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Biomedical subjects

I Olsen

Publications and source records attributed to I Olsen.

At least 235 records · Page 13Linked to original sources

Whole-body autoradiography of 63Ni in mice throughout gestation.

Whole-body autoradiography was used to study nickel uptake and retention in mice throughout gestation. After an intraperitoneal injection of 50 muCi 63NiCl2 into a 16-day-pregnant mouse, nickel appeared rapidly in connective tissues. Prominent sites of radioactivity 72 h after injection included the visceral yolk sac, lung, gastrointestinal tract and kidney. Nickel crossed the placental barriers throughout gestation, i.e. the visceral yolk sac during early gestation, the visceral yolk sac and chorioallantoic placenta during late gestation. A marked uptake of nickel was seen already in the 5- and 6-day embryo. Fetal accumulation of nickel took place up to 16 days gestation. Whereas nickel was distributed throughout the early embryo, distribution became more differentiated with increasing gestation, imitating that in the mother. Penetration of nickel into the mouse conceptus makes possible a similar ability in the human conceptus.

Animals↗

90Sr placentas, embryos and foetuses of mice, evaluated by whole-body autoradiography.

90Sr is a hazardous fission product from nuclear reactions. Its transplacental passage is of particular interest because of the high sensitivity of embryos/foetuses to ionizing radiation. We have used whole-body autoradiography to study the foetal uptake and retention of 90Sr and the embryonic/foetal transfer of this isotope as a function of gestational age. Fifteen minutes after an intraperitoneal injection of 50 muci 90Sr-nitrate into a 14-day-pregnant mouse, radioactivity was present in the placenta, but not in the foetus. During a 72-hour observation period, 90Sr gradually accumulated in the hard foetal tissues. In the soft foetal tissues, accumulation occurred up to 12--24 hours. After 72 hours, no 90Sr could be detected in the soft tissues. 90Sr crossed the visceral yolk sac placenta during early gestation, the visceral yolk sac and the chorioallantoic placentas during late gestation. Transfer increased considerably at the end of the latter period. There was a marked uptake of 90Sr in all structures of early embryos, whereas the isotope concentrated in the preskeletal and skeletal parts of the foetuses. Intake of 90Sr during early gestation may therefore be more injurious to the offspring than intake during late gestation.

Animals↗

Effect of cadmium acetate, copper sulphate and nickel chloride on organ cultures of mouse trachea.

Tracheas from albino mice were excised and cut into rings approximately 1 mm thick. After preincubation overnight in Medium 199 with 5% calf serum, they were placed into fresh medium. Cadmium acetate, copper sulphate or nickel chloride was added separately or in combination, to a final concentration of 10--200 micron. Each metal was also added (10 micron) to serum-free Medium 199. The percentage (0--100) of the inner intact epithelium and the rate (0--4) of the ciliary beat in each ring were assessed before and during a 4-hour incubation period and multiplied to yield a relative activity index (0--400). Cadmium acetate at 10--100 micron depressed the ciliary activity significantly more than 10--100 micron copper sulphate (each level P less than 0.05). With 200 micron a 50% reduction of the activity index was observed after approximately 35 min. with cadmium acetate and 85 min. with copper sulphate. At 10--200 micron, cadmium acetate was significantly more suppressive than nickel chloride (each level P less than 0.05). When comparing the inhibitory effects of copper sulphate and nickel chloride a significant difference appeared at 10--100 micron (each level P less than 0.01), but not at 200 microm (P less than 0.05). With 200 micron nickel chloride a 50% reduction in the activity index was observed after 90 min. There was a tendency towards reduced toxicity of cadmium acetate when combined with copper sulphate and of copper sulphate when combined with nickel chloride. In serum-free medium metal toxicity was increased.

Animals↗

Autoradiography of 90Sr in developing rats.

The distribution patterns of 90Sr in five littermate, 8-day-old Wistar rats were studied by whole body autoradiography. Rats were killed 15 min, 1, 4, 24, and 72 h after a single intraperitoneal injection of the isotope. Immediately after administration, 90Sr was distributed throughout most of the soft tissues of the body. The soft tissue deposits had practically disappeared after 4 h. In the hard tissues of the body 90Sr accumulated up to 24-72 h. Fifteen minutes after injection the uptake of 90Sr in the enamel of the teeth was highest in the occlusal and incisal regions. 90Sr gradually accumulated throughout the enamel and after 72 h its distribution in this layer was fairly uniform. Immediately after injection a narrow zone of radioactivity appeared in the dentin near the pulp. This zone broadened with time towards the dentinoenamel junction and included the entire dentin layer 72 h after injection. Initially, the uptake of 90Sr was higher in the dentin thatn in the enamel, particularly in the cervical areas of the crown. This difference became less apparent with time. There was good correlation between the uptake in teeth and bones, supporting the use of teeth as indicators of the 90Sr body burden.

Animals↗

Transport of DNA from lymphocytes to fibroblasts in culture.

The exchange of radioactivity between lymphocytes, labelled with (3H) thymidine after stimulation with Concanavalin A, and recipient V79 fibroblasts in culture was studied. The radioactive material involved in this exchange was macromolecular deoxyribonucleic acid as well as its breakdown products. This deoxyribonucleic acid from lymphocytes localised in the nuclei of the host cells soon after contact between donor and recipients. This occurred even when the V79 fibroblasts were confluent at high cell density, and thus in a steady, non-growing state with respect to cell numbers. The fate of the radioactive donor lymphocyte deoxyribonucleic acid, substituted with bromodeoxyuridine, was followed in the recipient cells by analysing its buoyant density in caesium chloride gradients. This deoxyribonucleic acid was found to become associated with the nuclear deoxyribonucleic acid of the host cells, involving both retention of relatively intact donor deoxyribonucleic acid as well as its breakdown and re-utilisation for host cell deoxyribonucleic acid synthesis. Non-growing recipient cells were found to retain the donor deoxyribonucleic acid in relatively intact form for much longer periods than when the same cells were in logarithmic growth phase.

Cell Division↗

Experimental Candida-induced denture stomatitis in the Wistar rat.

An experimental model of yeast-induced denture stomatitis has been set up in the rat by inoculating Candida albicans on the fitting side of a maxillary acrylic plate retained by an orthodontic band around the incisors. Thirty-eight Wistar rats were used in two series of experiments with an observation period of 2 weeks. In each of the series there were one control and three experimental groups. Control rats were left untreated, while rats of the experimental groups wore either uninoculated or inoculated plates, or had their palatal mucosa smeared with the yeast. For cytologic examination the palate was scraped in Series I and the fitting side of the plate in Series II. After 1 week a generalized simple inflammation had developed in the palate of most animals of the experimental groups. It was most severe and persistent in rats with inoculated plates. Histologic signs of inflammation and hyphal formation were also most pronounced in this group. Hyphae did not invade the epithelium. Except for an initial loss of body weight, which was restored by day 10 or 12, the rats tolerated their plates. The Wistar rat seems to be well suited for experimental studies on denture stomatitis.

Animals↗

The fate of concanavalin A-stimulated lymphocytes in the spleens of recipient mice.

The fate of mouse spleen cells, stimulated with Concanavalin (Con A) and labelled with [3H] thymidine in culture, has been followed after transfer into recipients, syngeneic to the cell donors. The labelled cells, localizing in the spleen, were found mainly in the white pulp in both germinal centre and periarteriolar sheath areas. The number of cells with labelled nuclei found in the spleens of recipients was much greater than could be accounted for simply on the basis of the radioactivity present. Using donor cells, whose DNA had been substituted with bromodeoxyuridine (BUdr) in sufficient amounts to increase its buoyant density, it was concluded that redistribution of label rather than cell division was responsible for this increase of labelled nuclei. In addition to these findings, the spleens of recipient mice showed evidence of a vigorous immunological response to the donor cells, very similar to that following injection of an antigen such as sheep red cells. These results show that caution must be exercised in interpreting the results of transfer of lymphocytes into recipients, even when a highly stable molecule such as DNA contains the radioactively-labelled material such as [3H] thymidine.

Animals↗

Bilateral surgical removal of impacted mandibular third molar teeth as a model for drug evaluation: a test with oxyphenbutazone (Tanderil).

Twenty-four healthy patients undergoing two separate operations for removal of an impacted third molar from one or the other side of the mandible, were included in a double-blind crossover study. On the two occasions either oxyphenbutazone (Tanderil) or placebo was given for 5 days, commencing on the day before surgery. Plasma analyses confirmed drug intake. A number of objective and subjective assessments were recorded for a paired comparison of the postoperative course, including swelling, trismus, local temperature and pain. On the 1st, 3rd and 5th postoperative days after the oxyphenbutazone-operation, the measured swelling averaged 86, 85 and 83%, respectively, of that after the placebo-operation; the corresponding P-values were less than or equal to 0.11, 0.03 and 0.06. Oxyphenbutazone did not significantly reduce the local hyperpyrexia. It exerted, however, an excellent pain relief, which may have contributed to less trismus and patient preference for the course with this drug. The results obtained with this model in humans showed considerable discrepancies with the analgesic and anti-inflammatory effects ascribed to oxyphenbutazone from results in animal models. Side effects were mild and infrequent, and no unfavorable effects on bleeding or wound healing were noted. Routine use of oxyphenbutazone in oral surgery, however, is not recommended.

Adult↗

Effects of mitogenic and antigenic stimulaton on the thymidine kinases of mouse spleen cells in vivo and in vitro.

The DNA-synthesizing ability of mouse spleen cells in vitro and in vivo is paralleled by their levels of cytoplasmic thymidine kinase. However, a very high level of nuclear-associated enzyme activity developed in cultures of both non-stimulated and mitogen-transformed lymphocytes. This activity did not appear in the spleens of mice during the primary immune response to sheep erythrocytes (SRC) or following administration of Convanavalin A (Con A). Feedback inhibition studies with TTP demonstrated that the nuclear enzymes were more sensitive than the cytoplasmic activities. The thermal stabilities of the nuclear enzymes were also found to be greater than the corresponding cytoplasmic ones. Furthermore, analysis of the rate of thermal inactivation indicated that both the cytoplasmic and nuclear enzymes present in transformed lymphocytes in vitro were far more heat-stable than those activities normally found in the mouse spleen, even after antigenic challenge with SRC in vivo or incubation in vitro in the absence of mitogenic stimulation.

Antigens↗

Initiation and aggravation of denture stomatitis by sucrose rinses.

The purpose of this study was to assess whether frequent exposure to sucrose would aggravate or initiate a palatal candidosis in denture wearers. Eight subjects with generalized simple or granular inflammation in the palate (inflammation group) and six with clinically healthy palatal mucosa (control group) carried out 1-min mouthrinses with 10 ml of a 25% sucrose solution four times daily for 15 d. In the inflammation group an aggravated palatal erythema was seen in two subjects after 7 d, and in another subject after 15 d. Among the controls a generalized simple inflammation had developed in the palate of one subject after 7 d, and in another one after 15 d. An increased number of yeast colonies on palatal and denture agar models and/or hyphae on palatal and denture smears was found in all subjects with clinical signs of aggravated or initiated denture stomatitis.

Candidiasis, Oral↗

Cell division and deoxyribonucleic acid (DNA) synthesis in cultures of stimulated lymphocytes.

The responses of lymphocytes cultured with various stimulants were analysed with respect to DNA synthesis and cell division. Autoradiographic labelling with [3H]thymidine indicated that similar proportions of cells had incorporated this labelled precursor for DNA synthesis during both short and long periods of exposure to this specific precursor for DNA synthesis. Changes in labelling index (LI) after pulsing these cells with [3H]thymidine showed that exchange of labelled material, which could not be chased out with unlabelled thymidine, was responsible for the increases of LI seen. Failure to prevent this increase with excess unlabelled thymidine indicated that direct incorporation of [3H]thymidine did not account for this exchange. Using hydroxyurea and colcemid arrest to analyse cell cycle events in these cultures, it was shown that approximately 70 per cent of the responding cells in cultures of stimulated lymphocytes, while actively synthesizing DNA, were not in cell cycle for division. It was concluded that DNA turnover, involving synthesis and exchange of newly synthesized material, possibly DNA, was occurring in these cells.

Animals↗

The effects of thymidine and its analogues on the differentiation of antibody-forming cells.

Thymidine (Tdr) and its analogues 5-fluorodeoxyuridine (FUdr) and 5-bromodeoxyuridine (BUdr) inhibited the development of antibody-producing cells (PFC) in cultures of explants of rabbit spleen stimulated with sheep red cells in vitro. They were effective in this respect, even at concentrations too low to inhibit cell division. The results indicated that Tdr had produced its effects by a selective action on DNA and RNA synthesis. In view of what is known about the mechanisms of action of Tdr and its analogues to interfere with DNA-dependent events in cells, these results supported the idea that DNA synthesis, unrelated to the needs for cell division, was required for the development of antibody-producing capacity by PFC in these cultures.

Animals↗

Bilateral surgical removal of impacted lower third molar teeth as a model for drug evaluation: a test with ibuprofen.

It was considered that double-blind crossover studies of therapeutic efficacy after acute injury could well be done in patients who required surgical removal of impacted wisdom teeth from both sides of the lower jaw. In the present trial 24 healthy patients received either placebo or ibuprofen (Brufen: 400 mg three times daily), a non-steroidal anti-inflammatory agent, for 5 days commencing the day before surgery. Treatments were given on the two occasions when impacted wisdom teeth were to be removed from one side or other of the lower jaw. A number of objective and subjective parameters were recorded for paired comparison of the post-operative courses, including swelling, trismus and pain. A mechanical device which allows simple and accurate measurement of cheek swelling is described. On the 1st, 3rd and 5th post-operative days in the ibuprofen group the measured swelling averaged 93, 89 and 82%, respectively, of that in the placebo group; the corresponding alpha-values were 0.35, 0.06 and 0.07. Patients with less swelling after ibuprofen were not always those with a high serum concentration of the drug. Ibuprofen significantly reduced pain on the day of the operation. This may at least partly account for less trismus and the preference of the patients for their post-operative courses with ibuprofen. Examination of various haematological parameters did not reveal any significant difference between the two operations. Subjective scores indicated that neither wound-healing nor bleeding was affected by ibuprofen, nor were any side effects detected.

Adolescent↗

Thymidine kinase of mouse spleen cells in vivo and in vitro.

The thymidine kinase activity of mouse spleen cells was found to parallel their DNA-synthesizing ability, both in vivo and in vitro. In the former case, more than 90% of the activity of these cells was found in the cytoplasmic fraction. This activity was labile, as was its template mRNA, compared with the nuclear component. The nuclear enzyme increased during culture of the lymphocytes in vitro. Mitogenic stimulation with concanavalin A resulted not only in a greater enhancement of the nuclear activity, but also in a marked increase in the amount of cytoplasmic enzyme. This effect appeared to be mediated via stabilization of the mRNA for the cytoplasmic component. These differences have been considered, especially with respect to the cellular changes that occurred during culture and mitogenic stimulation.

Animals↗

Sudden death in rheumatoid arthritis with atlanto-axial dislocation.

A post mortem material of 11 consecutive cases of severe atlanto-axial dislocation (a.a.d.) with cord compression is reported. The total number of deaths from rheumatoid arthritis (RA) during the period of 5 years was 104, and all were autopsied. Neurological symptoms correlated poorly to fatal a.a.d. Hemiplegia was found in three cases, one of which, however, was caused by thrombosis cerebri. Spastic signs were transiently recorded in two patients and dysphagia in a further two. Five patients had a history of recent vomiting. A.a.d. was the sole or main cause of death in 8 cases and contributory in 2. Sudden death occurred in 7 of the cases. Only 2 cases had obtained a correct diagnosis intra vitam. The CNS findings at autopsy consisted of cord compression (11/11 cases), cord malacia (2/11) and cerebral oedema (3/11). One case had polyarteritis and renal amyloidosis and one pulmonary carcinoma with metastatic spread. Signs of active inflammation in the axial joints were present in 4 cases. This study, based on systematic post mortem examinations, revealed an unexpectedly high and not previously reported incidence of fatal medulla compression in RA patients with a.a.d. (10%).

Arthritis, Rheumatoid↗