Biomedical subjects

A Andersen

Publications and source records attributed to A Andersen.

At least 109 records · Page 6Linked to original sources

PubMed1996

Incidence and risk factors of cancer among men and women in Norwegian agriculture.

OBJECTIVES: The objective of the study was to examine cancer incidence and identify risk factors among subjects born in 1925-1971 and engaged in agricultural activities in Norway. METHODS: A cohort was established through linkage between agricultural censuses in 1969-1989 and the Central Population Register, which identifies farm holders and their spouses. Available census information on the activity of the farm provided the exposure indicators. Incident cancer in 1969-1991 was identified in the Cancer Register. In an analysis for standardized incidence ratios (SIR), the cohort was compared with the total rural population of Norway. Associations with exposure indicators were investigated in a Poisson regression analysis. RESULTS: In the follow-up of 136,463 men for 1.5 million person-years and 109,641 women for 0.6 million person-years, 3333 and 2145 cancer cases were identified, respectively. The subset defined as farmers had an SIR of 77 [95% confidence interval (95% CI) 73-81] for the men and 92 (95% CI 85-99) for the women, with particularly low SIR values for lung cancer and other sites linked to life-style. The several positive associations found confirmed the a priori hypothesis of an association between dairy farming and acute leukemia among men [rate ratio 1.76, 95% CI 1.02-3.05]. Multiple myeloma was associated with pesticide indicators for both genders, mainly for subjects cultivating potatoes. CONCLUSIONS: The results support the hypothesis of a relationship between acute leukemia and animal contact and between multiple myeloma and pesticides in potato cultivation. Other exposure associations, especially for cancer among women, warrant further investigation.

Adult↗

PubMed1996

Exposure to styrene and mortality from nonmalignant diseases of the genitourinary system.

OBJECTIVES: A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. METHODS: The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. RESULTS: Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. CONCLUSIONS: In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized.

Air Pollutants, Occupational↗

PubMed1996

Testicular cancer and parental use of fertilizers in agriculture.

Testicular cancer incidence is increasing rapidly in several countries. Environmental causes acting early in life are suspected but have not yet been identified. We conducted a cohort study to identify parental risk factors for testicular cancer among farmers' sons. Children born in 1952-1991 to parents who were farm holders at the time of the agricultural censuses in 1969-1989 were identified in the Central Population Register (Oslo, Norway). The resulting cohort of male offspring (n = 166,291) were followed up in the Cancer Registry of Norway (Oslo, Norway) for 1965-1991. Exposure indicators were derived from census information on activities on the farm. The cancer incidence was compared with that of the total rural population, and potential risk factors were analyzed by Poisson regression. In a follow-up of 2,924,663 person-years, 158 incident cases of testicular cancer were identified. The study population had a higher incidence of testicular cancer than did the total rural population, particularly at ages 15-19 years and in western Norway. Specific fertilizer regimens on the farm were associated with testicular cancer (rate ratio = 2.44; 95% confidence interval = 1.66-3.56), in particular nonseminoma (rate ratio = 4.21; 95% confidence interval = 2.13-8.32). The rate ratio estimates were highest for boys ages 15-19 years and for a subset of study subjects who were considered more likely to have grown up on a farm. Nondifferential misclassification and bias toward unity are likely because exposure information was available only at the farm level and only for census years. The fertilizer indicators were not available early in life for most subjects, and precise interpretations are difficult. A hypothesis worth considering is that excess nutrient run-off from agriculture constitutes a risk. However, inferences concerning the biological basis of our observations can scarcely be made.

Adolescent↗

PubMed1995

Second primary cancer after treatment for cervical cancer. An international cancer registries study.

BACKGROUND: The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects. METHODS: Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors. RESULTS: Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer. CONCLUSIONS: Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels.

Europe↗

PubMed1995

Altered distribution of cholinergic cells in the narcoleptic dog.

Narcolepsy is characterized by excessive sleepiness and episodes of cataplexy brought on by emotional excitation. Cataplexy and sleep paralysis have been hypothesized to be produced by the triggering during waking of brain stem cholinergic mechanisms normally acting to induce atonia in REM sleep. We hypothesized that narcoleptics have an abnormal number of LDT and/or PPN cholinergic neurons. A comparison was made of cholinergic cell numbers in the brain stems of normal and narcoleptic canines. Cholinergic neurons were identified by NADPH-diaphorase histochemistry. We found increased numbers of cholinergic neurons at the R6-R7 level of the LDT and PPN in narcoleptic canines. This abnormality can explain alterations in cholinergic receptor number, acetylcholine release, and the occurrence of cataplexy and sleep paralysis that characterize narcolepsy.

Acetylcholine↗

PubMed1995

Quantitation of 6-thioguanine residues in peripheral blood leukocyte DNA obtained from patients receiving 6-mercaptopurine-based maintenance therapy.

The antimetabolite 6-mercaptopurine is widely utilized in maintenance therapy for childhood acute lymphoblastic leukemia. Following p.o. administration, this prodrug undergoes extensive biotransformation, resulting in the generation of a plethora of metabolites including 2'-deoxy-6-thioguanosine triphosphate. Incorporation of 6-thioguanine (6-TG) bases into DNA is generally considered to be central to thiopurine-mediated cytotoxicity. We have developed a novel precolumn derivatization HPLC technique for quantifying 6-TG base accumulation into leukocyte DNA obtained from acute lymphoblastic leukemia patients receiving 6-mercaptopurine maintenance therapy. The method is based on enzymatic degradation of DNA to 2'-deoxyribonucleosides and the derivatization of released 2'-deoxy-6-thioguanosine with a thiol-reactive reagent containing a 7-amino-4-methylcoumarin-3-acetic acid fluorophore. The 2'-deoxy-6-thioguanosine-7-amino-4-methylcoumarin-3-acetic acid adduct is resolved by reversed-phase HPLC and quantified fluorometrically. Assay response is linear from 15 pmol to 60 fmol 6-TG bases/microgram DNA with a limit of quantitation corresponding to the incorporation of 1 6-TG residue per 50,000 bases. In a small cohort of acute lymphoblastic leukemia patients receiving p.o. 6-mercaptopurine-based maintenance therapy, significant interindividual variation in the accumulation of 6-TG bases into leukocyte DNA was revealed. The determined levels of drug base incorporation ranged from 95 to 710 fmol 6-TG bases/microgram DNA (6-TG base:nucleotide ratio 1:32,000 to 1:4,000). The assay may provide a novel methodology for pharmacological monitoring of thiopurine therapy either in the routine clinical setting or during studies of alternative routes of drug delivery.

Cell Line↗

PubMed1995

[Malignant pleural mesothelioma in Norway 1960-1992].

The incidence of malignant pleural mesothelioma among men in Norway increased about eightfold from 1960 to 1992. A similar rise in incidence has been observed in many countries with large consumption of asbestos during the last 50 years. The causal relationship between malignant mesothelioma and previous exposure to asbestos is well established. The investigation shows incomplete notification to the Labour Inspection as compared with the number of cases recorded by the Cancer Registry. Patients may therefore lose compensation both from the National Insurance Administration and as authorized by the new Occupational Injury Insurance Act of 1990. Asbestos was prohibited in Norway in 1985. Owing to the long latency time, about 30-40 years, the rise in incidence will probably continue for the next 20 years or more. Strict preventive precautions are important in order to prevent a "third wave" of asbestos-related diseases in the future.

Adult↗

PubMed1995

Cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases.

Olomoucine (2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine) has been recently described as a competitive inhibitor (ATP-binding site) of the cell cycle regulating p34cdc2/cyclin B, p33cdk2/cyclin A and p33cdk2/cyclin E kinases, the brain p33cdk5/p35 kinase and the ERK1/MAP-kinase. The unusual specificity of this compound towards cell cycle regulating enzymes suggests that it could inhibit certain steps of the cell cycle. The cellular effects of olomoucine were investigated in a large variety of plant and animal models. This compound inhibits the G1/S transition of unicellular algae (dinoflagellate and diatom). It blocks Fucus zygote cleavage and development of Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the Laminaria gametophytes. Stimulated Petunia mesophyl protoplasts are arrested in G1 by olomoucine. By arresting cleavage it blocks the development of Calanus copepod larvae. It reversibly inhibits the early cleavages of Caenorhabditis elegans embryos and those of ascidian embryos. Olomoucine inhibits the serotonin-induced prophase/metaphase transition of clam oocytes; furthermore, it triggers the the release of these oocytes from their meiotic metaphase I arrest, and induces nuclei reformation. Olomoucine slows down the prophase/metaphase transition in cleaving sea urchin embryos, but does not affect the duration of the metaphase/anaphase and anaphase/telophase transitions. It also inhibits the prophase/metaphase transition of starfish oocytes triggered by various agonists. Xenopus oocyte maturation, the in vivo and in vitro phosphorylation of elongation factor EF-1 are inhibited by olomoucine. Mouse oocyte maturation is delayed by this compound, whereas parthenogenetic release from metaphase II arrest is facilitated. Growth of a variety of human cell lines (rhabdomyosarcoma cell lines Rh1, Rh18, Rh28 and Rh30; MCF-7, KB-3-1 and their adriamycin-resistant counterparts; National Cancer Institute 60 human tumor cell lines comprising nine tumor types) is inhibited by olomoucine. Cell cycle parameter analysis of the non-small cell lung cancer cell line MR65 shows that olomoucine affects G1 and S phase transits. Olomoucine inhibits DNA synthesis in interleukin-2-stimulated T lymphocytes (CTLL-2 cells) and triggers a G1 arrest similar to interleukin-2 deprivation. Both cdc2 and cdk2 kinases (immunoprecipitated from nocodazole- and hydroxyurea-treated CTLL-2 cells, respectively) are inhibited by olomoucine. Both yeast and Drosophila embryos were insensitive to olomoucine. Taken together the results of this Noah's Ark approach show that olomoucine arrests cells both at the G1/S and the G2/M boundaries, consistent with the hypothesis of a prevalent effect on the cdk2 and cdc2 kinases, respectively.

Animals↗

PubMed1995

Heavy drinking in the restaurant business: the role of social modelling and structural factors of the work-place.

The role of social modelling and structural factors of the work-place in predicting the probability of heavy drinking was investigated in a sample of 3267 Norwegian male and female waiters and cooks. In the logistic regression analysis, the probability of heavy drinking was increased by two social modelling factors and one structural factor. Having co-workers who, at least weekly, took an end-of-work drink at the work-place gave an odds ratio for heavy drinking of 2.8 (95% CI 1.9-4.1), and having co-workers who went out after work at least every week gave an odds ratio of 1.8 (95% CI 1.2-2.8). Working at a place with a liberal alcohol policy gave an odds ratio 1.5 (95% CI 1.1-2.2). Among the background factors, only household type significantly predicted heavy drinking. As compared with living with children, the odds for heavy drinking when living alone was 4.3 (95% CI 2.9-6.4). The results indicate that preventive measures in the restaurant business should not only concentrate on the individual, but also deal with factors related to the occupational activity that promote and sustain heavy drinking.

Adolescent↗

PubMed1995

A high-pressure liquid chromatographic method for measuring mitotane [1,1-(o,p'-Dichlorodiphenyl)-2,2-dichloroethane] and its metabolite 1,1-(o,p'-Dichlorodiphenyl)-2,2-dichloroethene in plasma.

The adrenolytic agent mitotane [o,p'-DDD or 1,1-(o,p'-dichlorodiphenyl)-2, 2-dichloroethane] has been employed in the nonsurgical treatment of patients with adrenal carcinoma for several decades. Its use is hampered by serious side effects, which may be limited by analytically guided dose modifications in the individual patient. Mitotane analyses have previously been undertaken by gas chromatography with electron capture detection. A sensitive high-pressure liquid chromatographic method for measuring mitotane in plasma is described. After protein precipitation with 1.5 vol of acetone, mitotane and its metabolite 1,1-(o,p'-dichlorodiphenyl)-2,2-dichloroethene (o,p'-DDE) are resolved by isocratic elution from a C18 reversed-phase support and quantified by ultraviolet detection at 230 nm. Recoveries of mitotane and o,p'-DDE after deproteinization were quantitative. Within-run and between-day coefficients of variation were < 4% over the entire therapeutic range. The limit of detection was 0.25 mumol/L and the standard curve was linear in the 1-100 mumol/L range. The method has been evaluated using samples obtained from an adolescent girl who had metastatic adrenocortical carcinoma. Data from this single patient may suggest that systemic absorption of mitotane is adequate, and toxicity possibly decreased, when mitotane is administered by the rectal route.

Absorption↗

PubMed1995

Guinea pig cellular immune responses to proteins secreted by Mycobacterium tuberculosis.

To study the immunological activity of proteins secreted by Mycobacterium tuberculosis, we carried out comparative studies in guinea pigs infected intravenously with 2.5 x 10(3) CFU of this organism or with 2.5 x 10(4) CFU of Mycobacterium bovis BCG. Groups of infected guinea pigs were skin tested with fractions of secreted proteins covering well-defined narrow-molecular-mass regions, or such fractions were used for lymphocyte stimulation experiments. The lymphocyte stimulation experiments showed that the fraction containing proteins with molecular masses below 10 kDa had a superior stimulating capacity in tuberculous guinea pigs whereas the 24- to 30-kDa fraction gave significantly higher skin reactions in this group compared with BCG-vaccinated guinea pigs. A precise mapping within the region from 23 to 35 kDa by using a combination of narrow overlapping fractions and purified proteins enabled the identification of the 24-kDa antigen MPT64 as a molecule specific for tuberculous infection. Thus, MPT64 is a promising candidate for a specific diagnostic skin test reagent for human tuberculosis.

Animals↗

PubMed1995

Mortality and cancer morbidity in workers from an aluminium smelter with prebaked carbon anodes--Part II: Cancer morbidity.

OBJECTIVE: To investigate associations between cancer incidence and exposure to coal tar pitch volatiles, asbestos, pot emissions (fluorides, sulphur dioxide), heat stress, and magnetic fields in workers from a Norwegian aluminium smelter that operated from 1914 to 1975. METHODS: Cancer incidence between 1953 and 1991 was recorded in a cohort of 1137 men hired between 1922 and 1975. The expected number of cancer cases was calculated from incidence rates in Norwegian men. A job exposure matrix with semiquantitative exposure estimates was used to investigate associations between cumulative exposure estimates was used to investigate associations between cumulative exposure and cancer incidence through exploring temporal relations by considering exposures only within specific time windows. RESULTS: A significant excess of cancer cases, 90 observed v 59.0 expected, was found in workers who had been employed for less than three years. No such excess was found in men with at least three years' employment, with 120 cases observed v 129.7 expected. In this subcohort an association was found between the incidence of bladder cancer and exposure to coal tar pitch volatiles 40 years or more before each person-year under observation, and between incidence of lung cancer and tar exposure 35-50 years before observation. An association was also found between incidence of kidney cancer and exposure to heat stress 20-35 years before observation. CONCLUSIONS: The results support previous findings that exposure to coal tar pitch volatiles in the aluminium industry has been associated with increased risk of bladder and lung cancer. They also add information about temporal relations, suggesting that exposure to tar in this smelter has acted on an early stage in the development of these cancers, followed by a latency period of 30-40 years.

Aluminum↗

PubMed1995

Experiences of the Janus Serum Bank in Norway.

The ongoing JANUS project was started in 1973. The serum bank comprises 424,938 serum samples consolidated from 293,692 donors. The specimens are stored at -25 degrees C. From 1 to 13 consecutive samples are available from each donor. Up to October 1993 about 14,000 of the donors had developed some form of cancer. Frozen serum samples collected from a few months to 19 years prior to clinical recognition of their disease are available for research purposes. The principle aim of the JANUS project is to search in the premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA-125 may be elevated months prior to the diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumor marker in subgroups of thyroid cancer; low levels of selenium in serum reflects increased risk of thyroid cancer; raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkins disease; prostate-specific antigen may be elevated years prior to clinical diagnosis of prostate cancer; and linoleic acid in serum phospholipids is inversely related to breast cancer risk. The serum bank is, in principle, suitable for environmental studies, e.g., human exposure assessment. The steering committee of the JANUS project is open to suggestions for collaborative research on this topic.

Biomarkers, Tumor↗

PubMed1995

Proliferation-associated nuclear antigen Ki-S1 is identical with topoisomerase II alpha. Delineation of a carboxy-terminal epitope with peptide antibodies.

Proliferation-linked expression of the nuclear Ki-S1 antigen is a significant prognostic indicator in mammary carcinomas. Here, we show staining of a protein of 170 kd by Ki-S1 antibody in immunoblots of Saccharomyces cerevisiae expressing human topoisomerase II alpha but not in the parental strain. In HL-60 cells containing both isoforms of human topoisomerase II, Ki-S1 antibody binds selectively to the 170-kd isoenzyme in a similar fashion as peptide-antibodies directed against amino acid residues 1 to 15 or 1512 to 1530 of human topoisomerase II alpha. Conversely, antibodies directed against carboxyl-terminal sequences of human topoisomerase II beta selectively stain a 180-kd protein. The immunoreactive pattern of V8 endoproteinase restriction digests of human topoisomerase II alpha was identical for Ki-S1-antibody and peptide-antibodies directed against residues 1512 to 1530 but different for peptide-antibodies directed against residues 1 to 15. The Rf values of the smallest fragment commonly recognized by Ki-S1 antibody and the carboxy terminus-specific peptide-antibody place the Ki-S1 epitope within the last 495 carboxyl-terminal amino acid residues of topoisomerase II alpha.

Animals↗

PubMed1994

Incidence of cancer among nitrate fertilizer workers.

The results are presented from a historical prospective cohort study on the incidence of cancer among 1756 male workers at a nitrate fertilizer plant. Workers employed for 1 year or more between 1947 and 1980 were included in the cohort. Surrogates for individual exposure to nitrogen derivatives and asbestos dust were recorded to identify subgroups. There were 195 cases of cancer observed versus 208.8 expected, as based on the rates among age-adjusted rural Norwegian males. A slight increase in stomach cancer was found: 28 observed versus 19.9 expected.

Asbestos↗

PubMed1994

Quantitation of cell-associated doxorubicin by high-performance liquid chromatography after enzymatic desequestration.

A method for measuring cellular concentrations of the anthracycline doxorubicin was developed. The assay involves cell lysis and protein degradation by detergent and proteinase K treatment followed by DNA hydrolysis using DNase I. Prior to high-performance liquid chromatography, samples are deproteinized by the addition of ZnSO4 and methanol. The assay is linear with respect to both the cellular drug content and the number of cells assayed over the ranges tested, and drug recovery is close to 100%. The method has a limit of detection of 50 fmol injected doxorubicin. Within run and between-day coefficients of variation have consistently been found to be in the 5% and 10% range, respectively, in different cell lines exposed to doxorubicin in vitro. The method has been evaluated in analyses of doxorubicin levels in mononuclear blood cells of patients. The assay offers several advantages over commonly used organic extraction techniques and may improve cellular drug monitoring during anthracycline therapy in patients.

Breast Neoplasms↗

PubMed1994

Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat.

To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 microM, and concentrations of 7-OH-MTX declined triphasically, showing a t1/2 alpha value of 2.45 min, a t1/2 beta value of 30.5 min, and a terminal half-life (t1/2 gamma) of 240 min. The total clearance value was 14.5 ml min-1 kg, and the postdistributional volume of distribution (V beta) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.

Animals↗

PubMed1994

Evaluation of methotrexate tissue exposure by in situ microdialysis in a rat model.

The feasibility of using a microdialysis technique to obtain pharmacokinetic data on tissue exposure to methotrexate (MTX) was investigated. Microdialysis probes were implanted in the jugular vein, femoral muscle, and liver of anesthetized male Wistar rats. MTX (100 mg/kg) was given as a bolus injection through an indwelling venous catheter, and blood samples were obtained through a second venous access and by microdialysis for a total of 6 h. Heparinized plasma, ultrafiltered plasma, and microdialysis effluent from tissue and venous probes were analyzed by high-performance liquid chromatography. Centrifugal ultrafiltration of rat plasma spiked in vitro with MTX (1-100 microM) revealed a mean binding to plasma proteins of 21%. In vitro microdialysis of this spiked plasma resulted in 23% relative recovery of the unbound fraction. In rats receiving MTX, plasma protein binding was 23% and the relative drug recovery as assessed with venous microdialysis probes was 18%. Plotting of unbound (i.e., ultrafiltrate) MTX concentrations in the blood against venous microdialysis perfusate values in the blood gave a good linear correlation with a coefficient of correlation (r2) of 0.98. There was also a linear correlation between the total MTX concentrations in venous blood and the drug levels in microdialysis samples from muscle and liver (r2 = 0.93 and 0.74, respectively). Area under the curve estimations were consistent with an MTX exposure of 30% and 46% for the muscle and liver as compared with the circulation. The present study demonstrates that the microdialysis technique can provide reproducible data on tissue exposure to MTX in an animal model and indicates that the methodology is adaptable to clinical settings.

Animals↗