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Biomedical subjects

F Hofstädter

Publications and source records attributed to F Hofstädter.

At least 73 records · Page 4Linked to original sources
PubMed1994

Induction of stress fibres and intercellular gaps in human vascular endothelium by shock-waves.

Human umbilical cords were exposed to high amplitude focussed ultrasonic pulses with focal energy densities 0.6 and 0.4 mJ mm-2. The endothelium of the exposed vessel (vein) was examined by means of confocal laser scanning microscopy and scanning electron microscopy. The degree of tissue change ranged from the induction of stress fibres and intercellular gaps to the complete detachment of endothelial cells combined with damage of the basement membrane. An increased number of stress fibres may indicate an increased vessel wall permeability. This might explain the enhanced effects in experimental tumour therapy that have been found by other authors when combining shock-waves with drugs.

Basement Membrane↗
PubMed1994

Shock wave induced endothelial damage--in situ analysis by confocal laser scanning microscopy.

For more than a decade, extracorporal shock wave lithotripsy has been a standard clinical method for the treatment of urinary stones. However, side effects that are likely to be correlated to vessel damage can often be observed using noninvasive diagnostic techniques, e.g., magnetic resonance imaging. To avoid side effects it is useful to understand the interaction between shock waves and the vascular system. In particular, this is important in view of new applications like gallstone lithothripsy. In the present study, we exposed human umbilical vessels to electromagnetically generated ultrasound shock waves to analyze subsequent alterations of their endothelial layer. Following en face preparation and fluorescent staining, the endothelium was examined in a confocal laser scanning microscope. Endothelial cells of the shock wave exposed vessels revealed permeabilization of plasma membranes and mitochondrial alterations as potentially lethal damage. An increase in the number of stress fibres may indicate functional changes possibly influencing vessel wall permeability.

Endothelium, Vascular↗
PubMed1994

A heterologous in vitro coculture system to study interaction between human bladder cancer cells and fibroblasts.

Three-dimensional multicellular spheroids of two fibroblast cell lines (WI-38 and N1) and two differently differentiated bladder carcinoma cell lines (RT4 and J82) were used for cocultures of multicellular tumor spheroids with multicellular spheroids of fibroblasts. The aim of the study was the establishment and characterization of a standardized three-dimensional model for studies of tumor cell-fibroblast interaction as one aspect of tumor-stromal cell interactions of in vivo tumor tissue. Interaction of multicellular spheroids of both fibroblast cell types was analyzed by staining with antibodies against cytokeratin, vimentin and different extracellular matrix molecules. Further, proliferation assessment and phenotypic characterization of the cocultures are presented. Interactions varied with tumor cell type and fibroblast cell type, reflecting intrinsic properties of tumor cells and fibroblasts. The coculture of tumor cells with N1 reflected the in vivo situation the closest, since invasive properties of J82 as well as noninvasive properties of RT4 were characteristics seen in coculture.

Cell Communication↗
PubMed1994

Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid.

OBJECTIVES: Tiny papillary tumors and flat urothelial lesions such as dysplasia or carcinoma in situ can easily be missed during routine cystoscopy. Various methods for in vivo detection of fluorescing agents (preferentially localized in malignant tissue) have been developed. Most of them are based on systemically administered synthetic porphyrin compounds and require sensitive detection devices and image processing units for fluorescence visualization. The usefulness of intracellularly accumulated endogenous protoporphyrin IX (PPIX), induced by 5-aminolevulinic acid (ALA), for diagnosis of early bladder cancer and the correlation with cystoscopic, microscopic, and fluorescence findings was investigated. METHODS: ALA was instilled intravesically in 68 patients, followed by fluorescence cystoscopy with violet light from a krypton ion laser that produced fluorescence excitation. There were 299 biopsies obtained from fluorescing and nonfluorescing areas of the bladder. RESULTS: ALA-induced fluorescence could be easily observed with the naked eye during cystoscopy under violet light illumination. All tumor lesions were sharply marked with brightly shining red fluorescence. Correlation of fluorescence and microscopic findings gave a sensitivity of 100% and a specificity of 68.5%. There were 26 malignant or precancerous lesions that were missed during routine cystoscopy but were detected only by ALA-induced fluorescence. CONCLUSIONS: Labeling of urothelial lesions by PPIX fluorescence induced by intravesically instilled ALA seems to be a promising diagnostic procedure for malignant lesions that are difficult to visualize with standard cystoscopy.

Administration, Intravesical↗
PubMed1994

Intravesical instillation of 5-aminolevulinic acid: the fluorescent metabolite is limited to urothelial cells.

OBJECTIVES: For photodynamic therapy 5-aminolevulinic acid is an attractive compound, since it is a physiologic endogenous substance, and its application in excess results in the accumulation of the metabolite protoporphyrin IX, a very effective photosensitizer. The topical application of 5-aminolevulinic acid in the urinary bladder led to pronounced fluorescence in neoplasias when excited with violet laser light during cystoscopy. The aim of this study was the determination of the transmural distribution of protoporphyrin IX in order to estimate potential efficacy and side effects of a therapeutic application of 5-aminolevulinic acid. METHODS: 5-Aminolevulinic acid was instilled prior to cystoscopy and biopsies were taken of lesions that were either fluorescing or nonfluorescing. Fluorescence distribution was analyzed by fluorescence microscopy on cryostat sections prepared from 72 biopsy specimens. In addition, multicellular spheroids grown from tumor cells and fibroblasts were exposed to 5-aminolevulinic acid and analyzed accordingly. RESULTS: Biopsy preparations showed that the fluorescence of protoporphyrin IX was limited to normal and neoplastic urothelial cells. Clinical findings were supported by the in vitro data, which showed negative protoporphyrin IX fluorescence in fibroblasts. CONCLUSIONS: Thus, 5-aminolevulinic acid might be superior in selective accumulation to conventional sensitizers known to localize also in endothelial cells of the tumor stroma. The data appear to hold great promise for 5-aminolevulinic acid in photodynamic diagnosis and therapy in bladder cancer, as phototoxicity will be limited to mucosal lesions. Bladder shrinkage due to photodamage of subepithelial structures even in case of high light doses is not expected.

Administration, Intravesical↗
PubMed1994

The combined effects of high-energy shock waves and cytostatic drugs or cytokines on human bladder cancer cells.

The effects of shock waves generated by an experimental Siemens lithotripter in combination with cytostatic drugs or cytokines on several bladder cancer cell lines were examined in vitro. Proliferation after treatment was determined with the 3-4,5-dimethylthiazol-2,5 diphenyl tetrazolium bromide assay. Dose enhancement ratios were calculated for each drug and each shock wave application mode in order to characterise the sensitising effect of shock wave pretreatment. The influence of the time between shock wave and drug treatment as well as the effects of different sequences of shock wave and drug treatment or concomitant treatment were assessed for selected combinations of cell lines and drugs. It was found that shock wave treatment could render certain cell lines more susceptible to subsequent cis-platinum, mitomycin C or actinomycin D incubation. Cell lines sensitive to tumour necrosis factor alpha or interferon alpha were further sensitised to these cytokines by shock wave pretreatment. The enhanced sensitivity to cis-platinum and actinomycin D decreased rapidly during the first hours after shock wave treatment. The antiproliferative effect was most pronounced after concomitant shock wave and drug treatment. The sensitisation to interferon alpha diminishes more slowly after shock wave exposure. From the results presented in this study it is concluded that transient shock wave-induced permeabilisation of cell membrane not only enhances drug efficiency, but also causes damage to cell organelles and alterations in cellular metabolism.

Antineoplastic Agents↗
PubMed1994

AgNOR quantification with special reference to staining patterns.

Silver staining of nucleolar organizer regions (AgNORs) is now widely used as a marker of malignancy in tumor pathology. Standardization of the AgNOR technique has thereby been shown to be of central importance. Basically, three types of AgNOR evaluation have been used: the counting method, image analysis and pattern recognition. Today, image analytical determination of AgNOR area per nucleus is considered to be the state of art method of AgNOR evaluation. In contrast, counting of every single AgNOR dot is laborious and less reproducible. For routine purposes, however, a rapid evaluation of AgNORs would be desirable. In order to elucidate the value of AgNOR distribution patterns systematic in vitro studies using four different urothelial cell lines (HU609, RT4, J82, MGHU1) were performed. AgNOR number (NORN) and AgNOR area (NORA) were closely related to the population doubling time (PDT) and increased during transition from G0/G1 to S/G2 cell cycle phase. In addition, both parameters were significantly elevated in the polyploid RT4 cell line. In contrast, number and area of AgNOR cluster (aggregates of at least two AgNOR dots) were less significantly correlated to PDT. Formation of large AgNOR clusters (maximum diameter over 6 microns) was, however, restricted to the well differentiated cell lines (HU609, RT4) although PDT was almost identical in all 4 cell lines at exponential growth phase. Thus, NORN and NORA are not only related to cell proliferation but also to cell cycle phases and ploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Cycle↗
PubMed1994

[Autologous blood transfusion in tumor operations].

OBJECTIVE: The potential and limits of autologous transfusion in tumor patients are discussed according to the literature. New aspects are derived from own recent studies. DATA SOURCES AND SELECTION CRITERIA: The critical review of the German and English literature is based on a Medline and DIMDI backsearch covering the last 20 years. Own data not yet published are presented. RESULTS: Predeposit autologous blood represents an important and practical alternative to homologous transfusion also for tumor patients. Predeposit programs are limited by tumor anemia, the urgent time schedule for surgery, and the variable need for transfusions. Intraoperative autotransfusion is contraindicated in these patients. Our own studies on the presence of tumor cells in the blood shed from the surgical field during oncologic surgery confirm the concerns about a systemic spread of tumor cells after retransfusion. Further efforts aim to an elimination of contaminating tumor cells. In contrast to the literature filters for white blood cell depletion were found to fail to completely remove tumor cells. A 3 log10 retention was measured. Proliferative activity of tumor cells was completely abolished by irradiation of the blood. CONCLUSIONS: Irradiation with 50 Gy allows safe retransfusion of blood salvaged during tumor surgery. This promising possibility is now to be tested in clinical studies.

Blood Loss, Surgical↗
PubMed1994

[Photodynamic diagnosis of urothelial neoplasms after intravesicular instillation of 5-aminolevulinic acid].

Following transurethral resection of bladder cancer, the fate of patients is clearly related to the presence or absence of precancerous or malignant lesions in the remaining mucosa. We report on a new procedure for in situ diagnosis of these flat, hardly visible urothelial lesions. The method is based on tumor-selective accumulation of endogenous protoporphyrin IX following intravesical instillation of 5-aminolevulinic acid. On excitation with violet light even tiny papillary tumors, dysplastic lesions and carcinoma in situ are bright fluorescing red. In 15 patients 26 neoplastic lesions had been diagnosed only by protoporphyrin IX fluorescence. False-negative results have not yet been observed. In 84% of 285 evaluable specimens the fluorescence findings corresponded correctly with the microscopic findings. It is expected that photodynamic diagnosis will become a matter of routine in detection of bladder cancer.

Administration, Intravesical↗
PubMed1993

Diagnostic value of AgNOR staining in follicular cell neoplasms of the thyroid: comparison of evaluation methods and nucleolar features.

The diagnostic value of argyrophil staining of nucleolar organizer regions (AgNOR) was studied in 95 nonneoplastic and neoplastic follicular lesions of the thyroid. Different AgNOR parameters such as number, size, and distribution pattern were determined using digital image analysis. In addition, nuclear and nucleolar size as well as the percentage of nucleoli touching the nuclear membrane (nucleolar margination) were assessed. A stepwise increase in nuclear size and AgNOR counts from normal thyroid tissue to follicular adenoma as well as from differentiated follicular to anaplastic carcinoma was found (mean nuclear area [micron2]/mean AgNOR number per cell: 21.5/1.6 vs. 34.4/3.5 and 45.3/5.0 vs. 66.5/10.8, p < 0.01/p < 0.001). There was, however, no clear separation between these diagnostic groups. In contrast, an almost total discrimination between follicular adenoma and carcinoma was achieved by quantification of AgNORs per tumor cell nucleolus (AgNOR distribution score). In benign adenomas, 3.3% (range, 0-8.8%) of the cells showed nucleoli with at least five AgNOR dots within one focal plane, whereas in follicular carcinomas, the corresponding value was 34.1% (range, 12-75%). Two of four cases of so-called atypical adenomas showed values in the range of benign adenomas, and two were in the range of follicular carcinomas. In comparison with other nuclear and nucleolar parameters, the AgNOR distribution score proved the most valuable diagnostic criterion for the cytomorphological differentiation between follicular adenoma and carcinoma of the thyroid.

Adenocarcinoma, Follicular↗
PubMed1993

[The traumatic origin of a glioblastoma].

A 56-year-old man is reported who had suffered a frontal, frontobasal open craniocerebral injury four years ago. He presented for treatment with a glioblastoma of which the location and extent precisely corresponded to that of the prior brain injury. After surgical exposure of the tumor, we had the impression that the tumor initially showed granulating growth from the frontal injury site and had then given rise to more highly vascularized and also necrotizing tumor tissue spreading into the frontal medullary layer with typical glioblastoma characteristics. In view of the surgical site, it is logical to consider a tumorigenesis after cerebral trauma, which is also corroborated by the histological results, since more proliferative tumor growth was found near to the injury and more highly vascularized but also necrotizing (i.e. more typical of a glioblastoma) tumor growth far away from the injury. After the comparison of our observation with the corresponding cases in the literature, it is shown that there is at least in part a causal correlation between the trauma and tumorigenesis: in the previously healthy patient, the tumor developed precisely in the region of the injury (with detection of destroyed brain tissue) after a sufficiently long time interval. Near to the site of damage, it showed granulative growth with a low degree of vascularization, and then passed into the typical glioblastoma. Observations of genetic changes in glioblastoma patients is not inconsistent with this possible trauma genesis, but render it probable that trauma is the factor which can give rise to tumor growth in a corresponding susceptibility to tumorigenesis.

Brain Neoplasms↗
PubMed1992

Establishment and characterization of a human papillary thyroid carcinoma cell line with oxyphilic differentiation (ONCO-DG 1).

In the present study the establishment and characterization of a new oxyphilic papillary thyroid carcinoma cell line--ONCO-DG1- is given. With immunohistological, histochemical and flow cytometric methods, ONCO-DG 1 cells revealed features of epithelial differentiation. Furthermore the cells formed von Kossa-positive deposits resembling psammoma bodies in monolayer and spheroid culture until late passages. The tumor cell line is now in the 40th subculture. Because of the ability to form multicellular tumor spheroids (MCTS), this cell line is a good model for examining the interaction between thyroid tumor cells and confluent human endothelial cells on extracellular matrix in vitro. It is also suitable for xenotransplantation studies, because it is tumorigenic in NMRI nude mice in vivo.

Animals↗
PubMed1992

In vitro investigations on cellular damage induced by high energy shock waves.

Single-cell suspensions of the prostate carcinoma cell line PCA were exposed to electromagnetically generated ultrasound shock waves (source and focusing lens identical to those used in the commercially available lithotripor Lithostar Plus). Cell loss of up to 40% occurred in sample tubes containing air. To expose multicellular tumor spheroids and cells growing on a microcarrier, an experimental setup was developed that prevented motion of the specimen. Intracellular damage of intact spheroids was analyzed by laser scanning microscopy following specific fluorescence staining. Different sensitivities of individual cell components with respect to the applied energy density of the pulses were found, namely defects on cell membranes (0.12 mJ/mm2), vimentin (0.21 mJ/mm2), mitochondria (0.33 mJ/mm2) and nuclear membranes (0.5 mJ/mm2). Loss of cells growing on a microcarrier was found after application of 200 pulses with 0.21 mJ/mm2.

Cell Count↗
PubMed1992

Effect of fluoride on aluminum-induced bone disease in rats with renal failure.

Aluminum (Al) accumulation in renal failure is an etiological factor in the pathogenesis of low turnover bone disease. Aluminum-induced impairment of mineralization has been related to a reduced extent of active bone-forming surface. The present study investigated the effect of fluoride, a potent stimulator of osteoblast number, on the toxicity of aluminum in rats with renal failure (Nx). Following a large parenteral aluminum load (3.2 mg/kg x day) over a period of nine weeks, bone histomorphometry of vertebral cancellous bone revealed a severe low-turnover osteodystrophy as evidenced by a fall in osteoblastic osteoid surfaces and mineral apposition rates. Concurrent administration of fluoride [20 mg/liter (F20) or 40 mg/liter (F40) supplied with the drinking water] resulted in a significant increase in the number of osteoblasts (Nx+Al+F40 vs. Nx+Al, 33.75 +/- 2.83 vs. 1.81 +/- 0.43 mm-1, P less than 0.001) together with an overall reduced deposition of aluminum in bone (469.3 +/- 24.6 vs. 592.2 +/- 28.3 micrograms/g, P less than 0.01). However, there was an increase in the fraction of osteoid surface exhibiting stainable aluminum at the bone-osteoid interface (70.7 +/- 7.1 vs. 44.3 +/- 6.0%, P less than 0.005). Fluoride-exposed rats accumulated a significantly larger osteoid volume, suggesting an exacerbation of the osteomalacic lesion, and furthermore, dynamic histomorphometric parameters remained depressed. These results indicate that fluoride has a distinct effect on the pattern of aluminum deposition in bone. In addition, fluoride antagonizes the aluminum-induced reduction in osteoblast number but provides no amelioration of the impaired mineralization in aluminum-intoxicated rats. Thus, in this model a decrease in the extent of osteoblast surface does not account for the development of aluminum-related bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1992

Induction of intestinal mucosal atrophy by difluoromethylornithine: a nonuremic model of enhanced aluminum absorption.

The intestinal absorption of aluminum (Al) appears to be enhanced in the uremic rat. Since atrophic changes of the intestinal mucosa have been observed in uremia the present study investigated whether intestinal atrophy induced by difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, could affect the absorption of Al. DFMO supplied with the drinking water (5%) to rats with normal renal function for 9 days resulted in a reduced number of microvilli with definite morphological alterations in small intestinal mucosa. Following an oral load of Al urinary excretion rates and 1-hour postload serum concentrations of Al were increased in DFMO-treated rats as compared to controls suggesting enhanced absorption of Al. Pattern and degree of urinary Al excretion as well as ultrastructural alterations of the intestinal mucosa were similar in DFMO-treated rats and uremic rats. The model of DFMO-induced intestinal alterations suggests that structural lesions of the intestine may be involved in the enhanced absorption of Al in uremia.

Aluminum↗
PubMed1991

[Immune competence of human tissue lymphocytes in contact with loosened hip joint prostheses. On the topic of cellular or humoral rejection reaction as the mechanism of loosening].

In several investigations rejections were accused of being a possible cause for the loosening of hip endoprostheses. Using immunocytochemical techniques we studied the number and type of lymphocytes in the tissue adjacent to loosened hip endoprostheses. Tissue samples were taken from 18 patients being reoperated for a loosened endoprostheses. Impressive lymphocyte infiltrates were found in 4 of 18 patients (22%). These infiltrates only consisted of T-cells. In the other samples only few lymphocytes were detected belonging to T- and B-lymphocyte population, respectively. In our patients T-cell mediated rejections were of minor importance for the loosening of total hip replacement. B-cell accumulations were detected in none of the samples.

Aged↗