Common antigenic determinant on ductular cells of normal pancreas, on mucosal cells of the gastrointestinal tract and on CEA

CEA is widely used as a human tumour marker and was first defined by Gold and Freedman in 1965 as an antigenic component in cancers derived from gastrointestinal tract epithelium. It is a member of a large family of immunologically related glycoproteins that vary in size and tissue distribution. Studies with c-DNA clones for CEA and NCA reveal that this family consist only of a limited number of different proteins with variable glycosylation, due to post-transcriptional modifications. The complete gene family includes about 10 closely related genes. Recently it was published that in contrast to mRNA coding for CEA, mRNA coding for NCA was expressed predominantly in cancerous tissues. A mono…

D-dimer for risk stratification in haemodynamically stable patients with acute pulmonary embolism

Patients with submassive pulmonary embolism (PE) have a higher short-term mortality than those with low-risk PE. Rapid identification of submassive PE is important for adequate treatment of non-massive PE. We aimed to investigate the utility of D-dimer for the prediction of submassive PE stadium in normotensive PE patients.Normotensive PE patients were classified into submassive or low-risk PE groups. In addition to the comparison of the groups, area under the curve (AUC) and D-dimer cut-off for the prediction of submassive PE stadium, multi-variate logistic regression for association between D-dimer values above this cut-off and submassive PE stadium were also calculated.The data of 129 no…

Blood pressure for outcome prediction and risk stratification in acute pulmonary embolism.

Abstract Introduction Risk stratification of patients with acute pulmonary embolism (PE) is crucial in deciding appropriate therapy management. Blood pressure (BP) is rapidly available and a reliable parameter. We aimed to investigate BP for short-term outcome in acute PE. Materials and methods Data of 182 patients with acute PE were analyzed retrospectively. Logistic regression models were calculated to investigate associations between BP and in-hospital-death as well as myocardial necrosis. Moreover, receiver operating characteristic (ROC) curves and cutoff values for systolic and diastolic BPs predicting in-hospital death and myocardial necrosis were computed. Results A total of 182 pati…

Stomach signet-ring cancer cell line (MZ-STO-1), established in tissue culture: Morphological characterization and antigenic profile

7-O-acetyl-GD3 in human T-lymphocytes is detected by a specific T-cell-activating monoclonal antibody.

The monoclonal antibody U5, which is a potent inducer of proliferation in human T-cells, was found to bind to an alkali-sensitive derivative of ganglioside GD3. Using immunochemical and spectroscopic methods, the structure of the U5 antigen was determined as 7-O-acetyl-GD3. The antibody U5 did not react with 9-O-acetyl-GD3 and bound severalfold more stronger to 7-O-acetyl-GD3 than to GD3. U5 is the first antibody known to detect preferentially 7-O-acetyl-GD3. Flow cytometric analysis showed that each major class of human leukocytes contained a significant fraction of cells binding the U5 antibody.

Chemotherapy in advanced pancreatic cancer

Patients with advanced adenocarcinomas of the pancreas have an exceptionally poor prognosis. Modest activity has been demonstrated with single agents (response rates of 25% at best with 5-fluorouracil [5-FU] and mitomycin). Better results have not been obtained by combination chemotherapy. Improvements in the palliation have been achieved by treatment with 5-FU, folinic acid (FA), and interferon-alpha-2A (IFN-alpha) weekly in the context of a phase II trial. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR), and 28 (49%) had no change of disease (NC). The median survival time was 10 mo for patients with progressive disease. Twenty-two out o…

Right ventricular dysfunction in hemodynamically stable patients with acute pulmonary embolism

Abstract Background Echocardiography for risk stratification in hemodynamically stable patients with pulmonary embolism (PE) is well-established. Right ventricular dysfunction (RVD) is associated with an elevated mortality and adverse outcome. The aim of our study was to compare RVD criteria and investigate the role of elevated systolic pulmonary artery pressure (sPAP) in the diagnosis of RVD. Methods We retrospectively analyzed the echocardiographic and laboratory data of all hemodynamically stable patients with confirmed PE (2006-2011). The data were compared with three different definitions of RVD: Definition 1: RV dilatation, abnormal motion of interventricular septum, RV hypokinesis or…

Right bundle branch block and SIQIII-type patterns for risk stratification in acute pulmonary embolism.

Abstract Introduction Risk stratification in acute pulmonary embolism (PE) is crucial for identification of patients with poor prognosis. We aimed to investigate the ECG alterations of right bundle branch block (RBBB) and S I Q III -type patterns for risk stratification in acute PE. Materials and methods Retrospective analysis of PE patients, treated in the Internal Medicine Department, was performed. Patients with RBBB and/or S I Q III -type were compared with those without both patterns. Logistic regression models for association between these ECG alterations and respectively right ventricular dysfunction (RVD), high-risk PE status and myocardial injury were computed. Results 175 patients…

Isolation of a novel repetitive antigen expressed in human carcinoma cells

Expression and regulation by interferon-γ of the membrane-bound complement regulators CD46 (MCP), CD55 (DAF) and CD59 in gastrointestinal tumours

The membrane-bound complement inhibitors CD46 (membrane cofactor protein), CD55 (decay-accelerating factor) and CD59 (protectin) protect tumour cells against lysis by activated complement. In this study, a total of 14 (3 gastric, 3 colonic and 8 pancreatic) gastrointestinal tumour cell lines were examined for the expression of CD46, CD55 and CD59 with respect to the regulatory efficacy of interferon-gamma (IFN-gamma). The effects of IFN-gamma on mRNA and protein expression levels of CD46, CD55 and CD59 were evaluated by Northern blot hybridisation, RT-PCR, flow cytometry and immunostaining. In unstimulated cell lines, CD46 and CD59 transcripts were expressed at comparable levels, whereas th…

Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and interferon alpha-2A: results of a phase II trial.

Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A phase II study was initiated to evaluate the effect of a combination of 5-FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously untreated patients with advanced adenocarcinoma of the pancreas were treated with 500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN-alpha was administered subcutaneously. The treatment was repeated once a week. Of 57 evaluable patients, eight (14%) had a partial response (PR),…

The risk factor age in normotensive patients with pulmonary embolism: Effectiveness of age in predicting submassive pulmonary embolism, cardiac injury, right ventricular dysfunction and elevated systolic pulmonary artery pressure in normotensive pulmonary embolism patients.

Abstract Introduction Right ventricular dysfunction (RVD), submassive pulmonary embolism (PE), elevated systolic pulmonary artery pressure (sPAP), elevated cardiac troponin I (cTnI) and old age are well-known risk factors for poor outcome in acute normotensive PE. The aim of this analysis was to calculate age cut-off values to predict submassive PE, cardiac injury, RVD and elevated sPAP in normotensive PE patients. Methods Retrospective analysis of clinical, laboratory, radiological and echocardiographic data of normotensive PE patients (2006–2011) was performed. Receiver operating characteristic (ROC) curves and Youden indexes were used to test the effectiveness of using patients' ages at …

Stimulation of pancreas and gastric carcinoma cell growth by interleukin 3 and granulocyte-macrophage colony-stimulating factor.

Hematopoietic growth factors have recently been well characterized by complementary DNA scloning. For human epidermal growth factor, granulocyte-macrophage colony-stimulating factor recombinant proteins have been expressed in Escherichia coli . To reduce the toxic side effects of chemotherapy on the bone marrow, recombinant human granulocyte-macrophage colony—stimulating factor and recombinant human interleukin 3 were applied to patients suffering of gastrointestinal cancers. To determine the influence of recombinant human granulocyte-macrophage colony—stimulating factor and recombinant human interleukin 3 on human pancreas and gastric cancer cell cells in vitro, a sensitive microculture te…

The role of the Thomsen-Friedenreich antigen as a tumor-associated molecule.

The Thomsen-Friedenreich antigen (Gal-GalNAc) represents a tumor-associated molecule, which is assumed to be one of the few chemically well-defined antigens with a proven association with malignancy. In order to analyze the role of the carbohydrate structure Gal-GalNAc for gastrointestinal tumors, we immunized Balb/c mice with MCF-7 breast tumor cells together with synthetic Gal-GalNAc linked to a BSA carrier. One monoclonal antibody (82-A6) was established which recognizes the Thomsen-Friedenreich antigen according to the biochemical and serological analysis presented here. In contrast to the studies performed in the past, immunohistochemical results using this antibody 82-A6 did not exhib…

Schleimhaut-Polyp-Karzinom: Ein molekulargenetisches Modell der Entstehung kolorektaler Tumoren

Evaluation of Risk Stratification Markers and Models in Acute Pulmonary Embolism: Rationale and Design of the MARS-PE (Mainz Retrospective Study of Pulmonary Embolism) Study Programme

An acute pulmonary embolism (PE) is a crucial event in patients’ life and connected with serious morbidity and mortality. Regarding a high case-fatality rate, early and accurate risk-stratification is crucial. Risk for mortality and complications are closely related to hemodynamic stability and cardiac adaptations. The currently recommended risk-stratification approach is not overall simple to use and might delay the identification of those patients, who should be monitored more closely and may treated with more aggressive treatment strategies. Additionally, some risk-stratification criteria for the imaging procedures are still imprecise. Summarized, the search for the most effective risk-s…

Adjuvante und palliative Therapie kolorektaler Karzinome

Synthetic Inhibitors of Cell Adhesion: A Glycopeptide from E-Selectin Ligand 1 (ESL-1) with the Arabino Sialyl Lewisx Structure

Particularly selective methods are required for the synthesis of arabino sialyl Lewisx glycopeptides owing to the acid-labile β-arabinopyranoside bond. It is important for the inhibition of cell adhesion that the arabino sialyl Lewisx glycopeptide 1, which contains the Gly 672 -Asp 681 sequence of the E-selectin Ligand 1 (ESL-1), binds ten times more strongly than sialyl Lewisx to E-selectin, although it is monovalent and does not contain L-fucose, which is considered essential.

D-Dimer and thrombus burden in acute pulmonary embolism.

Abstract Background Thrombus burden in pulmonary embolism (PE) is associated with higher D-Dimer-levels and poorer prognosis. We aimed to investigate i) the influence of right ventricular dysfunction (RVD), deep venous thrombosis (DVT), and high-risk PE-status on D-Dimer-levels and ii) effectiveness of D-Dimer to predict RVD in normotensive PE patients. Methods Overall, 161 PE patients were analyzed retrospectively, classified in 5 subgroups of thrombus burden according to clinical indications and compared regarding D-Dimer-levels. Linear regression models were computed to investigate the association between D-Dimer and the groups. In hemodynamically stable PE patients, a ROC curve was calc…

Hepatocellular carcinoma: Biochemical and antigenic markers of three established cell lines

Human parvovirus B19 infection associated with severe acute perimyocarditis in a 34-year-old man

Expression of epithelial antigens EPM-1 and EXO-1 in normal, transitional, inflammatory and neoplastic colorectal mucosa

EPM-1 (a high molecular weight glycoprotein) and EXO-1 (a carbohydrate epitope expressed on polar neutral glycolipids and mucins) are two developmental antigens of normal and neoplastic human epithelia and were characterised by monoclonal antibodies. Their distribution was investigated in normal and pathological human colorectal mucosa. In normal mucosa, EPM-1 and EXO-1 showed characteristic expression patterns. EPM-1 was differentially expressed along the crypt villus axis with maximum at the crypt basis. EXO-1 was present throughout the whole mucosa. The characteristic gradient of EPM-1 expression along the crypt axis in normal mucosa was no longer detectable in benign polyps. Intact grad…

Towards the Development of Antitumor Vaccines: A Synthetic Conjugate of a Tumor-Associated MUC1 Glycopeptide Antigen and a Tetanus Toxin Epitope.

Proliferation of cytotoxic T-cells, a prerequisite for the development of antitumor vaccines, was induced by 1, but not by its partial structures A and B. The conjugate 1 containing a tumor-associated Sialyl-TN -MUC-1 glycopeptide antigen A and a T-cell epitope B of tetanus toxin was synthesized by fragment condensation on a solid phase.

Anti-GD3 antibodies are potent activators of human gamma/delta and alpha/beta positive T cells.

The ganglioside GD3 has a variety of biological functions. These include stimulatory effects on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4+ and CD8+ as well as gamma/delta TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule. Apart from IFN-gamma and IL-2 production by T helper 1 and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 cells…

Analysis of liver-specific protein LSP using murine monoclonal antibodies.

. We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver-specific protein LSP. Among them, nine were directed against liver-specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24 000 and 60 000. Further differences were observed wi…

Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion.

E-selectin mediated cell-cell adhesion plays an important role in inflammatory processes and extravasation of tumor cells. Tumor necrosis factor-alpha (TNF-alpha) induces E-selectin gene and protein expression in primary human endothelial cells (HUVEC) and in an endothelial cell line (EA.hy-926). As shown by ELISA and FACS analyses, HMG-CoA reductase inhibitors (e.g., lovastatin) impair the TNF-alpha stimulated increase in E-selectin protein expression. Similar results were obtained for E-selectin mRNA expression and promoter activity, indicating that the effect of lovastatin is based on inhibition of gene expression. The effective inhibitory concentration of lovastatin was in a physiologic…

alpha GalNAc is essential for recognition of Exo-1 epithelial antigen by mouse monoclonal antibody Pa-G-14.

Mouse monoclonal antibody Pa-G-14 detects Exo-1, an antigen whose expression is regulated in the processes of epithelial-cell differentiation and transformation. The epitope recognized by Pa-G-14 is present both in glycosphingolipids and in mucin glycoproteins. To characterize the specificity of Pa-G-14, immuno-thin-layer chromatography, biochemical, and enzymatic treatment of glycosphingolipid extracts from human pancreas were used. The antibody bound to all blood-group-A substances; alpha GalNAc, but not fucose, was essential for reactivity. In ELISA, Pa-G-14 also reacted with ovine and bovine submaxillary mucins but not with porcine submaxillary mucin. Binding to ovine submaxillary mucin…

Impact of cancer on the effectiveness of cardiac Troponin I to predict right ventricular dysfunction in acute pulmonary embolism

Background Deep vein thrombosis (DVT) and pulmonary embolism (PE) are connected with a poor outcome in cancer patients. We aimed to investigate the impact of cancer on the effectiveness of cardiac Troponin I (cTnI) to predict right ventricular dysfunction (RVD) in acute PE. Methods We retrospectively analyzed the data of 182 patients with confirmed PE. PE patients were subdivided into two groups: (i) with concomitant active cancer disease or history of cancer, and (ii) without known cancer. Receiver operating characteristic (ROC) curves with area under the curve (AUC) was calculated for cTnI predicting RVD and related cut-off levels for both groups. Results Thirty-seven PE patients (20.3%) …

Ah receptor mediating induction of cytochrome P450IA1 in a novel continuous human liver cell line (Mz-Hep-1)

Abstract The Ah receptor regulates induction of cytochrome P450IA1 and mediates certain toxicities of polyhalogenated aromatics such as 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). It has been characterized previously in continuous cell lines, notably the mouse hepatoma line Hepa 1, the human squamous cell carcinoma line A431, and the human liver cell line Hep G2. The present work extends our knowledge of the Ah receptor in continuous human liver cell lines. Ah receptor can be detected in Mz-Hep-1, a hepatitis B virus-negative cell line derived from a Thorotrast-induced hepatocellular carcinoma. The mean concentration of Ah receptor in Mz-Hep-1 cells was 341 ± 22 fmol/mg cytosol protein (m…

Liver cell damage caused by monoclonal antibody against an organ-specific membrane antigen in vivo and in vitro

Summary Monoclonal antibodies have been raised against different antigenic determinants of normal rabbit hepatocytes. One antibody (2D3) recognized a liver-specific 43 kDa protein displayed exclusively on the basolateral portion of the hepatocellular membrane. Purified monoclonal antibodies were injected intravenously into rabits. Following the injection of antibody 2D3, a dose-dependent increase of liver enzyme activities in sera was observed. Within 8 h, marked morphological alterations of the hepatocytes, including multiple cell necroses, could be demonstrated by light and electron microscopy. When isolated vital rabbit hepatocytes in culture were used as targets, cytotoxic effects of th…

Inhibition of anti-GD3-ganglioside antibody-induced proliferation of human CD8+ T cells by CD16+ natural killer cells

The ganglioside GD3 has been described as a membrane component of human T cells which is involved in T cell growth. In the present study the activating function of GD3 for human CD4+ and CD8+ T cells was analyzed by five different monoclonal antibodies (mAb) directed against the GD3 molecule. Three mAb U5, Z21 and R24 induced strong proliferation of peripheral blood mononuclear cells and purified CD8+ and CD4+ T cells of normal donors containing less than 5% CD16+ natural killer (NK) cells. In contrast to CD4+ T cells, CD8+ T cells proliferated only weakly in the presence of 15% CD16+ NK cells. The proliferative response of purified CD4+ and CD8+ T cells (< 5% NK cells) correlated with the …

Elevated serum E-selectin in patients with liver metastases of colorectal cancer

E-selectin, an endothelial cell adhesion molecule, mediates the initial step of leucocyte adhesion to activated vascular endothelium. The soluble isoform of E-selectin promotes angiogenesis in rat cornea. In the present study, we investigated whether leucocyte adhesion and angiogenesis are also involved in tumour progression and metastasis of colorectal cancer. Therefore, we determined the level of circulating soluble E-selectin in serum samples of 38 patients with colorectal cancer; 20 patients with non-metastatic and 18 patients with metastatic disease. Median levels of soluble E-selectin were found to be significantly higher in metastatic tumour disease (88.7 ng/ml, range 25-203 ng/ml) t…

Neuron-specific enolase--a serum marker for malignant melanoma.

?(1,3)Fucosyltransferase expression in E-selectin-mediated binding of gastrointestinal tumor cells

E-selectin recognizes the oncofetal antigen sialyl-Lewis X, which is highly expressed in adenocarcinoma. Five α(1,3)fucosyltransferases (FT) have been cloned that confer cell-surface expression of sialyl-Lewis X on transfected cells. We show here that 12/18 gastrointestinal-tumor cell lines bind specifically to immobilized E-selectin and that in sialyl-Lewis-X-positive cells binding is inhibited with a monoclonal antibody against sialyl-Lewis X. Using RT-PCR, we determined the expression of the α(1,3)fucosyltransferases III, IV, V, VI and VII in gastrointestinal tumor cells. Transcripts of FT IV and FT VII are abundantly expressed in all tested cells. Therefore no single fucosyltransferase …

[Pseudoxanthoma elasticum (Grönblad-Strandberg syndrome) and rheumatoid arthritis].

A 72-year-old woman, not previously known to have coronary heart disease, was admitted to hospital with an acute anterior wall myocardial infarction. The history revealed that, when about 40 years of age, a coarse skin-fold and yellowish-white xanthoma-like efflorescences had been noted around her umbilicus, the inguinal regions and axillae. These changes subsequently developed into a pathognomonic picture of pseudoxanthoma elasticum (PE), which was a significant factor in the myocardial infarction. At the age of 69 years, rheumatoid arthritis (RA), stage II after Steinbrocker, had been diagnosed on the basis of morning stiffness, symmetrical arthritis in more than three joint regions and t…

Immunotherapy of Malignant Melanomas

A large number of antigens on human melanoma cells have been identified by means of monoclonal antibody technology [18, 21]. The availability of monoclonal antibodies has rapidly led to clinical investigations. Experience with monoclonal antibodies in the treatment of patients with melanoma is limited [4, 9, 10, 12, 13, 17, 19] because only small groups of patients have been treated so far. According to these studies, treatment with ganglioside antibodies appears most promising.

Sustained elimination of hepatitis B virus from serum induced in a patient with chronic hepatitis B and advanced human immunodeficiency virus infection

A 48-year-old male patient was admitted with acquired immunodeficiency syndrome (stage III, Centers for Disease Control 1993) and viremic hepatitis B. Blood CD4 count was 15/microliters. Discontinuation of prednisolone, previously prescribed by the patient's family practitioner because of elevated liver enzymes, resulted in severe hepatitis (alanine aminotransferase > 300U/l). Administration of interferon-alpha (9 x 10(6) U s.c. 3 x weekly) was initiated. Serum markers of viral replication disappeared, and aminotransferase levels returned to normal within a few weeks. The patient's serum was found negative for HBsAg after 3 months. Immunohistochemical analysis of liver biopsies before and d…

Ganglioside GD3 shedding by human malignant melanoma cells

Gangliosides appear to be important target molecules for immunological effector mechanisms on neuro-ectodermal tumors. Therefore in vitro studies were performed to examine whether ganglioside GD3, which is highly expressed on the cell surface of cultured human melanoma cells, is being shed into the culture medium. Measurable quantities of gangliosides GM3 and in particular GD3 were shed by the melanoma cells we have tested as detected on thin-layer chromatograms (TLC) stained with orcinol. Ganglioside GD3 was also evidenced by immunostaining with anti-GD3 MAb and by ELISA. The concentration of GD3 in the supernatant of human melanoma cells depended on the ganglioside pattern of the cell lin…

Recent Advances in the Morphology of Myositis

Summary Myositis in man may be divided into infectious and non-infectious forms. The myopathologist more often deals with the latter forms which comprise dermatomyositis/polymyositis, inclusion body myositis, mixed connective tissue disease/collagenoses, and granulomatous myopathies. Modern morphological techniques as enzyme-histochemistry, electron microscopy, immunohistology, and morphometry are of different value in various forms of myositis, but are often indispensable techniques in up-to-date diagnostic work up of a myositis.

De novo expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in pancreas cancer.

We examined the expression of intercellular--adhesion molecule-I (ICAM-I, CD54) in 6 surgically removed pancreatic tumors and 8 pancreatic tumor cell lines. Immunohistochemistry revealed a varying percentage of ICAM-I-positive pancreas tumor cells, while normal pancreatic tissue (except for slight reactivity of endothelial cells) was not stained. The presence of the ICAM-I molecule on the cell surface and the expression of ICAM-I mRNA were investigated for 8 different pancreatic tumor cell lines. Three of these (Capan-I, Capan-2, QGP-I) expressed ICAM-I constitutively. In 4 of the ICAM-I-negative pancreas cancer cell lines, it was possible to induce a remarkable expression of ICAM-I by incu…

New cell lines of gastric and pancreatic cancer: distinct morphology, growth characteristics, expression of epithelial and immunoregulatory antigens.

Two new cell lines from stomach cancers and one from a pancreatic carcinoma are presented. MZ-GC-1 was established from a hepatic metastasis of a well differentiated gastric adenocarcinoma. MZ-GC-2 was derived from ascites induced by a poorly differentiated gastric adenocarcinoma. MZ-PC-1 originated from the pleural effusion of a moderately well differentiated pancreatic ductal adenocarcinoma. MZ-GC-1 cells were adherent and partially polarized, connected tightly via desmosomes. In contrast MZ-GC-2 cells consisted of slightly adherent or floating subpopulations and displayed no desmosomes. MZ-PC-1 cells were adherent and showed polarized growth, connected by apical junctional complexes. Cel…

Gitelman syndrome DD thiazide diuretics abuse

Abstract Introduction. Gitelman syndrome (GS) is a rare inherited disorder. Mutations in SLC12A3 gene that encode tubular Na+Cl-cotransporter (NCCT) cause hypokalemic metabolic alkalosis, salt loss, hypomagnesaemia and hypocalciuria. The symptoms include weakness, vertigo, hypotension, tetany, paresthesia and nausea. Diagnostic criteria are a normal urine concentrating ability, normal glomerular filtration rate (GFR), hypomagnesaemia (&lt;0,65mmol/l), hypokalemia (&lt;3,6mmol/l) and hypocalciuria (&lt;0,1mmol/mmol creatinine). Previously, the diagnosis was made by exclusion. Today, genetic analysis can ensure diagnosis. Thiazide diuretics (TD) abuse with similar abnormalities can make the d…

Hepatozelluläre Karzinommarker bei einem primären Gallenblasenkarzinom

Eine Adenokarzinomzellinie, Mz-ChA-2, konnte kurzlich aus einem primaren Gallenblasenkarzinom, das lokal in die Leber eingewachsen war, in Gewebekultur etabliert werden (1). Zyto- und Histomorphologie dieser Tumorzellinie in vitro und nach Transplantation auf Nacktmause entsprechen dem Primartumor der 65jahrigen Patientin. Im Serum wurden leicht erhohte AFP-Werte bestimmt, wahrend die CEA-Werte normal waren. Im Gewebekulturuberstand dieser neuen Tumorzellinie MZ-ChA-2 konnte AFP nachgewiesen werden. Auf klonaler Ebene zeigten sich erhebliche quantitative Schwankungen in der AFP-Synthese. CEA konnte im Gewebekulturuberstand nicht nachgewiesen werden, dem Serumbefund bei der Patientin entspre…

Akutes Lungenversagen bei Malaria tropica in der Schwangerschaft: Erfolgreiche Behandlung durch extrakorporale CO2-Elimination

Eine 32jahrige Schwangere (26. Schwangerschaftswoche) erkrankte am 6. Tag nach der Ruckkehr von einem Indonesienaufenthalt mit Fieber bis 42°C, hamolytischer Anamie (Hamoglobin 7,6 g/dl) und Thrombozytopenie (7000/µl). Es wurde eine Malaria diagnostiziert; eine Prophylaxe hatte sie nicht durchgefuhrt. Unter antiparasitarer Chemotherapie mit Chloroquin, Chinin und Pyrimethamin kam es zur Elimination der Parasiten (Makrogametozyten von Plasmodium falciparum) aus dem peripheren Blut. Im weiteren Verlauf entwickelte sich jedoch ein progredientes Lungenversagen und eine therapierefraktare Pneumonie, die zu einem »adult respiratory distress syndrome« (ARDS; Morel-Stadium 4) fuhrten. Bei drohendem…

Concomitant history of cancer in acute pulmonary embolism is connected with poorer outcome

Abstract Purpose: Cancer increases the risk of venous thromboembolism (VTE) substantially. VTE is connected with poorer outcome in cancer patients. The aim of our study was to investigate the impact of cancer on the severity and short-term outcome of pulmonary embolism (PE). Methods: We retrospectively analyzed the data of 182 patients with confirmed PE. PE patients were subdivided in the group with concomitant active cancer disease or history of cancer or in the group without cancer. Groups were compared with Wilcoxon–Mann–Whitney Test. Logistic regression models were calculated to investigate the association between cancer and several parameters such as age and PE severity status as well …

Immunoreactivity of monoclonal anti-melanoma antibodies in relation to the amount of radioactive iodine substituted to the antibody molecule.

The damage to monoclonal anti-melanoma antibodies caused by iodination was investigated by comparing the results obtained using the chloramine-T method and the 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenyl-glycoluril (IODOGEN) method at different levels of iodine substitution to the molecule. The level of substitution at which losses in immunoreactivity occurred was evaluated in each monoclonal antibody (MAb) studied. This phenomenon was not dependent on the method of substitution, provided that mild conditions of reaction were used. Lineweaver-Burk plots and--in cases of alterations in binding affinity--Scatchard plots were found to provide an adequate description of the binding behaviour …

Persistent expression of hepatitis C virus genome in primary tumor and adrenal metastasis of a hepatocellular carcinoma developed in a non-cirrhotic liver

To the Editor: There is increasing evidence that chronic infection with hepatitis C virus (HCV) is a risk factor for hepatocellular carcinoma (HCC) in patients seronegative for hepatitis B virus (HBV) surface antigen (HBsAg). In western countries, HCCs occur in anti-HCV positive patients mostly in association with cirrhosis, which can be considered as a precancerous condition (1). However, there are rare cases of HCC that were found in anti-HCV positive patients without pre-existing liver cirrhosis (2). We report here the detection of HCV RNA in a primary HCC derived from an HCV-infected patient with a non-cirrhotic liver and its persistent expression in an adrenal metastasis that developed…

Biliary adenocarcinoma

Three human cell lines from adenocarcinomas of the extrahepatic biliary tract were established in permanent tissue culture. Mz-ChA-1 and Mz-ChA-2 were cultured from mechanically dissociated gallbladder adenocarcinoma metastases and SK-ChA-1 was grown from malignant ascites of a patient with primary adenocarcinoma of the extrahepatic biliary tree. Cell doubling times in tissue culture are 3-4 days for Mz-ChA-1 and approximately 2 days for Mz-ChA-2 and SK-ChA-1. All three tumour cell lines were successfully transplanted to nude mice, inducing progressive tumour growth. Histologically, nude mouse tumours resembled the original adenocarcinomas. In vitro formation of gland-like structures were r…

Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression o…

Renal function as a cofactor for risk stratification and short-term outcome in acute pulmonary embolism

Abstract Background In addition to right ventricular dysfunction (RVD) and myocardial injury, impaired renal function is connected with poorer prognosis in pulmonary embolism (PE). We aimed to investigate renal function as a cofactor for risk stratification in PE. Methods Data from 182 patients with PE, treated between May 2006 and June 2011, were analysed retrospectively. PE patients with elevated creatinine were compared with those with normal values. Logistic regression models were calculated to investigate associations between creatinine and myocardial necrosis, RVD and in-hospital death. Prognostic performance of creatinine for prediction of myocardial necrosis and RVD were computed. R…

Syncope and collapse in acute pulmonary embolism.

Abstract Background Syncope and collapse (= presyncope) are 2 symptoms of pulmonary embolism (PE), which are suspected of being connected with poorer outcome, regardless of haemodynamic instability. However, pathomechanisms are not completely understood. We aimed to investigate these pathomechanisms in regard to blood pressure and heart rate of syncope/collapse in PE. Methods We performed a retrospective study of consecutive PE patients, who were treated in the Internal Medicine Department. Patients with and without syncope/collapse were compared. Regression models for associations between syncope/collapse and blood pressure, heart rate and shock index (SI) were computed. Moreover we calcul…

Distribution of Ha-ras alleles in patients with colorectal cancer and Crohn's disease.

The allele distribution of the Ha-ras gene on chromosome 11p was analysed by the restriction fragment length polymorphism of the enzymes Mspl/Hpall in 238 individuals. The investigation covered 116 patients with colorectal carcinoma and 122 patients with Crohn's disease, representing two patient populations with the same ethnic origin, one with a malignant and the other a benign disease of the same organ system. A total of 17 different alleles were detected belonging to the common, intermediate, and rare classes according to the original nomenclature of Ha-ras alleles. Patients with Crohn's disease showed no difference in the distribution of Ha-ras alleles when compared with expected freque…

The 9-O-acetylated disialosyl carbohydrate sequence of CDw60 is a marker on activated human B lymphocytes

Gangliosides with a terminal 9-O-acetylated disialosyl group (CDw60 structures) show a restricted surface expression on human leukocytes. Hithereto, they have only been detected on subpopulations of human T lymphocytes. Using the defined CDw60 antibody UM4D4 and two new antibodies with preferential CDw60 activities, F6 and Z17, we demonstrate for the first time that CDw60 is an activation marker on human B lymphocytes. In vitro phorbol ester-stimulated human peripheral blood B lymphocytes as well as in vivo activated tonsillar B lymphocytes became CDw60 positive. CDw60 expression of these cells exceeds that of resting and activated T-lymphocytes.

Modulation of melanoma-associated antigens by monoclonal antibodies as visualized by radioimmunoelectron microscopy and radioantibody binding assay

There is a wealth of information about monoclonal antibody (MAb) specificity and function on fixed tissues, yet little is known about formation and release of antigen-antibody complexes and their functional behavior in vivo. We analyzed the pathway of radiolabeled MAbs directed against melanoma-associated antigens by radioimmunoelectron microscopy (RIEM) on metabolically active cells of the melanoma cell lines SK-MEL-28, MeWo and Colo 38 at different time intervals. In parallel, binding and release of MAbs were investigated by the radioantibody binding assay (RBA). Both procedures gave essentially concordant results. Preferentially stable binding of immune complexes (ICs) to the cell surfac…

Synthetische Inhibitoren der Zelladhäsion: ein Glycopeptid aus dem E-Selektin-Liganden 1 (ESL-1) mit Arabino-Sialyl-Lewisx-Struktur

Autosomal dominant polycystic kidney disease—in vitro culture of cyst-lining epithelial cells

The major form of autosomal dominant polycystic kidney disease (ADPKD) in humans is linked to the PKD1 gene on chromosome 16p. The identity of the gene and the underlying pathogenetic mechanisms are not yet defined. Cyst-lining epithelial cells derived from a polycystic kidney were successfully grown in culture and designated MZ-PKD-1 cells. By linkage analysis, the related pedigree of the nephrectomized patient could be linked to the PKD1 gene on chromosome 16p. Thus, these cells exhibit the genotype of a mutated PKD1 gene and represent an in vitro culture model for ADPKD involving chromosome 16p. The antigenic phenotype was characterized immunohistologically by epithelial differentiation …

ChemInform Abstract: Synthetic Inhibitors of Cell Adhesion: A Glycopeptide from E-Selectin Ligand 1 (ESL-1) with the Arabino Sialyl Lewisx Structure.

Elevated systolic pulmonary artery pressure for prediction of myocardial necrosis and right ventricular dysfunction in acute pulmonary embolism

Kontext: Echokardiografie je v soucasnosti hlavni metodou pro vysetřeni dysfunkce prave komory (right ventricular dysfunction, RVD) u akutni plicni embolie (PE). Dysfunkce prave komory je sice spojena s nepřiznivou prognozou, dosud vsak nebyla přijata žadna obecně uznavana definice. Systolický tlak v plicnici (systolic pulmonary artery pressure, sPAP) větsinou neni soucasti kriterii RVD. Cilem nasi studie bylo zhodnotit možnost použiti sPAP v predikci nekrozy myokardu a RVD u akutni PE.Metody: Retrospektivně byly analyzovany udaje 182 pacientů s akutni PE. Pacienti s PE a hodnotami sPAP ≤ 30 mm Hg byli srovnavani s pacienty s PE a hodnotami sPAP > 30 mm Hg. Vztahy mezi sPAP na jedne straně …

Zur Entwicklung von Antitumor-Impfstoffen: ein synthetisches Konjugat aus tumorassoziiertem MUC1-Glycopeptidantigen und dem Tetanustoxin-Epitop

Ionizing radiation-induced E-selectin gene expression and tumor cell adhesion is inhibited by lovastatin and all-trans retinoic acid

E-selectin mediated tumor cell adhesion plays an important role in metastasis. Here we show that ionizing radiation (IR) induces E-selectin gene and protein expression in human endothelial cells at therapeutically relevant dose level. E-selectin expression is accompanied by an increase in the adhesion of human colon carcinoma cells to primary human umbilical vein endothelial cells (HUVEC). The HMG-CoA reductase inhibitor lovastatin impairs IR-stimulated E-selectin expression as analyzed at the level of the protein, mRNA and promoter. Inactivation of Rho GTPases either by use of Clostridium difficile toxin A or by co-expression of dominant-negative Rho blocked IR-induced E-selectin gene indu…

Immunorecognition of different ganglioside epitopes on human normal and melanoma tissues.

There is increasing evidence that cell-surface gangliosides play a role in tumor growth, progression and metastases. In order to determine the frequency of ganglioside GD3 in patients with metastatic malignant melanoma for further therapeutic trials, GD3 ganglioside expression was determined in 119 tissue samples. Of these melanomas, 93% (111/119) were R-24-positive, which indicates the value of this diagnostic marker for melanoma. To study the structural epitopes of gangliosides, 10 ganglioside antibodies with defined specificities and affinities were tested on over 100 fresh-frozen tissue specimens of human normal and melanoma tissues. All the antibodies tested recognize the ganglioside G…

Antibodies to cell surface ganglioside GD3 perturb inductive epithelial-mesenchymal interactions

Abstract Most epithelial sheets emerge during embryogenesis by a branching and growth of the epithelium. The surrounding mesenchyme is crucial for this process. We report that branching morphogenesis and the formation of a new epithelium from the mesenchyme in the embryonic kidney can be blocked by a monoclonal antibody reacting with a surface glycolipid, disialoganglioside G D3 . In contrast, a more than 10-fold excess of antibodies to adhesive glycoproteins (N-CAM, L -CAM, fibronectin) fails to inhibit morphogenesis. Although the anti-G D3 antibody affected epithelial development, the disialoganglioside G D3 was expressed not in the epithelium, but in the mesenchyme surrounding the develo…

ChemInform Abstract: Glycoconjugates as Tumor-Associated Antigens and Ligands in Regulatory Processes

Expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in colonic epithelial cells.

The expression of intercellular adhesion molecule-1 (ICAM-1, CD54) was examined in 16 surgically removed colonic tumours and two colonic carcinoma cell lines. Immunohistochemistry showed a varying percentage of ICAM-1 positive colonic carcinoma cells in 9/16 tissue specimens, while normal colonic tissue (apart from a slight reactivity of endothelial cells) was not stained. The presence of the ICAM-1 molecule on the cell surface and the expression of ICAM-1 mRNA were investigated for two colonic carcinoma cell lines. It was possible to enhance the expression of ICAM-1 considerably by incubating the cells in the presence of inflammatory cytokines in HT-29 and CaCo-2 cells. The responsiveness …

Monoklonale Antikörper und Konjugate in der Krebsdiagnostik und Therapie

Bereits um die Jahrhundertwende betonte Paul Ehrlich die mogliche Bedeutung von Antikorpern als Mittel gegen Krebs. Ihre zytotoxische Aktivitat und ihre Spezifitat machen sie theoretisch zu idealen Werkzeugen, um abnorme Zellen zu erkennen und zu zerstoren und die umliegenden normalen Zellen zu verschonen. Leider waren bis vor kurzem die technischen Voraussetzungen nicht gegeben, spezifische Antikorper mit zytotoxischer Aktivitat in groser Menge herzustellen. Durch die von Kohler u. Milstein im Jahre 1975 neu etablierte Technik, monoklonale Antikorper zu erzeugen [9], anderte sich die Situation schlagartig. Diese Methodik erlaubt die Immortalisierung eines einzigen B-Lymphozyten, der schlie…