Biomedical subjects

B Baldetorp

Publications and source records attributed to B Baldetorp.

89 records · Page 5Linked to original sources

PubMed1984

Flow-cytometric DNA analysis in primary breast carcinomas and clinicopathological correlations.

Flow-cytometric DNA analyses of single cell nuclei were performed on nuclear suspensions prepared from biopsies of primary breast carcinomas in 638 patients. Propidium-iodide-stained cell nuclei were analysed in an Ortho 50-H Cytofluorograph. The patients were staged by the TMN classification. Sixty percent of all the patients had aneuploid primary breast carcinomas; of size T1, T2, T3, and T4 tumors, 51%, 63%, 67%, and 75% were aneuploid, respectively. The proportions of aneuploid tumors in each of the tumor stages SI, SII, SIII, and SIV were 47%, 62%, 67%, and 69%, respectively. This trend to increasing aneuploidy proportions with more advanced disease was significant in contrast to the degree of aneuploidy found in relation to axillary nodal tumor involvement. Multiple aneuploid cell populations were found in 109 (17%) tumors. With a mean follow-up time of 16 months, 92 patients have relapsed out of 540 completely staged patients with unilateral breast cancer with no distant metastases at the time of initial treatment. When the influence of various treatments and tumor stage are not considered, the recurrence rate was twice as high among patients with aneuploid primary tumors than among patients with euploid tumors. The differences in relapsing rates among patients with euploid and aneuploid primary tumors decreased with more advanced disease. Out of 170 patients with T1 tumors, 17 relapsed and 16 of these were aneuploid. No such difference in relapse rate in relation to ploidy was, however, found in patients with more advanced primary disease.

Adult↗

PubMed1984

Demonstration of histamine receptors on human platelets by flow cytometry.

Fluoresceinated human albumin conjugated with histamine (FHA-HIS) has been used for the demonstration of histamine receptors on human platelets. Such receptors were demonstrated on 40-63% of peripheral blood platelets in 4 healthy donors. The binding of FHA-HIS was inhibited on 35-79% of the platelets by the histamine H1 receptor antagonists diphenhydramine and clemastine. The histamine H2 receptor antagonist cimetidine blocked the FHA-HIS binding on 14-37% of the platelets. It is concluded that histamine H1 as well as H2 receptors occur on human platelets but the receptors are not equally distributed in the platelet population.

Blood Platelets↗

PubMed1984

Polyamine starvation prolongs the S and G2 phases of polyamine-dependent (arginase-deficient) CHO cells.

This study analyzes the effects of polyamine starvation on cell cycle traverse of an arginase-deficient CHO cell variant (CHO-A7). These cells grow well in serum-free medium, provided that it contains ornithine or polyamines or both. In the absence of ornithine or polyamines or both, the CHO-A7 cells develop severe polyamine deficiency and, as a consequence, grow more slowly. When grown to a stationary phase in the presence of ornithine or putrescine or both, the CHO-A7 cells became arrested in G0/early G1. However, when starved for ornithine and polyamines, they accumulated in the S and G2 phases. Ornithine and polyamine starvation of CHO-A7 cells causes an increase in ornithine decarboxylase activity. When this increase was prevented by treatment with DL-alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, growth was further suppressed, and a greater fraction of cells were found in the S and G2 phases of the cell cycle.

Animals↗

PubMed1984

Intracellular recording of potential oscillations in ciliated cells exposed to ionizing radiation.

Intracellular potential oscillations of the ciliated cells of the rabbit's trachea have been measured by means of glass capillary microelectrodes during exposure of the cells to ionizing radiation. The electrophysiologic activity was fairly stable during the entire exposure at a total administered dose of 10.0 Gy. This finding is contradictory to the change in mucociliary activity obtained under the same conditions when measured with a light beam reflex method, but is in agreement with the findings regarding the influence of radiation on the membrane potentials as far as nerves and muscles are concerned.

Action Potentials↗

PubMed1984

The effects of 10 Gy single-dose irradiation on the ciliated epithelium measured during and one-to-ten days following irradiation. A comparative physiological and morphological study.

Experiments recently done in this laboratory have shown that ionizing irradiation can result in an increase in the ciliary beat frequency of the trachea in vitro even during ongoing irradiation, implying an immediate stimulation of the physiological activity of the cells. This phenomenon is not fully understood and is by itself contradictory to general radio-biological concepts. Ultrastructural investigations on specimens taken immediately after irradiation (10 Gy) have, so far, not shown any changes. It has therefore seemed useful to extend the investigations by examining the effects of in vivo- irradiation (10 Gy) on rabbit trachea during the first 10 days after treatment. The following results have been obtained: Phase I: On days 1-3 after irradiation the beat frequency showed a slight increase (10%) within the irradiated part in comparison with a non-irradiated area of the trachea. No pronounced ultrastructural changes were found these days. Phase II: On days 4-7 after irradiation the mucociliary activity was reduced in those places where it could be measured. The surface of the cilia assumed a generally destructed appearance with elongated cilia and disorganisation. TEM-pictures showed an increased amount of goblet cells and signs of membrane damage such as cytoplasmic extrusions at the apical end of the cells. Phase III: On days 8-10 after irradiation a normalization of the tissue gradually took place with a beat frequency returning to normal. The ciliary surface showed a recovery process which also could be observed in the TEM-pictures.

Animals↗

PubMed1979

Studies of ciliated epithelia of the human genital tract. 3: Mucociliary wave activity in organ cultures of human Fallopian tubes challenged with Neisseria gonorrhoeae and gonococcal endotoxin.

Quantative determinations of the mucociliary activity of human Fallopian tube epithelium maintained as organ cultures were performed using a light beam reflex method. In non-infected organ cultures the mucociliary wave (MCW) frequency slowly decreased during the first 54 hours of culture maintenance. In organ cultures experimentally infected with fresh isolates of Neisseria gonorrhoeae producing T1/T2 colonies the MCW frequency either decreased to subnormal values or completely ceased whereas in organ cultured infected with a laboratory-adapted gonococcal strain the MCW frequencies remained within normal range. In organ cultures exposed to gonococcal endotoxin prepared from the laboratory-adapted strain, as well as in cultures in which cell-free filtrates of medium from organ cultures infected with N. gonorrhoeae (producing T1/T2 colonies) were added to the culture medium, the ciliary activity decreased and subsequently ceased. The same phenomenon occurred when organ cultures were challenged with Escherichia coli endotoxin. The ciliostatic effect appeared before any morphological changes in the surface epithelium, including the cilia, were demonstrable by scanning electron microscopy.

Adult↗

PubMedDate not supplied

A prospective population-based management program including primary surgery and postoperative risk assessment by means of DNA ploidy and histopathology. Adjuvant radiotherapy is not necessary for the majority of patients with FIGO stage I-II endometrial cancer.

A management program for FIGO stage I-II nonserous, nonclear-cell adenocarcinomas was evaluated. Histopathology and DNA ploidy were used to estimate postoperatively the risk of progression or death of disease and to tailor treatment. The patient material was a population-based consecutive cohort of all women with endometrial cancer in the Southern Swedish Health Care Region diagnosed between June 1993 and June 1996 (n = 553). Of these, 335 were eligible for the management program. Patients estimated to be at low risk were treated by surgery only, while high-risk patients also received vaginal brachytherapy. A large low-risk group consisting of 84% (n = 283) of the patients with an estimated disease-specific 5-year survival of 96% (95% CI = 93-98%) was identified. The high-risk group (n = 52, 16%) showed a worse outcome with an 80% 5-year disease-specific survival (95% CI = 65-89%). The difference in survival between the groups was highly significant (P < 0.0001). Half of the progressions were distant in the high-risk group. Although there is a clear indication for adjuvant therapy for this group, locoregional radiotherapy could be expected to fail in cases with distant progression. Thus, effective systemic treatments need to be developed. Low-risk patients, constituting the majority (84%) of the patients, can be safely treated by surgery only.

Adenocarcinoma↗

PubMedDate not supplied

Distribution of non-diploid flow-cytometric DNA indices and their relation to the nodal metastasis in squamous cell carcinomas of the head and neck.

Squamous cell carcinomas of the head and neck (HNSCC) evolve from diploid epithelial cells of the mucosa. At the time of diagnosis about two thirds of clinically diagnosed HNSCC are non-diploid according to flow-cytometric (FCM) analysis, indicating that during tumour progression there must be an acquisition and accumulation of chromosomal aberrations. At diagnosis one third to one half of HNSCC have clinically positive neck nodes. The objective of the present study was to see whether the progression to a metastatic phenotype is reflected in the distribution of FCM DNA ploidy in node-negative and node-positive HNSCC. The series comprised 200 patients with HNSCC. Tumour samples were obtained from diagnostic biopsies or primary surgery. A multistep preparation method and propidium iodide staining of nuclear DNA content was used for FCM. One hundred and forty one (71%) of the tumours were non-diploid. Only two tumours were hypodiploid (DNA index 0.73 and 0.93, respectively). Ten of the tumours exhibited two non-diploid stem cell lines. The frequency of non-diploidy in node-negative tumours was 65% and in node-positive ones about 80%. The frequency distribution of non-diploid DNA indices clustered in the hypotetraploid region (with a modal value of 1.71-1.74) and did not differ between node-negative and node-positive tumours. The hypothesis that the disposition to metastasis is reflected in the frequency distribution of non-diploid DNA indices could thus not be verified.

Adult↗

PubMedDate not supplied

Comparison between the immediate effects of photon and electron radiation on the ciliary activity of the trachea of the rabbit. An in vitro investigation.

The immediate effects of 6 MV roentgen rays and 4 MeV electron rays on the mucociliary activity of the trachea of the rabbit were studied. In spite of the same average LET for the two radiation qualities, there was a clear difference in their effects on the ciliary motility during irradiation. The increase of the mucociliary activity after an absorbed dose of 1.5 Gy roentgen rays reported earlier was confirmed by the present investigation when using 6 MV photons. Electron radiation increased the beat frequency to a corresponding degree already at an administered dose of 0.5 Gy. The differences found in the pattern of the mucociliary activity during irradiation are discussed. The results indicate that the conventional RBE values cannot be used for early physiologic effects of irradiation.

Animals↗

PubMedDate not supplied

Effect of repeat irradiation on the tracheal ciliary cell activity.

Rabbit tracheas were initially irradiated with 10 Gy in vitro. A second irradiation of 10 Gy was administered 2 hours later. The initial exposure caused a 25 per cent increase of the ciliary beat frequency during the irradiation--a response which was not found during the second irradiation. Between the exposures, the beat frequency dropped to 20 per cent below the reference level, followed by an 11 per cent overshooting before the second irradiation. Tracheas placed untreated in the experimental chamber for 2 hours and subsequently irradiated with 10 Gy showed a similar pattern of ciliary activity as induced by the initial radiation exposure in the first experiment. The storage during 2 hours did thus not affect the condition of the ciliae. The absence of a great increase of the beat frequency during a second irradiation period may be explained by damages caused by the initial exposure, morphologically seen first a few days later.

Adenosine Triphosphate↗

PubMedDate not supplied

Progression of human endometrial adenocarcinoma heterotransplanted into nude mice from hormone-sensitive to hormone resistant growth.

We have used a human tumor nude mouse model involving heterotransplantation and serial passage of an estrogen receptor (ER) positive, progesterone receptor (PgR) negative human endometrial adenocarcinoma. The effects of estradiol treatment on tumor growth, ER activation and PgR induction were investigated two and four years after heterotransplantation. In Experiment I, two years after initial heterotransplantation, tumor growth and proliferative rate showed a dose-related decrease, ER was activated by estradiol treatment (measured through an increased amount of ER bound with high affinity to nuclear element(s) (ERhs) and PgR was induced. Two years later (Experiment II), the amount of ER1s (ER measured in cytosolic fraction) as well as of ERhs was lower than at the beginning of Experiment I. ER could again be activated by estradiol treatment and PgR was also induced. However, in this experiment no effect either of tumor growth or of proliferative rate was observed during the estradiol treatment. Our study therefore indicates that an estrogen non-sensitive growth can develop during serial passages in intact, non-treated female nude mice, although the capacity for ER activation and PgR induction is maintained.

Adenocarcinoma↗

PubMedDate not supplied

Estradiol induced changes in tumor growth and steroid receptor content in a heterotransplanted human endometrial adenocarcinoma.

To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.

Adenocarcinoma↗

PubMedDate not supplied

Improved preparation technique of cervical carcinoma for flow cytometric DNA analysis with tissue disintegration in hydrochloric acid.

An one-step procedure using a nuclear isolation medium containing propidium iodide has been found to be a suitable preparation technique for flow cytometric DNA analysis in breast cancer samples. In the case of cervical squamous carcinoma, a pretreatment with HCl seems to be a methodological improvement. One advantage with the HCl modification is that some "false" near-diploid cell populations are abolished. These "false" G0/G1 peaks may represent diploid nuclei with a different stainability for propidium iodide compared to normal diploid nuclei. The HCl treatment has, furthermore, the advantage of increasing the elution of nuclei (mean factor of 4.0), especially non-diploid nuclei from higher differentiated squamous carcinomas.

Cell Nucleus↗

PubMedDate not supplied

Studies on ciliated epithelia of the human genital tract. IV. Mucociliary wave activity in organ cultures of human fallopian tubes challenged with Mycoplasma hominis.

Ciliary activity was studied in specimens of fallopian tube mucosa that were maintained as organ cultures and experimentally infected with Mycoplasma hominis. This activity was quantitated by an established method for recording of the light reflexes from the ridges and troughs in the mucous layer in which the cilia are beating. In organ cultures infected with M. hominis, a ciliostatic effect was observed; the proportion of organ cultures with no detectable ciliary activity was higher and the number of ciliary beats per minute in cultures with detectable activity was lower when M. hominis was present.

Adult↗

PubMedDate not supplied

Effect of estradiol on tumor growth, cell kinetics and p53 oncoprotein expression in human endometrial adenocarcinoma heterotransplanted into nude mice.

To study the importance of estradiol concentrations in which tumors are growing to progression of tumor growth and cell kinetics, we have used a human tumor-nude mice model. In this model a human endometrial adenocarcinoma with estradiol independent but estradiol-responsive growth phenotype (i.e. the tumor was capable of growing in absence of estradiol but its growth could be stimulated by estradiol at the start of preparation phase) was examined. In the preparation phase pieces from this tumor were transplanted into nude mice, randomly divided into two groups, one with and one without estradiol treatment. After 18 months growth in these different hormone conditions the tumors were measured for p53 protein expression and pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas cell kinetic parameters and steroid receptor concentrations were analyzed after the experimental phase. Our findings indicate that progression of the growth phenotype is independent of estradiol conditions in which human endometrial adenocarcinomas are grown. Long-term growth in estradiol-poor conditions results in estradiol resistance of the cell cycle, probably accompanied by overexpression of the p53 protein. Tumor growth in estradiol-rich conditions, however, may protect, at least to some extent, the same tumor, which retains higher sensitivity of cell proliferation to estradiol and normal production of the p53 protein despite progressive changes in growth regulation.

Animals↗

PubMedDate not supplied

Growth interaction between different tumor populations in human endometrial adenocarcinoma growing in nude mice.

In these studies of tumor cell growth interaction we have used two tumors differing from each other in sensitivity to estradiol, transplanted to opposite sites of the same nude mice. In the first experiment we found that the growth of an estradiol-sensitive tumor may be delayed by the presence of an estradiol-resistant tumor in the same animal. Although the growth pattern was changed, proliferative activity, as reflected in the S-phase fraction measured by flow cytometry, and the steroid receptor concentrations were unchanged. Increase of circulating estradiol, however, protects the estradiol-sensitive population from this down-regulation of growth. Findings in a second experiment suggest that this growth delay is probably caused by changes such as decrease in labelling index, increase of non BrdU-incorporating cells in the S-phase, and cell loss in estradiol-sensitive tumors. We concluded that the estradiol-resistant tumor population may secrete some factor(s) acting as endocrine product(s) which may delay the growth of estradiol-sensitive cell populations when the tumors are grown in an estradiol-poor environment. If our model also represents interactions between tumor subpopulations within a single tumor, these findings may have implications for our understanding of the biology of tumor progression in some hormone-related human tumors.

Adenocarcinoma↗

PubMedDate not supplied

Prospective malignancy grading, flow cytometry DNA-measurements and adjuvant chemotherapy for invasive squamous cell carcinoma of the uterine cervix.

In a prospective study comprising 310 consecutive patients with carcinoma of the cervix, FIGO stages I-IV, the prognostic significance of clinical and flow cytometric variable was evaluated in a univariate and multivariate analysis. The parameters studied included stage according to FIGO, age, histopathologic grade according to Ackerman and MGS scores, DNA ploidy, S-phase fraction as well as treatment with radiation only, surgery only or a combination thereof as well as adjuvant chemotherapy. Univariate analysis showed that patients in FIGO stages IA-IIA with MGS up to 14 points survived significantly better than other groups. MGS parameter mitosis, vascular invasion and type of invasion predicted survival as did clinical stage. Diploid cases with SPF > 15% survived less than remaining other cases. Multivariate analysis not including treatment indicated that FIGO stage and diploid cases with SPF > 15% predicted survival but not total MGS score and age. When treatment for FIGO stages IA-IIA was included, elderly women had a worse prognosis. Adjuvant chemotherapy, surgical alone or radiation alone did not demonstrate any differences within groups. In Figo stages IIB-IV, cases with radiotherapy only survived significantly better than patients with other treatment schedules. The frequency of low malignancy patients (< MGS 16) in relation to year of initial diagnosis was found to have decreased between years 1967 and 1988, probably as a result of screening activities.

Adult↗