Biomedical subjects

L E Ericson

Publications and source records attributed to L E Ericson.

At least 73 records · Page 4Linked to original sources

PubMed1986

Release of serotonin from human carcinoid tumor cells in vitro and grown in the anterior eye chamber of the rat.

Serotonin (5-HT)-producing human carcinoid tumors have been successfully transplanted to the anterior eye chamber of cyclosporine treated rats. Tumor transplants were rapidly vascularized and viable tumor cells could be demonstrated in transplants grown for 2 to 3 weeks in oculo. The release of 5-HT from carcinoid tumor cells grown in the anterior eye chamber and from tumor cells in suspension was studied after stimulation with various adrenoceptor agonists. A dose dependent release of 5-HT upon stimulation with isoprenaline was demonstrated for all viable carcinoid tumors in oculo. The isoprenaline-stimulated release of 5-HT from the tumor cells was further studied in vitro, and was efficiently antagonized by propranolol or nadolol, but not by phenoxybenzamine, indicating activation of beta-adrenoceptors on carcinoid tumor cells upon isoprenaline stimulation. Incubation of tumor cells with verapamil, a calcium channel inhibitor, also prevented the release of 5-HT upon isoprenaline stimulation. Thus, carcinoid tumors can be successfully transplanted to the anterior eye chamber of cyclosporine treated rats, offering new possibilities to study the pharmacologic and biologic features of this tumor. In the future, carcinoid tumors, as well as other endocrine tumors, may be grown in oculo in rats and receptor pharmacology and individual sensitivity to cytotoxic drugs can be studied, thus enabling optimal clinical treatment.

Aged↗

PubMed1986

Joint fluid leukocyte activation by preformed immune complexes.

Acute synovitis was induced in rabbit knee joints by intraarticular injection of preformed bovine serum albumin (BSA) -anti BSA immune complexes (ICs). Polymorphonuclear granulocytes (PMNGs) which had migrated into joints injected with ICs were degranulated and contained ICs as revealed by electron microscopy and were activated as revealed by the measurement of chemiluminescence (CL). In contrast, leukocytes from control joints injected with BSA and normal rabbit serum as well as glycogen-elicited peritoneal leukocytes did not display any morphological changes and did not show CL. Compared to cells from other sources, leukocytes from IC joints showed a decreased CL response when stimulated in vitro with ICs but not with opsonized zymosan, suggesting a stimulus-specific modification of the PMNG responsiveness. Inhibition experiments showed that oxygen radicals and formation of arachidonate metabolites, mainly of the lipoxygenase pathway, were involved in the CL response of the IC-stimulated joint fluid PMNGs. Our observations on morphology, activity, and responsiveness of emigrated cells from the various sources suggest, together with previous observations, that the reaction of leukocytes in IC-induced synovitis consists of an initial migration phase not related to an increased CL and a subsequent activation phase characterized by degranulation, phagocytosis of ICs and increased CL.

Animals↗

PubMed1986

Experimental hyperthyroidism stimulates axonal growth in mesothelial chambers.

An experimental model is presented for studying axonal growth after experimental hyperthyroidism and hypothyroidism. The left sciatic nerve of the rat was transected and transposed to the back. The proximal nerve stump was inserted into a 50-mm-long mesothelial chamber leaving the distal end of the chamber open. Different groups of young adult rats were given daily injections of thyroxine (10 micrograms/100 g body weight) or the goitrogen, thiamazol, in the drinking water (0.125 g/liter) for 12 weeks. Thyroxine treatment increased significantly the extent of axonal outgrowth from the proximal nerve stump compared with untreated rats. Experimental hypothyroidism (thiamazol treatment), evidenced by a retarded body growth, did not affect the extent of axonal outgrowth. In other experiments the left proximal nerve stump was cross-anastomosed with the right distal nerve stump. The two nerve stumps were bridged with a mesothelial chamber leaving a 15-mm gap. This gap distance is known from our previous studies to inhibit axonal overgrowth to the distal nerve stump. As evidenced by histological evaluation, in three of six thyroxine-treated rats, axons had bridged the 15-mm gap. We conclude that experimentally induced hyperthyroidism enhances axonal growth in mesothelial chambers.

Animals↗

PubMed1986

Graded response in the individual thyroid follicle cell to increasing doses of TSH.

The in vivo activation of rat thyroid follicle cells by increasing doses of TSH (1-100 mU) was studied by quantitative light and electron microscopy. The number of pseudopods induced after 20 min by 5, 20, 50 and 100 mU was the same but a dose-dependent increment of the individual pseudopod size (measured as profile area or membrane surface area) was observed, suggesting a graded response in the individual follicle cell. The number of pseudopods induced by 1 mU was only 10% of that in the other group. Another early effect of TSH, besides the induction of psuedopods, is stimulation of exocytosis. The number of exocytotic vesicles in pseudopod-bearing follicle cell profiles (the presence of a pseudopod taken as a sign of activation) decreased in a dose-dependent manner. This indicates that the follicle cell does not respond in an all-or-none mode (in which case a similar decrease in vesicle number in activated cells should be expected irrespective of the level of TSH) and that the response in the individual cell is graded depending on the level of TSH stimulation.

Animals↗

PubMed1986

Effect of cyanide and verapamil on sodium-free contractures in the frog heart.

Sodium-free contractures were studied in myocardial strips from R. pipiens with extracellular sodium (Na0+) replaced by choline chloride and extracellular calcium (Ca20+) varied with EGTA buffer. At calculated Ca02+ below 2.8 X 10(-7) mol/l, no contracture occurred in most of the experiments, even in the presence of cyanide. When Ca02+ was above 2.8 X 10(-7) mol/l, relatively short tension transients of up to 80 sec duration could be avoided if the myocardial strip was previously equilibrated for 20 min in a Na+-Ca2+-free solution. Instead, contractures developed slowly within one to several hours. The maximum contracture was dependent on Ca02+ in a dose-response-like pattern. The time-course of contracture development was not affected by verapamil, but KCN significantly increased the rate of resting tension increase. In solutions with normal Na+-Ca2+ content and even in a Na+-Ca2+-free milieu, the cellular ultrastructure was normal. Development of contracture after addition of Ca2+ to the Na+-free solution was combined with ultrastructural damage of the ventricular strip. It is concluded that Na+-free contractures depend on transsarcolemmal net-Ca2+ uptake as a sum of Na-Ca-exchange-dependent Ca2+ uptake and active sequestering of intracellular free calcium Ca2+ mediated by sarcolemmal and probably intracellular Ca2+-ATPases. The negative inotropic effect of the Ca blocker verapamil seems not to be mediated by the Na-Ca exchange.

Animals↗

PubMed1986

Location of epidermal growth factor receptors on porcine thyroid follicle cells and receptor regulation by thyrotropin.

By using a direct electron microscopic autoradiographical technique, we were able to demonstrate that the epidermal growth factor (EGF) receptor is asymmetrically located on polarized porcine thyroid follicle cells cultured on a collagen gel matrix. More than 80% of autoradiographical grains from [125I]EGF were associated with the basolateral cell surface compared to only about 2.5% at the apical cell margin. EGF stimulated growth only when the collagen gels were floating, indicating a basolateral location of functional EGF receptors. Preincubation with TSH or another stimulator of cAMP synthesis, forskolin, increased binding of [125I]EGF to the cells. Moreover, the subsequent mitogenic response to EGF was potentiated by such pretreatment. The results are in accordance with the hypothesis that TSH potentiates the response to EGF in the stimulation of thyroid growth.

Animals↗

PubMed1986

Implants in the abdominal wall of the rat.

An experimental model is presented that allows qualitative as well as quantitative studies of the soft tissue response to implant materials used in reconstructive surgery. Plugs of non-alloyed titanium and polymers (Teflon, Delrin) were inserted into the abdominal wall of rats, with a portion of the plug penetrating through the peritoneum into the abdominal cavity. The tissue reaction was evaluated by means of light and electron microscopy for up to 9 weeks after insertion. Titanium implants were in direct contact with the connective tissue without intervening inflammatory cells. The defect in the peritoneum was sealed by a close apposition of the mesothelial membrane to the titanium surface and no connective tissue surrounded the intra-peritoneal portion of the plug. In contrast, a fibrous capsule surrounded the intra-peritoneal portion of Teflon and Delrin implants. A reactive zone consisting of active macrophages and giant cells was present at the surface of these implants separating the implant from the surrounding fibrous capsule. This study shows that the tissue response at the interface to foreign materials can be studied using light and electron microscopic techniques and that profound differences in tissue response exist between different materials.

Abdominal Muscles↗

PubMed1985

Subcellular localization of serotonin immunoreactivity in rat enterochromaffin cells.

Serotonin immunoreactive material was localized to rat enterochromaffin cells (EC cells) at the subcellular level using antibodies to serotonin (5-HT) raised in rabbits. Ultrathin sections from paraformaldehyde fixed plastic embedded tissues were directly labelled with the 5-HT antiserum, using the protein A-gold technique to visualize the immunoreaction. The 5-HT immunoreactivity (5-HT-IR) in the rat gastrointestinal mucosa was exclusively localized to epithelial EC cells with a low background over other epithelial non-enterochromaffin cells. Quantitative evaluation of the immunoreaction revealed that most of the 5-HT-IR in the cytoplasm of EC cells (60%) was located over the dense cores of the secretory granules. However, a significant part of the cytoplasmic 5-HT-IR (40%) was located outside the dense cores of the secretory granules which suggests that different forms of 5-HT storage may exist.

Animals↗

PubMed1985

Ultrastructural demonstration of iodine binding and peroxidase activity in the endostyle of Oikopleura dioica (Appendicularia).

The endostyles of cephalochordates, ascidians, and larval petromyzontids have the capacity to organify iodine. A similar mechanism in the appendicularian endostyle has hitherto been unknown. Observations in this study of Oikopleura dioica with electron microscopic autoradiography and cytochemistry show that also the appendicularian endostyle has iodinating capacity and that the iodinating cells contain peroxidase, an enzyme responsible for iodination. After incubation in seawater containing 125I-, autoradiography revealed a selective labeling in the dorsal portion of the endostyle. The endostyle of O. dioica is on each side lined by four rows of corridor cells. The autoradiographic grains were mainly located over the endostylar lumen or associated with the luminal surface of the two central rows of corridor cells. These cells, but no other endostylar cells, also showed a positive reaction for peroxidase. The reaction product was distributed along the luminal plasma membrane and was also present in the cytoplasm within rough endoplasmatic reticulum, Golgi apparatus, and vesicles. The selective labeling as well as the cytochemical reaction were abolished by incubation in methimazole, an inhibitor of peroxidase. It is suggested that the two central rows of the corridor cells can be considered as homologs to iodine-binding zones in other endostyles and also as a primitive forerunner to the vertebrate thyroid gland.

Animals↗

PubMed1985

Light and transmission electron microscopy used to study the tissue morphology close to implants.

A methodological study was performed in order to allow the morphological investigation of the interface to titanium bulk implants by light (LM) and transmission electron microscopy (TEM). Titanium implants were removed 3-9 wk after insertion in the knee joints or the abdominal wall of rabbits and rats. After fixation, the implants were either removed before embedding or separated from the surrounding tissue after the embedding of tissue and implant en bloc. While implant removal before embedding often caused minor defects in the interface, separation after embedding left the interface intact. TEM showed a thin layer of amorphous substance separating intact cells and collagen fibrils. No tissue remnants were revealed by scanning electron microscopy (SEM) on the surface of implants separated after embedding. The good preservation of the interface and the possibility to also examine ultrastructurally the intact tissue surrounding bulk implants, including very thin cell layers, make the method useful for biocompatibility studies in vivo.

Animals↗

PubMed1985

Effects of TSH on iodination in rat thyroid follicles studied by autoradiography.

The possible functional relation between TSH-stimulated exocytosis and TSH-stimulated iodination in the thyroid gland was studied using quantitative EM autoradiography and cytochemistry. The study was performed in rats pretreated with thyroxine for 2 days. TSH, giving i.v. 10 min before sacrifice to thyroxine-treated rats, increased organification of 125I by about 50%. TSH decreased the number of peroxidase-positive vesicles in the apical cytoplasm and increased the width of the peroxidase reaction at the apical plasma membrane, suggesting a redistribution of peroxidase. EM autoradiography after labelling with [3H]leucine showed that TSH caused a rapid redistribution by exocytosis of newly synthesized protein to the follicle lumen. The protein deposited in the lumen remained to a large extent in the microvillus region. 10 min after injection of 125I, newly iodinated protein was distributed in a gradient in the lumen periphery. TSH, given 5 min before 125I, caused a significant increase in the labelling of the colloid in the microvillus region, indicating a selective incorporation of iodine into newly synthesized molecules deposited in this region by stimulated exocytosis. Our results confirm and extend earlier observations on a functional link between exocytosis and iodination. Redistribution of peroxidase as well as newly synthesized protein to the site of iodination might be of importance.

Animals↗

PubMed1985

Proliferative synovitis in rabbit knee joints induced by antigen and preformed immune complexes.

Knee joints of non-immunized rabbits were repeatedly injected with bovine serum albumin (BSA) and preformed BSA-anti-BSA immune complexes which had differing precipitation profiles and abilities to activate complement. Ten days after the last of six injections the antibody and lymphoproliferative responses to BSA were analysed and correlated to the degree of arthritis. Joint swelling, increased numbers of joint fluid leukocytes and morphological changes typical of proliferative synovitis were found only in those rabbits injected with a large dose of antigen or with immune complexes prepared in antigen excess of poor precipitation and complement-activating properties in vitro. The degree of arthritis correlated with the development of humoral and lymphoproliferative immune responses to BSA.

Animals↗

PubMed1984

In vivo shedding of apical plasma membrane in the thyroid follicle cells of the mouse.

Clusters of luminal dense bodies, limited by a triple-layered membrane, were found in all follicle lumina in thyroid glands of mice. After thyroxine treatment the number of luminal dense bodies increased, especially in the periphery of the lumen, where the intraluminal bodies often displayed a striking resemblance to microvilli. In hyperplastic goiters, obtained by feeding mice with propylthiouracil, luminal dense bodies were replaced by intraluminal vesicles. During goiter involution the vesicles were gradually replaced by luminal dense bodies; the presence of intermediate forms suggests that vesicles and dense bodies are basically the same formations. Luminal dense bodies were observed in colloid droplets indicating their removal by endocytosis. As demonstrated by electron-microscopic cytochemistry, luminal dense bodies contain a membrane-bound peroxidase, and electron-microscopic autoradiography after administration of 125I indicate that they possess an iodinating capacity. Our observations on mouse thyroid glands suggest that the luminal dense bodies, which appear as vesicles in hyperplastic glands, are formed by shedding of the apical plasma membrane of the follicle cell. The shedding process might be of importance for the turnover of plasma-membrane material.

Animals↗

PubMed1984

Diffusion artefacts and tissue fixation in thyroperoxidase cytochemistry.

The distribution of endogenous peroxidase activity in rat, mouse and human thyroid follicle cells was studied with electron microscopic cytochemistry after incubation in 3-3'-diaminobenzidine (DAB). In all three species enzyme activity was found at the apical plasma membrane (facing the follicle lumen) as well as in intracellular compartments. The enzyme activity in the apical plasma membrane was more sensitive to changes in fixation conditions than the activity in intracellular compartments. Under optimal conditions more than 90% of the follicle cells in normal rat thyroids displayed a cytochemical reaction at the apical plasma membrane. In all three species the reaction product at the apical plasma membrane formed a gradient which extended into the colloid which otherwise was unreactive. Evidence obtained indicated that this gradient was not due to the presence of soluble peroxidase in the lumen but most likely signified the diffusion of the reaction product from the membrane-bound enzyme.

3,3'-Diaminobenzidine↗

PubMed1984

Ultrastructural morphology and evidence of iodide uptake and protein synthesis in normal human thyroid transplants in nude mice.

Normal human thyroid tissue was xenotransplanted to athymic mice. Well preserved structural properties of the transplants were observed at both light and electron microscopical level. Analysis of the soluble proteins in the transplants by polyacrylamide gel electrophoresis showed that the major fractions were the 19S thyroglobulin, the 27S iodoprotein and a larger protein fraction. Protein synthesizing capacity of the transplants, as measured by in vivo 3H-leucine incorporation into the soluble transplants proteins was demonstrated. The observed 3H-leucine incorporation was in the same magnitude as that found in the original donor tissue at the time of transplantation. Four weeks after transplantation a significant 125I-iodide uptake (2.0%) was observed in the transplants. Corresponding value for the host thyroids was 6.6%. The biological half-time of the accumulated 125I-iodide in the transplants was reduced from 97 days to 38 days between 2 and 4 weeks after transplantation. The biological half-time in the host thyroid increased from 27 days to 32 days during the same period. This investigation shows that normal human thyroid tissue can be transplanted to nude mice with preserved tissue organisation and maintained cellular function.

Animals↗

PubMed1984

Effect of a second dose of thyrotropin on exocytosis and endocytosis in the rat thyroid gland.

The effect of TSH on exocytosis and endocytosis in thyroid follicle cells was studied with electron microscopic stereology. Groups of rats, pretreated with T4 for 2 d, were injected iv with TSH (500 mU) 20 min, 2, 4, 6, and 8 h before perfusion fixation. Parallel groups were given a second dose of TSH 2, 4, 6 and 8 h after the first one and the thyroids were fixed after 20 min. In controls, injected with saline, the membrane surface area (msa) of exocytotic vesicles was about the same as that of the apical plasma membrane. Pseudopods and colloid droplets were not present. TSH induced exocytosis. The msa of exocytotic vesicles was reduced by about 85% already after 20 min and was even more reduced after 2 h. At later times after injection of TSH the msa of exocytotic vesicles increased gradually to reach control levels after 8 h. TSH also induced endocytosis. After 20 min the increase in msa of endocytotic structures (pseudopods, colloid droplets and micropinocytotic vesicles) corresponded to the decrease in msa of exocytotic vesicles during the same time interval. The msa of endocytotic structures remained high at 2 h but decreased gradually at later time intervals and after 8 h no pseudopods and colloid droplets remained in the apical cell region. A second injection of TSH given 2 h after the first one when few exocytotic vesicles were present did not influence the msa of endocytotic structures. At later time intervals a second dose of TSH stimulated exocytosis as well as endocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Iodine binding in the endostyle of larval Branchiostoma lanceolatum (Cephalochordata).

The asymmetrical endostyle of Branchiostoma larvae contains two different zones of mucus-producing cells which metamorphose to the paired zones 2 and 4 respectively in the endostyle of the adult. In both the larva and the adult these zones are parts of the food-trapping mechanism. An endostyle zone, which has a position corresponding to that of the paired iodinating zones in the endostyle of the adult, binds iodine selectively. The ultrastructure and labeling pattern indicate that the labeled cells in the larval endostyle belong to functionally different types. In one region of the iodinating zone iodine is mainly bound extracellularly at the apical cell surface. Also in the second region grains are located at the apical cell surface as well as over the cytoplasm and extracellularly at the basal plasma membrane. It is possible that iodination takes place in the lumen close to cells in the first region and that the labeled product is taken up and eventually released by cells of the second region. Our observations show that this primitive endostyle already has iodinating capacity and may synthesize and release thyroid hormones.

Animals↗

PubMed1984

Intraluminal iodination of thyroglobulin.

The intraluminal distribution of newly synthesized (injection of [3H]leucine) and newly iodinated (injection of Na125I) proteins in thyroids of rats given T4 for 2 days was studied with quantitative electron microscopic autoradiography. Three, 4.5, and 6 h after [3H]leucine about 90%, 85%, and 65%, respectively, of the luminal label was confined to the microvillus region. This distribution differed from that of newly iodinated protein; already 2 min after injection only about 30% of the grains was located over the microvillus region. The remaining 70% of the grains located outside the microvillus region formed a gradient towards the center of the lumen. The grain distributions 30 min and 2 h after Na125I were similar to that present after 2 min. The distribution of grains after pulse labeling with Na125I (injected 2 min before propylthiouracil and 2 h before fixation) was also similar to that found in rats injected with Na125I alone, indicating that diffusion of labeled proteins in the lumen was very slow in T4-treated rats. A slow diffusion was also suggested by the presence of an unlabeled peripheral ring in follicle lumens of T4-treated rats injected with Na125I 48 h before fixation. In normal rats given [3H]leucine 3 h before fixation or Na125I 1 h or 48 h before fixation the grains were homogeneously distributed in most follicle lumens. Together our findings indicate that (1) administration of T4 has effects on the diffusion properties of the colloid; (2) iodine is incorporated not only into newly synthesized thyroglobulin recently delivered to the follicle lumen but also into molecules already stored in the lumen; (3) a portion of the iodine incorporated into proteins is bound to molecules which are not in direct contact with thyroperoxidase in the apical plasma membrane.

Animals↗