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A Quentmeier

Publications and source records attributed to A Quentmeier.

36 records · Page 2Linked to original sources
PubMed1994

Differential expression of beta 1 integrins in nonneoplastic smooth and striated muscle cells and in tumors derived from these cells.

Integrins are a superfamily of transmembrane alpha beta heterodimers that play an important role in cell-matrix and cell-cell interactions by acting as receptors for extracellular matrix proteins and for cell adhesion molecules. Using monoclonal antibodies against beta 1, alpha 1 to alpha 6, and alpha v subunits, the in situ distribution pattern of beta 1 integrins was examined immunohistochemically in nonneoplastic smooth and striated muscle cells and in their tumors. Nonneoplastic smooth muscle cells were beta 1+, alpha 1+, alpha 3+, alpha v+ and, in diverse localizations, also alpha 5+ or even alpha 6+. The expression of the beta 1 chain was conserved in all leiomyomas and leiomyosarcomas. The distribution pattern of the alpha subunits by contrast underwent several changes during malignant transformation of smooth muscle cells. These alterations consisted in a neoexpression of alpha 2, alpha 4, and alpha 6 as well as in an abnormal abrogation of alpha 1 and alpha 3 in some leiomyosarcomas. Except for the absence of alpha 5 in the majority of epithelioid leiomyosarcomas, expression of the alpha 5 and alpha v subunits was mainly conserved. In addition, tumors with epithelioid differentiation differed from typical cases by the absence of alpha 1 and the simultaneous presence of alpha 4. Adult striated muscle cells were beta 1+ but alpha 1- to alpha 6- and alpha v-, whereas fetal striated muscle cells were not only beta 1+ but also alpha 3+/-, alpha 4+/-, alpha 5+ and alpha 6+. In all rhabdomyosarcomas the expression of beta 1 was retained. Furthermore, the majority of cases showed the expression of one or more alpha subunits most of which, ie, alpha 4, alpha 5, and alpha 6, were also found in fetal striated muscle cells. In conclusion, beta 1 integrins exhibited a differential expression pattern along the two lines of myogenic differentiation. This integrin profile underwent characteristic changes during malignant transformation. Nevertheless, the compiled distribution patterns of the alpha 1, alpha 3, and alpha v subunits allowed in most instances the discrimination between tumors of smooth (alpha 1+/alpha 3+/alpha v+) and striated muscle (alpha 1-/alpha 3-/alpha v-) differentiation.

Cell Transformation, Neoplastic↗
PubMed1994

Differential expression of beta 1, beta 3, and beta 4 integrin subunits in nonneoplastic neural cells of the peripheral and autonomic nervous system and in tumors derived from these cells.

BACKGROUND: Extracellular matrix proteins and their receptors take part in physiologic neural development and organization and also in abnormal neoplastic growth and spread. There is increasing evidence for the implication of integrins in these processes. EXPERIMENTAL DESIGN: Human tissues containing nonneoplastic neural cells of the peripheral and autonomic nervous system and a comprehensive series of neural tumors were examined for the in situ expression of beta 1, beta 3, and beta 4 integrins. Serial frozen sections of each tissue sample were immunostained using an indirect streptavidin/biotin-peroxidase method and monoclonal antibodies against beta 1, alpha 1 to alpha 6, beta 3, alpha v, and beta 4 subunits. RESULTS: Both small- and large-diameter nerve fibers of normal peripheral nerve trunks were consistently beta 1+, alpha 6+, and beta 4+ in the absence of alpha 3, alpha 4, alpha 5, and beta 3. Small-diameter nerve fibers further expressed alpha 1, alpha 2, and alpha v. Meissner's corpuscles and inner cores of Pacinian corpuscles shared the integrin repertoire of small-diameter nerve fibers with additional expression of alpha 3; outer cores of Pacinian corpuscles were beta 1+, alpha 3+, alpha 6+, and beta 4+. Regenerating nerve fibers paralleled the integrin profile of normal peripheral nerves. By contrast, malignant schwannomas showed considerable changes in integrin expression. These alterations consisted mainly in a neoexpression of alpha 3, alpha 4, and alpha 5 and in an abnormal loss of alpha 6 and beta 4. Expression of alpha 1, alpha 2, and alpha v was variable; absence of beta 3 was generally conserved. In ganglion cells, integrin expression was restricted to beta 1 and alpha 3 subunits, and chromaffine cells of the adrenal medulla even lacked any detectable beta 1, beta 3, and beta 4 integrin subunits. (Ganglio)-neuroblastomas, however, were beta 1+, alpha 1+, and alpha 3+, whereas primitive peripheral neuroectodermal tumors were beta 1+ and alpha 5+. CONCLUSIONS: Nonneoplastic human neural cells exhibit a complex and, at the same time, differential pattern of beta 1, beta 3, and beta 4 integrin subunit expression. Malignant transformation leads to considerable changes in this integrin profile. The observation of neoplasia-associated abnormalities underlines the important role of integrins in the orderly development and maintenance of human neural tissue. Some aspects of the emerging integrin subunit patterns are useful for the differential diagnosis of neural soft-tissue tumors.

Adrenal Glands↗
PubMed1993

Insulin-mimetic actions of phorbol ester in cultured adult rat hepatocytes. Lack of phorbol-ester-elicited inhibition of the insulin signal.

The actions of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on glucose metabolism, amino acid transport and enzyme inductions were studied in primary cultures of adult-rat hepatocytes and compared with the effects of insulin. PMA and insulin stimulated glycolysis 5- and 7-fold respectively. The half-maximal effective dose of PMA was 60 nM. Stimulation of glycolysis was accompanied by an insulin- or PMA-dependent and okadaic acid-sensitive activation of 6-phosphofructo-2-kinase and pyruvate kinase, as well as by an increase in fructose 2,6-bisphosphate. Glucose production from glycogen was decreased to 50% by PMA and to 15% by insulin, whereas glycogen synthesis was stimulated 2- and 7-fold respectively. PMA also increased aminoisobutyrate uptake, induced ornithine decarboxylase and counteracted the glucagon-dependent induction of phosphoenolpyruvate carboxykinase. PMA strongly antagonized the hormonal activation of glycogen synthesis, but all other insulin actions assayed were not decreased by the phorbol ester. Whereas additive effects of PMA and insulin were not detected, PMA and a simultaneous increase in the glucose concentration had additive effects on glycolysis and glycogen metabolism. Cell exposure to insulin resulted in receptor autophosphorylation and a more than 10-fold activation of the receptor tyrosine kinase. PMA did not alter these effects, and also had no effect on the receptor phosphorylation status in the absence of insulin. Long-term (15 h) pretreatment of the cells with PMA abolished all PMA effects, but not the insulin effects. It is concluded that PMA does not generally antagonize the action of insulin in differentiated adult hepatocytes, and that insulin and PMA may use related signal-transduction pathways.

Aminoisobutyric Acids↗
PubMed1993

Attenuation of insulin actions in primary rat hepatocyte cultures by phenylarsine oxide.

Phenylarsine oxide (PAO), a trivalent arsenical which complexes vicinal dithiols, prevented the action of insulin in primary cultured adult rat hepatocytes. Simultaneous short-term treatment of 48-h old cells with insulin and 2 microM PAO resulted in complete attenuation of the insulin-dependent increase in the level of fructose 2,6-bisphosphate and the activation of phosphofructokinase 2, pyruvate kinase, glucokinase flux and glycolysis. Basal rates of glucose transport and glycolysis were not affected. PAO also abolished stimulation of glycogen synthesis and amino-acid transport and the decrease of glycogenolysis evoked by insulin. The 20-fold activation of the insulin receptor tyrosine kinase by insulin was, however, not reduced by PAO. The data suggest that in differentiated hepatocytes insulin signal transduction involves vicinal sulhydryls located at a post-receptor step.

Amino Acids↗
PubMed1993

[Methodology, technical prerequisites and postoperative morbidity of intraoperative radiotherapy (IORT) of soft tissue sarcomas. Heidelberg Krankengut 6/91-9/92].

Since June 1991 the IORT facility has operated a dedicated linear accelerator, which was installed within the central operating theater of the Department of Surgery. As of 9/92 a total of 28 patients suffering from peripheral (n = 20) or centrally (n = 8) located soft tissue sarcomas had been were treated. Thirteen patients revealed a primary and 15 patients a recurrent tumor. Tumor resection with negative margins was performed in 20 patients, positive margins remained in 5 patients, and gross macroscopic residual disease in 3 patients. Combined intraoperative and external beam radiotherapy was applied in 22 patients, using IORT doses of 10-20 Gy and an external beam dose of 26-50 Gy. Three patients were irradiated intraoperatively twice with a time interval of 24 h. After a median follow-up of 9.9 months, 20 patients are disease free. Two patients died 4 and 5 months after the end of therapy with rapidly progressive distant metastases. An infield failure within the external beam target volume was seen in 1 patient and local failure at the field margin of the external field in 3 patients. So far, there have been no IORT infield failures. Follow-up is performed with magnetic resonance imaging. In 3 patients a second operation was necessary because of a severe wound infection, including one patient suffering from osteomyelitis of a neighboring bone. Mild sensory neuropathy occurred in 1 patient 7 months after treatment. Overall only mild and reversible postoperative and posttherapeutic complications were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Re-operation for recurrent colorectal cancer: the importance of early diagnosis for resectability and survival.

Between 1978 and 1986, 179 patients with recurrent colorectal cancer were treated and 137 patients were operated a second time.82.1% of the patients showed elevated CEA levels (greater than or equal to 5 ng/ml) at the time of diagnosis. In 58.1% of the patients the CEA increase preceded the recognition of recurrence, and in 13.4% the diagnosis could be confirmed only by a second-look operation. In 46.7% of the re-operated patients a potentially curative resection of the locally recurrent or metastatic disease could be performed. The resectability was significantly lower in patients with symptomatic recurrent disease (34.5%) as compared to asymptomatic patients with CEA-directed positive imaging (52.7%) and the second-look patients (62.5%) respectively. A significant improvement in survival could be achieved especially in the second-look operated patients.

Adult↗
PubMed1989

Stimulation by insulin of glycolysis in cultured hepatocytes is attenuated by extracellular ATP and puromycin through purine-dependent inhibition of phosphofructokinase 2 activation.

Activation of glycolysis by insulin in cultured rat hepatocytes is preceded by an activation of phosphofructokinase 2 (PFK 2) and subsequent rise of the fructose 2,6-bisphosphate [Fru(2,6)P2] level. Extracellular addition of ATP or puromycin prevented the hormonal effect on glycolysis. The mechanism through which the purines abolished glycolytic stimulation was investigated. 1. 50 microM ATP completely prevented the 3-5-fold insulin-dependent increase of glycolysis, irrespective of whether the cells initially possessed a low or a high Fru(2,6)P2 content. 50 microM puromycin prevented the stimulation of glycolysis by insulin only in cells whose initial Fru(2,6)P2 levels were low and had to be increased by insulin prior to the increase in glycolysis. It did not antagonize the action of insulin cells with initial high Fru(2,6)P2 content. 2. ATP exerted effects on its own; it decreased initially high Fru(2,6)P2 levels by 95% within 10 min and decreased the basal glycolytic rate by 60%. Half-maximal effects on the Fru(2,6)P2 level were obtained with about 25 microM ATP or 15 microM adenosine 5'[beta, gamma-methylene]triphosphate. ADP and adenosine-5-[gamma-thio]triphosphate were as effective as ATP, whereas 100 microM adenosine 5'[alpha, beta-methylene]triphosphate elicited no effect. Puromycin neither decreased high Fru(2,6)P2 levels nor inhibited basal glycolysis. 3. Extracellular ATP (100 microM) led to inhibition of the active form of PFK 2. Intracellular levels of Glc6P, citrate, ATP, ADP and AMP were increased by extracellular ATP, the phosphoenolpyruvate content was decreased, Fru6P and glycerol 3-phosphate levels stayed constant. Puromycin did not inhibit PFK 2. 4. Both puromycin and ATP prevented the insulin-dependent rise of the Fru(2,6)P2 level, they abolished the activation of PFK 2 by the hormone. Puromycin did not block the accumulation of Fru(2,6)P2 provoked by glucose addition; ATP also antagonized the glucose-dependent increase. 5. 100 microM ATP elevated the cAMP-dependent protein kinase activity ratio from 0.1 to 0.38 and increased the level of inositol trisphosphate by 16-fold within 5 min, whereas puromycin was without effect on either level. It is concluded that the two purines block the insulin effect on glycolysis by preventing the hormone increasing the Fru(2,6)P2 level. The mode of action, however, seems to be different: ATP antagonizes insulin action in that it leads to increased inhibition of PFK 2 whereas puromycin prevents the activation of PFK 2 by insulin.

Adenosine Triphosphate↗
PubMed1989

Assessment of serial carcinoembryonic antigen: determinations to monitor the therapeutic progress and prognosis of metastatic liver disease treated by regional chemotherapy.

It is difficult, time-consuming, and expensive to evaluate the therapeutic efficacy of regional chemotherapy of metastatic liver disease by means of imaging procedures. Therefore it was the aim of this study to find out whether serial carcinoembryonic antigen (CEA) determinations yield reliable data on the therapeutic progress and the individual prognosis of these patients. Since there exists no generally accepted modality to assess CEA curves of patients receiving chemotherapy, we developed our own criterion and tested it in a group of 35 patients. For each patient an individual reference level (CEA-means) was fixed which was obtained as the arithmetical mean of serial CEA values taken during the first three courses of chemotherapy (reference time). On the basis of CEA-means the marker curves of the 35 patients could be divided into two groups. After the reference time the CEA values of group 1 (12 patients) never decreased below CEA-means. Survival of these patients was significantly (P = 0.00001) shorter than that of the 23 patients (group 2) who showed a decrease in their CEA curves below CEA-means after the reference time. Beyond this it could be observed that the improvement in survival was significantly greater in those patients who showed a CEA decrease below CEA-means for a prolonged period (3 months). This difference in prognosis is not an artefact due to different pretherapeutic conditions but is a sign of different responses to therapy. The decrease in CEA values below the individual reference level (CEA-means) is a certain sign of the efficacy of the chosen chemotherapy. A continuous rise of the CEA curve above CEA-means signifies an ineffective intrahepatic chemotherapy or extrahepatic tumor manifestation. In this case an intensive diagnostic workup of the patient and possibly a modification of the therapy are indicated.

Adult↗
PubMed1989

Immunoradiometric assay of carcinoembryonic antigen with use of avidin-biotin labeling.

In evaluating an enzyme-linked immunoassay of carcinoembryonic antigen (CEA) we found that the IgG fraction of polyclonal anti-CEA antibodies (DAKO) bound very well to the walls of polypropylene test tubes. We therefore developed an immunoradiometric CEA assay based on this binding of polyclonal anti-CEA antibody. We biotinylated a commercially available monoclonal antibody (Hybritech) and bound this to the CEA-anti-CEA bound to the tube wall. For detection we used 125I-labeled streptavidin. In comparison with several immunoassays for CEA this system offered several advantages such as greater linearity of the standard curve (from 0 to 74 micrograms/L), a steeper dose-response curve, and smaller coefficients of variation in the clinically useful range. This assay system may be used for other large molecules, so that only one tracer, the 125I-labeled streptavidin, has to be labeled; thus the technique seems suited for several different assays.

Antibodies, Monoclonal↗
PubMed1987

Carcinoembryonic antigen, CA 19-9, and CA 125 in normal and carcinomatous human colorectal tissue.

In 115 primary colorectal carcinomas and 64 normal colorectal mucosa specimens the concentrations of carcinoembryonic antigen (CEA), CA 19-9, and CA 125 were measured. The determinations were performed in cytosols by use of radioimmunometric and enzymeimmunometric assays and related to the wet tissue weight. In the cancer tissue the CEA levels ranged from 5.5 to 1990 micrograms/g tissue and were significantly higher (P less than 0.0001) than those found in the normal mucosa (1.2-58.6 micrograms/g). The CA 19-9 content in carcinoma specimens (120-72660 U/g) was also significantly higher (P = 0.011) than in the normal mucosa (37-5800 U/g). In contrast, no significant difference of the CA 125 concentrations between the normal and the cancer tissue was found. The relative operating characteristic (ROC) curves for the three markers corroborate CEA as the marker superior to CA 19-9. On the other hand is shown that CA 125 is completely unable to discriminate between normal and cancer tissues. A decreasing CEA tissue concentration and an increasing dedifferentiation of colorectal cancers were significantly (P = 0.018) related with each other. Higher tumor stages implied significantly higher tissue marker values of CA 19-9 (P = 0.027) and CA 125 (P = 0.0008). The findings correspond quite well with serum examinations of the three markers which have been reported earlier.

Antigens, Neoplasm↗
PubMed1987

Reevaluation of citrate lyase from Escherichia coli.

The subunit structure of citrate lyase from Escherichia coli was shown to be similar to that of all other lyases investigated so far. The three different subunits with molecular masses of 55.5 kDa, (large subunit) 35 kDa (medium-sized subunit) and 12.5 kDa (small subunit, acyl carrier protein) occurred in a ratio of 1:1:1. Using high-pressure liquid chromatography, it was possible to demonstrate that the reported large acyl carrier protein, with a molecular mass of 85 kDa was a contaminating protein associated with citrate lyase multienzyme complex; it could be removed by anion-exchange chromatography with Q-Sepharose. The typical two configurations of citrate lyase, the 'star' form and the 'ring' form with a diameter of 14.3 nm and 15.4 nm, respectively, could be detected by electron microscopy.

Bacterial Proteins↗
PubMed1987

Evaluation of Ca 12-5 as a tumor marker for gastric and colo-rectal cancer in comparison to CEA and Ca 19-9.

We performed simultaneous measurements of CA 12-5, CEA and Ca 19-9 in the preoperative sera of 87 patients with gastric cancer, 177 patients with colo-rectal cancer and 55 patients with benign diseases. 5.6% of the control patients, 13.8% of the gastric cancer patients and 9.6% of the colo-rectal cancer patients showed Ca 12-5 values of 27.0 U/ml and more. In contrast, the sensitivity of the tumor markers CEA (greater than or equal to 5.0 ng/ml in 17.1% of the gastric cancer and 36.2% of the colo-rectal cancer patients examined) and Ca 19-9 (greater than or equal to 25.0 U/ml in 16.1% of the gastric cancer and 19.8% of the colo-rectal cancer patients) was distinctly higher. The simultaneous determination of three markers on the one hand increased the rate of 'marker-positive' patients (up to 34.5% in gastric cancer and 45.2% in colo-rectal cancer) but on the other hand diminished the specificity (from 96.4% to 89.1%) of the examination.

Antigens, Neoplasm↗
PubMed1986

[Key role of the CEA test in the diagnosis and surgical therapy of recurrent colorectal cancer].

Between 1978 and 1984, 87 patients with recurrent colorectal cancer have been operated upon. In 10 of 35 patients with locoregional recurrence and 24 of 52 with distant metastases therapy was potentially curative. Of 87 patients 73 had elevated CEA levels (greater than or equal to 5 ng/ml) at the time of diagnosis. In 65 of 73 patients the CEA increase preceded the recognition of recurrence and in 14 patients the diagnosis could be confirmed only by a second-look operation. Patients with metastases (91.3%) showed CEA elevation more often than those with locoregional recurrence (71.4%). Patients with operable disease had significantly (p less than 0.05) lower CEA values (median 19.7 ng/ml) than those with inoperable recurrent carcinomas (median 36.9 ng/ml).

Adult↗
PubMed1985

Characterization of citrate lyase from Clostridium sporosphaeroides.

Cells of Clostridium sporosphaeroides which were grown on citrate contained citrate lyase and citrate lyase acetylating enzyme, but no detectable citrate synthase and citrate lyase deacetylase activities. Citrate lyase from C. sporosphaeroides was purified to homogeneity as judged by polyacrylamide gel electrophoresis and high performance liquid chromatography. In contrast to the enzyme from Clostridium sphenoides, the addition of L-glutamate was not necessary for activity and stabilization of the enzyme. The purified enzyme had a specific activity of 34 U/mg protein and was comparable to other citrate lyases with respect to its molecular weight and subunit composition. Electron microscopic investigations showed that similar to the lyase from C. sphenoides and in contrast to all other citrate lyases examined so far, the majority of the enzyme molecules was present in "star" form.

Catalysis↗
PubMed1981

[Anterior resection and abdomino-perineal extirpation in patients with rectal cancer: a retrospective analysis (author's transl)].

Eighty-seven patients with an abdomino-perineal extirpation of the rectum and 75 patients with an anterior resection of the rectum could be analysed retrospectively. The mean observation period was 36 months for anterior resection and 38 months for abdomino-perineal extirpation. The rate of recurrences, mortality, and postoperative complications of each surgical method was correlated to tumor-localization, -staging, and -grading. The poor prognosis of patients with abdomino-perineal extirpation was mainly due to relatively more cases in advanced tumor stage. In rectal cancer above 7 cm anterior resection should be performed.

Female↗