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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↗
PubMed1990

Combined cervicothoracic approach in thymectomy for myasthenia gravis.

Thymectomy was performed for myasthenia gravis on 30 patients, using a new approach with a collar incision which gave full exposure of the retrothyroid space and was directly connected to a median sternotomy. The thymus was removed en bloc without pleural incision. There was no perioperative mortality and the only complications were transient respiratory insufficiency in two cases. The postoperative hospital stay was 3-9 (mean 5.8) days. The effect of thymectomy was evaluated after 2-8 years at the Department of Neurology, when changes in symptoms (stages I-IV) or medication (need for cholinesterase inhibitors) were registered. The total clinical improvement rate was 97%, with 3% of the patients improved three stages, 33% two stages and 60% one stage compared with the preoperative classification. Twenty patients (67%) were asymptomatic at follow-up and six (20%) also required no medication. The medication need was reduced in 70% of cases (mean reduction 42%). Our cervicothoracic approach resulted in the same rate of improvement as in studies using more extensive transsternal procedures, but the morbidity was lower, with no complications requiring prolonged hospital stay. The morbidity was also less than after only transcervical procedures aiming to perform total thymectomy--a prerequisite for maximal and lasting benefit from surgery. Moreover, as this cervicothoracic approach is simple and safe, it can be recommended as an option in the surgical management of myasthenia gravis.

Adolescent↗
PubMed1989

Follow-up of two treatment modalities for ductal cancer in situ of the breast.

In a mammography screening programme for the early detection of breast cancer 66 cases of ductal cancer in situ of the breast (DCIS) were diagnosed between 1978 and 1984 and prospectively followed up. In the beginning of the study period, DCIS was treated by mastectomy without axillary clearance but sector resection has been performed increasingly. Since 1982 the latter procedure has become standard treatment. Radical resection was confirmed by specimen X-ray and histopathological examination of whole organ sections. No postoperative radiotherapy was given. Twenty-eight women had mastectomy and 38 had sector resection. The median follow-up times were 77 and 60 months respectively. In the mastectomy group postoperative monitoring did not reveal any local recurrence but one contralateral new invasive cancer was discovered. In the sector resection group five recurrences were found. Three of the latter were new cases of DCIS and two appeared as small invasive cancers (stage I). Mastectomy will cure ductal cancer in situ but has a greater morbidity. Sector resection has been established as the method of choice in stage I invasive cancer and is probably also safe in DCIS. The possible beneficial effect of postoperative local radiotherapy after sector resection for DCIS is currently being analysed in a randomized trial which started in Sweden in 1987.

Adult↗
PubMed1989

TSH binding correlates with TSH-stimulated thyroid adenylate cyclase activity in human thyroid tissues.

Thyroid-stimulating hormone (TSH) stimulates adenylate cyclase (AC) activity and the growth and differentiation of thyroid cancers of follicular cell origin. Thyroid neoplasms generally have higher TSH-stimulated AC activity than normal thyroid tissue from the same patients. To determine whether differences in TSH receptors could account for the differences in AC activity, we studied the 8000 g membrane particulate fraction from 28 thyroid tissues (10 papillary carcinomas, 6 multinodular goiters, 4 follicular adenomas, 3 follicular carcinomas, 2 Graves, 1 normal, 1 Hürthle cell adenoma, and 1 thyroiditis). TSH receptors were measured by competitive inhibition using radioactive iodine-labeled bovine TSH (125I-bTSH). Maximal binding capacity (Bmax) and dissociation constant (Kd) were calculated by Scatchard analysis. AC activity was measured by the conversion of alpha-[32P]-ATP to [32P]-cAMP in the maximally (300 mU/ml) TSH-stimulated state. The basal and forskolin-stimulated (100 mmol/L) AC activity were also measured, and the ratios to TSH-stimulated AC activity were calculated (TSH/Basal ratio and TSH/Forskolin ratio). We found a strong correlation between the percent specific binding (%SB) of 125I-bTSH and TSH/Basal ratio (r = 0.70, p = 0.0001), between Bmax and the TSH/Basal ratio (r = 0.71, p = 0.001), between %SB and TSH/Forskolin ratio (r = 0.44, p = 0.02), and between Bmax and TSH/Forskolin ratio (r = 0.65, p = 0.0002). This strong correlation between TSH binding and the TSH-stimulated AC activity suggests that in some thyroid neoplasms the higher AC response to TSH may be due to an increased number of TSH receptors.

Adenylyl Cyclases↗
PubMed1988

Plasma membrane shedding and colloid vacuoles in hyperactive human thyroid tissue.

The ultrastructural appearance of colloid vacuoles, considered to be a typical sign of hyperactivity in the human thyroid gland, was studied in human thyroid tissue transplanted to nude mice and in human thyroid tissue fixed directly after surgical removal in patients with thyrotoxicosis. Transplanted normal thyroid tissue and toxic diffuse goiter (TDG) tissue was fixed by vascular perfusion with glutaraldehyde 5 or 12 weeks after transplantation. Light microscopic quantification showed that daily injections for 2 weeks of a gamma globulin fraction of patient sera containing thyroid-stimulating immunoglobulins (TSI) greatly increased the number of colloid vacuoles in both types of transplants. The vacuoles were mainly located in the periphery of the follicle lumen, giving the colloid a scalloped appearance. Electron microscopy of TSI-exposed tissue revealed, in addition to colloid vacuoles, the presence of large amounts of membrane material in the follicle lumen. Only sparse amounts of intraluminal membrane material were present in controls. The colloid vacuoles were almost invariably associated with such membrane material, which lined the border between the vacuole and the surrounding colloid. The intraluminal material consisted of spherical and elongated formations, each structure limited by a triple-layered membrane and often containing a dense interior. The elongated structures were often of the same dimensions as microvilli. The apical surface of follicle cells in TSI-exposed tissue expressed numerous microvilli, of which many showed a similar dense interior as the intraluminal membrane structures. The intraluminal membranes frequently showed, like the apical plasma membrane of the follicle cells, a positive reaction for peroxidase. Organelles, such as mitochondria, lysosomes or rough endoplasmic reticulum, were not encountered among the intraluminal membrane structures. These observations indicate that the intraluminal membrane material is derived from the apical plasma membrane of the follicle cells, presumably by shedding of microvilli. A similar association between colloid vacuoles and membrane material was also found in thyroid tissue from patients with thyrotoxicosis fixed directly at operation. It is suggested that the presence of membrane material in the follicle lumen precipitates the formation of colloid vacuoles in hyperactive thyroid tissue. The possible involvement of intraluminal membrane material in the development of microsomal autoantibodies in Graves' disease, i.e. exposure and presentation of thyroid microsomal antigen (identical to thyroperoxidase) to the immune system, is discussed.

Animals↗
PubMed1988

The role of aspiration cytology in the management of thyroid nodules.

In the hands of an experienced cytologist aspiration cytology is a safe and hitherto the best diagnostic tool in the evaluation of nodular thyroid lesions. In histologically verified case series 50-90% of confirmed thyroid cancers can be detected by aspiration biopsy, the sensitivity being dependent on sampling errors, microscopic misinterpretation and the variation in attitude towards indeterminate diagnosis in the decision for diagnostic surgery. The number of proven benign cases that are correctly identified as such by biopsy varies accordingly and approx. 75% (specificity). In comparison with imaging procedures, including those giving information of functional activity, the combined sensitivity and specificity rates of aspiration cytology come closest to the ideal discriminatory situation. In combination with case history and careful clinical examination, fine needle aspiration cytology is the best guidance for an optimal selection of patients for therapeutic or diagnostic surgery. Future development of sensitive markers for malignant degeneration will probably increase the selective power of this diagnostic technique.

Biopsy, Needle↗
PubMed1987

Naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of mouse thyroids.

The proliferation pattern of some scattered clones of naturally occurring follicular cells with an exceedingly high intrinsic growth potential was investigated in the mouse thyroid gland. In particular, evidence was sought to demonstrate that the high propensity to replicate is a stable trait transmitted from the progenitor cells to their offspring. We hypothesize that these cell clones are at the origin of the multiple adenomas that invariably arise in chronically stimulated thyroid. Growth stimulation was induced either by hemithyroidectomy or by methimazole feeding. In a first series of experiments, involving hemithyroidectomized animals, [3H]thymidine was administered continuously for 3 weeks by means of osmotic minipumps, so that all cells entering the mitotic cycle during that time were labeled. Hemithyroidectomy led to a 3-fold increase of the fraction of labeled cells in the remaining lobe. The increase was prevented by thyroxine treatment in thyroid-stimulating hormone-suppressing doses. Autoradiographs of contiguous serial sections across whole follicles showed that roughly 75% of the labeled cells were clustered in groups of 3 or more, rather than being randomly distributed. In a second set of experiments, glands stimulated by methimazole-induced thyroid-stimulating hormone hypersecretion were pulse-labeled by a single i.p. injection of [3H]thymidine. Animals were sacrificed either 2 h or 3 weeks after the administration of the label. The thyroids were excised and the fate of labeled thyroid cells was analyzed autoradiographically. In the 2-h exposure, about 95% of all labeled follicular cells were single and the remaining 5% were in pairs. In contrast, about 50% of all labeled cells were clustered in groups of 3 to 12 cells 3 weeks after the pulse labeling. The number of silver grains per nucleus was compared to that of the identically exposed controls. The intensity of label per cell appeared to be decreased in proportion to the size of the labeled clusters, indicating that clusters had generated several subsequent generations of cells. The results support previously produced evidence that highly growth-prone cells naturally occur within the normal thyroid and demonstrate, in addition, that their high intrinsic growth rate is a stable, inheritable trait. Cells which replicate at a rate faster than that of the average epithelial cell have a tendency to overgrow during goitrogenesis. They may be at the very origin of the nodules and adenomas commonly found in experimentally produced and naturally occurring goiters.

Animals↗