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Biomedical subjects

R Nilsson

Publications and source records attributed to R Nilsson.

At least 19 recordsLinked to original sources

Genotoxic effects of sodium arsenite on human cells.

The effects of sodium arsenite (SA) were studied either alone or in combination with X-rays in peripheral blood lymphocytes, and with short-wave ultraviolet (UV) radiation in primary human fibroblast culture systems. It was found that SA (i) inhibited the cell cycle progression of phytohaemagglutinin (PHA)-responsive lymphocytes, (ii) induced chromatid-type aberrations and sister-chromatid exchanges (SCEs) as a function of concentration and (iii) potentiated the X-ray- and UV-induced chromosomal damage. Our results suggest that SA interferes with the DNA repair process, presumably by inhibiting the ligase activity. This accounted for an increase in the DNA replication-dependent processes, chromatid aberrations and SCEs and synergistic enhancement of the X-ray- and UV-induced chromosomal damage. This ability of arsenite may be responsible for its comutagenic properties with different types of mutagens and hence its carcinogenicity.

Arsenic

Phase behaviour and molecular species composition of oat root plasma membrane lipids. Influence of induced dehydration tolerance.

Tolerance to dehydration induced by repeated water-deficit stress is well correlated to changes in the lipid composition of oat root cell plasma membranes. The molecular species of the two dominant phospholipids phosphatidylcholine and phosphatidylethanolamine were determined. The four major species were 16:0/18:2, 16:0/18:3, 18:2/18:2 and 18:2/18:3. In contrast to the large changes in plasma membrane lipid composition in other respects, induced tolerance resulted in very weak alterations concerning the phospholipid molecular species pattern. Only minor alterations, appearing as a decrease in the 18:3-containing lipids, occurred. Total lipids of microsomes and isolated plasma membranes of root cells were analysed by X-ray crystallography at different degrees of hydration. The lipid phase behaviour at different degrees of hydration was further confirmed by polarization microscopy. In the presence of excess water all membrane lipids adopted a reversed micellar configuration. The plasma membrane lipids from root cells with induced dehydration tolerance formed upon dehydration two coexisting lamellar structures. The importance of the phase behaviour at different degrees of hydration for the membrane properties and the relation to membrane composition is discussed.

Edible Grain

Histopathologic and cytochemical characteristics of interval breast carcinomas from the Stockholm Mammography Screening Project.

Combined morphological and cytochemical malignancy grading in addition to tumor stage was applied to assess the malignant potential of so-called interval carcinomas from the Stockholm randomized mammography screening study. Only interval carcinomas surfacing within two years from screening were included. Fifty-four percent of the tumors were in stage I and 46% of the carcinomas eligible for DNA analysis were diploid, i.e. low-malignant. An overrepresentation of prognostically unfavorable tumor characteristics was found only within the subgroup 'true' and 'early' interval cancer.

Adult

Multiple primary colorectal adenocarcinomas: cytometric DNA ploidy patterns and histopathologic features.

The nuclear DNA distribution pattern was studied by means of image cytometry in 18 patients with synchronous and 7 patients with metachronous colorectal adenocarcinomas. About 80 percent of a total number of 53 carcinomas were found to consist of neoplastic cells where the nuclear DNA distribution pattern was of the aneuploid type. In 19 of the 25 patients, all carcinomas in the individual colon had identical nuclear DNA distribution patterns. Aneuploid tumors tended to appear more frequently in the sigmoid colon and the rectum than in the right colon. Carcinomas associated with an adenoma were more common in the rectum and in Dukes' A carcinomas. The results of cytometric assessments of the nuclear DNA ploidy pattern of the neoplastic cells in colorectal carcinomas have previously been found to be an independent prognostic variable. From the observations made in the present study, it is concluded that the cytometric DNA ploidy pattern of multiple primary colorectal carcinomas corresponds to that found in single carcinomas. The similarity between the two groups of cancer patients is also supported by conformity between histopathologic features and prognosis.

Adenocarcinoma

On the mechanism of the hepatocarcinogenicity of peroxisome proliferators.

The absence of a genotoxic action in the rat of several peroxisome proliferators (PP) has been confirmed by measuring gross degradation, unscheduled DNA-synthesis (UDS), as well as by measurement of single strand breaks using alkali unwinding in absence and presence of inhibitors of DNA-repair. Similar results were obtained even after drastically lowering the glutathione content of liver. Further, after oral administration of ciprofibrate, no potentiating effect was found in vivo on the generation of micronuclei in hepatocytes by ionizing radiation. The metabolically inert PP, perfluorooctanoic acid, was found to act as a promoter of liver tumors in the rat induced by diethylnitrosamine in an initiation-selection-promotion protocol. The results are discussed in light of available information concerning the mechanism of action of PPs.

Animals

Quantitative assessment of a human carcinogenic potency for propylene oxide.

The potential for causing carcinogenic and mutagenic effects is the main concern when assessing the risks associated with low-level exposures of humans to the industrially important epoxide, propylene oxide (PO). The available basic information used in estimation of carcinogenic risk has been reviewed. It is concluded that the published data from gavage studies in rodents are less appropriate and that observed cancer incidences from long-term inhalation should preferably be utilized for quantitative risk assessment. Furthermore, PO and ethylene oxide (EO) are directly acting alkylating agents which exhibit several similarities. Although data are less comprehensive for PO than for EO, PO appears to yield a rather uniform alkylation pattern in various tissues. Also, similarly to EO, PO is probably detoxified at a rate which does not vary widely in various mammalian species, including man. For these reasons, the surface-based extrapolation model for estimation of the human equivalent dose may not be appropriate, and the previously derived carcinogenic potency factors should be revised downward. Alternative risk estimates are provided. From the most relevant available studies, we propose a carcinogenic potency factor of 0.001 (mg/kg/day)-1 for PO in humans by inhalation.

Animals

Increased hip-fracture incidence in the county of Ostergötland, Sweden, 1940-1986, with forecasts up to the year 2000: an epidemiological study.

The incidence of hip fractures in the county of Ostergötland in Sweden has increased dramatically from 1940 to 1986, mainly due to an increase in age-specific incidence of trochanteric fractures. The increase is most pronounced in people over 80 but is present even in age groups down to 50 years. If the age-specific incidence rates continue to increase, and the population of the elderly grows in accordance with the forecast, there will be 70% more hip fractures in the year 2000 than in 1985.

Age Factors

Nodular fasciitis and fibromatosis of the female breast simulating breast cancer. Case reports.

One case of nodular fasciitis and one of fibromatosis of the female breast are reported. These rare lesions simulated breast cancer clinically and mammographically. Histological diagnosis was obtained by excision of the lesions. A literature search in three large databases gave only 4 reported cases of nodular fasciitis of the female breast, fibromatosis was relatively more common in this location.

Biopsy, Needle

Quantitation of protein A in human plasma is possible after heat inactivation of the samples.

Quantitative determination of staphylococcal protein A in plasma is often hampered by the interaction between protein A and immunoglobulins. In human plasma, these interactions may not only involve the non-immune binding to the Fc or Fab regions of Ig but also antigen/antibody interaction by specific antibodies directed against protein A. In this paper we describe a method which can be used to quantitate nanogram amounts of protein A in the presence of human plasma. The ELISA used for the quantification of protein A is based on a double antibody solid-phase assay utilizing chicken anti-protein A as both capture and detector antibody. Protein A may be measured down to 5 ng/ml in plasma and 0.5 ng/ml in buffer. The plasma samples were heat-inactivated before analysis and this eliminated interference in the assay caused by interaction of protein A with an excess of immunoglobulins. This assay provides a reliable and convenient method for the detection and quantitation of soluble protein A in human plasma.

Animals

An optimized assay of specific IgE antibodies to reactive dyes and studies of immunologic responses in exposed workers.

Methods of assaying reactive dye-specific IgE antibodies were investigated with a RAST. Sera from three patients, occupationally exposed to a reactive dye, Remazol black B (Chemical Abstract registry number 17095-24-8), were used. Directly dyed disks, that is, disks without any carrier protein, resulted in poor and unreliable measures of specific IgE. In contrast, optimized preparation of conjugates between the dye and human serum albumin resulted in efficient binding of specific IgE. The patients' RAST results were strongly positive, whereas sera from 36 exposed workers but without symptoms and sera from unexposed subjects with high levels of total IgE were negative. The hapten and carrier specificity of the IgE antibodies was studied by direct RAST and RAST inhibition. In one patient, the antibodies were principally hapten specific, whereas another patient was found to have antibodies with a high degree of specificity to the carrier. The third patient's antibodies were intermediate between the other two patients' antibodies in this respect, suggesting that antibody specificity is dependent not only on the nature of the hapten but also on individual immune response factors. The study demonstrates that it is important to use an optimized preparation of dye-protein conjugates to elicit reliable results and a high degree of specific IgE binding in the RAST.

Antibody Specificity

Peroxisome proliferation and modulation of rat liver carcinogenesis by 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, perfluorooctanoic acid and nafenopin.

Using an initiation--selection--promotion protocol for induction of liver tumors in Wistar rats, the modulating action of various peroxisome proliferators on neoplasia as well as on selected biochemical parameters was studied. After treatment with diethylnitrosamine (DEN), the animals were subsequently subjected to a selection procedure involving feeding of 2-acetylaminofluorene (2-AAF), and in the middle of the 2-AAF treatment, a single necrogenic dose of carbon tetrachloride. Following a recovery period, the rats were fed a diet containing 0.1% nafenopin (NAF), 0.015% perfluorooctanoic acid (PFOA), 0.05% 2,4-dichlorophenoxyacetic acid (2,4-D), 0.05% 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) or 0.05% phenobarbital (PB) as a positive control. When the animals were killed, 7 months after initiation, the incidence of hepatocellular carcinoma was 83, 33 and 16% in the animals treated with NAF, PFOA or 2,4,5-T respectively. No cancers were observed in controls, or in the 2,4,-D groups. In comparison with controls, NAF and PFOA caused a 60-and 24-fold increase inthe peroxisomal beta-oxidation of fatty acids respectively, but only about a 2-fold increase in the catalase activity, 2,4-D and/or 2,4,5-T were much less active in this respect, giving approximately a doubling in the rate of fatty acid oxidation. The specific activity of D-amino acid and glycolate oxidases were significantly depressed, whereas the urate oxidase levels were apparently unaffected by the NAF and PFOA treatment. The results suggest that the selective induction of peroxisomal fatty acid oxidation is consistent with the hypothesis that imbalance between H2O2 overproduction and its destruction could play a role in the modulation of hepatocarcinogenesis by peroxisome proliferators.

2,4,5-Trichlorophenoxyacetic Acid

Lymphocyte transformation test for diagnosis of isothiazolinone allergy in man.

The lymphocyte transformation test (LTT) has been used for evaluation of in vitro lymphocyte responses in 18 patients with dermatitis and positive patch tests to 200 ppm of a combination of 5-chloro-2-methylisothiazolinone and 28methylisothiazolinone (MCI) in nine patients with dermatitis unrelated to MCI and in seven subjects without skin diseases. Two workers sensitized by occupational exposure to a formulation containing 1,2-benzisothiazolin-3-one (BIT) were also studied. Lymphocytes from nine patch-test-positive patients proliferated vigorously to MCI in vitro. Lymphocytes from the remaining nine patients were not stimulated. Lymphocytes from two BIT-sensitized workers responded to BIT in vitro. The lymphocyte proliferation to isothiazolinones indicates the presence of memory cells in the patients' blood and confirms immunologic reaction to the inducing agent. To establish clinical relevance of LTT results, 12 MCI patch-test-positive patients underwent "use test" with lotion containing 15 ppm MCI. Four of five LTT-positive patients were use-test-positive, whereas seven of seven LTT-negative patients were use-test-negative. LTT-positive and lotion-positive patients responded to 100 ppm or lower concentrations of MCI on patch testing, whereas seven of eight LTT-negative and lotion-negative patients responded to 200 ppm only. In the case of MCI, proliferation was due to the chlorinated component, indicating that this part contains an allergenic epitope. Finally, MCI-specific lymphocyte proliferation was observed only in patients with MCI-positive skin test, but not in nine patients with dermatitis induced by other agents, or in seven subjects without skin diseases. Thus, the lymphocyte transformation test is able to distinguish between irritant and allergic skin responses. It may also be valuable in establishing the clinically relevant patch-test concentration of allergens with irritative properties.

Adult

Extracorporeal immunoadsorption therapy on rats. In vivo depletion of specific antibodies.

A technique for extracorporeal immunoadsorption of circulating specific antibodies from the plasma of rats is described. Catheterization of rats was performed using the carotid and the jugular blood vessels. The rats were treated non-anaesthetized. Blood was pumped continuously through a hollow-fibre plasma filter at a rate of 1.5 ml/min and plasma was separated and passed through an adsorbent column at a flow of 0.2 ml/min. The treated plasma was mixed with the blood cells before being returned to the rat. The column contained the antigen covalently linked to agarose beads. About three plasma volumes were treated during a period of 3 h and 30 min, which resulted in an antibody depletion of about 90-95%. The antibody levels returned to pre-adsorption levels after 4-5 days, or in some cases even exceeded the titres before treatment.

Animals

Passive expiratory flow-volume recordings in immature newborn rabbits. Effect of surfactant replacement on the time constant of the respiratory system.

Immature newborn rabbits with a gestational age of 27 days were paralyzed and kept in body plethysmographs. They were ventilated for 10 min with a tidal volume of approximately 10 ml/kg, with or without previous surfactant treatment via the airways. Tidal volumes and flow were recorded with a pneumotachograph connected to the body plethysmograph, and the expiratory time constant of the respiratory system (trs) was determined from flow-volume diagrams. The values of trs after 10 min were significantly higher in surfactant-treated animals than in controls (50 +/- 7 vs. 23 +/- 4 ms; p less than 0.002), indicating stabilization of the alveoli. There was also a close correlation between trs and the compliance values calculated from tidal volumes and ventilator pressure (r = 0.80; p less than 0.001), as well as between trs and the alveolar volume density in histological lung sections, determined by automated image analysis (r = 0.71; p less than 0.001).

Animals

Immunologic basis for adverse reactions to radiographic contrast media.

The lymphocyte transformation test (LTT) was used to elucidate whether certain side effects induced by radiographic contrast media have an immunologic etiology. Groups studied were: 8 patients who had previously experienced adverse reactions in association with urography, 6 patients who underwent urography without notable side reactions, 17 occupationally exposed nurses, and 9 unexposed controls. The lymphocytes from 2 hypersensitive patients and from 11 nurses exhibited a positive proliferative response to amidotrizoate. Five nurses who had shown a positive response, had a previous history of hypersensitivity reactions when handling contrast media, whereas the remaining 6 were free of symptoms. Amidotrizoate-specific memory cells were absent in patients who underwent urography without signs of hypersensitivity and in 7/9 of unexposed control subjects. Lymphocytes from patients sensitive to amidotrizoate cross-reacted to structurally related ionic contrast media while non-ionic contrast agents did not induce proliferation of the lymphocytes. Thus, ionic radiographic contrast agents have antigenic properties in man. Irradiated mixtures of radiographic contrast media and serum proteins were, in general, not effective in inducing an LTT response.

Adult

Clinical appearances in severe ischaemic colitis. Case report.

Ischaemic colitis was not diagnosed until laparotomy in five cases. In two it was secondary to hypotension and multiple organ failure, in two it was atherosclerotic, and one had polycythemia vera. The diagnosis should always be considered in patients with abdominal distension--with or without diarrhoea and abdominal pain--so that treatment may be instituted before the onset of peritonitis.

Aged