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S Smeds

Publications and source records attributed to S Smeds.

At least 19 recordsLinked to original sources
PubMed1992

The importance of the centroacinar region in cerulein-induced mouse pancreatic growth.

Early proliferation events within different exocrine pancreatic cell compartments were studied in mice with or without cerulein administration. A technique with 3H-thymidine labeling of DNA-synthesizing cells was used. Groups of five animals were given either cerulein (20 micrograms/kg/24 h) or saline subcutaneously twice daily. 3H-thymidine was given as a single injection, 300 microCi intraperitoneally, on the 3rd and 8th day of cerulein or saline administration, and the fraction of labeled cells in each cell compartment (3H-thymidine labeling index, TLI) was calculated on the basis of autoradiographic analyses of the tissue. In a second set of experiments the distribution of the tracer between cell compartments, when given on the 3rd day of cerulein (saline) administration, was followed over a 5-day period. The highest proliferative rate was observed in the centroacinar cell compartment (TLI, 6%), and newly formed cells were accumulated during the 5-day 'chase' period. During the same time the relative amount of labeled centroacinar cells increased and comprised 40% of all labeled exocrine cells. The relative size of the compartment did not increase, indicating increased cell turnover with loss of or possibly migration of centroacinar cells into other pancreatic cell compartments. Weak and no trophic effects of cerulein were seen on the acinar and ductal cell populations, respectively. In the control group labeled ductal cells were significantly reduced during the chase period. This was not observed in the cerulein group, indicating addition of labeled cells to this compartment from other sources. A significant non-cerulein-dependent relative increase and decrease of the ductal and acinar cell compartments, respectively, were observed during the chase period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hormone receptors, ploidy and proliferation rate in breast cancers up to 10 mm.

A total of 191 malignant mammary lesions of 10 mm or less in diameter have been analysed with regard to hormone receptor content (107 of 179) and ploidy (112 of 191) in a repeated mammography screening population (second to fourth screening round). Forty-eight per cent were diploid and 68% oestrogen receptor-positive. Mean proliferation rate, calculated as S-phase fraction (SPF), was 6.2 +/- 5.0. Significantly lower SPF was observed in diploid tumours. In very small tumours (less than or equal to 5 mm) SPF was higher as was the fraction of receptor-negative tumours. Among these small cancers a hypothetical high-risk group with SPF greater than or equal to 10% and receptor-negativity will contain 7% of the patients. If SPF and receptor content are chosen as prognostic factors, the latter patients may be a group suitable for adjuvant therapy in treatment schedules.

Adult↗
PubMed1991

Suramin inhibits growth of human osteosarcoma xenografts in nude mice.

The effect of suramin on tumor growth and morphology in two different human osteosarcoma xenografts (L-I OSM and L-II OSM) grown in BALB/cA-nu/nu mice was studied. Suramin (total dose, 720 mg/kg) given by i.p. injection (60 mg/kg/dose) for up to 9 weeks significantly inhibited osteosarcoma cell growth in both tumors, suramin-treated tumors showing only one-third or less of the volume of nontreated controls. Cell cycle distribution of tumor cells measured by DNA flow cytometry demonstrated that suramin treated caused accumulation of cells in the S and G2 phases of the cell cycle, in both L-I OSM and L-II OSM. In the aneuploid L-II OSM tumor suramin preferentially inhibited the growth of aneuploid cells, leading to a decrease in the ratio of aneuploid to diploid cells. Both osteosarcomas retained their histological appearance and the liver, spleen, heart, and kidneys of the treated animals were unaffected by suramin. These results are compatible with the view that suramin inhibits the growth of human osteosarcomas by cytostatic effects.

Animals↗
PubMed1991

Cell proliferation rate and tumor volume in human osteosarcoma during exposure to methotrexate. A study on tissue transplants in nude mice.

The growth inhibitory effect of methotrexate (MTX) on osteosarcoma cells was studied in dysthymic nude mice bearing tumor transplants obtained from a patient before (PRE-CHEM) and after (POST-CHEM) preoperative chemotherapy for osteosarcoma of the distal femur. Cell proliferation was analyzed by autoradiographic evaluation of the fraction of labeled cells after continuous administration of 3H-thymidine for seven days. Histomorphometric analysis of the tissue distribution of cells in the partly ossified tumors was performed. The PRE-CHEM sarcoma transplants showed a significant reduction of labeled interphases from 52 to 1.7 percent upon daily MTX treatment of the mice as compared to controls. In contrast, MTX treatment did not inhibit cell proliferation in the POST-CHEM tumor transplants in which approximately 70 percent of the cells were labeled. Tumor volume increased by 65 and 54 percent in the MTX-treated PRE- and POST-CHEM groups, respectively. During the same eight-day period, control transplant volume increased by 30 percent (PRE-CHEM) and 20 percent (POST-CHEM). Tumor cell densities in the MTX-treated groups were reduced by a factor of approximately 11 in the PRE-CHEM transplants and by a factor of approximately 1.5 in the POST-CHEM transplants. The results show that in this patient the osteosarcoma cells had changed their responsiveness to MTX during the preoperative chemotherapy period. In both the MTX-sensitive and non-sensitive tumor lines, exposure to MTX induced increased tumor volume by increasing the extra cellular matrix volume, irrespective of the neoplastic cell proliferation rate. This effect of MTX was most pronounced in the MTX-sensitive tumor line. These results indicate that in the clinical situation it is difficult to judge the response to chemotherapy even from morphologic parameters.

Adolescent↗
PubMed1991

Coexpression of functionally active receptors for thyrotropin and platelet-derived growth factor in human thyroid carcinoma cells.

In the present study we show the simultaneous expression of functionally active receptors for TSH and platelet-derived growth factor (PDGF) in a newly established human anaplastic thyroid carcinoma cell line, HTh 74. In Northern blot analysis of RNA extracted from HTh 74 cells a low expression of both TSH and PDGF receptor messenger RNA was found. These observations in conjunction with the fact that the cells contain cytokeratin clearly demonstrate that the cells are bona fide epithelial thyroid cells. Stimulation of HTh 74 cells with TSH led to a concentration-dependent increase in cAMP formation, showing a functional activity of the TSH receptors. Northern blot analysis, immunoprecipitation, immunofluorescence staining, and binding experiments showed the presence of both alpha- and beta-type PDGF receptors in the HTh 74 cells. The functional activity of the PDGF receptors was demonstrated by ligand-induced internalization of the receptors and PDGF-induced growth of the HTh 74 cells. The significance of the expression of PDGF receptors on thyroid epithelial cells is not clear. However, it might reflect the gain of a new growth stimulatory pathway participating in the transformation of the epithelial thyroid cells. Alternatively, the PDGF receptors may be remnants from an immature progenitor cell from which the undifferentiated carcinoma has evolved.

Carcinoma↗
PubMed1991

Thyroid epithelial cell proliferation in xenotransplanted human toxic nodular goitre is increased by Graves' IgG.

Human toxic nodular goitre tissue was xenotransplanted to athymic mice. Transplant function was analysed as 18-h thyroid transplant uptake of iodide-125 at day 21 and again at 10 weeks after transplantation. Graves' IgG or IgG from healthy donors was given intraperitoneally daily day 22-35. Epithelial cell proliferation in thyroid tissue transplants from human toxic nodular goitre and from normal thyroid glands was analysed by continuous [3H]thymidine administration for 4 days between day 21 and 24 and for 12 days between day 21 and 33 in separate series given daily injections of Graves' IgG or normal IgG during the same period. After administration of Graves' IgG, the 18-h iodide-125 uptake by the toxic nodular tissue transplants was 7 times higher at 10 weeks than at 3 weeks. Control IgG gave a corresponding 1.6-fold increase. The fraction of labelled cells after [3H]thymidine incorporation was 18 and 56% in toxic nodular goitre transplants and 4 and 48% in normal thyroid tissue transplants after daily Graves' IgG administration for 4 and 12 days, respectively, but only 1.3% in both types of tissue transplants after administration of normal IgG. Graves' IgG therefore seems to be able to stimulate cell proliferation in toxic nodular goitre tissue.

Animals↗
PubMed1991

Proliferative response of different exocrine pancreatic cells after surgical pancreaticobiliary diversion in the rat.

Pancreaticobiliary diversion (PBD) is known to induce chronic, endogenous hypercholecystokininemia causing pancreatic growth in rats. In the present study the proliferative response of the different exocrine pancreatic cells was studied by administration of 3H-thymidine, 1 mCi/kg, given 1 h before the rats were killed and 5, 10, 20, and 40 days after PBD. DNA and 3H-thymidine uptake, both expressed per 1 mg of pancreatic tissue, were significantly increased on day 5. The nuclear labeling index was increased fivefold in both the acinar and ductal cell group. In the centroacinar cell group the labeling index was increased on day 10. In conclusion, we found that the proliferative activity after PBD occurred during the first 10 days and that the ductal cells were forced into proliferation to the same extent as the acinar ones. These findings are of interest for future studies of hormonal influences on the development of pancreatic carcinoma.

Animals↗
PubMed1991

Cholecystokinin is not a major determinant for the changes in beta-cell function seen after pancreatico-biliary diversion in rats.

The influence of longterm increase in the plasma CCK levels on beta-cell function in rats was studied by using the pancreatico-biliary diversion (PBD) model. An intravenous glucose load (800 mg glucose/kg) was performed three weeks after the PBD operation. Additionally a group of PBD operated animals as well as an unoperated group received the CCK receptor antagonist L364,718 continuously during the three week study period. The proliferation rate of endocrine pancreatic cells was studied by means of 3H-thymidine administration. PBD caused a decrease in basal levels of insulin and glucose and an augmented insulin secretory response after glucose injection. There was no appreciable influence on the glucose elimination rate. When PBD animals were given the CCK receptor antagonist no differences were observed with regard to insulin and glucose compared to PBD animals without antagonist. The CCK-antagonist did not influence the beta-cell function in unoperated animals. Further, the proliferation rate of the endocrine pancreatic cells was not significantly changed in the PBD rats. The results suggest that PBD is accompanied by significant changes in basal and stimulated insulin secretion. These changes are probably not a direct consequence of the increased plasma CCK levels that follows PBD. Moreover, the insulin secretory response to glucose in normal rats was not influenced by longterm administration of the CCK receptor antagonist. Our observations should encourage further studies on the complex entero-insular interactions following pancreaticobiliary diversion.

Animals↗
PubMed1990

Proliferative response of different exocrine pancreatic cell types to hormonal stimuli. I. Effects of long-term cerulein administration.

The trophic effect on the exocrine pancreas of the cholecystokinin analogue cerulein was studied in a long-term experiment (20 or 160 micrograms/kg/24 h for 14 days) in mice by measuring changes in pancreatic weight and protein, amylase, and DNA content. Further, the selective cell growth stimulation exerted by various doses of cerulein (4, 20, 54, 160 micrograms/kg/24 h) on different exocrine pancreatic cell types was studied by continuous administration of 3H-thymidine. In the first experiment animals given 20 micrograms/kg/24 h of cerulein had increased pancreatic weight and amylase and protein content, whereas the animals given the higher dose had unchanged weight and a less pronounced increase in amylase and protein content. The pancreatic DNA content was unaffected in the 20-micrograms group but was clearly decreased by the higher dose. In the second experiment a statistically significant increase over controls was found in the fraction of labeled ductal cells when 20, 54, and 160 micrograms of cerulein was administered. However, in the acinar cell population an increase was measured only in the 160-micrograms group. A tendency to nadir in cell labeling was observed in both acinar and ductal cell groups at less stimulation. Labeling of centroacinar cells increased in all cerulein-treated groups. The results show that all cell types of the exocrine pancreas can be forced into proliferation by the cholecystokinin analogue used and that there is preferential cell growth stimulation in the ductal and centroacinar cell populations.

Amylases↗
PubMed1990

Proliferative response of different exocrine pancreatic cell types to hormonal stimuli. II. Effects of long-term secretin administration.

The effect of graded doses of secretin on exocrine pancreatic growth and cell proliferation was studied in a long-term experiment. After 16.5 and 150 micrograms/kg/24 h of secretin, each administered as two subcutaneous injections daily for 14 days, the pancreatic wet weight decreased, whereas the protein and DNA content of the gland was uninfluenced. When administered as described above for 14 days, 16.5, 50, 150, and 450 micrograms/kg/24 h of secretin did not affect the proliferation rate of ductal, acinar, or centroacinar cells as measured by a labeling index after 7 days of continuous 3H-thymidine administration. In the control groups a higher labeling index was found for ductal cells (19.9%) than for acinar cells (11.0%). During the 7 days of 3H-thymidine administration 80-90% of ductal and acinar cells remained in the G0 phase. There was a significantly higher labeling index in interlobular than in intralobular duct cells.

Amylases↗
PubMed1979

Depletion of colloid 27S and larger thyroid iodoproteins following treatment with propylthiouracil.

By means of a micropuncture technique and microgel electrophoresis the luminal content of single rat thyroid follicles were analyzed during PTU treatment for 4 weeks. The relative amount of aggregates of thyroglobulin (i.e. the 27S iodoprotein and larger complex) was reduced from 15 per cent to approximately 3 per cent after 48 h. The aggregates were practically absent after 2 weeks. The thyroglobulin fraction was the predominant colloid constituent. The protein concentration of the colloid was not changed at the end of the period of PTU treatment (8.9 g/100 ml). It is concluded that PTU inhibits the aggregation of thyroglobulin to a larger complex. The results further indicate that the aggregates of thyroglobulin are preferentially localized to the periphery of the lumen in the larger follicles.

Animals↗
PubMed1978

Change of the protein composition of the thyroid colloid during treatment with propylthiouracil and thyroxine: a microgel electrophoretic study of single rat thyroid follicles.

Prophylthiouracil and thyroxine were given daily to rats for 4 weeks. Samples of colloid were collected in vivo from the superficial thyroid follicles during this period and their protein composition was analysed by gel electrophoresis. It was observed that the aggregates of thyroglobulin, i.e., the 27-S thyroid iodoprotein and the heavier fractions, were reduced to 50% after 1 week and were almost absent after 2 weeks. A faster migrating thyroglobulin fraction was observed in the samples of colloid and in the homogenate of the whole gland after 48 h of treatment. During the following period of treatment there was an increase in the relative amount of the faster migrating thyroglobulin fraction compared to 19-S thyroglobulin in the colloid, the former comprising approx. 75% of the globulins after 4 weeks, It can be concluded that propylthiouracil inhibits the formation of the 27-S iodoprotein and that a structurally altered and iodine-poor thyroglobulin fraction is accumulated in the follicle lumen.

Animals↗
PubMed1977

On the distribution of thyroglobin and larger iodoproteins in single rat thyroid follicles.

The distribution of the large iodoproteins in the lumen of thyroid follicles was tested. Samples of the colloid in rat thyroid follicles were obtained in vivo by micropuncture of superficial follicles in the isthmus of the gland. One sample was collected per follicle and several follicles were punctured in each gland. The protein composition of the samples was analysed by microgel electrophoresis. The protein separation patterns were recorded by microdensitometry after staining of the proteins and the amount of protein in the fractions was estimated from the densitometric recordings. Thyroglobulin (TG) and the aggregates of TG--here designated the S-TG fractions--were present in all samples of colloid. It was observed that there was a significant positive co-variation between TG and S-TG when the colloid contained only TG, S-TG and a prealbumin fraction. When the albumin-like protein was present in the samples the co-variation was less significant. The results show that the relative amount of the aggregates of TG is constant in the albumin free colloid and that these aggregates most probably are randomly distributed in the follicle lumen. The results further indicate that the aggregates of TG are non-randomly distributed in the larger peripheral follicles when the colloid contains the albumin-like protein.

Animals↗
PubMed1977

A microgel electrophoretic analysis the colloid in single rat thyroid follicles during thyroxine suppression.

A sequential study of the effect of thyroxine (T4) on the protein composition of the colloid in the rat thyroid gland has been carried out in 24 rats. Daily ip injections of 20 mug thyroxine were given and the colloid was analyzed after 1, 2, 3 and 4 days and 1, 2 and 3 weeks. The protein constituents were separated by microgel electrophoresis and measured by microdensitometry. The incorporation of [3H]leucine into the thyroglobulin fraction and into the albumin-like protein in the homogenate of the gland was analyzed after T4 suppression for 2 days. The 2 h thyroidal iodine uptake was analyzed during the first week of T4 administration. During the second and the third day of T4 administration, the amount of 27S and larger complexes of thyroglobulin was reduced by 30-40 per cent and the amount of the albumin-like protein was significantly increased and present in almost all samples. Preliminary data indicated that during the same period the relative amount of [3H]leucine activity was increased in the albumin-like protein fraction compared to the thyroglobulin fraction in the thyroid. It is concluded that the exocytotic vesicles contain the albumin-like protein. The results further indicate that the administration of T4 temporarily changes the relative rates of formation of thyroglobulin and of the albumin-like protein in the follicle.

Animals↗
PubMed1977

Protein concentration of the rat thyroid colloid during thyroxine treatment.

Sprague-Dawley rats were given daily doses of 20 mug thyroxine for varying periods between 1 and 21 days. Samples of colloid were obtained by micropuncture in vivo of follicles in the thyroid isthmus. The protein content of the samples was determined by gel electrophoresis and the volume by a technique based on radioactivity measurement. The relative volume of the follicle lumina was determined by light microscopy. Treatment with thyroxine resulted in an increase in the protein concentration of the colloid. This increase was statistically significant after 2 days and the concentration remained elevated throughout the experimental period. The size of the follicle lumina also increased, most rapidly during the first week. It is suggested that the increase in protein concentration of the colloid during thyroxine treatment is due to inhibition of endocytosis of colloid in combination with the discharge into the follicle lumen of highly concentrated protein.

Animals↗
PubMed1975

Metabolic studies in human skeletal muscle tissue. Evaluation of an in vitro preparation intended for clinical metabolic studies.

An in vitro preparation of human skeltal muscle tissue aimed to be a model for clinical metabolic studies was functionally and structurally characterized. Muscle fibres from biopsy specimens obtained at surgical operations were teased away and collected in incubation vessels for the following determinations: exchangeable water content, extracellular space, potassium content, incorporation rate of labeled leucine into proteins, uptake of labeled cycloleucine, alpha-aminoisobutyric acid (AIB), and 3-o-methy1-glucose into the intracellular space, and the incorporation rate of glucose into various metabolites. After various times of incubation, muscle fibre samples were also taken for light and electron microscopy. During the incubation of the muscle fibres a transient intracellular oedema was demonstrated by electron microscopy and by determination of the exchangeable water content. The restitution of this oedema was associated with an increasing intracellular potassium concentration. Active transport of leucine, cycloleucine and AIB showing competitive inhibition was registered. The incorporation of labeled leucine into proteins was linear during 4 h of incubation and optimal stimulation of this incorporation was demonstrated in the presence of a complete amino acids mixture at a concentration corresponding to 10 times the normal plasma concentration in man. Insulin stimulated the incorporation rate of glucose-carbon into all metabolites and ouabain stimulated its incorporation in to glycogen. Monoidoacetate inhibited the incorporation of glucose into all metabolites.

Amino Acids↗