Biomedical subjects

M Frieser

Publications and source records attributed to M Frieser.

12 recordsLinked to original sources

PubMed2005

Contrast-enhanced sonography for the characterisation of hepatocellular carcinomas--correlation with histological differentiation.

AIM: We aimed to characterise the vascularisation patterns of hepatocellular carcinomas in contrast-enhanced sonography in correlation to the histological differentiation of hepatocellular carcinomas (HCC), and we also compared the diagnostic value of contrast-enhanced sonography in addition to B-scan sonography and power Doppler sonography. METHODS: 51 hepatocellular carcinomas (21 well differentiated, 27 moderately differentiated, 3 poorly differentiated) were examined: by B-scan sonography, power Doppler sonography and contrast-enhanced sonography using phase or pulse inversion harmonic imaging with a low mechanical index (< 0.3) and second generation microbubble contrast medium (Optison, Sonovue) as echo-enhancing agent. Lesion vascularity and the kinetics of contrast enhancement within the lesions in the early arterial phase, arterial phase, portal phase and late phase were analysed. The final diagnosis of a HCC was assessed after B-scan sonography, power Doppler sonography and contrast-enhanced sonography. RESULTS: Hypervascularisation and/or irregular tumour vascularisation could be detected in 18/48 HCCs (37.5%) by power Doppler sonography. After contrast application, 46/51 HCCs (90.2%) were identified as hyperechoic lesions during the early arterial or arterial phase with no correlation to histological differentiation. In the portal phase and late phase, the echogenicity of HCCs after contrast application was variable. A hypoechoic appearance was noted in 17/51 HCCs (33.3%) in the portal phase and in 21/51 HCCs (41.2%) in the late phase. Moderately differentiated HCCs were more often hypoechoic than well differentiated HCCs (p = 0.04). CONCLUSION: Contrast-enhanced sonography is highly efficient for the detection of tumour vascularity in HCCs. The majority of HCCs--regardless of histological differentiation--can be characterised as hypervascular lesions in the early arterial and arterial phase with irregular tumour vessels using contrast-enhanced sonography. In addition to B-scan sonomorphology, contrast-enhanced sonography may offer helpful information in patients with liver cirrhosis and focal liver lesions.

Carcinoma, Hepatocellular↗

PubMed2003

[Detection of liver metastases--comparison of contrast--enhanced ultrasound using first versus second generation contrast agents].

AIM: To compare detection rates for liver metastases for conventional ultrasound, US using tissue harmonic imaging (THI), echo-enhanced pulse inversion harmonic imaging using Optison and Levovist. METHOD: In 73 patients with histologically proven gastrointestinal tumors spiral CT (S-CT), conventional US, US in the THI-mode, echo-enhanced ultrasound in the portal venous phase (ECI Optison ) and in the liver specific late phase (ECI Levovist) were performed and reviewed by blinded readers. RESULTS: 73 patients (25 female, 48 male, age 63 +/- 11) were included. S-CT detected 158 liver metastases. Conventional US detected 117, THI 119, ECI Optison 169 and ECI Levovist 166 liver metastases. Especially for small (< 2 cm) liver metastases and metastases near the diaphragm echo-enhanced ultrasound exceeded conventional US (p < 0.001). Between both echo enhancers there was no significant difference. CONCLUSION: Using echo enhancers increases the ultrasound detection rate significantly. Examination in the portalvenous phase using a second generation enhancer (Optison) is equal to a late-phase examination using Levovist.

Contrast Media↗

PubMed2003

Radiofrequency ablation of hepatocellular carcinoma with a saline solution perfusion device: a pilot study.

PURPOSE: The majority of patients with hepatocellular carcinoma (HCC) cannot be treated with surgery. This study evaluated the treatment of patients with radiofrequency ablation (RFA) with use of needle applicators perfused with isotonic saline solution. MATERIALS AND METHODS: Twenty patients with a maximum of three HCCs as large as 60 mm and a contraindication to partial liver resection or orthotopic liver transplantation were enrolled in the study. They were treated with ultrasound-guided RFA with use of perfused needle applicators and followed with sonography and computed tomography. RESULTS: Twenty patients (14 men, six women) with a total of 29 HCCs were treated with RFA. In total, 56 RFA treatments were performed. Mean HCC size was 31 mm (range, 10-60 mm). Two cases of self-limiting bleeding requiring transfusion of blood products took place. Complete response (CR) was achieved in 85% of patients (17 of 20). Partial response occurred in three tumors 45 mm in diameter or larger. There was a total of six local recurrences in five patients (25% of patients, 21% of tumors). Six patients (30%) exhibited distant recurrence, two of whom also showed local recurrence. In three patients, repeat treatment led to renewed CR. After a median follow-up of 445 days (range, 114-1,071 days), 12 patients (71% of the 17 patients with initial CR) still showed CR. Twelve patients (60% of all patients, 71% of those with initial CR) survived. Three of the eight patients who died were free of viable tumor at the time of death. CONCLUSIONS: RFA with use of perfused needle applicators shows promise as an effective method for treating inoperable HCC. The most frequent complication was bleeding.

Aged↗

PubMed2001

Synthetic 2-aroylindole derivatives as a new class of potent tubulin-inhibitory, antimitotic agents.

A new class of simple synthetic antimitotic compounds based on 2-aroylindoles was discovered. (5-Methoxy-1H-2-indolyl)-phenylmethanone (1) as well as analogous 3-fluorophenyl- (36) and 3-methoxyphenyl (3) derivatives displayed high cytotoxicity of IC(50) = 20 to 75 nM against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines. The inhibition of proliferation correlated with the arrest in the G2/M phase of the cell cycle. In in vitro assays with tubulin isolated from bovine brain, in general antiproliferative activity correlated with inhibition of tubulin polymerization. Thus, the antimitotic activity of 2-aroylindoles is explained by interference with the mitotic spindle apparatus and destabilization of microtubules. In contrast to colchicine, vincristine, nocodazole, or taxol, 1 did not significantly affect the GTPase activity of beta-tubulin. Interestingly, selected compounds inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. In xenograft experiments, 1 was highly active after oral administration at 200 mg/kg against the human amelanocytic melanoma MEXF 989 in athymic nude mice. We conclude, that 2-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.

Allantois↗

PubMed2001

Dendritic hypertrophy of Stach type VI neurons within experimentally altered ileum of pigs.

Myenteric neurons were investigated morphometrically to answer the question if type-specific somal hypertrophy of type VI neurons in mechanically stressed ileum of pigs, which was known from an earlier study, is correlated with an increased dendritic arborization, that is, with dendritic hypertrophy. Muscular hypertrophy was induced in the ileum of two juvenile pigs by narrowing the gut circumference (mechanical stenosis) and by reversing a loop of ileum which results in an antiperistaltic segment (functional stenosis), respectively. After a survival time of 6 weeks, wholemounts from the pre- and poststenotic ileal regions, from the antiperistaltic segment as well as from an age matched control animal, were silver impregnated. Dendritic parameters of Stach types IV and VI neurons were recorded using a computer-aided morphometric program and analysed statistically. Type IV neurons showed no change of dendritic parameters, neither within control nor within stenosed ileal segments. In contrast, the type VI neurons displayed increased dendritic parameters within zones of muscular hypertrophy such as total dendritic length, numbers of dendrites, of dendritic branching points and of dendritic endings. We suggest that type VI neurons may participate as descending nitrergic interneurons or motorneurons in the control of muscular function, thus, undergoing plastic changes in case of experimental muscular hypertrophy. Type IV neurons which are involved in the regulation of mucosal processes were not affected by muscular hypertrophy.

Animals↗

PubMed2000

Experimental hypertrophy of myenteric neurones in the pig: a morphometric study.

Muscular hypertrophy in the ileum of two pigs aged 6 weeks was induced using two different surgical techniques, narrowing of the gut circumference (mechanical stenosis) and segmental reversal of an ileal loop which results in a persistent antiperistalsis of that segment (functional stenosis). These pigs were sacrificed 5-6 weeks postoperatively. Cross sections through the gut wall at various distances from the operation sites revealed marked muscular hypertrophy in the pre-stenotic regions and in the reversed segment. Whole mounts from pre- and post-stenotic, as well as reversed ileal regions, were silver- impregnated. The corresponding ileal region of a third, nonoperated pig served as control. Using a computer-aided morphometric device, somal areas of five morphological neurone types were measured at various distances orally and anally from the operation sites and along the control ileum. Values between hypertrophic and nonhypertrophic zones as well as between two corresponding zones of nonoperated ileum were compared statistically. Along the control ileum, values revealed no differences in soma sizes. Within the experimentally altered material, somal areas of type VI neurones showed marked hypertrophy related to the sites of muscular hypertrophy whereas the other types remained constant throughout (II, IV in segmental reversal) or showed slightly larger somal areas within the post-stenotic, nonhypertrophied zones (I, V, IV in stenosis). Additionally, within the reversed segment, neuronal perikarya of type I, II, IV and V neurones were larger as compared to the neighbouring regions. However, this enlargement of perikarya within the reversed segment may not be correlated with muscular hypertrophy but rather with the transections of intramural axons before reversing this segment. The results suggest that morphologically distinct neurone types may play different roles within the mechanically stressed small intestine and possibly also in the coordination of normal muscular function.

Animals↗

PubMed1997

Developmental regulation of the laminin alpha5 chain suggests a role in epithelial and endothelial cell maturation.

We have previously shown that mouse and bovine endothelial cells express a novel 400-kDa laminin alpha chain complexed to beta1 and gamma1 laminin chains. We describe here purification of this laminin isoform from the conditioned medium of a mouse peripheral lymph node endothelial cell line, SVEC. The laminin alpha chain was isolated from the laminin complex, subjected to Edman digestion, and the amino acid sequences of the resulting peptides were determined. Amino acid sequence revealed 100% identity to the predicted amino acid sequence of the recently reported laminin alpha5 gene. A monoclonal antibody to the laminin alpha5 chain was raised (4G6), allowing investigation of its distribution in embryonic, newborn, and mature mouse tissues. The laminin alpha5 chain was expressed mainly by epithelial, endothelial, and myogenic cells: In both embryonic and mature tissues the laminin alpha5 chain was strongly expressed by epithelial cells, the bronchi of the lungs and the developing kidney tubules being the sites of strongest expression. However, laminin alpha5 was not associated with early stages of epithelial cell development, but rather with epithelial cell maturation. Widespread expression of laminin alpha5 in endothelial cells was apparent only in tissues of mature mice, its appearance correlating approximately with sexual maturity. During embryogenesis and in newborn tissues, laminin alpha5 occurred in basement membranes of larger blood vessels only, excluding a role in angiogenic processes. Smooth muscle and skeletal muscle cells were the only other cell types which showed considerable laminin alpha5 expression, with skeletal muscle exhibiting a developmentally regulated pattern of expression: The laminin alpha5 chain occurred in skeletal muscle fiber basement membranes early in embryogenesis (E13-E15) but decreased with development, remaining strongly expressed only at the neuromuscular junction. The data show that laminin alpha5 expression is associated with epithelial and endothelial cell maturation, implicating a role for this laminin chain in the maintenance of differentiated epithelial and endothelial cell phenotype.

Animals↗

PubMed1997

Cloning of the mouse laminin alpha 4 cDNA. Expression in a subset of endothelium.

Endothelial cells express a 400-kDa or 240-kDa laminin alpha chain, depending on their tissue of origin or physiological state [1, 2]. Using differential display and subsequent screening of a mouse endothelial cell cDNA library we here identify the gene coding for the 240-kDa laminin chain as the laminin alpha 4 gene. The complete mouse laminin alpha 4 cDNA sequence is reported and compared with other laminin alpha chains. In situ hybridization of embryonic and new born mouse tissues revealed expression of laminin alpha 4 mRNA in a subset of endothelium, in particular aortic endothelium, endocardium and endothelium of blood vessels in the skin and in the brain. Strong laminin alpha 4 expression by aortic endothelia was confirmed by data obtained from cultured bovine aortic endothelial cells (BAEC). Isolation of laminin from BAEC conditioned medium revealed a Y-shaped molecule in rotary shadowing. Subsequent sequencing of BAEC laminin resulted in laminin alpha 4, beta 1 and gamma 1 amino acid sequences, confirming that laminin alpha 4 is one of the major laminin alpha chains expressed by aortic endothelium not only in the mouse. In addition, strong laminin alpha 4 mRNA expression occurred in peripheral nerves, cardiac muscle, fat, the dermis of the skin and lung stroma of mouse tissues. The data demonstrate a cytokine and progesterone-regulated differential expression of laminin alpha 4 mRNA in mouse endothelium, suggesting a distinct functional role for this laminin chain in endothelium.

Amino Acid Sequence↗

PubMed1997

Integrin-mediated intracellular Ca2+ signaling in Jurkat T lymphocytes.

T lymphocytes interact with components of the extracellular matrix after transendothelial migration on their way to sites of inflammation. To characterize the molecular basis of the interaction between T lymphocytes with different extracellular matrix proteins, we investigated the role of intracellular Ca2+ as a signal mediating such interactions and identified the cell surface integrins involved in this process. When Jurkat T lymphocytes loaded with the calcium-sensitive fluorescent dye fura-2 were placed on coverslips coated with human fibronectin, human collagen types I, IV, and VI, human tenascin, human laminin I, or mouse laminin I, an elevation in intracellular Ca2+ concentration was observed. In contrast, contact of the Jurkat T lymphocytes with vitronectin and thrombospondin did not induce Ca2+ signals in more cells as compared with control measurements in which cells were in contact with only BSA or polylysine. Furthermore, the percentage of Jurkat T lymphocytes responding with Ca2+ signals to collagen types I and IV, fibronectin, and laminin I was completely reduced to levels observed on BSA or polylysine when the cells were pretreated with specific anti-integrin Abs, suggesting a role for cell surface integrins as mediators of cell matrix-induced intracellular Ca2+ signaling. Similar results were obtained with peripheral human T lymphocytes activated by phytohemagglutinin.

Antibodies, Blocking↗

PubMed1996

Mouse polymorphonuclear granulocyte binding to extracellular matrix molecules involves beta 1 integrins.

The mechanism of adhesion of purified mouse polymorphonuclear granulocytes (PMN) to extracellular matrix proteins characteristic of basement membranes and the interstitium has been investigated and compared with the adhesion of a mouse progranulocytic cell line, 32DC13, and a mouse monocytic cell line, WEHI 78/24. All three cell types bound specifically to fibronectin and vitronectin to different degrees under different cellular activation states. 32DC13 bound to fibronectin and vitronectin strongly, and this binding increased upon cellular activation with phorbol 12-myristate-13-acetate (PMA) but not with formyl-Met-Leu-Phe. Only 32DC13 showed significant binding to laminin-1. By contrast, WEHI 78/24 and PMN bound only fibronectin and vitronectin; this binding was weak and was altered only marginally upon activation with PMA. In the case of WEHI 78/24, a slight increase in adhesion both to fibronectin and to vitronectin was observed after cellular activation with PMA, while PMN adhesion to both substrates was slightly reduced. The mechanism of binding to fibronectin and vitronectin was similar in the three cell types. The integrin alpha5 beta1 mediated fibronectin adhesion, demonstrating for the first time the existence of a functionally active beta1 integrin on mouse PMN. Vitronectin binding was mediated by alpha(v) beta3, as demonstrated by the ability of alpha(v)-specific cyclic L-Arg-L-Gly-L-Asp-D-Phe-L-Val (RGDfV) peptide (EMD66203), and anti-beta3 antibody to inhibit cell adhesion. 32DC13 adhesion to laminin-1 was via the alpha6 beta1 integrin. None of the three cell types tested bound to the basement membrane proteins collagen type IV and perlecan, or to the interstitial stromal constituents tenascin, collagen types I, V and VI. Interestingly, perlecan and collagen type IV were found to repel all three cell types. The relative inability of PMN, WEHI 78/24, and 32DC13 to bind to extracellular matrix proteins characteristic of basement membranes and their ability to bind inflammatory markers of the interstitium is discussed with respect to leukocyte extravasation processes.

Animals↗

PubMedDate not supplied

Radiofrequency ablation of liver tumors: how to enlarge the necrotic zones?

In an attempt to increase necrotic zones in liver tissue by radiofrequency ablation fresh bovine liver was coagulated by means of a needle electrode continuously perfused with NaCl solution. Power output (60 W) and application time (15 min) were kept constant while the perfusion was varied in terms of saline concentration (0.9, 5.85 and 10%) and perfusion rate (40 or 80 ml/h). Our results showed that the use of higher osmolar saline solutions in radiofrequency ablation with perfused needle electrodes did not lead to significantly larger coagulation volumes. By contrast, increasing the perfusion rate produced significantly larger necrotic zones. Doubling the perfusion rate made it possible to reach higher temperatures (>60 degrees C) within significantly shorter time.

Animals↗

PubMedDate not supplied

Radiofrequency ablation using perfused needle electrodes - study of intermittent and continuous triple needle application ex vivo.

To increase necrotic zones, bovine livers were treated by means of three parallel-oriented radiofrequency ablation (RFA) needles spaced at 3 cm using a puncture guide. The triple application was varied as a continuous and intermittent energy application compared to a single needle applicator. In all three study arms the applied energy (60 W) and the perfusion rate (240 ml/h) were kept constant. After treatment the smallest necrosis diameter was determined. In addition, temperature and the device's power output were monitored. Our study shows that synchronous use of three RFA application needles achieves significantly larger necrosis zones ex vivo than does single needle application. Intermittent energy application heats up the necrosis faster and more evenly with highest average temperature than continuous energy application.

Animals↗