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Biomedical subjects

O Schneider

Publications and source records attributed to O Schneider.

33 records · Page 2Linked to original sources

Production of follistatin in porcine endothelial cells: differential regulation by bacterial compounds and the synthetic glucocorticoid RU 28362.

Follistatin (FS) is the specific binding protein of activin; it has a broad tissue distribution and is also found in serum. The ovary has the highest level of FS expression, but ovariectomy does not cause a permanent reduction in the serum FS level. Therefore, the source of FS in serum is still elusive. As a regulatable, nongonadal source of serum FS could influence ovarian and pituitary-derived hormone secretion and thus reproductive function, we searched for a source of extragonadal FS expression that might contribute to the FS protein level in serum. We found that endothelial cells from blood vessels express FS messenger RNA (mRNA) and protein; therefore, we studied the regulation of steady state levels of FS mRNA in porcine endothelial cells from aorta (AEC) and brain microvessels (BMVEC) in tissue culture. For detection of FS mRNA, a specific 32P-radiolabeled antisense probe and a S1-nuclease protection assay were used. FS steady state levels of AEC decreased with time in culture, i.e. postconfluent AEC had lower FS mRNA levels than confluent cultures, which, in turn, had lower FS mRNA levels than subconfluent cell cultures. FS mRNA levels in AEC were induced by increasing concentrations of FCS and stimulated by 30 micrograms/ml endothelial cell growth supplement. FS mRNA levels in AEC and BMVEC increased approximately 20-fold within 4 h during incubation of the cells with 100 nM phorbol 12-myristate, 13-acetate, whereas 0.5 nmol/ml forskolin tested in AEC for between 4-48 h had no significant effect. Furthermore, 0.1 microM ocadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, caused a significant increase in FS mRNA levels. FS mRNA levels in AEC were not significantly affected by various concentrations of porcine FSH, epidermal growth factor, or retinoic acid for between 4-48 h. Treatment of the cells with 0.01-10 micrograms/ml bacterial lipopolysaccharides (LPS) caused a dose-dependent increase (up to 10-fold) in FS mRNA steady state level in AEC, whereas 1-1000 nM RU 28362, a synthetic glucocorticoid, inhibited FS mRNA steady state levels in a dose-dependent manner. The induction of FS mRNA with 1 microgram/ml LPS was completely blocked by 100 nM RU 28362, and the stimulatory effects of LPS were only visible after 4 h of treatment, not after 24 or 48 h. The same effects were observed with BMVEC. We, furthermore, analyzed FS protein secretion of AEC by Western blotting and demonstrated that FS proteins were secreted into the culture medium upon stimulation with LPS. None of these treatments had an obvious effect on the ratio of the two different forms of FS mRNA (FS 344:FS 317). Besides the expression of FS mRNA in AEC and BMVEC, FS mRNA is also expressed in uncultured plexus choroideus epithel and meninges, and FS protein is found in human cerebrospinal fluid. From this study it is concluded that 1) endothelial cells from different tissues produce FS mRNA; 2) the FS mRNA levels of AEC and BMVEC are subjected to regulation by FCS, endothelial cell growth supplement, bacterial LPS, and the glucocorticoid RU 28362; 3) phosphatases and the protein kinase C-dependent, but not the protein kinase A-dependent, pathway are involved in regulating the steady state levels of FS mRNA in AEC and BMVEC; and 4) endothelial cells produce and secrete FS protein and are thus a likely source of FS in serum.

Androstanols↗

Cytotoxic and transforming effects of some iron-containing minerals in Syrian hamster embryo cells.

Four physicochemically characterized iron-containing minerals, one fibrous (a nemalite [brucite]) and three nonfibrous (a biotite [phyllosilicate], a magnetite (Fe3O4), and a goethite [FeOOH alpha]), were studied for cytotoxicity and morphological transformation of Syrian hamster embryo (SHE) cells. When colony-forming efficiency was used as a measure of cytotoxicity, it appeared that the nemalite was about 1.7-fold more cytotoxic than the biotite and magnetite. However, if the inhibitory effect on the cell growth was considered the nemalite appeared to be 8-fold more effective. The analysis of the cell cycle kinetics by flow cytometry revealed a time- and dose-dependent delay in the progression of cells through the cell cycle, with the accumulation of cells in S and G2-M phases, more particularly in the cultures treated with nemalite. While the goethite was neither cytotoxic nor transforming, the other three dusts were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. According to their transforming potency they ranged as follows: nemalite > biotite > magnetite. A 18-fold higher treatment concentration of magnetite than that of nemalite was necessary to induce the same transformation frequency. The iron chelator desferrioxamine abolished the transforming effect of nemalite. The results suggest that (i) the cytotoxicity and the transformation are induced by some divalent iron-containing minerals and that they are two distinct processes; (ii) there is a varying ability among these dusts to induce cell transformation; and (iii) the bioavailability of divalent iron leading to formation of reactive iron-oxygen species could mediate the transforming potency of a mineral. Physicochemical studies correlated to biological effects of many metallic mine dusts are the only approach for understanding their mechanisms of action and their role in occupational pathology.

Aluminum Silicates↗

[Intraosseous lipoma of the calcaneus].

This report presents one case of rare benign intraosseus lipoma of the os calcis, which is analysed under the clinical, histopathologic and radiologic view. Not only the radiographic but also the computed tomographic findings has shown a typical picture of an intraosseous lipoma including a central calcification. In order to exclude a malignant transformation and as a prophylaxis of a pathological fracture the operative removal and bone graft transplantation is considered as therapy of choice.

Bone Neoplasms↗

[Special aspects in diagnosis and treatment of open craniocerebral injuries including basilar skull fractures].

The possibility of CSF leakage means that open head injuries and skull base fractures are serious and sometimes dangerous. An operation should be considered in cases of open depressed skull fractures with or without space-occupying haematoma, compound fractures of the rhinobasis and orbita, dislocated fractures of the dorsal wall of the frontal sinus, CSF leakage for longer than 1 week, and posttraumatic intracranial infection. Operative and posttraumatic intracranial infection is also potentially dangerous. The operative approach depends on the type and localization of the fracture. The transsphenoidal and frontoorbital approaches are less traumatic, but offer only limited visibility. The transfrontal intradural approach offers by far the best view of the frontobasis and is therefore indicated in most cases.

Bone Plates↗

Appearance of poststenotic jets in MRI: dependence on flow velocity and on imaging parameters.

A flow model was used to study the appearance of poststenotic jets in MRI. Jets in CuSO4-doped water and bovine blood were imaged by spin-echo (SE) and fast-field-echo (FFE) pulse sequences at different degrees of stenosis and various flow rates. On flow-compensated FFE images, the jets were characterized by signal void if the mean flow velocity within the stenosis exceeded a limit, which was independent of the degree of the stenosis and the type of the fluid. On SE images and on FFE images without flow compensation, signal void occurred at significantly lower flow velocity. The extension of the poststenotic signal void on flow-compensated FFE images was increased by either reduction of the pixel diameter or by prolongation of the echo time. However, it was independent of the orientation of the imaging plane relative to the direction of flow. The results have an impact on attempts to use signal void for the assessment of turbulent jets with MRI.

Animals↗

Cytotoxic and neoplastic transforming effects of industrial hexavalent chromium pigments in Syrian hamster embryo cells.

Twenty eight moderately water-soluble to insoluble chromium (VI) compounds, such as zinc and lead chromate, industrial and laboratory synthesized pigments, and the analytical reagents strontium, barium and calcium chromate, were physicochemically characterized and studied for cytotoxicity and morphological transformation in cultured Syrian hamster embryo (SHE) cells. In vivo validation of malignancy of transformed SHE cells was performed. A high physicochemical diversity among the complex chromium pigments was revealed. The solubility of the compounds was greatly increased after incubation in a complete medium and even higher under cell culture conditions. The cytotoxic effects appeared to be due principally to extracellular solubilized chromium because the most solubilized compounds. Zn, Ca and Sr chromates, were equitoxic at about the same Cr concentration treatment and 8-fold more cytotoxic than less soluble compounds such as some Pb chromates and Ba chromate. However, certain physicochemical properties of lead chromate pigments could also influence their cytotoxic activity. All test compounds were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. Many of the Cr pigments, although physicochemically different, were similarly effective in transformation induction. Nevertheless, compounds among Zn and Pb chromates had various transforming potencies. Ba chromate was the least active in inducing transformation. Certain physicochemical properties could mediate the transforming activity but no particular relationship could be established between any one of the physicochemical parameters and the transforming potency. Cloned morphologically-transformed colonies of SHE cells were grown in soft agar medium and showed true neoplastic behaviour by tumour formation in syngeneic animals. These results show that various chromate pigments containing either Zn or Pb, of medium to very low aqueous solubility, induced neoplastic transformation of SHE cells.

Animals↗

Chromosome aberrations in peripheral blood lymphocytes of welders and characterization of their exposure by biological samples analysis.

Chromosomal aberrations in cultured lymphocytes obtained from 55 welders and 55 matched controls were analyzed. Depending on the welding techniques and the nature of the consumables and metals welded, three separate groups of welders were examined. Chromium, nickel, and manganese levels in serum and urine were measured to assess the exposure to welding fumes. A statistically significant increase of chromosomal aberrations was found in one of the three analyzed groups of welders. This group used the semi-automatic metal active gas welding process with cored wire containing nickel for welding mild steel. These welders had significantly higher concentrations of serum and urine manganese and, unlike the other welders, significantly elevated concentrations of nickel, both in serum and urine. However, no significant correlations between nickel or manganese levels and the frequency of chromosomal aberrations were found. There was a significant correlation between the length of welding employment of these welders and the frequency of chromosomal breaks, although there was no significant correlation between age and the frequency of chromosomal aberrations. The other two groups of welders, for which the analyses of biologic fluids proved chromium and manganese exposure, had no statistically significant higher frequency of chromosomal aberrations. One of these groups used the manual metal arc welding process with coated electrodes for welding mainly mild steel and the other group used the tungsten inert gas welding process for welding stainless steel. A significant correlation between the daily amount of cigarettes smoked and the frequency of chromosomal breakages, in controls as in welders, was observed. The present data indicate that certain welding processes may generate fumes that seem to have a clastogenic activity.

Adult↗

Cellular uptake, cytotoxic and mutagenic effects of insoluble chromic oxide in V79 Chinese hamster cells.

The cellular uptake, the cytotoxicity and the induction of resistance to 6-thioguanine (6-TG) in Chinese hamster V79 cells exposed to insoluble crystalline trivalent chromium [Cr(III)], Cr2O3, were investigated. Intracytoplasmic Cr2O3 crystalline particle-containing vacuoles were observed by electron microscopy. Concentrations of 50-200 micrograms/ml did not have a marked killing effect but did show a predominantly concentration-dependent inhibitory effect on cell cycle progression with accumulation of cells in G2 phase. Exposure for 18 h to Cr2O3 induced a statistically significant (p less than 0.001) increase in the mutation frequency of up to 10-fold over the controls. Expression time was 6 days for the lowest concentration and 9 days for the highest. Culture of 6-TGr clones in selective media indicated that they were mutants at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. Examination of growth patterns of Cr2O3-induced mutants showed that, after a delay in reinitiating cell growth, they had varying growth kinetics. The results indicate the ability of a particulate (Cr(III) compound to induce mutation in a mammalian cell system and the usefulness of such systems for detecting genotoxic insoluble metal compounds.

Animals↗

Sister chromatid exchanges in Chinese hamster V79 cells treated with the trivalent chromium compounds chromic chloride and chromic oxide.

The induction of sister chromatid exchanges (SCEs) in Chinese hamster V79 cells exposed to soluble CrCl3 and insoluble Cr2O3, compounds of trivalent chromium (Cr3+), was determined. Their ability to induce SCEs was compared with those of three hexavalent chromium (Cr6+) compounds: K2CrO4, Na2CrO4 and Na2Cr2O7. Both the delay in progression through the cell cycle induced by Cr3+ compounds and the SCE frequencies in the delayed cells were also evaluated. The exposure for 28 h to CrCl3 and Cr2O3 at concentrations of 9.7-39 micrograms and of 34-136 micrograms of Cr3+ per ml, respectively, induced a statistically significant (p less than 0.001) dose-dependent increase in SCEs up to 1.9-fold (CrCl3) and 4-fold (Cr2O3) over control levels. Compared with the effective concentrations of Cr6+ compounds, which produced up to 4-fold increase of SCEs, inducing concentrations of CrCl3 and Cr2O3 were 300- and 1000-fold higher in terms of chromium. By prolongation of treatment time up to 48 h, a progressive dose- and time-related enhancement in SCE frequencies induced by Cr3+ compounds in delayed cells was observed. Lower concentrations of Cr2O3, without effect after 28 h of treatment, induced an increase of SCEs by prolongation of exposure time.

Animals↗

Separation of human bone marrow cells by sedimentation.

Sedimentation at unit gravity of human bone marrow cells, for 15 h at 4 degrees C on linear density gradient of Ficoll in culture medium ranging from 1.020 to 1.065 g/ml shows that a differential migration of the bone marrow cell sub-populations exists with precise mean densities 1.021 +/- 1 x 10(-3) g/ml for lymphocytes; 1.024 +/- 2.5 x 10(-3) g/ml for non-eosinophil granulocytes; and 1.055 +/- 10 x 10(-3) g/ml for metamyelocytes; 1.030 x 3.5 x 10(-3) g/ml for other myeloid cells (myeloblasts, promyelocytes, myelocytes); 1.040 +/- 1.040 +/- 3 x 10(-3) g/ml for eosinophil granulocytes; and 1.055 +/- 10 x 10(-3) g/ml for megakaryocytes. The highest percentages of S phase cell and G2 and M phase cells determined by a cytofluorograph correspond to the peaks of immature myeloid cells (myeloblasts, promyelocytes and myelocytes). This method of bone marrow cell separation may be used to study the cell cycle in pathological bone marrows (leukaemia in particular) and to determine the effects and the efficiency of some antimitotics.

Bone Marrow Cells↗

[Application of sedimentation at 1 g on a Ficoll gradient to the separation of bone marrow cells].

Sedimentation at unit gravity of human bone marrow, during 15 hours at 4 degrees C on a linear density gradient of Ficoll in culture medium ranging from 1.020 to 1.065 g/ml shows that it exists a differential migration of bone marrow cells subpopulation with a precise mean densities : we find successively : 1.021 +/- 1.10(-3) g/ml for the lymphocytes, 1.024 +/- 2.5.10(-3) g/ml for the non eosinophil granulocytes, 1.025 +/- 2.5.10(-3) g/ml for the metamyelocytes, 1.030 +/- 3.5.10(-3) g/ml for the immature myeloid cells (myeloblasts, promyelocytes, myelocytes), 1.040 +/- 3.10(-3) g/ml for the eosinophil granulocytes, 1.055 +/- 10.10(-3) g/l for the megakaryocytes. The highest percentages of S phase cells, G2 and M phase cells determinated with a cytofluorograph correspond to peaks of immature myeloid cells (myeloblasts, promyelocytes and myelocytes). This method of bone marrow cells separation may be used to study the cell cycle in pathological bone marrows (leukaemia in particular) and to determine the effects and the efficiency of some antimitotics.

Bone Marrow Cells↗

[In vitro and in vivo sensitivity of animal and human melanomas to various chemotherapeutical agents].

Thin slices of s.c. implanted B-16 melanomas as well as of human melanomas have been incubated for 5 h with (H3) Uridine and (H3) Thymidine in the presence of different chemotherapeutical agents, whose concentration was equivalent to the tenfold therapeutical daily dose in men. In this short term test model, the sensitivity of a melanoma to a chemotherapeutical agent is indicated by the inhibition of the nucleoside uptake by more than 50%. The in vitro sensitivity rates, each based on 10--30 melanomas, are compared to the in vivo sensitivity rates. Sensitivity is indicated by the increase of life span (greater than 25%) in the melanoma bearing mice respectively by the regression of human melanoma metastases (greater than 50%). -- The in vivo sensitivity of the B-16 melanomas, evaluated by the uridine and/or thymidine uptake, was in line with the in vivo sensitivity to all chemotherapeutical agents with the exeption of Adriamycine and DTIC. The in vitro sensitivity of human melanomas to Dactinomicine, Vincristine, BCNU and DTIC corresponds to the in vivo sensitivity whereas no in vitro/in vivo correspondence could be observed in testing Bleomycine, Procarbacine and 5-Fluorouracile. Comparing the sensitivity of B-16 and human melanomas, similarity was observed in vitro but not in vivo.

Animals↗

[Serum level of prostatic specific antigen in 100 patients with prostatic biopsy].

OBJECTIVE: To define the PSA levels (Prostatic Specific Antigen) in our patients with benign or malignant prostatic biopsy. METHODS: 100 patients with clinical suspicion of prostatic carcinoma (high levels of PSA and/or abnormal findings at digito-rectal examination) and who underwent a prostatic needle biopsy were reviewed. RESULTS: There were 66 benign and 34 carcinomas. The median PSA was 11.2 ng/mL in the benign cases and 45.6 in cancer. In cases with small increases in PSA (49.9 ng/mL), 94% were benign; there was still a majority of benign cases (63%) in patients with a PSA of 10-29.9 ng/mL. Only in those with levels of 30+, malignancy was a majority (81%). CONCLUSIONS: There was a considerable overlap of PSA levels in our benign and malignant patients, and only values of 30+ ng/mL were highly suggestive of carcinoma. Our levels are higher than those informed in the literature and may have been due, at least partly, to the source of our reagent kits for PSA assays (Cedex from France and Diagnostic Products Corp from the U.S.).

Biopsy, Needle↗