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T Lindmo

Publications and source records attributed to T Lindmo.

At least 55 records · Page 3Linked to original sources
PubMed1982

The diagnostic value of flow cytometric DNA measurements in selected disorders of the human thyroid.

A flow cytometric (FCM) analysis of biopsies from 19 patients with thyroid lesions (Hashimoto's thyroiditis, hyperplastic goiter, colloid and adenomatous nodular goiter, follicular adenoma, follicular carcinoma, anaplastic carcinoma) was performed to evaluate the relevance of such results for the individual diagnosis and prognosis and prognosis of such diseases. All cases of Hashimoto's thyroiditis, the colloid nodular goiters, and the hyperplastic goiter had a unimodal diploid pattern, while the anaplastic carcinomas were aneuploid. These lesions are, however, easily diagnosed on morphological grounds and their FCM classification would only be redundant. Follicular adenomas and follicular carcinomas may be either unimodal diploid or aneuploid, and our single case of adenomatous colloid goiter showed a bimodal DNA distribution. This means that a diploid modal DNA content in a follicular tumor does not rule out malignancy, while aneuploidy is not an unequivocal sign on malignancy. The evaluation of the percentage of cells in S-phase did not seem to contribute valuable information for the individual diagnosis of malignancy within the group of thyroid lesions studied. Our study indicates a rather limited clinical value of FCM measurements of DNA in the individual case of thyroid disease.

Adolescent↗
PubMed1982

Kinetics of protein and DNA synthesis studied by mathematical modelling of flow cytometric protein and DNA histograms.

Mathematical models for histograms of cellular protein content as measured by flow cytometry were developed, based on theoretical protein distributions. These were derived from the age distribution of cells and the accumulation function for cellular protein content as a function of age within the cell cycle. A model assuming an exponential age distribution and an exponential protein accumulation function was found to give the best representation of protein histograms of exponentially growing NHIK 3025 cells. This is in good agreement with the known kinetic behaviour of such cells. By the combined use of the protein histogram model and a similar model for DNA content, and assuming linear DNA accumulation during S, the fraction of cells in S, as a function of cellular protein content, was simulated. This function showed good agreement with values of the [3H]TdR labelling index scored in cells sorted by flow cytometry from 5-channel intervals of the protein histogram. The protein and DNA histogram models were combined into a two-dimensional model for correlated protein/DNA measurements. Comparison between simulated data and experimentally derived two-dimensional protein/DNA histograms gave further support to the cell kinetic assumptions underlying the models, but also identified some minor deviations which could not be recognized in the analysis of the one-dimensional histograms.

Cell Cycle↗
PubMed1982

Growth characteristics of human melanoma xenografts.

The growth of twelve human malignant melanomas in athymic nude mice was studied. Gompertz curves were fitted to volumetric growth data. DNA histograms were obtained with flow cytometry. Each of the twelve melanomas exhibited a characteristic growth pattern, indicating that inherent properties of the tumours are important for the growth control. The theoretical maximum volumes (Vmax) ranged from 208 to 12,900 mm3, the volume doubling times (Td) from 2.8 to 15.3 days (V = 50 mm3) and from 3.8 to 64.6 days (V = 200 mm3), and the fraction of cells in S from 5 to 21%. Tumours with short Td were characterized by a higher growth fraction and probably by a lower cell loss factor than those with long Td. The growth was also influenced by the nude mouse host, as indicated by the values for Vmax, which were similar to those reported for mouse tumours (geometric mean = 8100 mm3), but considerably lower than the volumes of many tumours in man. Also the Td-values for the xenografts were generally lower than those reported for tumours in man, presumably due to a lower cell loss factor. During serial transplantation the growth rate of one of the melanomas increased abruptly, probably because of both an increased growth fraction and a reduced cell loss factor. The latter result demonstrates the necessity of keeping basic biological parameters of xenografts under observation during serial transplantation.

Animals↗
PubMed1982

High-sensitivity optical lymph flow-meter.

An optical flow-meter is described which allows precise and continuous registration of the flow of lymph from cannulated human lymph vessels. The cannula from the lymph vessel is connected to the measurement tubing of the instrument where the flow is measured by automatically monitoring the movement of an air bubble introduced into the flow at the beginning of the measurement. The limit of sensitivity of the instrument is about 0.1 microliter, allowing reliable registration of stroke volumes of about 1 microliter which typically occur in human leg lymphatics. The size and capacity of the instrument were chosen to be suitable for clinical use. A technical description of the instrument is given. Application of the instrument is illustrated with recording of lymph flow and lateral intralymphatic pressure in a prenodal lymph vessel of the human leg.

Lymph↗
PubMed1981

Measurements of the distribution of time intervals between cell passages in flow cytometry as a method for the evaluation of sample preparation procedures.

It is expected that the time sequence of cells passing through the sensing region of a flow cytometer should follow the statistics of a Poisson process. Thus, measurement of time intervals between passages of fluorescent microspheres and cells stained with mithramycin demonstrated the negative exponential distribution characteristic of such a process. However, analysis of cells stained with fluorescein-iso-thiocyanate showed marked deviations from a negative exponential distribution of time intervals. The distribution had an additional component due to time intervals with mean value about 60 times shorter than the population mean, and in certain cases more than 50% of the cells were registered with such short time intervals. This percentage could, however, be reduced to acceptable levels by modifications of the sample preparation procedures. Measurement of the distribution of time intervals between cell passages is proposed as a method for the evaluation of possible improvements in sample preparation procedures.

Cell Line↗
PubMed1981

Effect of serum step-down on protein metabolism and proliferation kinetics of NHIK 3025 cells.

Human NHIK 3025 cells growing exponentially in 30% or 3% serum had population doubling times of 19.1 and 27.6 hours, respectively. These values were equal to the calculated protein doubling times (17.6 and 26.5 hours, respectively), showing that the cells were in balanced growth at both serum concentrations. Stepdown from 30% to 3% serum reduced the rate of protein synthesis within 1--2 hours, from 5.7%/hour to 4.3%/hour, while the rate of protein degradation was unchanged (1.7%/hour). In cells synchronized by mitotic selection from an exponentially growing population, the median cell cycle durations in 30% and 3% serum were 17.2 and 23.6 hours, respectively, which were also in good agreement with the protein doubling times. The median G1 durations were 7.1 and 9.6 hours, respectively. Thus the duration of G1 relative to the total cell cycle duration was the same in the two cases. Complete removal of serum for a period of 3 hours resulted in a 3-hour prolongation of the cell cycle regardless of the time after mitotic selection at which the serum was removed. For synchronized cells, the rate of entry into both the S phase and into the subsequent cell cycle were reduced in 3% serum as compared to 30% serum, the former rate being significantly greater than the latter at both serum concentrations. Our results thus indicate that these cells are continuously dependent upon serum throughout the entire cell cycle.

Blood↗
PubMed1981

The role of protein accumulation in the cell cycle control of human NHIK 3025 cells.

The cell cycle kinetics of NHIK 3025 cells, synchronized by mitotic selection, was studied in the presence of cycloheximide at concentrations (0.125-1.25 microM) which inhibited protein synthesis partially and slowed down the rate of cell cycle traverse. The median cell cycle duration was equal to the protein doubling time in both the control cells and in the cycloheximide-treated cultures at all drug concentrations. This conclusion was valid whether protein synthesis was continuously depressed by cycloheximide throughout the entire cell cycle, or temporarily inhibited during shorter periods at various stages of the cell cycle. These results may indicate that cell division does not take place before the cell has reached a critical size, or has completed a protein accumulation-dependent sequence of events. When present throughout the cell cycle, cycloheximide increased the median G1 duration proportionally to the total cell cycle prolongation. However, the entry of cells into S, once initiated, proceeded at an almost unaffected rate even at cycloheximide concentrations which reduced the rate of protein synthesis 50%. The onset of DNA synthesis seemed to take place in the cycloheximide-treated cells at a time when the protein content was lower than in the control cells. This might suggest that DNA synthesis in NHIK 3025 cells is not initiated at a critical cell mass.

Cell Cycle↗
PubMed1981

Low concentrations of misonidazole counteract effects of extreme hypoxia on cells in S.

Populations of NHIK 3025 cells synchronized by mitotic selection were exposed at 37 degrees C to extreme hypoxia in absence and presence of misonidazole (MISO). Cells in G1, S or G2 and mitosis were treated for 3 h. Inhibition of cell-cycle progression by this treatment was measured by flow cytometry of DNA histograms and cell inactivation was measured by colony formation. The exposure to hypoxia alone of cells in G1 or in G2 and mitosis led to only minor cell-cycle inhibition, and hardly reduced cell survival. However, the exposure of cells in S to hypoxia alone had a strong inhibitory effect on cell-cycle progression, and cell survival was only 40% of untreated cells. Low concentrations of MISO (0.05-0.4 mM) during exposure of cells in S to hypoxia, produced less cell-cycle inhibition than after hypoxia alone, and cell survival was restored to 100%. The presence of MISO during the 3h exposure to hypoxia of cells in G1 or in G2 and mitosis only increased the effects of hypoxia alone. MISO at concentrations greater than 0.8 mM during hypoxia produced cell inactivation, for all phases of the cell cycle, comparable to that already known from the literature.

Cell Cycle↗
PubMed1981

Cell kinetic characteristics in different parts of multicellular spheroids of human origin.

The growth fraction, the cell cycle time, and the duration of the individual cell cycle phases were determined as a function of distance from the surface of multicellular spheroids of the human cell line NHIK 3025. The techniques employed were percentage of labelled mitoses and labelling index measurements after autoradiography and flow cytometric measurements of DNA histograms. To separate cell populations from the different parts of the spheroid, fractionated trypsinization was employed. The results were compared with corresponding values in NHIK 3025 cell populations grown as monolayer cultures. While practically all cells in exponentially growing monolayer populations are proliferating, the growth fraction was between 0.6 and 0.7 in the outer parts of the spheroid. The inner region was mainly occupied by a necrotic mass. The proliferating fraction of the recognizable cells in the inner region was slightly below 0.5. The mean cell cycle time of NHIK 3025 cells in monolayer culture is 18 hr. The mean cell cycle time of proliferating cells in the periphery of the spheroid was 30 hr, compared to 41 hr in the inner region (150 micrometer from the spheroid surface). All phases of the cell cycle were prolonged compared to populations of exponentially growing monolayer cells. Within each part of the spheroid the distribution of cell cycle times was considerably broadened compared with monolayer populations.

Cell Line↗
PubMed1981

Effects of steroids and different culture media on cell cycle of the androgen-sensitive human cell line NHIK3025.

The median cell cycle of synchronized NHIK3025 cells grown in Eagle's MEM with 10% foetal calf serum was 23.6 h, compared to 18 h observed earlier in Puck's E2a medium with 30% serum (20% human and 10% horse). This difference is due to prolongation of both G1 and G2 in the MEM type medium. Testosterone and 4-androstene-3 beta, 17 beta-diol reduced the cell cycle of synchronized populations of NHIK3025 cultured in MEM type medium. Dexamethasone gave cell cycle prolongation while estradiol had no effect. These results are in accordance with steroid-induced changes in growth of asynchronous cell populations observed earlier. The androgen growth stimulation was partly due to a shortening of G2 but was not exclusively located in one particular phase of the cell cycle.

Androstenols↗
PubMed1981

Immunological subsets in human B-cell lymphomas.

Fifty human B-cell lymphomas have been studied with regard to surface markers (surface immunoglobulins (sIg) and complement receptors (CR)), capping of sIg, and relative amounts of sIg by single-cell flow cytometry. The results show that these lymphomas can be subdivided into distinct immunological subsets. Whereas one histological subgroup (lymphocytic) consisted of only one immunological subtype, others were heterogeneous with regard to immunological subtypes. This was most striking in nodular lymphomas of germinal centre cell origin (centroblastic/centrocytic). Our studies provide further evidence for the existence of a large number of subsets in the B-cell compartment of the immune system, sIgD was only found in association with sIgM. The relative amounts of sIgD varied, especially in nodular lymphomas. A discrepancy between capping of sIgM and sIgD was also found in some lymphomas belonging to this group. These findings together with other observations suggest that sIgD plays a role in B-cell maturation and differentiation events taking place in germinal centres and becomes lost during this process. A close association was found between the presence of CR and capping of sIgM but not capping of sIgD or sIgG. Nodular lymphomas expressing sIgG only, lacked CR. These findings suggest that CR may become lost during maturation and differentiation processes also taking place in germinal centres. Lymphoplasmacytoid lymphomas, which show morphological evidence of differentiation towards plasma cells, could be subdivided into three immunological subsets, indicating that plasma cell maturation may take place from different subsets of B cells.

B-Lymphocytes↗
PubMed1981

Cell-associated immunoglobulin in human non-Hodgkin lymphomas. A comparative study of surface immunoglobulin on cells in suspension and cytoplasmic immunoglobulin by immunohistochemistry.

Eighty-three non-Hodgkin lymphomas classified according to the Kiel classification have been studied with regard to surface immunoglobulin (sIg) on cells in suspension and cytoplasmic immunoglobulin (cIg) by the peroxidase anti-peroxidase method (PAP) on formaline-fixed tissue sections. Fifty-six out of 66 examined (i.e. 85%) revealed a monoclonal staining pattern for sIg, whereas 37/70 (53%) gave a monoclonal staining pattern for cIg by PAP. The methods combined gave a monoclonal staining pattern in 73/83, i.e. in 88%, of the biopsies tested. The discrepancies between the two methods were largest in centroblastic/centrocytic and lymphocytic lymphomas. With regard to the light chain staining patterns, complete agreement between the two methods was obtained in the 20 cases that allowed such analysis to be made. This suggests that the specificity of PAP, as carried out in this study with reagents purified by immunoabsorbent techniques, is satisfactory. On a basis of heavy chain isotypes centroblastic/centrocytic, lymphoplasmacytoid, and immunoblastic lymphomas could be divided into distinct immunological subgroups. In four biopsies the sIg heavy chains were mu + delta, whereas mu + gamma chains were detected by PAP. This finding may be relevant to the mu leads to gamma switch known to occur during normal B-cell differentiation. Immunoglobulin inclusions were found in 8 cases--3 belonging to the immunoblastic group, and 5 to the lymphoplasmacytoid group.

Adult↗
PubMed1981

A flow cytometric deoxyribonucleic acid analysis of papillary thyroid carcinoma.

We present the first comprehensive flow cytometric analysis of papillary carcinoma of the human thyroid. All but one of the 22 papillary carcinomas showed a unimodal distribution of the nuclear DNA content. The mean modal DNA was significantly lower in papillary carcinomas than in normal thyroid tissue, a finding which is contradictory to some earlier reports based on conventional cytophotometry. Tumors predominantly composed of Hürthle cells had a significantly higher mean modal DNA, whereas no significant difference was found between tumors with many ground glass nuclei and those lacking this nuclear feature. A very low percentage of S-phase cells was found both in the primary tumors and their metastases. This percentage was even lower than in normal thyroid tissue. The low proliferative activity may in part explain why most papillary thyroid carcinomas run such a surprisingly indolent course even after the establishment of regional lymph node metastases.

Adult↗
PubMed1980

Effect of single dose irradiation on the proliferation kinetics in a human malignant melanoma in athymic nude mice.

The effect of single dose irradiation on the proliferation kinetics in a human malignant melanoma grown in the athymic mutant nude mouse was analysed. DNA-histograms were obtained with flow cytofluorometry. Percentage labelled mitoses curves were established by the use of conventional autoradiographic techniques. Changes in the fraction of clonogenic cells with time after irradiation were measured in vitro in soft agar. In non-irradiated tumours the fraction of cells in G1/G0, S and G2 + M was 66.21 and 13 per cent, respectively. The median duration of G1, S, G2, M and Te was 19.0 h, 13.3 h, 5.0 h, 1.0 h and 41.4 h, respectively. The growth fraction was calculated as 0.66 and the cell loss factor as 0.67. The growth fraction was increased after irradiation and the cell cycle time reduced, due to a shortening of G1. These effects were dose dependent and decreased with time after exposure, but were still present after the tumours had resumed a continuous volume growth. The rate of volume growth was slower for irradiated tumours than for non-irradiated tumours of the same size, due to a larger cell loss factor for the former.

Animals↗