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Biomedical subjects

R Nilsson

Publications and source records attributed to R Nilsson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Symptoms, lung and liver function, blood counts, and genotoxic effects in coastal tanker crews.

OBJECTIVE: The deck crew on tankers can be exposed to high concentrations of benzene and other chemicals during loading, unloading and tank-cleaning operations. The objective of this study was to investigate whether genotoxic or other early health effects of cargo vapour exposure could be detected in coastal tanker crews. METHODS: The association between exposure to cargo vapours and clinical symptoms and signs, spirometry, blood cell count, blood test for liver function, and the frequency of micronuclei and sister chromatid exchanges in peripheral lymphocytes was studied in a cross-sectional investigation of 107 male crew members (66 deck crew and 41 others) on ten coastal tankers. RESULTS: Seven of the tankers had automatic cargo level gauging systems but some of the ships still had open hatches during loading and unloading operations. Acute symptoms such as headache, nausea, vertigo, fatigue and dizziness after loading or tank-cleaning operations were reported by 56 of the 66 deck crew members (85%). Irritation of the mucous membrane in eyes and upper respiratory tract by cargo vapours were also common in this group. Obstructive symptoms were more common in the group with the highest exposure to cargo vapours but persistent effects on lung function (vital capacity and forced expiratory volume in 1 s), nervous system, liver enzymes or blood counts were not found. The frequency of micronuclei after mitotic stimulation with phytohaemagglutinin was higher among the deck crew (mean 4.2 SEM 0.40) than in other crew members (mean 3.6, SEM 0.35). although the difference was not statistically significant. We found no association between exposure and the frequency of sister chromatid exchanges or micronuclei after stimulation with pokeweed mitogen. CONCLUSION: This study indicates that exposure to cargo vapours in coastal tanker crews may cause symptoms in the respiratory and nervous systems.

Adolescent↗
PubMed1997

Cancer incidence of workers in the Swedish petroleum industry.

OBJECTIVES: To estimate the risk of cancer due to occupational exposure to petroleum products in the Swedish transport and refinery industries. METHODS: In a retrospective cohort study the cancer incidence in 4128 men and 191 women, who had worked for at least one year in the petroleum industry, was compared with the incidence in the general population. The job titles and employment times for each person were found in personal files in the industries. The men had on average worked in jobs exposed to petroleum for 11.6 years at the end of the observation period. The cases of cancer were identified by record linkage with the Swedish cancer register. RESULTS: In total there were 146 cases of cancer v 157.6 expected (standardised mortality ratio (SMR) 0.93 90% confidence interval (90% CI) 0.80 to 1.1). Operators at refineries had an increased risk of leukaemia (6 cases v 1.7 expected, 90% CI of relative risk (RR) 1.5 to 7.0). Five of the six cases had started to work at the refineries in the 1950s or later. No other significantly increased risk of cancer was found. Distribution workers had a decreased incidence of lung cancer (no cases, 90% CI of RR 0 to 0.4). CONCLUSIONS: Operators at Swedish refineries had an increased risk of leukaemia. A possible cause is exposure to benzene. There was no increased risk of leukaemia in distribution workers. Distribution workers had a decreased risk of lung cancer.

Adolescent↗
PubMed1997

Extracorporeal whole-blood immunoadsorption enhances radioimmunotargeting of iodine-125-labeled BR96-biotin monoclonal antibody.

UNLABELLED: This study investigates the efficacy of tumor radioimmunotargeting with 125I-labeled BR96-biotin monoclonal antibody using a new method, whole-blood immunoadsorption (WBIA), based on direct adsorption of unbound monoclonal antibody (MAb) from blood without preceding separation of plasma. METHODS: Highly tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor-associated Lewis-type (Le(Y)) cell surface antigen. Forty-six Brown Norwegian male rats were inoculated intramuscularly and beneath the liver or kidney capsule with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, and investigated. The rats were injected intravenously with 3.5-4.5 MBq 125I-labeled BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 12 hr after injection. About six blood volumes were passed through an avidin-gel adsorption column during 2 hr. RESULTS: By using WBIA, whole-body radioactivity was reduced by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33 hr later, the activity uptake in tumors manifested only a nonsignificant decrease as compared with corresponding controls (p > 0.05) and had approximately similar time-activity curves. Uptake ratios for tumor (T):bone marrow, T:liver, T:kidney and T:lung were enhanced 2.3- to 3.5-fold in all three tumor models, as compared with controls. The ratio of liver tumor to bone marrow was improved from 10:1 to 30:1. CONCLUSION: This new method of WBIA yields significantly improved radioimmunotargeting of highly tumor-reactive, internalizing MAb BR96.

Animals↗
PubMed1996

In vivo dosimetry of ethylene oxide and propylene oxide in the cynomolgus monkey.

In mammals, including the cynomolgus monkey, a striking difference between the potencies of ethylene oxide (EO)* and propylene oxide (PO) with respect to induction of certain clastogenic effects has previously been observed. In order to clarify to what extent such differences can be ascribed to a difference in detoxification rate, cynomolgus monkeys were administered an equimolar mixture of the two epoxides at two dose levels, and the blood doses were determined by measurement of the degree of alkylation of N-terminal valines in hemoglobin (Hb). For the highest exposure a saturation in the detoxification of PO was evident from a marked increase in adduct level. At the lower exposure, the dose in blood resulting from exposure to PO was about one fourth of that from EO. Although playing a great role, differences in detoxification rate, therefore, cannot fully account for the much lower clastogenic potency of PO, which has been found in earlier studies. Furthermore, the determination of doses in blood gives data on relationship between in vivo dose and exposure dose (accounting for detoxification), with relevance for risk estimation.

Alkylation↗
PubMed1996

Chromosomal aberrations in peripheral blood lymphocytes from native Andean women and children from northwestern Argentina exposed to arsenic in drinking water.

For conducting an adequate human cancer risk assessment of inorganic arsenic (As) in the low-dose region, it is important to establish its mode of action. In this context, the nature of genotoxic effects induced by this agent is of considerable interest. However, the results from such investigations in human have been conflicting. In an attempt to resolve this issue, the clastogenic and aneugenic potential of As was investigated in women and children from native population exposed to high levels (around 0.2 mg/l) of natural As via drinking water in San Antonio de los Corbes in the Andean region of Salta, Northwestern Argentina. The water did not contain elevated levels of heavy metals, such as lead or cadmium, nor was the investigated population exposed to significant industrial pollution or to pesticides. An ethnically similar control group from Rosario de Lerma, Salta, where only extremely low concentration of arsenic in drinking water could be detected, was used as a control. To evaluate the genotoxic effects in peripheral blood lymphocytes, micronuclei (MN) in binucleated cells, sister-chromatid exchanges (SCEs) and the fluorescence in situ hybridization technique (FISH) in combination with chromosome specific DNA libraries were employed. The data obtained clearly indicate a highly significant increase in the frequency of MN and of trisomy in lymphocytes from exposed children and women in comparison with controls, but no notable effects were found on the frequencies of SCEs, specific translocations, or on cell cycle progression. As supported by FISH analysis, at least a proportion of MN appears to originate from whole chromosome loss. An additional finding was the unusually low background levels of MN in unexposed individuals from this ethnic group as compared to other populations, e.g., Caucasians.

Adolescent↗
PubMed1996

Glucosylceramides of oat root plasma membranes--physicochemical behaviour in natural and in model systems.

Glucosylceramides from oat root plasma membranes have been characterized using HPLC-particle beam-mass spectrometry, differential scanning calorimetry, low angle X-ray diffraction and surface balance technique. 24:1-OH was dominating fatty acid (90%) together with 24:0-OH and 22:1-OH. The sphingosine base was sphingadienine isomers and the monosaccharide alpha and beta glucose. Differential scanning calorimetry of an aqueous dispersion of glucosylceramide revealed during heating an endothermic gel-liquid crystalline transition with double peaks at 47 degrees and 51 degrees C, the lowest known for naturally occurring glucosylceramides. A cooling scan after the endothermic gel-liquid transition showed one exotherm at 15 degrees C and if this was followed by another heating scan a large exotherm appeared with a peak at 18 degrees C. During the second heating the matrix was hydrated and the exotherm at 18 degrees C reflects then the transition between the supercooled metastable gel phase and the corresponding hydrated form. The calorimetric data indicate a lamellar phase which during the cooling scan appeared as an supercooled liquid crystalline phase. Low angle X-ray diffraction confirmed these calorimetric data. The surface pressure-area-curves of pure oat glucosylceramides were more expanded than those of bovine origin. Mixtures of oat glucosylceramides and phosphatidylcholine species similar to those present in oat root plasma membranes showed molecular miscibility but no interaction.

Animals↗
PubMed1996

Environmental tobacco smoke and lung cancer: a reappraisal.

It is biologically plausible that environmental tobacco smoke (ETS) has a contributory role in the induction of lung cancer in nonsmoking individuals. However, recent findings have strengthened previous assumptions that a major part of the observed increase in lung cancer risk reported from epidemiological studies on ETS-exposed nonsmokers can be related to misclassification of smoking status and inappropriate selection of controls as well as to certain confounding factors related to life-style, and possibly also to hereditary disposition. Dose-response extrapolation-supported by a more solid database for active smokers-reflects a possible increase in lung cancer that appears to be more than one order of magnitude lower than indicated by the epidemiological studies that have been used to support regulatory action in the United States. The epidemiological studies on ETS conducted so far lack the required sensitivity to confirm increases in risk of such low magnitudes. Self-reported information on exposure to tobacco smoke has been found to be unreliable, and data from interviews with proxy respondents even more so. In addition, determination of cotinine to establish smoking status is inadequate for use in this context, i.e., to assure that misclassification in the range 5-10% does not occur; due to genetically based differences in the rate of nicotine metabolism, some active smokers will not be detected. Further, due the short half-life of cotinine in the organism, a self-reported nonsmoker may, in principle, have been a lifelong heavy smoker until just before the sampling takes place. For some of the major studies, preferential inclusion of disease-prone individuals of very low socioeconomic status among cases seems to have been present to a varying extent. Due to inclusion of this group, life-style and hereditary disposition may result in a disproportionally large impact on the recorded overall lung cancer rate. Further, a possible major confounder causing inflated risk estimates, and that was not controlled for, is apparently a high intake of saturated fat, which to a varying extent is coupled to inadequate intake of anticarcinogens present in certain foods of plant origin. The one-sided preoccupation with ETS as a causative factor of lung cancer in nonsmokers may seriously hinder the elucidation of the multifactorial etiology of these tumors.

Diet↗
PubMed1996

Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasia.

UNLABELLED: Bronchopulmonary dysplasia (BPD) is a chronic lung disease often occurring in ventilator-treated very low birth weight infants. The aetiology of BPD is multifactorial and pulmonary immaturity, high oxygen concentrations, peak inspiratory pressure levels and large tidal volumes during prolonged mechanical ventilation are important factors. We measured in tracheobronchial aspirate fluid (TAF) the concentrations of the pro-inflammatory cytokines tumour necrosis factor alpha, interleukin-1 beta (IL-1 beta), IL-6, IL-8, and IL-1 receptor antagonist in infants requiring artificial ventilation for BPD (n = 17) or respiratory distress syndrome (RDS) (n = 15) or postoperatively after surgery (n = 15). The median levels of all studied cytokines in TAF were higher in infants with BPD without local or systemic corticosteroid treatment compared to the median TAF levels of BPD neonates treated with corticosteroids (P = 0.06-P < 0.01). The neonates with BPD not treated with corticosteroids also showed higher levels of the five studied cytokines in TAF compared to infants on short-time ventilator treatment (P < 0.01-P < 0.001) and compared to neonates with RDS (P = 0.07-P < 0.001). The corticosteroid treated neonates with BPD had TAF cytokine levels approaching those of the control neonates. CONCLUSION: Tumour necrosis factors alpha, IL-1 beta, IL6, IL8 and IL1ra were markedly elevated in tracheobronchial aspirate fluids from neonates with bronchopulmonary dysplasia. Corticoid treatment seemed to reduce these levels.

Body Fluids↗
PubMed1996

Energy turnover in a sailing crew during offshore racing around the world.

Energy turnover during offshore sailing was studied in 11 male crew members of one team during the first three legs of the 1993-1994 Whitbread Round The World Race. The effect of racing on the energy balance of the crew members was studied by anthropometric measurements and dietary intake as calculated from food inventories before and after each leg. Energy turnover, calculated from dietary intake and release of endogenous energy as a result of changes in body composition, was higher than expected (about 18-20 MJ.d-1). These findings were confirmed using the doubly labeled water technique in six crew members during the third leg, in which mean energy turnover was found to be 19.3 MJ.d-1. Changes in body weight and composition indicated a negative energy balance during all legs.

Adult↗
PubMed1996

Assessment of exposure to polycyclic aromatic hydrocarbons in engine rooms by measurement of urinary 1-hydroxypyrene.

OBJECTIVE: Machinists have an increased risk of lung cancer and bladder cancer, and this may be caused by exposure to carcinogenic compounds such as asbestos and polycyclic aromatic hydrocarbons (PAHs) in the engine room. The aim of this study was to investigate the exposure of engine room personnel to PAHs, with 1-hydroxypyrene in urine as a biomarker. METHODS: Urine samples from engine room personnel (n = 51) on 10 ships arriving in different harbours were collected, as well as urine samples from a similar number of unexposed controls (n = 47) on the same ships. Urinary 1-hydroxypyrene was quantitatively measured by high performance liquid chromatography. The exposure to PAHs was estimated by a questionnaire answered by the engine room personnel. On two ships, air monitoring of PAHs in the engine room was performed at sea. Both personal monitoring and area monitoring were performed. The compounds were analysed by gas chromatography of two types (with a flame ionisation detector and with a mass spectrometer). RESULTS: Significantly more 1-hydroxypyrene was found in urine of personnel who had been working in the engine room for the past 24 hours, than in that of the unexposed seamen. The highest concentrations of 1-hydroxypyrene were found among engine room personnel who had experienced oil contamination of the skin during their work in the engine room. Stepwise logistic regression analysis showed a significant relation between the concentrations of 1-hydroxypyrene, smoking, and estimated exposure to PAHs. No PAHs were detected in the air samples. CONCLUSION: Engine room personnel who experience skin exposure to oil and oil products are exposed to PAHs during their work. This indicates that dermal uptake of PAHs is the major route of exposure.

Carcinogens↗
PubMed1996

Extracorporeal immunoadsorption from whole blood based on the avidin-biotin concept. Evaluation of a new method.

This study of 36 rats with rat colon adenocarcinoma transplants was carried out to investigate the efficacy of a new method of whole blood immunoadsorption (WBIA) in removing biotinylated monoclonal antibodies (MAbs) directly from unseparated blood, in order to increase 'the tumor/normal-tissue uptake ratio', as compared with extracorporeal immunoadsorption (ECIA) of antibodies from plasma. Compared with the ECIA system, the overall volume of the WBIA system (comprising only a pump, an adsorption column, a drop-chamber and tubings) was less (3.6 vs. 6.2 ml), and procedure duration 2 h less. The 17 rats undergoing the WBIA procedure, started 12 h after i.v. injection of 4.0-4.5 MBq 125I-BR96-biotin, manifested neither hemolysis nor any other complication; no signs of organ edema were found at dissection; whole body and blood radioactivity values were reduced by 51% and 89.5%, respectively. The WBIA method was as effective as ECIA, but technically simpler, safer and more reliable.

Adenocarcinoma↗
PubMed1995

A unique metabolism of inorganic arsenic in native Andean women.

The metabolism of inorganic arsenic (As) in native women in four Andean villages in north-western Argentina with elevated levels of As in the drinking water (2.5, 14, 31, and 200 micrograms/1, respectively) has been investigated. Collected foods contained 9-427 micrograms As/kg wet weight, with the highest concentrations in soup. Total As concentrations in blood were markedly elevated (median 7.6 micrograms/1) only in the village with the highest concentration in the drinking water. Group median concentrations of metabolites of inorganic As (inorganic As, methylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in the urine varied between 14 and 256 micrograms/1. Urinary concentrations of total As were only slightly higher (18-258 micrograms/1), indicating that inorganic As was the main form of As ingested. In contrast to all other populations studied so far, arsenic was excreted in the urine mainly as inorganic As and DMA. There was very little MMA in the urine (overall median 2.2%, range 0.0-11%), which should be compared to 10-20% of the urinary arsenic in all other populations studied. This may indicate the existence of genetic polymorphism in the control of the methyltransferase activity involved in the methylation of As. Furthermore, the percentage of DMA in the urine was significantly higher in the village with 200 micrograms As/1 in the water, indicating an induction of the formation of DMA. Such an effect has not been observed in other studies on human subjects with elevated exposure to arsenic.

Adult↗
PubMed1995

Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats.

The present study investigates whether tumor:normal tissue uptake ratios of radiolabeled monoclonal antibodies can be further improved by a combination of extracorporeal immunoadsorption (ECIA) and preload with unlabeled idiotypic monoclonal antibody. Athymic rats, heterotransplanted with human lung carcinoma under the kidney capsule (SR tumor) and i.m. (IM tumor), were divided into four study groups: controls, ECIA, preload, and combined preload+ECIA. The preload+ECIA procedure reduced the whole-body and plasma activity by 48 and 89%, respectively. After such combined procedure, the uptake of 125I-labeled L6-biotin in SR tumors was unchanged, while the uptake in normal tissues was considerably reduced. Tumor (T):bone marrow ratio was then increased by 17.5 times (after ECIA) and by 4.5 times (24 h after ECIA). Similar enhancements were achieved for T:liver and T:kidney ratios. For the IM tumors, the ratios were not as high as for SR tumors. The effects on T:normal ratios of preload+ECIA in combination were synergistic. The combined procedure resulted both in an increased uptake and prolonged persistence of 125I-labeled L6-biotin in the SR tumors and also in a reduction of corresponding uptake values in organs critical for radiation.

Animals↗
PubMed1995

Lack of methylation of inorganic arsenic in the chimpanzee.

Most mammals methylate inorganic arsenic (As) to methylarsonic acid (MMA) and dimethylarsinic acid, which are rapidly excreted in the urine. Previous studies have shown that, in contrast to humans, all experimental animals excrete very little MMA. With the aim of finding an appropriate animal model for studies on inorganic As metabolism and toxicity, we have investigated the metabolism of As in two male chimpanzees after a single iv dose of [73As]arsenate (5.8 micrograms As/kg body wt). The initial clearance from plasma was rapid with an apparent half-time of about 1 hr. Urine was found to constitute the major excretory pathway with very little excretion in the feces. About 60% of the administered 73As dose was excreted in the urine within 96 hr in a biphasic manner. The second phase of slow urinary excretion was characterized by first-order kinetics with a half-time of about 7 days. Upon ion-exchange chromatography of ultrafiltrated plasma and urine, only inorganic As could be detected, a finding confirmed by thin-layer chromatography. Thus, the results indicate that the chimpanzee, as previously shown for the marmoset monkey, but unlike all other mammals studied so far, including humans, is unable to methylate and detoxify inorganic As.

Animals↗
PubMed1995

ELISA procedures for the quantitation of glutathione transferases in the urine.

The proximal portion of the human kidney tubular system contains the alpha form, while the distal portion contains the pi form of glutathione transferase. These cytoplasmic proteins are released into the urine under pathological conditions, and an ELISA procedure has been developed for their quantitation. Optimal conditions with respect to concentrations of antibody and antigen and incubation times were determined. The procedure developed can detect as little as 0.5 ng enzyme per ml urine, even in the presence of high concentrations of other proteins. No cross reaction between these two isoenzymes or with a number of other proteins in the urine was observed. Antibodies interacted with these antigens in urine samples in the same manner as they interacted with the purified proteins. Storage of samples without loss of antigen required the presence of low concentrations of detergent, such as Tween 20, which both stabilized the enzymes and prevented their adsorption to the walls of the plastic tubes. The results indicate that increased urinary levels of these two enzyme proteins, as determined by the ELISA procedure, are useful markers for tubular damage.

Animals↗