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Biomedical subjects

F Bittinger

Publications and source records attributed to F Bittinger.

At least 55 records · Page 3Linked to original sources
PubMed1998

Production of superoxide by human malignant melanoma cells.

Metastasis is a complicated multi-step process involving interactions between tumour cells, the extracellular matrix and the vessel walls. Experimental observations suggest that leucocyte migration and function could be a suitable model in order to understand tumour cell dissemination. In the present report we show and quantify the production of free radicals by human malignant melanoma cells (St-ml12) by means of a spectrophotometrical method, using an enzyme immunoassay reader. Endothelial cells and activated polymorphonuclear leucocytes were used as controls. Melanoma cells without stimulants produced large amounts of superoxide anion at an increasing rate in relation to time, which could be inhibited by superoxide dismutase. Production of hydrogen peroxide was minimal. The endothelial cells produced a negligible amount, in contrast to the activated polymorphonuclear leucocytes, which released large quantities of both free radicals. A rapid assay to analyse the production of free radicals by tumour cells is presented here. Using this, we demonstrated that melanoma cells produce superoxide anions, supporting previous observations which implicate superoxide anion in the mechanism of metastasis.

Humans↗
PubMed1998

Current trends in biocompatibility testing.

Biocompatibility remains the central theme for biomaterials applications in medicine. It is generally accepted that this term means not only absence of a cytotoxic effect but also positive effects in the sense of biofunctionality, i.e. promotion of biological processes which further the intended aim of the application of a biomaterial. The national and international standards for testing regimes represent a lowest common denominator for such applications and do not necessarily ensure that optimal function will be achieved. The authors' thesis is that biocompatibility testing has scope for extensive development with respect to biofunctionality. The present paper reviews current trends in the in vitro aspects of biocompatibility testing. As well as a critical appraisal of the recent literature, future trends are also stressed, which the authors regard as essential for a meaningful integration of a modern biological approach into new developments in the material sciences. These include the application of modern techniques of cell and molecular biology, the concepts of tissue remodelling, hybrid organ development and encapsulated cell technology.

Animals↗
PubMed1998

Superior labrum and labral-bicipital complex: MR imaging with pathologic-anatomic and histologic correlation.

OBJECTIVE: The purpose of this study was to analyze the anatomic relationship between the superior labrum, the superior glenoid rim, the superior glenohumeral ligament, and the long head of the biceps tendon. MATERIALS AND METHODS: Seventeen cadaveric shoulder specimens underwent axial, oblique coronal, and oblique sagittal MR imaging on a 1.5-T imager. Unenhanced proton density- and T2-weighted spin-echo images with and without fat suppression, and T1-weighted fat-suppressed spin-echo images after intraarticular injection of gadolinium, were obtained of each specimen. The shoulders were then frozen and sectioned into 4-mm-thick slices, either transversely or oblique coronally. After gross anatomic correlation, histologic analysis was performed on 32 sections. RESULTS: A sublabral recess was present in 12 (71%) of 17 shoulders. MR arthrography was significantly better at showing the sublabral recess than was unenhanced MR imaging. Histologically, the synovial recess in all cases was covered by synovial lining cells. Intralabral altered histologic patterns were found in 20 (63%) of 32 labral sections. In addition to signs of degeneration, five sections of two specimens showed proliferating fibroblasts and vessels, as well as fibrosis, suggesting trauma. The presence or absence of altered intralabral histologic patterns was better assessed with T1-weighted fat-suppressed arthrograms than with unenhanced MR images. We found a close association grossly and histologically between the superior labrum and the biceps tendon. CONCLUSION: The attachment of the superior glenoid labrum to the glenoid rim shows great variability. In MR imaging, an overlap appears to exist between physiologic recesses of the superior labrum and a type 2 superior labrum anterior-posterior lesion. T1-weighted fat-suppressed MR arthrograms provided the best view of the superior labrum and the labral-bicipital complex.

Aged↗
PubMed1997

Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma.

Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 22), carcinoma in situ (n = 15), invasive squamous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 permanent esophageal squamous cell carcinoma cell lines were analyzed immunohistochemically for Bax expression using a polyclonal anti-Bax antibody. Immunostaining was evaluated according to a score system (0-8 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium. In contrast, a gradual loss of immunoreactivity for Bax was found in a fraction of pre-neoplastic and neoplastic lesions. Upon comparison of the amount of Bax expression between the different types of lesion, however, no significant differences were found between severe squamous cell dysplasias, carcinomas in situ, invasive carcinomas and lymph-node metastases. In both esophageal carcinoma cell lines, immunoreactivity for Bax was found and confirmed by means of Northern blot analysis. In invasive carcinomas, Bax immunoreactivity was inversely correlated with Bcl-2 expression (p = 0.0243) and decreased continuously with decreasing tumor differentiation (p = 0.0011). No correlation was found between Bax expression and the following parameters: depth of invasion, nodal status and tumor size. Bax expression had no influence on the post-operative survival of esophageal cancer patients.

Adult↗
PubMed1997

Reconstruction of peritoneal-like structure in three-dimensional collagen gel matrix culture.

The peritoneum is a serous membrane consisting of different kinds of cells and extracellular matrix components (ECM). The aim of the present study was to develop a three-dimensional (3D) in vitro culture system for possible investigation of pathological conditions of the peritoneum. Human omental mesothelial cells (MC) and endothelial cells from the umbilical vein (EC) were cultivated either on (MC) or in (EC) a preformed type I collagen matrix. In 3D culture mesothelial cells showed their phenotypical in vivo characteristics and the synthesis of a new basal membrane (BM). Endothelial cells developed vessel-like structures, produce a BM and express E-selectin after TNF-alpha stimulation. This 3D culture system presents extended possibilities for analyzing mesothelial and endothelial cell behavior as well as the cell-cell and cell-matrix interactions involved in several pathological processes in the peritoneum.

Adipose Tissue↗
PubMed1997

Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis.

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract. METHODS: In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus. RESULTS: Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found. CONCLUSIONS: BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

Actins↗
PubMed1997

Day-night rhythm of acetylcholine in the rat pineal gland.

Using high-performance-liquid-chromatography (HPLC) measurement of acetylcholine, choline acetyltransferase (ChAT) enzyme assay and anti-ChAT immunohistochemistry, we have investigated the expression of the cholinergic system in pineal glands of male rats. Glands procured during the day period (1200 h) contained significant amounts of acetylcholine (0.5 pmol/gland). A similar content was found in pineal glands after a 48 h culture period, i.e. when the intrapineal nerve fibres have degenerated. This strongly indicates that the pinealocytes are the cells which contain acetylcholine. To confirm this conclusion we demonstrate substantial ChAT-like immunoreactivity in pinealocytes. ChAT enzyme activity measured in homogenized glands (day period) was 7 +/- 3 nmol/mg per h. Acetylcholine content as well as ChAT enzyme activity increased about 10-fold in pineal glands during the night period (2400 h). The present study demonstrates for the first time the presence of a day-night rhythm of ChAT and acetylcholine in rat pinealocytes. The function of pineal acetylcholine is not clear, but there are indications that acetylcholine may depress noradrenaline release from intrapineal sympathetic fibres and hence melatonin synthesis.

Acetylcholine↗
PubMed1997

Non-neuronal acetylcholine, a signalling molecule synthezised by surface cells of rat and man.

Acetylcholine acts as a prominent transmitter in the central and peripheral nervous system. The aim of the present study was to investigate whether mammalian non-neuronal cells can synthesize and store acetylcholine. A cotton tipped applicator (Q-tip) was used to collect surface cells from airways and alimentary tract. Histological inspection indicated that rubbing of the luminal surface of human bronchi did not penetrate the basal membrane. Acetylcholine was measured by an HPLC-method using substrate-specific enzyme reactor-columns. Non-neuronal acetylcholine was found in cells covering inner and outer surfaces of rat and man. For example, acetylcholine was detected in the surface epithelium of human bronchi (33 pmol/g), mouth (female 0.7 and male 8 pmol/sample), small and large intestine (800 and 16 pmol/g, respectively), gall bladder (12 pmol/g), vagina (6 pmol/sample), skin 1000 (pmol/g) and in pulmonary pleura (5 pmol/sample). Somewhat higher amounts of acetylcholine were found in rat tracheal and intestinal epithelium and in rat skin. The synthesizing enzyme choline acetyltransferase (ChAT) was demonstrated in human surface epithelium by immunohistochemistry and by Western blot analysis. Enzymatic ChAT activity was demonstrated in isolated epithelial cells of human bronchi and small intestine (3.5 and 28 nmol/mg protein/h, respectively). Applied acetylcholine (in nM concentrations) increased, whereas inhibition of ChAT activity by bromoacetylcholine (10 microM) reduced the growth of cultured human bronchial epithelial cells. Inhibition of cell growth occurred also in the presence of atropine (1 microM) together with (+/-)-tubocurarine (30 microM). In conclusion, the present experiments demonstrate a widespread existence of non-neuronal acetylcholine in surface cells of man. Non-neuronal acetylcholine may act as a local signalling molecule.

Acetylcholine↗
PubMed1997

The cell and molecular biological approach to biomaterial research: a perspective.

The past two decades have witnessed a revolution in our understanding of chemical processes in living organisms. This is mainly a result of the massive advances in the fields of cell and molecular biology. These techniques are highly relevant to the biomaterials sector, as they offer the scientist the possibility to better understand the mechanisms involved in the interactions between cells and a material surface-a prerequisite for the rational development of medical devices with optimal biocompatibility. The purpose of the present article is to explain the rationale of the cell and molecular biological approach to biomaterial research and to present typical examples from the authors' laboratory, as well as from the literature, to illustrate its application. Important aspects of interfacial biology, including the underlying biological mechanisms and methodology, are presented. Of the latter the combination of morphological techniques with methods of cell and molecular biology as well as molecular genetics (so-called "combinative techniques") are particularly useful. The applicability of this approach is illustrated from a study on the pathomechanisms of metal ion-induced inflammation. In addition, the approach is essential to the development of targeted intervention strategies, as for example in the luminal surface modification of vascular prostheses to permit endothelial cell seeding.

Journal Article↗
PubMed1997

Physiology and cell biology of the endothelium: a dynamic interface for cell communication.

This manuscript presents a brief overview of the physiology and cell biology of the endothelium, which is the basis for understanding the role of endothelial cells in pathological processes as diverse as atherosclerosis, tumour intravasation and multiple organ failure. Following consideration of general aspects of endothelial function in regulating haemostasis, vascular tone and growth, special emphasis will be placed on endothelial regulation of the inflammatory response, which centres on the microcirculation. A particular role in inflammation is played by cell adhesion molecules (CAM), expressed both on endothelial and blood cells. Cell and molecular biological methods to investigate the expression of CAM in endothelial cells in vitro will be presented, as well as novel data, indicating that cytokine-induced up-regulation of CAM in the endothelium may involve signal transduction pathways other than those culminating in the activation of NF-kappa B. Finally, the phenomenon of angiogenesis will be briefly reviewed as a characteristic of endothelial cell activity of central importance to both physiology and pathology and new experimental data presented from an in vitro model to study the ability of individual endothelial cells to form vessel-like structures. In comparative studies to investigate the roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, the dominant role of VEGF in the formation of capillary networks could be unequivocally demonstrated.

Animals↗
PubMed1997

[Surgical therapy of differentiated thyroid gland carcinoma].

Surgical excision is the treatment of choice for differentiated thyroid carcinoma. Because no prospective randomized clinical trials are available, decisions regarding the extent of surgical resection and the mode of lymph node dissection must be made on the basis of imperfect retrospective data. Recommendations for surgical strategy in differentiated thyroid cancer are discussed.

Adenocarcinoma, Follicular↗
PubMed1996

bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus.

The bcl-2 proto-oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl-2-protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous-cell carcinomas of the esophagus. For comparison, bcl-2-protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl-2 immunoreactivity was found in 40 out of 150 invasive squamous-cell carcinomas; the remaining carcinomas were completely negative. bcl-2-protein expression was found more frequently among poorly differentiated than among well-differentiated tumors (p < 0.0001). No correlation was found between bcl-2-protein expression and the parameters tumor size, depth of invasion and nodal status. Moreover, bcl-2-protein expression had no significant influence on overall survival. Whereas in normal mucosa bcl-2 immunoreactivity was restricted to the basal-cell layer, in 9 out of 15 severe squamous dysplasias and in 7 out of 14 carcinomas in situ bcl-2 staining was detected in all epithelial layers. Thus, bcl-2-protein is frequently expressed in invasive squamous-cell carcinomas of the esophagus and in precursor lesions of esophageal cancer, but has no significant impact on the outcome of esophageal cancer.

Adult↗
PubMed1996

The role of the microcirculation in multiple organ dysfunction syndrome (MODS): a review and perspective.

Major advances in intensive care medicine during the past two decades have altered the spectrum of disease encountered by intensive care physicians, anaesthesiologists, traumatologists and pathologists. One of the most important manifestations of severe trauma or infections is the multiple organ dysfunction syndrome (MODS), a life-threatening condition that often ends in multiple organ failure (MOF) and death. Evidence gathered from clinical and morphological observations in humans, taken together with experimental animal studies and a vast accumulation of in vitro data, clearly indicate that the microcirculation lies at the centre of this complex process, which results in peripheral vascular insufficiency, inadequate oxygen delivery to vital organs, and hence, severe organ dysfunction. The multifunctional nature of the endothelium makes it a prime candidate for study of the pathomechanisms of MODS. This paper reviews the evidence for the hypothesis that the microcirculation, and in particular its endothelial component, has a central role in the pathogenesis of MODS. The evidence is reviewed principally from the standpoints of classical morbid anatomy and cell pathobiology.

Animals↗
PubMed1996

The prognostic significance of tumour cell proliferation in squamous cell carcinomas of the oesophagus.

Tumour samples from 150 patients with squamous cell carcinoma of the oesophagus were investigated immunohistochemically with the monoclonal antibody MIB-1, which recognises proliferating cells. Using light microscopy, the number of MIB-1-positive tumour cells was counted in the areas with the highest proliferative activity. The MIB-1 index was determined as the proportion of MIB-1-positive and MIB-1-negative tumour cells. A considerable variation of the MIB-1 indices was found between the different tumours with a minimum of 6% and a maximum of 95% (median, 33%). The MIB-1 index correlated significantly with the mitotic activity in the tumour tissue (r = 0.33; P = 0.0001) and with the proportion of apoptotic tumour cells (r = 0.25; P = 0.0017). No significant correlation was found between the MIB-1 index and various other prognostic parameters including pT classification, pN classification, tumour grade, blood vessel invasion and lymphatic vessel invasion. In the univariate survival analysis no significant difference was found between tumours with low (< or = 33%) and high MIB-1 index (> 33%) 5-year survival rate: low MIB-1 index, 19.2%; high MIB-1 index, 22.2%). In a Cox proportional hazard regression analysis only the parameters lymphatic vessel invasion (P = 0.0001), pT classification (P = 0.0034) and pN classification (P = 0.0256), but not the MIB-1 index, could be verified as independent prognostic variables. In conclusion, evaluation of the MIB-1 index does not provide prognostic information for oesophageal cancer patients.

Adult↗
PubMed1996

PECAM-1 expression in human mesothelial cells: an in vitro study.

Mesothelial cells are actively involved in inflammatory processes by expressing a set of cell adhesion molecules (CAMs). Transmigration of leukocytes into inflamed tissues requires a chemotactic stimulus and engagement of platelet-endothelial cell adhesion molecule-1 (PECAM-1). To investigate the kinetics involved in peritonitis, pure cultures of mesothelial cells are necessary. In previous studies, we have found that human mesothelial cells (HOMES) show a weak constitutive expression of PECAM-1, which cannot be further stimulated by cytokines. It is known that all serous cavities and body fluids contain numerous macrophages which strongly express this adhesion molecule. To identify the cells responsible for the expression of PECAM-1, mesothelial cells freshly obtained from omental tissue were isolated using PECAM-1-conjugated magnetic beads by cell sorting. For these studies, the negative as well as the positive fraction of isolated cells were used. As a control, freshly isolated monocytes were studied. Cell cultures were characterized by light and electron microscopy, as well as immunocytochemistry. The negative cell fraction was cultivated and stimulated for different times with tumor necrosis factor-alpha (30 and 300 U/ml), interleukin-1 beta (10 and 100 U/ml) and interferon-gamma (500 U/ml) and PECAM-1 expression was analyzed by a comparative quantitative cell enzyme immunoassay (EIA). The positive cell fraction was treated in the same manner. Both fractions of isolated cells showed strong positivity for cytokeratins 8, 18, 7 and 19, as well as vimentin. CD68, a monocyte marker, was not detected on mesothelial cells. In addition, EIA analysis confirmed the constitutive expression of PECAM-1 obtained from previous studies. This expression on HOMES was not inducible, irrespective of the type and concentration of cytokine studied. These data confirm PECAM-1 expression on mesothelial cells obtained from human omental tissue and suggest a critical role in transmigration of leukocytes during peritoneal inflammation.

Cell Separation↗
PubMed1995

Prognostic value of histopathologic parameters of esophageal squamous cell carcinoma.

BACKGROUND: The grading of squamous cell carcinoma (SCC) of the esophagus as proposed by the World Health Organization (WHO) has not yet proved to be prognostically significant. Therefore, the prognostic impact of various histologic parameters was investigated and compared with that of the WHO grading. METHODS: Hematoxylin and eosin-stained tumor samples from 138 patients with SCC of the esophagus who underwent potentially curative resection (no residual tumor or distant metastases) were evaluated for the following histologic parameters: degree of keratinization, nuclear polymorphism, pattern of invasion, mitotic activity, and inflammatory response. The prognostic impact of these parameters was analyzed by univariate and multivariate survival analyses. RESULTS: In the univariate analysis, the inflammatory response (P = 0.0006), pattern of invasion (P = 0.0011), and nuclear polymorphism (P = 0.0161) were the only parameters that correlated with survival. However, in a multivariate survival analysis including these parameters, only pattern of invasion (P = 0.0010) and inflammatory response (P = 0.0076) were prognostically significant. Based on these results, a new prognostic score system was defined that correlated significantly with survival in the univariate survival analysis (P = 0.0002). In contrast, the WHO histologic grade was not prognostically significant. In the multivariate Cox regression analysis, the new prognostic score system proved to be an independent prognostic parameter (P = 0.0062), ranking next to pT classification (P = 0.0001) and pN classification (P = 0.0014). CONCLUSIONS: For SCC of the esophagus, histologic grading based on pattern of invasion and inflammatory response had an independent prognostic impact, whereas the grading system proposed by the WHO had no significant prognostic value.

Adult↗
PubMed1995

Comparative studies on vascular endothelium in vitro. 2. Hypoxia: its influences on endothelial cell proliferation and expression of cell adhesion molecules.

Recent studies have presented evidence that the processes of hypoxaemia and reperfusion are involved in several pathogenetic mechanisms of atherosclerotic lesions. The ability of hypoxaemia to activate circulating white blood cells (WBCs) and enhance WBC-endothelial cell (EC) interactions is suspected to be a major factor in deleterious processes in the blood vessel wall. Various groups have suggested that cell adhesion molecules (CAMs), such as ICAM-1, VCAM-1 and E-selectin and their leukocyte ligands are involved in intercellular activities of the relevant cell types. We studied the effects of different oxygen tensions, simulating normoxic conditions, hypoxia and hyperoxia in vitro with the help of an umbilical vein EC model in order to determine the effects of oxygenation on CAM presentation on vascular ECs with and without further cytokine and endotoxin (lipopolysaccharides; LPS) stimulation. Semiquantitative analysis of ICAM-1, E-selectin and VCAM-1 was performed using cell enzyme immunoassay techniques. The presentation of ICAM-1, E-selectin and VCAM-1 remained on the whole unaffected by both hypoxia and hyperoxic conditioning after both 7 and 24 h. Stimulation of ICAM-1 by cytokines and LPS was only marginally influenced by the oxygen tension. Cytokine induction of E-selectin was not affected after 7 h and was even reduced under hypoxia, compared to the control culture after 24 h, while stimulation was increased by hyperoxia. VCAM-1 was reduced in both the hypoxic and hyperoxic culture, while being maximally stimulated by cytokines and LPS after 7 h. In general, an effect of hypoxia was not found without any further stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules↗