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Biomedical subjects

R Nilsson

Publications and source records attributed to R Nilsson.

At least 55 records · Page 3Linked to original sources
PubMed1994

A general extracorporeal immunoadsorption method to increase tumor-to-tissue ratio.

The idea of applying extracorporeal immunoadsorption (ECIA) in radioimmunodiagnosis and radioimmunotherapy has been proposed previously. The authors here report on the development of new concept using a general method for ECIA based on biotinylated MoAb adsorbed on an avidin column. Athymic rats heterotransplanted with either human melanomas or human lung carcinoma were injected with iodine-125-labeled biotinylated 96.5 or L6 MoAb, respectively. At 24 or 48 hours after the injection, ECIA was performed by pumping blood through a hollow-fiber plasma filter. The separated plasma then was passed through an absorbent (avidin-agarose) column. The whole ECIA procedure lasted for 3 hours. By this ECIA method, the tumor-to-normal tissue ratios were increased in various tissues (i.e., radiosensitive and blood rich organs) by a factor of four to five.

Animals↗
PubMed1994

In vivo tissue dosimetry as a basis for cross-species extrapolation in cancer risk assessment of propylene oxide.

The potential for causing carcinogenic and mutagenic effects has been the main concern when assessing the risks associated with low-level exposures of humans to the industrially important epoxide, propylene oxide (PrO). For regulatory purposes, surface-based extrapolation has been used to determine the human equivalent dose from cancer data obtained in rodents. In this context the tissue dose will more adequately reflect inter- and intraspecies differences with respect to pharmacokinetic parameters than is the case for conventional representations of exposure. The formation of adducts in nucleophilic molecular targets by directly acting electrophilic agents, like epoxides, is thought to be closely linked to the process of cancer initiation. To investigate whether tissue dose is correlated to surface area of the exposed organism, the in vivo adduct levels in hemoglobin and DNA have been determined in mice, rats, and dogs after exposure to PrO by injection as well as by inhalation. The results obtained indicate that the dose in blood is virtually the same in the three investigated animal species, whereas surface-area based extrapolation predicts a difference by a factor of about seven between the mouse and the dog. Although the data base is more limited, this conclusion is also supported by measurements of DNA alkylation is selected tissues. The variations actually observed are not related to the surface area of the animal. No significant differences could be found between administration of PrO by injection or by inhalation. For this reason, the surface-based extrapolation model for estimation of the human equivalent dose is not appropriate, and the carcinogenic potency factors for PrO as previously derived by the U.S. EPA should probably be revised downward by a factor of 10 to 13.

Alkylating Agents↗
PubMed1994

Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection. Report of eight cases.

PURPOSE: The aim of this study was to describe our experiences of surgical removal of inflamed bowel in cytomegalovirus enterocolitis. METHODS: Eight homosexual males with a mean age of 41 years (range, 29-59 years) and a mean CD4 count of 21 x 10(6)/l (1-60 x 10(6)/l) with advanced human immunodeficiency virus infection and severe cytomegalovirus enterocolitis were treated with ileocecal resection (4 patients) or right-sided hemicolectomy (4 patients). Symptoms were lower abdominal pain, severe diarrhea, fever, and weight loss, unrelieved by anticytomegalovirus therapy. Radiologic examination showed that ulcerative inflammation was limited to the right colon and terminal ileum. Microscopic examination confirmed the cytomegalovirus enterocolitis. Intermittent cytomegalovirus treatment, usually with foscarnet for 10 to 14 days every 4 to 6 weeks was given postoperatively. RESULTS: Two minor postoperative complications occurred: a lesser wound infection and a moderate bleeding from the abdominal wound edges. One patient died after three weeks because of gastrointestinal bleeding from an ulcerating Kaposi's sarcoma lesion and another patient died from unrelated causes three weeks after discharge from the hospital. The remaining 6 patients experienced complete or partial palliation of the abdominal symptoms for a mean of 14 months (range, 5-35 months) until death or the end of observation time. One patient is still alive two years after the operation. The overall mean survival was 12 months (range, 0.5-35 months). Recurrent or persistent symptoms and/or signs of cytomegalovirus enterocolitis occurred in four patients after a mean of seven months. CONCLUSION: Resection of inflamed bowel combined with postoperative anticytomegalovirus treatment leads to excellent palliation and a relatively favorable survival in AIDS patients with cytomegalovirus enterocolitis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Modulating influence of inorganic arsenic on the recombinogenic and mutagenic action of ionizing radiation and alkylating agents in Drosophila melanogaster.

In bacterial systems and in mammalian in vitro cell cultures, inorganic arsenic has been found to potentiate the mutagenic action of UV as well as of a number of mutagenic agents, probably by interfering with the later steps of DNA-repair. The Drosophila wing spot test (SMART) was used to study the modulating action of inorganic arsenic on the recombinogenic and mutagenic effects of the alkylating agents ethylnitrosourea (ENU), methylmethane sulphonate (MMS), and ethylene oxide (EO) as well as of gamma-rays. It was found, that arsenic in this in vivo test system exerted an inhibitory effect on mitotic recombination induced by alkylating agents and gamma-irradiation. These results are in contrast to the synergistic effect of inorganic arsenic on point mutations and deletions as reported for human lymphocytes and primary fibroblasts. The reason for the discrepancy between the mammalian systems and Drosophila with respect to the modulating action of arsenic is discussed.

Alkylating Agents↗
PubMed1994

Complexity of the bovine MHC class-II specificity DW3 as defined by alloantisera.

Alloantisera related to the bovine major histocompatibility complex (MHC) class-II specificity Dw3 were investigated by cross-absorption experiments and by application of the monoclonal antibody-specific immobilization of lymphocyte antigen assay (MAILA). The absorption study revealed antibodies specific for an antigenic determinant shared by all Ds03 (Dw3)-positive animals, and several other antibody populations recognizing the locally defined specificities Ds10, Ds11 and Ds15, that are closely associated with Ds03. The results of the MAILA-assay indicate that the Ds03 specificity is probably encoded by DQ, whereas specificities Ds10 and Ds 11 are more closely associated with DR molecules. The data presented here provide the first evidence that bovine DR and DQ specificities can be identified separately by serological methods using alloimmune antisera.

Animals↗
PubMed1994

Glutathione transferases in the urine: sensitive methods for detection of kidney damage induced by nephrotoxic agents in humans.

With the aid of immunohistochemical methods the localization of the various isoenzymes of glutathione S-transferase was investigated. The alpha isoenzyme was present solely in the proximal tubular cells of the human kidney, while the pi form was restricted to the distal convoluted tubules, the thin loop of Henle, and the collecting ducts. Damage to the epithelial cell membranes results in the increased excretion of these enzymes with the urine. The alpha and pi isoenzymes have been isolated in a highly purified form and used for the production of polyclonal antisera. Subsequently, radioimmunological and ELISA techniques were developed for quantitation of these proteins in the urine; the methods exhibited a high specificity and were sufficiently sensitive to determine nanogram quantities or less. Disease affecting tubular function, cyclosporine A treatment, administration of nephrotoxic antibiotics, and exposure to cadmium all resulted in characteristic changes in the pattern of the glutathione transferase isoenzymes present in urine. Such effects were seen also in patients who had previously been exposed to nephrotoxic agents, but in whom conventional tests for kidney function were apparently normal. Thus, it appears that radioimmunologic or immunochemical quantitation of alpha and pi forms of the enzyme can be used as sensitive and relatively simple markers for the early detection of toxic effects with respect to the renal tubuli.

Clinical Enzyme Tests↗
PubMed1994

Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats.

In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.

Animals↗
PubMed1993

Why different regulatory decisions when the scientific information base is similar?--Human risk assessment.

The main objective of this analysis has been to characterize the role of science, in a broad sense, in relation to social, economical, political, and other factors in explaining why regulatory decisions vary in different countries, although they are based on more or less identical scientific data. Eleven countries from different geographical areas and with varying cultural background have provided information in response to an extensive questionnaire aimed at identifying procedures for registration, restricting, or banning registration for certain selected pesticides. Although many of these responses lacked sufficient detail in certain aspects, together with other documentary sources they nonetheless provided insight with respect to some of the main concerns among and between nations regarding decisions in pesticide management. Among the main conclusions presented in this analysis, the following deserves particular emphasis: The underlying reasons for introducing restrictions on pesticide use on the national level will have to be more explicitly stated and openly declared by regulatory bodies of all nations. Although more pronounced in some countries, there is a strong influence of nonscientific considerations in pesticide management, that is not always based on rational considerations. In the field of hazard and risk assessment differences in scientific opinion have primarily, but not exclusively been identified regarding the evaluation of carcinogenic effects in experimental animals. In this area debated issues are the interpretation of the significance for man of certain types of tumors, methods for dose-response extrapolation, genotoxic versus nongenotoxic carcinogens, the use of MTD in long-term studies, mechanistic approaches to interpret cancer induction, and others. Another area identified to cause divergence is exposure assessment. Evaluation of pesticides on the national level for the purpose of regulation involves a tremendous duplication of efforts that could be substantially reduced by effective cooperation on the international level.

Environmental Health↗
PubMed1993

Correlations between radiological and cytological findings in early development of bronchopulmonary dysplasia.

Sequential chest radiographs from 40 newborn infants requiring assisted ventilation for respiratory distress syndrome or other conditions were evaluated with a new scoring system aiming at identifying abnormal expansion patterns and interstitial infiltrates representing an early stage of bronchopulmonary dysplasia (BPD). Age at examination ranged from 3 to 23 days. Tracheal effluent samples obtained from the babies during the same period of observation were examined cytologically for evidence of regenerating airway epithelium with squamous metaplasia, indicating BPD. According to the radiological scoring system 24 babies (60%) developed BPD, first diagnosed at a median age of 9 days. By cytological criteria 20 babies (50%) developed BPD, first diagnosed at a median age of 10.5 days. The results from radiological and cytological diagnosis of BPD were concordant in 16 babies (P < 0.05 by chi-square test). Using oxygen dependency at the age of 28 days as evidence of established BPD, the radiological scoring system alone had a sensitivity of 93% and a specificity of 53%. The corresponding figures for cytological assessment alone were 73% and 58%, respectively. By combining radiological and cytological findings, values for sensitivity and specificity were 67% and 68%, respectively.

Bronchopulmonary Dysplasia↗
PubMed1993

The interaction between different domains of staphylococcal protein A and human polyclonal IgG, IgA, IgM and F(ab')2: separation of affinity from specificity.

Binding properties of staphylococcal protein A (SpA) to different human immunoglobulins have been investigated. In this analysis, intact SpA as well as SpA-derived fragments containing one to five IgG-binding domains of different compositions, were used. The affinity binding constants of the different proteins to human polyclonal IgG, IgA, IgM and F(ab')2-fragments as well as their binding capacity to the immunoglobulin molecules were determined. The results show that although all the proteins bound to IgG, regardless of size or composition, the binding strength differed significantly. Proteins containing five domains have a stronger affinity for IgG than those containing one or two. There were no marked differences in binding strength between different domains. However, the binding ability to IgA and IgM showed a marked difference between the various SpA-derived proteins of different compositions. This discrepancy was correlated to differences in their relative binding properties to isolated F(ab')2-fragments of IgG. Hence, we conclude that the binding affinity is mainly affected by the number of domains, whereas the binding specificity is to a large extent determined by which domains are selected.

Antibody Affinity↗
PubMed1993

A standard protocol for phototoxicity testing. Results from an interlaboratory study.

Based on experience accumulated in a number of laboratories, a standardized protocol for phototoxicity testing in experimental animals by the dermal route is presented. By conducting a limited interlaboratory study, demonstrating a high degree of consistency using 8-methoxypsoralen (8-MOP) and acridine, the sensitivity and reproducibility of the proposed methodology is demonstrated. Important aspects of performing phototoxicity testing are discussed.

Acridines↗
PubMed1993

Asthma, rhinitis, and dermatitis in workers exposed to reactive dyes.

A survey was conducted at 15 textile plants with dyehouses in western Sweden. Employees with a history of work related rhinitis, asthma, or skin symptoms were offered a clinical and immunological investigation including skin prick tests, skin patch tests, and radioallergosorbent tests (RASTs) to detect specific allergy to reactive dyes. Among the 1142 employees, 162 were exposed to reactive dyes and 10 of these (6%) reported work related respiratory or nasal symptoms. An allergy to reactive dyes could be confirmed in five (3%, 95% confidence interval 1-7%). All but one had been exposed to reactive dyes for one year or less before the onset of symptoms. Positive RASTs could be detected in four of the five patients. All of the RAST positive patients were positive to remazol black B, but six out of eight additional remazol dyes also elicited positive results. RAST and RAST inhibition showed a cross reactivity between some of the dyes. Seven persons with work related dermatitis and three with urticaria or Quincke oedema were found. In one patient contact dermatitis to a monoazo dye was shown, but no positive patch test reactions to reactive dyes. IgE-mediated allergy to reactive dyes seems to be an important cause of respiratory and nasal symptoms among dyehouse employees exposed to dust from reactive dyes.

Adult↗
PubMed1993

Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA).

Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat model with two tumor sites--one intramuscular (im) and one below the subrenal capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose column after injection of 125I-labeled biotinylated L6 MAb. The animals received 10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy of the procedure in removing plasma activity was 80-95%. For both tumor sites, the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6 (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of larger amounts of MAb, probably causing a higher degree of tumor saturation, will not necessarily improve the T/N ratio after ECIA.

Adenocarcinoma↗
PubMed1993

A general, extracorporeal immunoadsorption method to increase the tumor-to-normal tissue ratio in radioimmunoimaging and radioimmunotherapy.

The aim of this study was to investigate a new extracorporeal immunoadsorption method to improve tumor-to-normal tissue ratios in radioimmunoimaging (RII) and radioimmunotherapy (RIT). We have developed and investigated a general method using biotinylated antibodies and an agarose-avidin column for extracorporeal immunoadsorption. The studies were made in an animal model and extracorporeal immunoadsorption (ECIA) was performed 24 or 48 hr after the injection of 125I-labeled biotinylated antibodies. In athymic rats, heterotransplanted with human malignant melanoma, 90%-95% of the circulating activity was removed with ECIA. The tumor-to-normal tissue ratios at 24 hr was increased 4 times (from 1.2 to 5.1) in the liver, 2.5 times (0.7 to 1.8) in the lung, 4 times (1 to 4) in the kidneys and 4 times (1.4 to 5) in the bone marrow. Whole body activity was reduced by 40%-50%. Tumor-to-organ ratios at 48 hr were increased 3.5 times (from 1.5 to 5.2) in the liver, 2 times (0.9 to 1.7) in the lung, 3 times (1.3 to 3.8) in the kidneys and 4 times (1.4 to 5.5) in the bone marrow. Whole body activity was reduced by 35% when ECIA was performed 48 hr after injection. This study proves that an important reduction in background activity, and thereby an improvement in the tumor-to-background ratio, can be achieved by using this generally applicable, biotin-avidin ECIA method. For RII, the improved ratio increases the possibilities of detecting tumors and metastases in blood-rich organs. For RIT, the procedure may lead to a decreased absorbed dose to bone marrow and other critical organs.

Animals↗
PubMed1992

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↗