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  • Articles: DFG German National Licenses  (13)
  • 1
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. There are not many publications describing long-term follow-up of persistent hyperparathyroidism requiring surgical treatment after kidney transplantation (PHSKT). In some patients adenomas, rather than multiglandular disease, have been incriminated as the cause of PHSKT. We reviewed the charts of 45 patients followed for 12 to 146 months (median 45 months) after parathyroidectomy for PHSKT. We compared them with (1) those of 951 patients receiving a kidney graft during the same period but not submitted to parathyroidectomy or (2) 90 matched controls selected from this cohort to determine the characteristics of PHSKT patients. The duration of pretransplant dialysis was significantly longer in PHSKT patients than in controls (5.78 ± 0.41 vs. 3.41 ± 0.24 years; p 〈 0.0001). A total of 166 glands were removed or biopsied. Except for one questionable case, no true adenoma was observed even when only one gland was enlarged. The outcome of surgery was not influenced by the technique (subtotal parathyroidectomy versus total parathyroidectomy and autografting) but depended on the amount of resected parathyroid tissue: no failures and 4 cases of hypoparathyroidism in 34 cases with no missing gland at cervical exploration; 3 failures and no permanent hypoparathyroidism in 11 cases with one or two missing glands. Excision of the enlarged glands only was sufficient to cure the patient. No recurrence was observed. Our results suggest that single gland enlargement in PHSKT results in most cases from different rates of involution of the parathyroids after successful kidney transplantation. When fewer than four glands are discovered, resection of all visible glands with or without grafting corrects hypercalcemia in more than 70% of the cases.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: Key words Cell loss ; Growth fraction ; Cell proliferation ; Cell density ; Gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The object of this work was Purpose: to develop a methodology that enables net tumour growth, a balance between actual tumour growth and tumour cell loss, to be approximately evaluated. Methods: The methodology proposed relies on detecting the growth fraction immunohistochemically by means of MIB-1 antibody labelling combined with cell density determination, carried out on 5-μm-thick Feulgen-stained histological sections with computer-assisted microscopy. The series investigated included 25 oligodendrogliomas (OLG-II), 9 anaplastic oligodendrogliomas (OLG-III), 13 astrocytomas (AST), 14 anaplastic astrocytomas (ANA) and 8 mixed oligoastrocytomas (OLG-AST). Results: The results show that the biological characteristics of some cases were in total accordance with their histopathological diagnoses. This was the case for the “weakly proliferating weakly dense” OLG-II and AST-II tumours, and for the “highly proliferating highly dense” OLG-III and AST-III ones. In contrast, the biological characteristics of some cases seemed to contradict the histopathological case labels. This was the case for the “highly proliferating highly dense” OLG-II and AST-II tumours, the biological aggressiveness of which would be undervalued on the basis of the morphology-based grading system alone, and also for the “weakly proliferating weakly dense” OLG-III and AST-III tumours, the aggressiveness of which would be overvalued. Conclusions: Combining the determinations of the MIB-1 and the cell density variables appears to be satisfactory in terms of the cell kinetic characterization of glial tumours as a complement to the prognostic information given by a morphology-based grading system alone.
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  • 3
    ISSN: 1432-1335
    Keywords: Key words Soft-tissue tumour ; In vitro cell proliferation ; Hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 β-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2% of fetal calf serum and (2) a nutritionally rich one containing 5% or 10% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most “factor-sensitive”. Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.
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  • 4
    ISSN: 1432-1335
    Keywords: Key words Soft tissue tumour ; In vitro ; Cell growth ; Lectins ; Neoglycoconjugates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose : The aim of our study is to investigate the in vitro effects of plant lectins, galectins and neoglycoconjugates on the proliferation of three human sarcoma cell lines. Methods : Proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. In addition, glycohistochemistry was used to make visible the plant-lectin-specific binding sites; the intensity of the lectin binding pattern was quantified by means of image analysis. Results : Depending on the cell lines, the staining intensity and the percentage of labelled cells were different. With respect to growth modulation, the cell lines also responded differently to the probes used. Besides a predominant inhibitory effect elicited by the probes at 50 μg/ml, dose-dependent effects, including growth stimulation, were detectable in several instances. These effects relate to the animal galectins tested and several neoglycoconjugates, e.g. the lactose- and blood-group-A-trisaccharide-bearing probes. Conclusions : Endogenous lectins and lectin-reactive cellular glycoconjugates can apparently affect the regulation of the growth of human sarcoma cells. We suggest that these results are relevant for further histopathological monitoring in correlation with prognosis and in vitro assays to reveal possible clinical applications.
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  • 5
    ISSN: 1432-1335
    Keywords: Key words Human thyroid ; Multinodular goiters ; Adenomas ; Cancer ; Cell proliferation ; Hormone sensitivity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose : To characterize the influence of six factors on human thyroid tissues at the cell-proliferation level. These six factors were the epidermal growth factor (EGF), the luteinizing-hormone-releasing hormone (LHRH), triiodothyronine, thyroxine, estradiol and gastrin. Methods : Forty-eight human thyroid specimens were obtained from surgical resection and maintained alive for 48 h ex vivo (in vitro) under organotypic culture conditions. These specimens comprised 35 benign cases (17 multinodular goiters and 18 adenomas) and 13 cancers. Cell proliferation in the control and treated conditions (at a 5 nM dose) was assessed by means of the thymidine labeling index, which enables the percentage of cells in the S phase of the cell cycle to be determined in accordance with autoradiographic procedures. Results : The results show that, of the six factors tested here, EGF significantly (P 〈 0.05 to P 〈 0.001) increased cell proliferation in the greatest number of cancers as compared to what happened with the remaining five. Each of these six factors significantly increased or decreased proliferative cell activity in some 10%–30% of the cases under study. Conclusions : Triiodothyronine, thyroxine, LHRH and gastrin may increase or decrease cell proliferation in human thyroid tissues, whether benign or malignant, to the same extent as other hormones and/or growth factors such as thyrotropin, EGF, insulin-like growth factor 1, transforming growth factor β1 and estradiol the effects of which on thyroid cell proliferation are already well documented in the literature.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1335
    Keywords: Key words Breast cancer ; Quantitative immuno histochemistry ; ER ; PgR ; Cell proliferation ; Hormone sensitivity ; Organotypic culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the “static” and “dynamic” level. Methods: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. Results: Of the 14 breast cancers under study, one with an unequivocally “very ER-rich”/“very PgR-rich” immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an “ER-poor”/“PgR-poor” immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. Discussion: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Cell death is an essential event in the functioning of multicellular organisms. It plays a role opposite to that of mitosis in the regulation of cell populations. In the present work, we describe an original methodology which permits the easy detection and count of apoptotic cells in a given tissue. This methodology is based on the digital cell image analysis of Feulgenstained nuclei, which also permits the calculation of the proliferation index, i.e. the precentage of cells in the S phase of the cell cycle. This percentage of cells in the S phase is strongly related to the mitotic index. Our methodology, which involves the multivariate analysis of 14 morphonuclear parameters computed by means of the digitized cell image analysis of Feulgen-stained nuclei, was applied here to a well-known biological apoptosis model, namely glucocorticoid-treated rat thymocytes. The parameters that permitted the detection of apoptotic cells were the integrated optical density, a parameter that describes the nuclear DNA content, and the run length percentage and long run length parameters which are related to the pattern of chromatin condensation. This determination can be carried out on a relatively small number of cells.
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  • 8
    ISSN: 1432-1335
    Keywords: Brain metastases ; Primary nervous tumours ; DNA ploidy ; Image cytometry ; Prognosis ; Feulgen staining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nuclear DNA content (NDA ploidy) level was determined in a series of 83 human brain metastases, for which 35 complete clinical follow-ups were available. The DNA ploidy level determination was carried out by means of DNA histogram types. The results show that certain brain metastases were diploid, while others exhibited aneuploidy levels ranging from low to very high. The present study also shows that a significant proportion, i.e. 18%, of the 83 brain metastases, exhibited very high levels of aneuploidy, i.e. hypertetraploidy, hyperpentaploidy and octoploidy. We had previously observed that this feature appeared only rarely, i.e. in less than 2% of primary nervous tumours. Furthermore, the present study shows that DNA ploidy level in brain metastases is related significantly (P〈0.001) to patient survival. Indeed, while 9/13 (69%) patients with diploid brain metastases survived longer than 9 months, none (0%) of the 22 patients with aneuploid brain metastases survived longer than the 9 months following the diagnosis of their brain metastases.
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  • 9
    ISSN: 1573-7373
    Keywords: hormones ; growth factors ; neutralizing antibodies ; proliferation ; clone architecture ; human ; astrocytic tumors ; in vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of five anti-hormone and/or anti-growth factor neutralizing antibodies on thein vitro proliferation of four human astrocytic tumor cell lines (U87, U138, U373, H4) is quantitatively described by means of a new tool which makes it possible to evaluate cell growth and cell clone architecture concomitantly. This tool relies upon the combined use of the digital cell image analyses of Feulgen-stained nuclei and the Delaunay and Voronoi mathematical triangulation and paving techniques. Of the five anti-hormone and/or anti-growth factors tested here, the anti-luteinizing hormone-releasing hormone (LHRH) antibody induced the most marked perturbation in the U138 and U373 cell lines, whereas this role was played by the anti-epidermal growth factor (EGF) antibody in the U87 and H4 cell lines. The anti-gastrin (G) antibody significantly modified the growth and/or cell clone architecture of the U138, U87 and H4 cell lines, as did the anti-transforming growth factor alpha (TGFalpha) antibody. The anti-transforming growth factor beta (TGFbeta) antibody modified the growth and/or cell clone architecture of the four cell lines under study. If the five antibodies are taken into consideration, the results strongly suggest that four (the anti-G, the anti-EGF, the anti-LHRH and the anti-TGFalpha) act as inhibitory agents on some glioma cell line proliferation, while the fifth one, i.e. the anti-TGFbeta, act as a stimulator of cell proliferation, perhaps by abrogating the inhibitory effects of TGFbeta on proliferation. A comparison of cell growth data with cell clone architecture characteristics provided further evidence of some specific influence exercised by a given hormone and/or growth factor on glioma cell proliferation. Indeed, the anti-LHRH antibody caused the most pronounced perturbations in the U138 and U373 cell clone architecture; this feature was observed in the H4 cell line and, to a lesser extent in the U87 one after the anti-EGF antibody had been used.
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  • 10
    ISSN: 1573-7373
    Keywords: lectin histochemistry ; cell proliferation ; astrocytic tumor ; human ; in vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of lectins as biosignalling molecules oras markers of human astrocytic tumors remains relativelyunexplored. The aim of the present work isto investigate (1) whether or not human astrocytictumors express specific glycans, evidenced experimentally by meansof lectin histochemistry, and (2) whether, in turn,these lectins can significantly modulate astrocytic tumor cellproliferation. Using a cell image processor, we thereforebegan by quantitatively measuring the histochemical binding patternof 5 lectins (WGA, PNA, PHA-L, GSA-IA4 andCon A) in 5 astrocytomas, 5 anaplastic astrocytomasand 5 glioblastomas. Secondly, we measured the influenceof these 5 lectins on the proliferation of3 astrocytic tumor cell lines (SW1088, U373 andU87) growing in vitro as monolayers. Cell proliferationwas assessed by means of the colorimetric MTTassay. The histochemical lectin staining markedly varied intra-and inter-group. However, some constant results were obtained.Indeed, the staining increased markedly from GSA-IA4 andPHA-L through WGA and PNA to Con Ain the three histopathological groups. The assessment ofcell proliferation demonstrated that WGA, Con A andPHA-L very significantly decreased proliferation in the 3astrocytic cell lines in a dose-dependent manner. Astrocytictumor cells in the confluent growth phase wereless sensitive to the WGA, Con A andPHA-L lectin-induced effects than cells in the loggrowth phase. The GSA-IA4 and PNA lectins hadglobally very weak effects on the proliferation ofthe astrocytic tumor cell lines. Increasing the fetalcalf serum from 1% to 10% in theculture media significantly antagonized the WGA-, Con A-and PHA-L-induced cell proliferation decrease in the 3astrocytic cell lines. In conclusion, the present datastrongly suggest that some lectins (including WGA, ConA and PHA-L) significantly influence the proliferation ofastrocytic tumor cells.
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