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C Frenzel

Publications and source records attributed to C Frenzel.

9 recordsLinked to original sources

Subchronic alpha- and beta-adrenergic regulation of cardiac gap junction protein expression.

Gap junction channels are essential for intercellular electrical communication in the heart. The most important cardiac gap junction proteins are connexin43 (predominantly) (Cx43), connexin40 (Cx40), and in early developmental stages connexin45. Since catecholamines play an important role in cardiac (patho)physiology, we wanted to elucidate whether catecholamines may affect expression of Cx43 and Cx40. Cultured neonatal rat cardiomyocytes were exposed for 24 h to increasing concentrations of noradrenaline (1-10000 nM) (physiological agonist at alpha and beta-adrenoceptors), resulting in significantly increased Cx43-expression, while Cx40 was unaffected. In further experiments cells were incubated with either phenylephrine (alpha-adrenergic agonist) or isoproterenol (beta-adrenergic agonist) (0.1-1000 nM) for 24 h. Both catecholamines lead to a concentration-dependent increase in Cx43 protein and mRNA expression (EC50: 10-20 nM). Inhibition experiments showed that the phenylephrine effect was transduced via PKC, while the isoproterenol effect was mediated by PKA. Dual whole-cell voltage clamp demonstrated that increased Cx43-expression was accompanied by significant increases in gap junction current. In additional in vivo experiments, adult rats were subjected to 24-h infusion of isoproterenol or phenylephrine showing again significant increase in Cx43 but not Cx40. Adrenergic stimulation of cardiomyocytes can enhance Cx43 expression thereby increasing cellular coupling, indicating a possible role for catecholamines in the regulation of cardiac gap junction expression in cardiac disease.

Adrenergic alpha-Agonists↗

Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer.

Preparations of stress protein gp96 from tumor cells are active as tumor vaccines by eliciting immune responses against mixtures of individual tumor peptide antigens which are complexed to gp96. Due to the individual antigenicity of tumors, a vaccine consisting of tumor-derived gp96 has to be prepared individually for each patient from autologous tumor tissue. So far, gp96 expression by human tumors has not been analyzed. Here, we report stable and mostly homogenous expression of gp96 by colorectal cancer, which was enhanced compared to surrounding tumor stroma in 70% to 80% of colorectal cancer specimens. Fewer non-metastatic than metastatic primary cancer specimens showed enhanced gp96 expression. Glucose deprivation increased gp96 protein and RNA expression in the human colon cancer cell line HT-29 in accordance with the role of gp96 as a glucose-regulated stress protein. Additionally, TNF-alpha, interferons and other cytokines induced an increase of gp96 RNA expression in HT-29 cells, suggesting that gp96 expression by colorectal cancer cells can be influenced by different methods of immunomodulation. The stable and homogenous expression of gp96 in 19 primary and metastatic colorectal cancer specimens and the up-regulation of gp96 in colon cancer cells by glucose deprivation point to an essential role of this stress protein in colorectal cancer, presumably by protecting against hostile conditions of the tumor micro-environment like glucose deprivation. In view of these results, loss of gp96 expression by colorectal cancer cells as an immune escape mechanism is unlikely.

Colorectal Neoplasms↗

Single needle venovenous extracorporeal membrane oxygenation using a nonocclusive roller pump for rescue in infants and children.

In 1993, J.Y. Chevalier described a single needle venovenous extracorporeal membrane oxygenation (ECMO) system using a nonocclusive roller pump and alternating clamps for pulmonary support in neonates. We modified this system to use it in older children as well and for additional indications. Introducing a double raceway and 2 different sizes of tubing sets and performing percutaneous approach, we treated 21 children (age 1 day to 49 months) using this system. Indications for treatment were hypoxia and hypoxic induced myocardial dysfunction resulting from pulmonary failure, sepsis, and congenital defects. Of the children treated for neonatal indications, 7/9 survived. For 2 children ECMO was terminated because of intraventricular hemorrhage (IVH). In the pediatric group 5/7 of the children could be weaned from ECMO, and 2 children died after more than 30 days on ECMO. Two of the children who had been almost completely weaned died later because of therapy withdrawal following a brain death diagnosis. In the cardiac group, 3/5 of the children survived. We conclude that the described system is an effective venovenous ECMO system that reduces invasivity and expenditure.

Anticoagulants↗

Respiratory compliance assessed from chest expansion and inflation pressure in ventilated neonates.

We evaluated a bedside method of assessing respiratory compliance from chest expansion, which is judged by eye and classified into three tidal volume categories, and from the inflation pressure read on the respirator's manometer. Compliance assessed by this method was compared with the compliance measured by the injection technique in 45 randomly chosen newborns ventilated for various diseases. The compliance assessed from chest expansion and inflation pressure correlated significantly with the measured compliance (r = 0.86, p < 0.001). Interobserver reliability was acceptable for clinical practice and improved within 6 months of training (weighted kappa = 0.67 versus 0.86). Within ten individuals, changes of compliance assessed by this method were also significantly correlated with those of measured compliance (r = 0.85, p < 0.01). This method, termed "optical compliance," is instantaneously and always available for all patients on ventilators without any additional apparatus and thus might improve the assessment of respiratory function in routine care and emergency situations.

Humans↗

[Hypersynchronous EEG activity and conditioned avoidance reflexes in rats].

The influence of dimethylsulfolane on active avoidance conditioning with simultaneous registration of EEG was investigated. Dimethylsulfolane, which shows some pharmacological properties of pentylenetetrazole causes a decrease of the amount of conditioned reactions. There was no strong correlation between the impairment of learning ability and the number of EEG spindle discharges after dimethylsulfolane.

Animals↗