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Biomedical subjects

F Bittinger

Publications and source records attributed to F Bittinger.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Significance of eosinophilic granulocytes in relation to allergy and aspirin intolerance in patients with sinusitis polyposa].

BACKGROUND: The development of nasal polyps might be influenced by different factors such as mucosal inflammation. Infiltration with eosinophils is a common finding, although in largely different quantitis. PATIENTS AND METHODS: We investigated 58 patients suffering from nasal polyps who were assigned for endonasal sinus surgery based on endoscopic and CT findings. Out of these patients, 52% have already had sinus surgery and had recurrent polyps. All patients were subjected to both, allergy testing and a functional in vitro test for aspirin intolerance. During surgery, tissue samples were gained and send for histological examination with special respect to eosinophil infiltration. RESULTS: Eosinophil infiltration was observed in 66% of all patients. 37 patients (64%) exhibited aspirin intolerance only, four (7%) had a positive allergy test only, in 9 patients (15%) both, allergy and aspirin intolerance were diagnosed. Allergy and aspirin intolerance were accompanied by eosinophil tissue infiltration. Eosinophil infiltration was more common and more severe if allergy and aspirin intolerance were found together compared with the tissue eosinophilia in patients with either one entity. CONCLUSION: This study confirms the importance of eosinophil infiltration in the pathogenesis of severe or recurrent nasal polyps based on allergy and aspirin intolerance. A coincidance of allergy and aspirin intolerance was found in an unexpected high number of patients.

Adult↗
PubMed1999

Induction of stress proteins in human endothelial cells by heavy metal ions and heat shock.

In the present study, we compared the induction of heat shock proteins (HSPs) by heat and heavy metal ions in three different endothelial cell types, namely, human umbilical vein endothelial cells, human pulmonary microvascular endothelial cells, and the cell line EA.hy 926. Our results show that especially Zn(2+) and Cd(2+) are inducers of 70-kDa (HSP70), 60-kDa (HSP60), 32-kDa (HSP32), and 27-kDa (HSP27) HSPs. The strength of inducibility is specific for each HSP. Ni(2+) and Co(2+) only show an inducible effect at very high concentrations, that is, in the clearly cytotoxic range. Furthermore, we investigated the time course of HSP expression and the involvement of heat shock factor-1. Our study demonstrates that the three endothelial cell types that were under investigation show comparable stress protein expression when treated with heavy metal ions or heat shock. The expression of stress proteins may be used as an early marker for the toxic damage of cells. This damage can be an inducer of acute respiratory distress syndrome in which microvascular endothelial lesions occur early. Our study provides evidence that human umbilical vein endothelial cells or EA.hy 926 cells, which are much more easily isolated and/or cultivated than pulmonary microvascular endothelial cells, could be used as alternative cell culture systems for studies on cellular dysfunction in the lung caused by toxic substances, certainly with respect to the expression of HSPs.

Blotting, Western↗
PubMed1998

Glucocorticoids mediate reduction of epithelial acetylcholine content in the airways of rats and humans.

The cholinergic system in rat and human airways and the effects of glucocorticoids were investigated by assay of choline acetyltransferase activity, by high-pressure liquid chromatography measurement of acetylcholine, and by anti-choline acetyltransferase immunocyto-/histochemistry. Human bronchi were obtained at surgery from patients with lung cancer. Group 1 patients did not suffer from additional lung diseases and had not been treated with glucocorticoids. Group 2 patients, who suffered in addition to lung cancer from chronic obstructive bronchitis, had been treated for at least 6 weeks before surgery with four puffs of flusinolid daily. Isolated bronchial epithelial cells as well as intact surface epithelium of human bronchi expressed choline acetyltransferase immunoreactivity and choline acetyltransferase enzyme activity (3 +/- 1 nmol/mg protein per h). Ciliated epithelial cells showed strong choline acetyltransferase immunoreactivity at the basal body and the roolet of cilia. Surface epithelium in group 1 and 2 bronchi contained 23 +/- 6 (n = 14) and 1.8 +/- 0.3 pmol/g acetylcholine) (n = 7, P < 0.001), respectively, whereas the transmural acetylcholine content did not differ significantly between both groups. The amount of choline acetyltransferase immunoreactivity appeared similar in the surface epithelium of both groups. In an animal (rat) study the effects of oral dexamethasone (3 mg/day, 1 week) on choline acetyltransferase activity and acetylcholine levels were investigated. Dexamethasone treatment reduced epithelial acetylcholine in the airways and small intestine by about 80% and inhibited epithelial choline acetyltransferase activity. In conclusion, epithelial cells of human airways possess components of the cholinergic system, i.e., contain the synthesizing enzyme choline acetyltransferase and store acetylcholine. The data obtained from the animal study indicate that glucocorticoids can inhibit epithelial acetylcholine.

Acetylcholine↗
PubMed1998

Differential expression of cell adhesion molecules in inflamed appendix: correlation with clinical stage.

The diagnosis of 'early inflamed', 'recurrent' or 'sub-acute' appendicitis is often difficult and accompanied by controversies between clinical data, histological findings, and their interpretation. The expression of the intercellular cell adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1), and E-selectin has been studied in 61 appendicectomy specimens for possible use as a diagnostic tool. This study demonstrates a different expression of CAM by endothelial (EC) and mesothelial cells (MC) in the various stages of appendicitis, with early E-selectin and ICAM-1 expression in EC, followed by VCAM-1 in EC and MC. Appendices from patients with prolonged clinical symptoms defined by clinicians as 'chronic' appendicitis showed VCAM-1 expression and occasionally weak expression of E-selectin in EC. In several cases, discrepancies were found between the pre-operative 'clinical' diagnosis, the histomorphological findings, and the immunohistological results. In this context, the expression of E-selectin and VCAM-1 in comparison with the histological features has potential significance in the diagnosis of 'early acute', 'sub-acute' or 'recurrent' appendicitis. In addition, a correlation was demonstrated between the histological stages of appendicitis and the kinetics of CAM expression. The study also indicates that the time course of E-selectin expression in vivo is longer than is suggested from in vitro data.

Acute Disease↗
PubMed1998

[Prognostic value of e-cadherin in papillary thyroid carcinoma].

The prognostic significance of e-cadherin in papillary thyroid carcinoma was evaluated in a retrospective study. From September 1985 to December 1996, 113 patients underwent surgery for papillary thyroid carcinoma. Seventy-eight formalin-fixed, paraffin-embedded tissue samples were available for immunohistochemical analysis of e-cadherin expression. In 74 of these 78 patients the postoperative course is known for 2 months to 35.2 years (median 3.6 years, mean: 4.9 +/- 4.8 years). Reduced or negative e-cadherin expression (< or = 20%) was associated with advanced T categories of the primary tumours and higher rates of synchronous lymph node involvement and distant metastasis. During follow-up in this group of patients locoregional tumour recurrence occurred more frequently and survival was shorter than in patients with tumours which exhibited e-cadherin expression of > 20%. Statistical analysis revealed e-cadherin expression (< or = 20%/ > 20%), synchronous distant metastasis (M0/pM1, cM1) and radicality of resection (R0/R1, 2) as significant risk factors for survival. Our findings provide evidence that e-cadherin is a prognostic factor in papillary thyroid carcinoma.

Adult↗
PubMed1998

[Confocal laser scanning microscopy (CLSM) for validation of non-destructive histotomography of healthy bone tissue].

OBJECTIVES: Fixation (formalin), decalcification (sections) or mechanical treatment (grinding) all bear the risk of artifacts occurring during hard-tissue histology. Because studies on the etiology of pathological changes mostly focus on subclinical lesions, artifacts can simulate early changes or even be superimposed on existing changes. The objective of this study was to determine how artifacts can be reduced. MATERIAL AND METHODS: In confocal laser scanning microscopy (CLSM) a focused laser beam scans the surface of the specimens and penetrates into the tissue. The intensity of the remitted light is recorded. The confocal effect is due to an extremely small aperture (pin-hole), excluding light from out-of-focus planes of the sample. By stepwise movement of the object table, a tomographic series of tomographic images is obtained. Sound cortical bone samples of the lower jaw (n = 20) were studied by light microscopy and by CLSM, visualizing identical areas of a ground sectioned sample after H&E staining. Additionally, embedded and fresh blocks of tissue of the same bone sample were studied histotomographically in the CLSM. RESULTS: (1) Light microscopic micromorphology of cortical bone can be visualized adequately in the CLSM; (2) many structures that can be visualized by light microscopy only after special staining (e.g., osteozyte processes) can be visualized by the CLSM using sample blocks without pretreatment. CONCLUSION: (1) Nondestructive subsurface histotomography by CLSM totally excludes mechanical artifacts; (2) physicochemical artifacts can be handled more easily because fresh samples can be studied; (3) pseudo-three-dimensional imaging allows histological interpretation of the tissue that is equivalent to macroscopic tomographic techniques (CT, MRT).

Artifacts↗
PubMed1998

Endosonography of the adrenal glands: normal size--pathological findings.

Transabdominal sonography of the adrenal glands frequently is non-successful. It was the aim of this project to improve the imaging of the adrenal glands using high resolution sonography in order to obtain information about even small changes in these organs. Therefore, endosonographic imaging was investigated using an endosonoscope PENTAX FG32UA. The correct identification of the adrenal glands was examined in five human cadavers. A total of 58 patients with 113 adrenal glands (in 3 cases history of unilateral adrenalectomy) were investigated. 109 adrenal glands (97%) were identified and evaluated. Healthy adrenal glands are slightly hyperechoich and regarding their echogeneity comparable to other endocrine organs such as the testes or the thyroid. Adrenal size can be determined as largest cross sectional area and was found to be 216 +/- 93 mm2 right and 231 +/- 98 mm2 left. In the adrenal glands which could be imaged by endosonography, all findings detected by CT (n = 33) or MRI (n = 19) could also be demonstrated endosonographically. Additional information as compared to CT/MRI was obtained in 7 out of 33 and in 6 out of 19 patients. This concerns in particular differentiation between tumor and hyperplasia and detection of small adrenal adenomas. High resolution endosonography of the adrenal glands can provide information about adrenal gland morphology which cannot be obtained by any other diagnostic approach.

ACTH Syndrome, Ectopic↗
PubMed1998

[Endosonographic imaging of the adrenal glands: a new method].

UNLABELLED: In contrast to the reliable imaging of the adrenal gland in infants and children, transabdominal sonography of the adrenal glands is often unsuccessful. AIM: To improve the imaging of the adrenal glands with high resolution in order to obtain information on even small changes in these organs. METHOD: Adrenal glands taken from human cadavers were investigated using a 7.5 MHz transducer. Thereafter, endosonographic imaging was investigated in 5 human cadavers using an endosonoscope PENTAX FG32 UA (longitudinal sector scanning. 7.5 MHz). Furthermore, the adrenal glands were imaged in a total of 30 patients with different indications for endosonography. RESULTS: The adrenal glands in 5 human cadavers could be identified in each case. This was proved in one human cadaver by endosonographically guided fine needle puncture with consecutive preparation of the tissue damage caused by the needle. In a total of 30 patients with 56 adrenal glands (in 4 cases preview history of unilateral adrenalectomy), 55 adrenal glands were correctly identified and evaluated. The only exception was the left adrenal gland of a patient with Billroth-II-stomach, which was slightly pulled to the right and very small. Healthy adrenal glands are slightly hyperechoic as compared to the parenchyma of the kidney and have echogeneity comparable to other endocrinal organs such as the testicles or the thyroid. Endosonographic imaging of the adrenal glands is far superior in resolution and determination to transabdominal sonography. In 18 of 30 patients (60%) endosonography provided additional diagnostic information compared to conventional sonography. CONCLUSION: Endosonography of the adrenal glands enables imaging of these organs with high resolution using a 7.5 MHz transducer from a distance of 1-2 cm.

Adenoma↗
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

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↗