mutation in male genital warts, pre-malignant lesions or malignant squamous cell carcinomas. Our study thus suggests that p53 mutations are not important, or at least not early, events in male genital carcinogenesis.
PubMed ID
9688297 View in PubMed
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Ambient and biological monitoring of exposure to polycyclic aromatic hydrocarbons at a coking plant.

https://arctichealth.org/en/permalink/ahliterature208158
Source
Sci Total Environ. 1997 Jun 20;199(1-2):151-8
Publication Type
Article
Date
Jun-20-1997
Author
L. Pyy
M. Mäkelä
E. Hakala
K. Kakko
T. Lapinlampi
A. Lisko
E. Yrjänheikki
K. Vähäkangas
Author Affiliation
Oulu Regional Institute of Occupational Health, Finland. lpyy@occuphealth.fi
Source
Sci Total Environ. 1997 Jun 20;199(1-2):151-8
Date
Jun-20-1997
Language
English
Publication Type
Article
Keywords
Air Pollutants, Occupational - analysis
Benzo(a)pyrene - adverse effects
Biological Markers - urine
Chromatography, High Pressure Liquid
Coke
Dust - analysis
Environmental Monitoring - methods
Finland
Humans
Longitudinal Studies
Mutagens - adverse effects - analysis - metabolism
Occupational Exposure
Polycyclic Hydrocarbons, Aromatic - urine
Pyrenes - analysis - metabolism
Reference Standards
Regression Analysis
Abstract
The exposure to polycyclic aromatic hydrocarbons (PAH) was measured in a Finnish coking plant over a 7-year period (1988-1994), since the beginning of production. Hygienic measurements including dust and vapour sampling were performed and the correlations between the concentrations of airborne pyrene with the levels of pyrene metabolite 1-pyrenol in urine were calculated. The profile of measured 12 or 15 PAHs was very similar between mean concentrations of personal samples, which suggests that it is possible to calculate the concentrations of total PAH by using e.g. pyrene as a marker compound. Measurements suggest that the progress of working conditions has been very favourable because the mean exposure level of shift workers to benzo[a]pyrene has decreased from 2.5 micrograms/m3 to 0.3 micrograms/m3. This points to successful measures of technical prevention. The mean concentration of 1-pyrenol in urine has been 0.2-0.6 mumol/mol creatinine. The concentration increases slightly towards the end of the working day, but the correlation urinary pyrenol and air pyrene was weak. Therefore the usefulness of pyrenol level for predicting the pyrene concentration at low exposure level in the ambient air is very limited.
PubMed ID
9200858 View in PubMed
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An examination of whether human placental perfusion allows accurate prediction of placental drug transport: studies with diazepam.

https://arctichealth.org/en/permalink/ahliterature63401
Source
J Pharmacol Toxicol Methods. 2002 Nov-Dec;48(3):131-8
Publication Type
Article
Author
P. Myllynen
K. Vähäkangas
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland. paivi.k.myllynen@oulu.fi
Source
J Pharmacol Toxicol Methods. 2002 Nov-Dec;48(3):131-8
Language
English
Publication Type
Article
Keywords
Anticonvulsants - blood - pharmacokinetics
Antipyrine - blood - pharmacokinetics
Chromatography, High Pressure Liquid
Comparative Study
Diazepam - blood - pharmacokinetics
Female
Humans
Hydrogen-Ion Concentration
Maternal-Fetal Exchange
Perfusion
Placenta - metabolism
Pregnancy - blood
Reference Standards
Time Factors
Abstract
INTRODUCTION: Presently, no well-validated predictive tools are available for human placental transfer. We studied the transplacental passage of diazepam (DZP) in a recirculating dual human placental perfusion and compared the data with in vivo clinical data from the literature. METHODS: Term placentas from healthy mothers without medication were used. The dual, recirculating perfusion technique was used. DZP (2 microg/ml, n = 4; 200 ng/ml, n = 3) and the reference compound antipyrine (100 microg/ml) were added into the maternal circulation simultaneously. The disappearance of drugs from the maternal circulation and appearance into the fetal circulation were followed every 15 min for 2 h. RESULTS: DZP was detectable in the fetal circulation within 15 min in all of the perfusions indicating rapid transfer. DZP concentrations in the maternal circulation were higher than in the fetal circulation throughout the perfusion with both initial concentrations. At the end of the perfusion, the feto-maternal ratio was 0.48 +/- 0.11 (mean +/- S.D.) and the transfer from the maternal to the fetal compartment 18.4 +/- 3.6% with 2 microg/ml of DZP and 0.55 +/- 0.10 and 20.5 +/- 3.1% with 200 ng/ml of DZP, respectively. DZP concentrations in the perfused area of the placenta were in average 2 times higher than in the maternal perfusate and 3.6 times higher than in the fetal perfusate. Total recovery of DZP from samples, perfusion fluid, and perfused tissue was 37.6 +/- 21%. DISCUSSION: Since animal studies in vivo do not accurately predict human placental transfer and it is problematic to study placental transfer of drugs in humans in vivo, the present human placental perfusion system could serve as one part of a test battery for fetotoxicity. However, although our earlier studies and those from the literature indicate a good correlation between in vivo and placental perfusion data, the present study shows this is not the case for all drugs.
PubMed ID
14986861 View in PubMed
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Apoptosis in operated small cell lung carcinoma is inversely related to tumour necrosis and p53 immunoreactivity.

https://arctichealth.org/en/permalink/ahliterature22201
Source
J Pathol. 1997 Feb;181(2):172-7
Publication Type
Article
Date
Feb-1997
Author
A K Eerola
U. Törmänen
P. Rainio
R. Sormunen
R. Bloigu
K. Vähäkangas
V P Lehto
Y. Soini
P. Pääkkö
Author Affiliation
Department of Pathology, University of Oulu, Finland.
Source
J Pathol. 1997 Feb;181(2):172-7
Date
Feb-1997
Language
English
Publication Type
Article
Keywords
Apoptosis
Carcinoma, Small Cell - metabolism - pathology - surgery
Cell Division
Humans
Immunoenzyme Techniques
Lung Neoplasms - metabolism - pathology - surgery
Necrosis
Neoplasm Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Research Support, Non-U.S. Gov't
Tumor Suppressor Protein p53 - metabolism
Abstract
The present study was undertaken to analyse the extent of apoptosis in operated small cell lung carcinoma (SCLC) by using in situ labelling of the oligonucleosomal DNA fragments by terminal transferase. The extent of apoptosis was compared with the cell proliferation activity, as determined by Ki-67 immunohistochemistry; with the volume density of necrosis (per cent), as determined by the morphometric point counting method; and with the occurrence of immunohistochemically detectable p53 and bcl-2 proteins. By in situ labelling, remarkably high apoptotic indices (from 0.08 to 8.10 per cent) were seen in SCLC. A high percentage of SCLSs also showed an exceptionally high proliferation activity. Aberrant accumulation of p53 protein was seen in 37.5 per cent and bel-2 overexpression in 50 per cent of SCLCs. Necrosis was seen in 82.5 per cent of SCLCs. The extent of apoptosis was inversely related to the extent of tumour necrosis (P = 0.05) and to p53 protein accumulation (P = 0.008). A positive association was found between the extent of apoptosis and bel-2 immunoreactivity (P = 0.02). The apoptotic indices (per cent) correlated with the age (P
PubMed ID
9120721 View in PubMed
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Assessment of PAH-exposure among coke oven workers.

https://arctichealth.org/en/permalink/ahliterature67812
Source
Pharmacogenetics. 1992 Dec;2(6):304-8
Publication Type
Article
Date
Dec-1992
Author
K. Vähäkangas
L. Pyy
E. Yrjänheikki
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Pharmacogenetics. 1992 Dec;2(6):304-8
Date
Dec-1992
Language
English
Publication Type
Article
Keywords
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - metabolism
Air Pollutants, Environmental - administration & dosage - adverse effects - analysis
Coke - adverse effects
DNA - metabolism
DNA Adducts
Dust - analysis
Finland
Humans
Lymphocytes - drug effects - metabolism
Occupational Exposure
Polycyclic Compounds - administration & dosage - adverse effects - analysis
Research Support, Non-U.S. Gov't
Abstract
Coke oven workers are exposed to high concentrations of polycyclic aromatic hydrocarbons. Only recently have methods been developed to try to assess the individual, biologically significant exposure. The only coke oven plant in Finland started to function in 1987, in Raahe, enabling the implementation of a cohort study among the workers to determine the usefulness of some currently available biomonitoring methods, e.g. methods of measuring PAH-DNA adducts. Urine and blood samples were taken several times from a sample of workers starting from before they worked at the plant. A questionnaire (smoking, diet, former and current occupations) was filled in by the workers at every sampling, and air samples (personal and stationary) were collected at the same time. The mean values of both benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were measured by synchronous fluorescence spectrophotometry (SFS) and the antibodies to these adducts increased somewhat after the work at the plant started. However, all the adduct values were low, and no differences between the smokers and non-smokers at any time point were detected. Battery workers had slightly increased means of BPDE-DNA adducts compared to non-battery workers. Also, coke oven workers had slightly higher adduct values than age, sex and smoking matched controls.
PubMed ID
1306131 View in PubMed
Less detail

Benzo[a]pyrene-DNA-adducts and monooxygenase activities in mice treated with benzo[a]pyrene, cigarette smoke or cigarette smoke condensate.

https://arctichealth.org/en/permalink/ahliterature69112
Source
Chem Biol Interact. 1989;70(1-2):51-61
Publication Type
Article
Date
1989
Author
N. Bjelogrlic
M. Iscan
H. Raunio
O. Pelkonen
K. Vähäkangas
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Chem Biol Interact. 1989;70(1-2):51-61
Date
1989
Language
English
Publication Type
Article
Keywords
7-Alkoxycoumarin O-Dealkylase
Animals
Aryl Hydrocarbon Hydroxylases - biosynthesis
Benzo(a)pyrene - metabolism - pharmacology
Cytochrome P-450 CYP1A1
Cytochrome P-450 Enzyme System - biosynthesis
DNA - metabolism
Enzyme Induction
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mixed Function Oxygenases - biosynthesis
Oxidoreductases - biosynthesis
Oxygenases - biosynthesis
Plants, Toxic
Research Support, Non-U.S. Gov't
Smoke
Spectrophotometry - methods
Tobacco
Abstract
Synchronous fluorescence spectrophotometry (SFS), developed to study benzo[a]pyrene-7,8-diol-9,10-epoxide(BPDE)-DNA, was used to measure the in vivo formation of DNA-adducts in genetically responsive C57BL/6 (B6) and non-responsive DBA/2 (D2) mice. Treatment with cigarette smoke by inhalation for 3-16 days, or i.p. injection of cigarette smoke condensate or neutral fraction did not lead to detectable levels of BPDE-DNA-adducts in either lungs or liver, although aryl hydrocarbon hydroxylase (AHH) activity, an indicator of benzo[a]pyrene (BP) metabolism, was clearly induced in lungs of B6 mouse. A dose-dependent amount of BPDE-DNA-adducts in lung and somewhat less in liver was found after i.p. injection with BP (20-80 mg/kg). Mice treated with vehicle or 4 mg/kg of BP were negative for adducts by SFS. In B6 mice AHH was induced both in lungs and livers while there was no AHH induction in D2 mice although the levels of BPDE-DNA-adducts were somewhat higher than in B6 mice. Thus, no clear correlation seems to exist between AHH activity and the formation of BPDE-DNA-adducts. Also, according to our results SFS can be used to quantitate adduct-formation in in vivo animal studies.
PubMed ID
2786769 View in PubMed
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[Biochemical study procedures for verifying non-smoking: evaluating the usefulness of biochemical indicators of exposure to cigarette smoke]

https://arctichealth.org/en/permalink/ahliterature67966
Source
Z Arztl Fortbild (Jena). 1989;83(21):1061-4
Publication Type
Article
Date
1989
Author
K. Vähäkangas
O. Pelkonen
Author Affiliation
Institut für Pharmakologie und Toxikologie, Universität Oulu.
Source
Z Arztl Fortbild (Jena). 1989;83(21):1061-4
Date
1989
Language
German
Publication Type
Article
Keywords
Carboxyhemoglobin - metabolism
Cotinine - urine
Humans
Nicotine - urine
Smoking - physiopathology - prevention & control
Sulfides - metabolism
Thiocyanates - metabolism
Tobacco Smoke Pollution - adverse effects
PubMed ID
2698551 View in PubMed
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Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood.

https://arctichealth.org/en/permalink/ahliterature64619
Source
Epilepsia. 1995 Mar;36(3):241-8
Publication Type
Article
Date
Mar-1995
Author
P. Pienimäki
A L Hartikainen
P. Arvela
T. Partanen
R. Herva
O. Pelkonen
K. Vähäkangas
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Epilepsia. 1995 Mar;36(3):241-8
Date
Mar-1995
Language
English
Publication Type
Article
Keywords
Antipyrine - metabolism - pharmacokinetics
Biological Transport
Blood - metabolism
Carbamazepine - analogs & derivatives - blood - metabolism - pharmacokinetics
Chromatography, Gas
Chromatography, High Pressure Liquid
Female
Fetal Blood - metabolism
Humans
Maternal-Fetal Exchange
Placenta - metabolism
Pregnancy
Spectrum Analysis, Mass
Abstract
Placental transfer and metabolism of carbamazepine (CBZ) was studied in a dual recirculating placental cotyledon perfusion system and was also evaluated in 16 pairs of maternal venous and cord blood samples. Among the parameters studied as possible indicators of a successful perfusion, volume changes in perfusate divided the perfusions into two groups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the maternal circulation crosses the placenta in the beginning quicker than antipyrine which is in agreement with the different lipid solubilities of these compounds. Because the transfer rates of antipyrine and CBZ were about the same, the mechanism of transfer of CBZ is probably similar to that of antipyrine (passive diffusion). No metabolites of CBZ could be detected in the perfusate by high-performance liquid chromatography (HPLC) or gas chromatography/mass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected in clinical samples, including 10-hydroxy-10,11-dihydro-CBZ (10-OH-CBZ), which has been described earlier in only 1 uremic patient. Relative levels of metabolites showed significant individual differences. CBZ crosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.
PubMed ID
7614907 View in PubMed
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Comparative analysis of p53 protein immunoreactivity in prostatic, lung and breast carcinomas.

https://arctichealth.org/en/permalink/ahliterature24610
Source
Virchows Arch A Pathol Anat Histopathol. 1992;421(3):223-8
Publication Type
Article
Date
1992
Author
Y. Soini
P. Pääkkö
K. Nuorva
D. Kamel
D P Lane
K. Vähäkangas
Author Affiliation
Department of Pathology, University of Oulu, Finland.
Source
Virchows Arch A Pathol Anat Histopathol. 1992;421(3):223-8
Date
1992
Language
English
Publication Type
Article
Keywords
Adenocarcinoma - chemistry
Breast Neoplasms - chemistry
Carcinoma - chemistry
Comparative Study
Female
Genes, Tumor Suppressor
Humans
Immunohistochemistry
Lung Neoplasms - chemistry
Male
Prostatic Neoplasms - chemistry
Research Support, Non-U.S. Gov't
Tumor Markers, Biological - analysis
Tumor Suppressor Protein p53 - analysis
Abstract
In this study we analysed the expression of p53 protein in a total of 143 carcinomas immunohistochemically. These consisted of 34 prostatic adenocarcinomas, 59 lung and 50 breast carcinomas. In 28 cases, an average of 2-3 additional sections from different tumour areas were analysed. Forty-nine of the 143 carcinomas (34%) showed typical nuclear immunoreactivity by immunohistochemical staining with the p53 antibody CM-1. Two of the 34 prostatic carcinomas (6%) were p53 positive while 25 of the 59 lung carcinomas (43%) and 22 of the 50 breast carcinomas (44%) showed positivity for p53. By grade: 49% of grade III tumours, 36% of grade II and 5% of grade I tumours were p53 positive. There were significantly more p53-positive cases in grade II-III tumours than in grade I tumours (P = 0.001) when all tumours were taken into account. Further, there were significantly more p53-positive cases in grade III than in grade I-II tumours (P = 0.001). In lung tumours there were significantly more p53-positive cases in grade II-III tumours than in grade I tumours (P = 0.018). Similarly, there were significantly more p53-positive tumours in grade III breast tumours than in grade I-II tumours (P = 0.003). The low incidence of p53 positivity in prostate carcinomas suggests that mutations of the p53 gene are not as frequent in the neoplastic transformation of these tumours as in lung or breast carcinomas. The association of p53 positivity with tumours of higher grade suggests that p53 mutations lead to tumours of a more aggressive type. The analysis of tumours by multiple sections indicates that p53 positivity is not evenly distributed in tumour tissue. Therefore, analysis of additional tumour areas may reveal positivity some cases, which is not evident if only one section is studied.
PubMed ID
1413488 View in PubMed
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43 records – page 1 of 5.