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F Bittinger

Publications and source records attributed to F Bittinger.

At least 19 recordsLinked to original sources
PubMed2006

Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia.

AIM: To determine DNA aneuploidy in mucosal biopsies of achalasia patients for subsequent rapid diagnosis. METHODS: Biopsies from the middle third of the esophagus were obtained in 15 patients with achalasia. Immunohistochemical staining was carried out with monoclonal antibodies MIB-1 for Ki67 and PAb 1801 for p53, in addition to the conventional histologic examination for dysplasia. Nuclei of fresh biopsy material were enzymatically and mechanically isolated, and the DNA content was determined with image cytometry after Feulgen staining. DNA grading of malignancy was assessed according to Boecking to determine the variability of DNA values noted around the normal diploid peak. Further indices measured included the aneuploid rate, and the 5c-, 7c- and 9c-exceeding rate. RESULTS: The histological examination did not demonstrate dysplasia; while MIB-1 (basal) showed a positive reaction in 8/15 achalasia specimens, p53 was negative in all specimens. Image cytometric DNA analysis detected aneuploidy in 4/15 (26.7%) specimens. Samples from 15 patients with squamous cell carcinoma as well as specimens obtained exclusively 2 cm proximal to the tumor served as reference tests. All carcinomas (15/15) as well as 9 of the peritumoral samples (9/15) were aneuploid. The comparison of biopsies from achalasia patients with peritumoral and carcinoma specimens revealed statistically significant differences regarding the aneuploid rate (diploid: P < 0.0001; tetraploid: P = 0.001), grading of malignancy according to Boecking (P < 0.0001) and the 5c- (P < 0.0001), 7c- (P < 0.0001), and 9c- (P = 0.0001) exceeding rate with progredient DNA alterations in the respective order. CONCLUSION: The finding that DNA aneuploidy was identified by image cytometry in esophageal specimens of patients with achalasia, which may be due to specific chromosomal alterations presenting as precancerous lesions in 27% of patients, leads us to conclude that image cytometry represents a valuable screening tool.

Adult↗
PubMed2006

[Second reading of breast imaging at the hospital department of radiology: reasonable or waste of money?].

PURPOSE: To assess the effect of a second diagnostic reading of breast imaging at a university department of radiology. MATERIAL AND METHODS: The diagnostic reports of first readers from different private radiology practices and the reports of second readers from the university department of radiology were compared with the histological results (n = 214) and outcome of follow-ups for 4 years (n = 74) in 236 patients (mean age 55 years). BI-RADS categories were used for this purpose. The initial examinations had been performed because of symptoms (n = 117), early detection outside an organized screening program (n = 102), evaluations following breast cancer therapy (n = 13) and unknown primary tumors (n = 4). In addition, the number of complementary examinations and the influence of a second reading on patient management were evaluated. RESULTS: A total of 140 lesions were malignant and 148 were benign. Of the 288 lesions, 49 % were classified identically in the second reading; 36 % (79/217) of the lesions initially classified as BI-RADS 4 and 5 were downgraded to benign; and 41 % (29/71) of the lesions classified as BI-RADS 1 to 3 were upgraded as suspected of being malignant. The kappa value between the first and second readers was 0.34 with respect to each BI-RADS category separately and 0.18 with respect to categories 1 to 3 (benign) versus 4 and 5 (malignant). A second reading increased the sensitivity from 81 % (114/140) to 96 % (135/140) and the specificity from 30 % (45/148) to 78 % (116/148). Second readers detected 23 additional malignant lesions, changed two lesions correctly classified as malignant to benign categories and caused 6 additional false-positive findings. In all, 38 surgical biopsies could be prevented, one biopsy was erroneously delayed and three unnecessary excisional biopsies were initiated. In the study group, 49 MRI examinations revealed 5 additional malignant lesions and positively influenced surgical planning in 28 patients. In addition to these MRI examinations, 221 patients were examined using ultrasonography, 62 patients using complementary mammography, and 7 using galactography. CONCLUSION: The benefit of a second reading outweighs the expenditure.

Biopsy↗
PubMed2006

[Massive hemorrhage in a 28-year-old male patient with intestinal Behçet's disease].

A 28-year-old man was admitted to the emergency room of our hospital after syncope and acute gastrointestinal bleeding. On the basis of numerous oral and genital ulcerations as well as uveitis anterior and erythema nodosum, the diagnosis of Behçet's disease had been confirmed previously. The bleeding focus could not be detected by endoscopy. During the next days recurrent massive hemorrhages occurred in spite of immunosuppressive therapy with steroids. Angiography revealed a circumscribed bleeding source in the colon transversum near the left colonic flexure, which was treated by superselective coil embolization. A massive hemorrhage reoccurred and required a surgical approach with a Hartmann procedure. Histology depicted bleeding into the submucosa and mucosa and an ulcer in this area as well as lymphatic infiltration of the mucosa. Immunosuppressive therapy was intensified with azathioprine and resulted in a dramatic improvement of the oral and genital ulcers. In addition, no further gastrointestinal hemorrhage occurred. Due to its higher prevalence in patients from eastern Asia, Behçet's disease poses an important differential diagnosis of intestinal hemorrhage in patients of this descent.

Adult↗
PubMed2004

[Hilar cholangiocarcinoma -- results of en bloc resection of tumor and liver].

The increasingly performed en bloc resection of liver and hilar tumor has contributed to the improvement of long-term survival in patients with hilar cholangiocarcinoma. Based on preoperative definition of operative strategy we tried to avoid any traumatization of the hilar region. Between September 1997 and September 2002, 82 patients with hilar cholangiocarcinoma were treated at our department. Three patients were excluded from any surgery. The resection rate was 75% (59 of 79); 79% (38 of 48) of en bloc resections of the hilar tumor and adjacent liver were formally curative. The hospital mortality was 7%. The 1- and 3-year survival rates of patients after explorative laparotomy, palliative and curative resection was 27 and 7%, 67 and 26%, 89 and 45% ( p<0.001), respectively. The 1- and 3-year survival rates of patients after en bloc resection were 78 and 49%, respectively. In patients with formally curative en bloc resection ( n=38), the 3-year survival rate was 63%; in patients with N0/R0 resection ( n=31) it was 71%. Lymph node involvement proved to be the only independent prognostic marker if patients who underwent hilar and en bloc resection were included in the multivariate analysis. The R situation was the only significant predictor for patients after en bloc resection. These data justify the extended diagnostic work-up and the principal liver resection in hilar cholangiocarcinoma.

Aged↗
PubMed2004

Complete gangrene of penis in patient with arterial vascular disease.

We present a clinical case of distal penile gangrene in a patient with peripheral vaso-occlusive disease that did not correlate with the extension of the intraoperative finding and required total penectomy. Surgical intervention at the onset of wet gangrene avoids the complication of sepsis.

Blood Coagulation Disorders↗
PubMed2004

Preoperative imaging of hilar cholangiocarcinoma: surgical evaluation of standard practises.

UNLABELLED: It was the goal of this study to compare the results of the preoperative diagnostic workup (ERC, MRC, and PTC) with the tumor extent of the surgical specimen in patients with hilar cholangiocarcinoma (hilCC). PATIENTS AND METHODS: Between 9/97 and 12/2002 82 patients with hilCC were treated at our institution. In 59 patients tumor resection was feasible. Preoperative ERC, MRC and PTC - blinded for the idendity of the patients - were analysed retrospectively and compared with the surgical specimen. RESULTS: PTC resulted in significantly superior visualization of the bile ducts including the hilar lesion compared to ERC and MRC (p < 0.01). ERC, MRC and PTC were correct in predicting tumor extent in 29, 36 and 53 % of cases, respectively. The extent of the tumor was overestimated in 42 % (ERC), 41 % (MRC) and 31 % (PTC). Underestimation or wrong assessment or no decision at all occurred in 31, 23 and 16 %, respectively. In 20 patients results of all three diagnostic methods were available allowing a statistical comparison regarding the resection to be performed: PTC was superior to ERC (McNemar test:p < 0.01), but not to MRC. In the patients with overestimated tumor extent both the rate of curative resections and survival were similar to the other resected patients. DISCUSSION: In contrast to most reports in the literature, ERC and MRC were found to be of limited reliability regarding the assessment of tumor extent. PTC proved to be the most reliable approach. Overestimation of the tumor extent, which may lead to exclude the patient from potentially curative surgery, was the most common mistake in each diagnostic modality.

Bile Duct Neoplasms↗
PubMed2004

[Diagnostic imaging of hilar cholangiocarcinoma: preoperative evaluation of ERC, MRC and PTC in comparison with histopathology].

PURPOSE: To compare the results of the preoperative workup consisting of endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography (MRC), and percutaneous resonance cholangiography (PTC) with the tumor extent of the surgical specimen in patients with hilar cholangiocarcinoma (hilCC). MATERIALS AND METHODS: Between 9/1997 and 12/2002, 59 patients with hilCC tumor underwent surgical resection. Preoperative ERC, MRC, and PTC were analyzed, blinded for the identity of the patient, and compared with the surgical specimen. For this retrospective analysis, 55 of the initial 59 ERCs, 39 of the initial 40 MRCs and 32 of the initial 38 PTCs were available. Most of the ERCs and MRCs had been performed at referring institutions by various investigators. In 20 patients, all three imaging modalities were available for direct comparison. RESULTS: The mean scores of the visualization of the bile ducts and tumor differ considerably for ERC, MRC and PTC, with PTC visualizing the bile ducts better than ERC (p < 0.001) and MRC (p = 0.019). The tumor classification according to Bismuth and Corlette was correctly predicted by ERC in 29 %, by MRC in 36 % and by PTC in 53 %. The tumor extent was overestimated in 40 % (ERC), 41 % (MRC) and 31 % (PTC) and underestimated in less than 10 % for all modalities. Twenty patients, who underwent all three imaging modalities, were included in an additional analysis for a direct comparison of ERC, MRC and PTC. PTC provided correct or acceptable information on tumor extent in 19 of 20 patients, MRC in 15 of 20 patients, and ERC in only 11 of 20 patients. The statistical analysis revealed a significant superiority of PTC to ERC (McNemar test: p < 0.01) but not to MRC (p = 0.22). DISCUSSION: The management of patients with hilar cholangiocarcinoma requires a high degree of expertise in diagnostic imaging techniques. Cholangiography should not only define the location but also visualize the uppermost extent of the tumor to determine resectability. In contrast to most reports in the literature, ERC and MRC were found to be of limited reliability regarding the assessment of the tumor extent. ERC may be more and more reserved for patients considered for nonsurgical intervention or palliation. PTC proved to be the most reliable approach. MRC represents a noninvasive diagnostic tool for the evaluation of malignant perihilar biliary obstructions, but should be performed at highest quality using state-of-the-art MRI techniques. The most common mistake of each diagnostic modality was an overestimated tumor extent, which may exclude patients from potentially curative surgery.

Aged↗
PubMed2003

[Endosonographically controlled transluminal fine needle aspiration biopsy: diagnostic quality by cytologic and histopathologic classification].

BACKGROUND AND OBJECTIVE: EUS-guided fine needle aspiration (EUS-FNA) has emerged as a highly accurate technique for detecting and classifying mediastinal and pancreatic lesions as well as abdominal and recently retroperitoneal masses with a minimum of risk for the patient. PATIENTS AND METHODS: To objectify these statements, we evaluated the quality of 72 EUS-FNA specimens by cytologic and histopathologic classification, investigated their contamination with tissue from the needle pathway and observed puncture-related complications in a retrospective study of 44 EUS-FNA in 41 consecutive patients (56 +/- 14 years, m = 24, f = 17; 13 pancreatic, 9 adrenal, 6 abdominal and 13 mediastinal masses). EUS-FNA was performed using a PENTAX 32 UA endosonoscope (longitudinal 7.5 MHz sector array) in combination with a needle system type "Hancke-Vilmann". RESULTS: 16 vs. 11 of 34 histopathologic and 38 cytologic specimens were classified "excellent", 7 vs. 10 "sufficient", 7 vs. 13 "poor" and 4 vs. 4 "failed". Analysis of contamination with tissue from the needle pathway showed 4 vs. 2 specimens "highly", 3 vs. 14 "clearly", 8 vs. 19 "slightly" and 19 vs. 3 "not" contaminated. Specimens classified "excellent" were less contaminated (p = 0,037). EUS-FNA identified 35 benign and 24 malignant masses. Definite diagnosis failed in 13 specimens. One nonfatal complication occurred. EUS-FNA is an accurate (89 %) and low-risk procedure to examine primary undiagnosed mediastinal, pancreatic, intraabdominal and especially adrenal lesions in most of the cases. Contamination with tissue from the needle pathway seems to be a major predictive factor of poor specimen quality and failed diagnosis. CONCLUSION: EUS-FNA expands the diagnostic approach of mediastinal, abdominal, pancreatic and adrenal masses and provides accurate specimens for reaching new differential-diagnostic competence, especially in endocrinologic cases.

Abdominal Neoplasms↗
PubMed2003

Chromosomal aberrations in premalignant and malignant squamous epithelium.

Biopsies of oropharyngeal cancer were screened for chromosomal imbalances by comparative genomic hybridization (CGH) performed on 22 primary tumors and morphologically nonmalignant surrounding mucosa. The aim was to determine early chromosomal changes of tumor development and to draw conclusions on the mechanisms leading to multiple tumors. The most prominent chromosomal imbalances observed were over representations of genomic material on 3q, 15q, 8q, and 11q and losses on 9p, 3p, and 11q. In morphologically normal mucosa collected at 1 cm from the primary tumor border (M1), amplifications on 15q and 21q were most frequent. Far fewer gains and losses were found in M1 than in the primary tumor (average 2.2 vs. 6.9). Gains dominated over losses, but a tendency toward an increasing proportion of losses in the primary tumor (PT) was observed (ratio of gains to losses: PT, 4.75; M1, 6.3). Almost all the imbalances in M1 were detected in the primary tumor. No chromosomal alterations were identified with CGH in tissue samples dissected at 2 cm from the primary tumor (M2). In all samples, dysplastic morphologic changes decreased with distance from the primary tumor, which correlates with the observed lower level of genetic changes. We suggest that gains of genetic material on 15q and 21q are early events in malignant progression of squamous cell carcinoma, followed by gains on 3q, 8q, and 11q, and losses on 3p and 9p at later stages. Based on our cytogenetic data, we discuss the monoclonal model followed by lateral epithelial spread as an explanation of multiple head and neck squamous cell carcinomas.

Adult↗
PubMed2003

Expression of KIT (CD117) in biphasic pulmonary blastoma. Novel data on histogenesis.

Biphasic pulmonary blastoma (BPB) is a rare primary neoplasm of the lung and its histogenesis is still uncertain. It has been proposed that BPB is derived from mesoderm or endoderm. Others suggested an origin from a single pluripotential cell. We present a case of a BPB with emphasis on expression of the stem cell factor receptor KIT (CD117). We describe a 61-year-old male patient with a BPB of the upper right lobe. Immunohistochemical analysis was performed using a panel of several antibodies including anti-CD117. Strong cytoplasmic expression of CD117 was found in the epithelium (cytokeratin-positive) as well as in the spindle cells (cytokeratin-negative). Expression of CD117 in both mesenchymal and epithelial cells suggests a single origin and supports the idea that BPB arises from a pluripotential cell that can differentiate into both stromal and epithelial morphologies. The role of CD117 in the pathogenesis of BPB and its possible therapeutic relevance require further investigation.

Humans↗
PubMed2002

Tissue response and biomaterial integration: the efficacy of in vitro methods.

Implantation involves tissue trauma, which evokes an inflammatory response, coupled to a wound healing reaction, involving angiogenesis, fibroblast activation and matrix remodelling. Until now the type and extent of such reactions to give optimal integration of various biomaterials are practically unknown. Three principal fields of research can yield useful data to understand these phenomena better: studies on explanted biomaterials, animal models and relevant in vitro techniques. This paper will present examples of the latter field and the application of endothelial cell (EC) culture systems to study the effects of important tissue (e.g. pro-inflammatory cytokines, chemokines) and material (e.g. metal ions, particulate debris) factors on the regulation of the inflammatory and angiogenic response. A central feature is the use of microvascular endothelial cells (MEC), which can be used in both 2-and 3-dimensional (3-D) assays. We have also used genetic manipulation to develop a permanent MEC line from the human lung (HPMEC-ST1), which is being tested for its suitability to study cell-biomaterial interactions. In addition, suitable in vitro techniques are being developed in order to investigate drug delivery systems (DDS). Of particular interest is the targeting of the central nervous system, our approach being to establish a human model of the blood-brain barrier (BBB). A mainstay of our scientific philosophy is that such in vitro methods can make an important contribution to understanding biological reactions at the tissue-biomaterial interface and thus further a causal approach to tissue engineering (TE) and drug delivery applications.

Animals↗
PubMed2001

Endosonography of insulin-secreting and clinically non-functioning neuroendocrine tumors of the pancreas: criteria for benignancy and malignancy.

OBJECTIVE: Endosonography is a powerful tool in the diagnosis of gastroenteropancreatic neuroendocrine tumors. This study was performed in order to characterize endosonographic criteria of malignant and benign neuroendocrine pancreatic tumors focussing on those typically presented to endocrinologists, i.e. insulin-secreting tumors and clinically non-functioning tumors in MEN-1. DESIGN: We studied six benign insulinomas, four hormone inactive benign neuroendocrine adenomas in MEN-1, and three non-metastatic neuroendocrine carcinomas with clinically symptomatic insulin secretion. METHODS: Endosonography was performed using Pentax FG 32 UA endosonoscope with a longitudinal 7.5 MHz sector array. RESULTS: Tumor diameter was larger in malignant tumors (19 - 70 / 47.0 +/- 25.9 mm) than in benign lesions (2.3 - 19 / 9.7 +/- 5.8 mm). Hypoechoic echogeneity was more or less present in benign and in malignant tumors and could not be used as a criteria for differential diagnosis. Heterogeneous or multinodular structure on endosonographic imaging however, was an exclusive feature of malignant tumors. Echo-free areas representing cystic transformation or necrosis and vascular invasion were additional signs of malignancy. CONCLUSIONS: Molecular genetic diagnosis of MEN-1 and new therapeutic developments such as endoscopic surgery make sufficient imaging procedures in the management of neuroendocrine pancreatic tumors mandatory. Besides valid detection and exact localization, endosonography provides criteria for benign and malignant tumors and thus may be helpful in planning therapeutic strategies.

Carcinoma, Neuroendocrine↗
PubMed2001

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I-IV), the most relevant clinical parameters. Similarly, a significant association between c-erbB-2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly, c-erbB-2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II-IV), median survival of patients with undetectable c-erbB-2 expression was 274 days compared with only 23 days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p = 0.0031; log-rank test). Similar results were obtained for patients with extensive disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c-erbB-2 expression was not associated with survival in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent prognostic factor of survival. The effect of c-erbB-2 expression seems to become more important in advanced stages of the disease. Since c-erbB-2 is a therapeutical target in other types of cancer, further studies to identify the role of c-erbB-2 in SCLC are clearly warranted.

Age Factors↗
PubMed2001

Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine.

The synthesis and release of non-neuronal acetylcholine, a widely expressed signaling molecule, were investigated in the human placenta. This tissue is free of cholinergic neurons, i.e. a contamination of neuronal acetylcholine can be excluded. The villus showed a choline acetyltransferase (ChAT) activity of 0.65 nmol/mg protein per h and contained 500 nmol acetylcholine/g dry weight. In the absence of cholinesterase inhibitors the release of acetylcholine from isolated villus pieces amounted to 1.3 nmol/g wet weight per 10 min corresponding to a fractional release rate of 0.13% per min. The following substances did not significantly modify the release of acetylcholine: oxotremorine (1 microM), scopolamine (1 microM), (+)-tubocurarine (30 microM), forskolin (30 microM), ouabain (10 microM), 4alpha-phorbol 12,13-didecanoate (1 microM) and tetrodotoxin (1 microM). Removal of extracellular calcium, phorbol 12,13-dibutyrate (1 microM) and colchicine (100 microM) reduced the acetylcholine release between 30% and 50%. High potassium chloride (54 mM and 108 mM) increased the acetylcholine release slightly (by about 30%). A concentration of 10 microM nicotine was ineffective, but 100 microM nicotine enhanced acetylcholine release gradually over a 50-min period without desensitization of the response. The facilitatory effect of nicotine was prevented by 30 microM (+)-tubocurarine. Inhibitors of cholinesterase (physostigmine, neostigmine; 3 microM) facilitated the efflux of acetylcholine about sixfold, and a combination of both (+)-tubocurarine (30 microM) and scopolamine (1 microM) halved the enhancing effect. In conclusion, release mechanisms differ between non-neuronal and neuronal acetylcholine. Facilitatory nicotine receptors are present which are activated by applied nicotine or by blocking cholinesterase. Thus, cholinesterase inhibitors increase assayed acetylcholine by two mechanisms, protection of hydrolysis and stimulation of facilitatory nicotine receptors.

Acetylcholine↗
PubMed2001

Generation of human pulmonary microvascular endothelial cell lines.

The limited lifespan of human microvascular endothelial cells in cell culture represents a major obstacle for the study of microvascular pathobiology. To date, no endothelial cell line is available that demonstrates all of the fundamental characteristics of microvascular endothelial cells. We have generated endothelial cell lines from human pulmonary microvascular endothelial cells (HPMEC) isolated from adult donors. HPMEC were cotransfected with a plasmid encoding the catalytic component of telomerase (hTERT) and a plasmid encoding the simian virus 40 (SV40) large T antigen. Cells transfected with either plasmid alone had an extended lifespan, but the cultures eventually entered crisis after several months of proliferation. Only those cells that were transfected with both plasmids acquired the capacity to grow in vitro without demonstrating major crisis, and these cells have been in culture for 24 months. HPMEC isolated from two different donors were used, generating two populations of immortalized cells, HPMEC-ST1 and HPMEC-ST2. Single cell-derived clones of the immortalized cells HPMEC-ST1 exhibited growth characteristics that were similar to those of the parental HPMEC. One selected clone, HPMEC-ST1.6R, displayed all major constitutively expressed and inducible endothelial phenotypic markers, including platelet endothelial cell adhesion molecule (PECAM-1, CD31), von Willebrand factor (vWF), and the adhesion molecules, intercellular adhesion molecule (ICAM-1), vascular adhesion molecule (VCAM-1), and E-selectin. In addition, an angiogenic response was demonstrated by sprout formation on a biological extracellular matrix (Matrigel). The HPMEC-ST1.6R cells did not form tumors in nude mice. The microvascular endothelial cell line, HPMEC-ST1.6R, will be a valuable tool for the study of microvascular endothelial physiology and pathology including gene expression, angiogenesis, and tumorigenesis.

Adult↗
PubMed2001

Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters.

1. The release of acetylcholine was investigated in the human placenta villus, a useful model for the characterization of the non-neuronal cholinergic system. 2. Quinine, an inhibitor of organic cation transporters (OCT), reduced acetylcholine release in a reversible and concentration-dependent manner with an IC(50) value of 5 microM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 microM. 3. Procaine (100 microM), a sodium channel blocker, and vesamicol (10 microM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4. Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylcholine in a concentration-dependent manner with an IC(50) value of 2 microM. 5. Substrates of OCT subtype 1, 2 and 3 (amiloride, cimetidine, guanidine, noradrenaline, verapamil) inhibited acetylcholine release, whereas carnitine, a substrate of subtype OCTN2, exerted no effect. 6. Long term exposure (48 and 72 h) of villus strips to anti-sense oligonucleotides (5 microM) directed against transcription of OCT1 and OCT3 reduced the release of acetylcholine, whereas OCT2 anti-sense oliogonucleotides were ineffective. 7. It is concluded that the release of non-neuronal acetylcholine from the human placenta is mediated via organic cation transporters of the OCT1 and OCT3 subtype.

Acetylcholine↗
PubMed2001

Differential adhesion of polymorphous neutrophilic granulocytes to macro- and microvascular endothelial cells under flow conditions.

OBJECTIVE: As one of the important active barriers in the human organism, endothelial cells (EC) play a central role in the biological reaction to a variety of stimuli, e.g. during the induction and regulation of inflammation, as well as in the reaction to transplantation and biomaterial implantation. In the study of endothelial function, the most widely used in vitro model is that of human umbilical vein EC (HUVEC), i.e. an EC type of embryonic and macrovascular origin. However, many of the important pathological processes occur at microvascular level, thus questioning the validity of the HUVEC model. Moreover, the morphological and functional heterogeneity of the endothelium in the various organs, e.g. kidney, liver and lung, must be taken into consideration. The purpose of the present study was to use a dynamic cell culture system to compare the reactions of HUVEC and human pulmonary microvascular EC (HPMEC) to pro-inflammatory stimulation. METHODS: HUVEC and HPMEC in monolayer culture were stimulated by tumor necrosis factor-alpha (TNFalpha) in a parallel-plate flow chamber. Short- (4 h) and long-term (12 h) stimulation were compared. As a functional parameter, the adhesion of human peripheral blood polymorphonuclear granulocytes (PMN) to EC was quantitated both under venous and arterial flow conditions. RESULTS: Short-term (4 h) TNFalpha stimulation and venous flow conditions elicited a 32% higher PMN adhesion to HPMEC compared with HUVEC, whereas under arterial flow conditions no statistically significant differences were found. Following longer-term (12 h) TNFalpha stimulation, PMN adhesion to HPMEC was 65% higher than to HUVEC under venous flow. Under arterial flow no differences were detected. CONCLUSION: The present results provide new data on the heterogeneity of the endothelium and affect a central element in microvascular pathology, namely granulocyte-endothelial interactions. Moreover, this paper emphasizes the necessity to evaluate the in vitro models of the endothelium with respect to the extrapolation to the situation in vivo.

Cell Adhesion↗