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R Kopp

Publications and source records attributed to R Kopp.

At least 37 records · Page 2Linked to original sources
PubMed2001

[A patient with nodal tachycardia after general anesthesia during medication with a selective serotonin reuptake inhibitor].

We report on a 62 year old female patient treated with paroxetine, a selective serotonin reuptake inhibitor, because of an anxiety neurosis undergoing a vaginal hysterectomy in general anesthesia. Apart from a dietary treated diabetes mellitus there were no other diseases. There were no complications during the operation. At the end of the anesthesia an A-V nodal tachycardia appeared which spontaneously changed to a sinus rhythm ten hours after the end of the operation. No clinical or laboratory findings indicated a cardiac ischemia and an additional Holter ECG-Recording showed no further cardiac arrhythmias. No other complications occurred afterwards and the patient was discharged after two weeks. This case report demonstrates clearly that despite a reduced rate of cardiovascular complications compared to other types of antidepressants selective serotonin reuptake inhibitors can lead to perioperative cardiac arrhythmias.

Anesthesia, General↗
PubMed2000

[Virtual coloscopy with multi-slice computerized tomography. Preliminary results].

SUBJECT: Using multi-slice computed tomography (MSCT) large body areas can scanned with high spatial resolution. In this study, MSCT was employed for virtual colonoscopy in various pathologies of the colon. MATERIALS AND METHODS: For MSCT a Somatom Plus 4, Volume Zoom scanner, (Siemens, Forchheim) was employed, equipped with four parallel detector rows. Twenty-five patients were included in this trial, prior to colonoscopy or partial colon resection. After cleaning the colon, distension was achieved by insufflation of room air using a rectal tube. The parameters of acquisition and reconstruction were as follows: collimation 4 x 1 mm and 4 x 2.5 mm respectively; tube charge per slice: 140-160 mAs; pitch 5-6; i.v. contrast medium: 120 ml Ultravist 300 (Schering) with a flow rate of 3 ml/s; delay: 35 s. For 3D reconstruction we used edge-enhanced volume rendering, virtual colonoscopy and extraluminal views of volume-rendered images. RESULTS: Nine polyps and four of five colon carcinomas were detected using MSCT virtual colonoscopy. In three patients with ulcerative colitis virtual coloscopy revealed morphological alterations compatible with this disease. In two of four patients with multiple diverticula of the colon the true extent of the disorder could be assessed in virtual colonoscopy. CONCLUSION: Utilizing virtual MSCT colonoscopy polyps and cancer of the colon can be reliably detected, if proper cleaning and distension is provided. On axial images alone smaller polyps may be assessed. The high z-axis resolution of MSCT offers superior conditions for CT-based virtual colonoscopy.

Colitis, Ulcerative↗
PubMed2000

Effects of phorbol ester treatment on dibutyryl cyclic adenosine-5' monophosphate- and carbachol-stimulated aminopyrine accumulation in isolated rat parietal cells.

BACKGROUND: The functional role of the intracellular diacylglycerol/protein kinase C second-messenger pathway in the regulation of gastric acid secretion and the effects on the involved inositotrisphosphate/Ca2+/calmodulin system are not well understood, and contradictory data have been reported. We therefore evaluated the effects of phorbol ester treatment (tetradecanoylphorbol-12,13-acetate (TPA)) on dibutyryl cyclic adenosine-5' monophosphate (dBcAMP)- and carbachol-stimulated aminopyrine (AP) accumulation in comparison with intracellular alterations of the phospholipase C/inostol phosphate signal transduction pathway in isolated rat gastric parietal cells. METHODS: [14C]AP accumulation was determined as an indirect measure of gastric acid secretion. Inositolphosphate second-messenger activation was investigated with [3H]inositolmonophosphate release in [3H]-myoinositol prelabeled rat gastric parietal cells. RESULTS: TPA at a low concentration of 5 nM caused a small (45%) but significant increase in carbachol (0.1 mM)-stimulated AP accumulation, which was dose-dependently inhibited by higher concentrations of TPA with corresponding shifts in the dose-response curve for carbachol-stimulated AP accumulation. AP uptake stimulated by dBcAMP (0.1 mM) and the synergistic stimulatory effect induced by carbachol together with dBcAMP were inhibited by TPA at all concentrations investigated. In the presence of increasing concentrations of the calcium ionophore ionomycin (10(-8)-10(-5) M) TPA at 5 nM increased AP accumulation (AP ratio was 4.02 with 5 nM TPA versus 1.23 in the absence of TPA; P < 0.05), indicating that phorbol ester stimulates AP uptake in rat parietal cells. Simultaneous investigation of [14C]AP accumulation and [3H]inositol monophosphate release showed that inhibitory effects of TPA on carbachol- and carbachol plus dBcAMP-stimulated cells are mediated by an inhibition of the receptor/G-protein/phospholipase C interaction, leading to a reduction of inositolphosphate release. The costimulation of rat parietal cells with dBcAMP, ionomycin, and TPA (5 nM) did not reproduce the synergistic effects of carbachol together with dBcAMP on AP accumulation, suggesting that carbachol-stimulated AP uptake seems to be additionally mediated by a still unknown pathway independent of intracellular calcium release or protein kinase C activation.

Aminopyrine↗
PubMed1999

Chemical behaviour of seven aromatic diisocyanates (toluenediisocyanates and diphenylmethanediisocyanates) under in vitro conditions in relationship to their results in the Salmonella/microsome test.

There are conflicting results on the mutagenicity of toluenediisocyanate (TDI) and diphenylmethanediisocyanate (MDI). It was found that the organic solvent chosen to dissolve the compounds dictates the outcome of the bacterial tests. The Salmonella/microsome tests showed uniformly mutagenic effects for all the compounds that were predissolved in DMSO. Due to the instability of aromatic diisocyanates in DMSO this solvent was replaced by ethyleneglycoldimethylether (EGDE). TDI and MDI endured the dissolving and were therefore still available for the subsequent bacterial tests. Furthermore, no aromatic diamines (TDA or MDA) could be detected in EGDE prior to the start of the assays. The Salmonella/microsome tests, however, revealed unexpected differences between TDI and MDI. As previously published the four types of MDI showed negative results, whereas the data presented in this paper demonstrated mutagenic effects of all three types of TDI if EGDE is the solvent. To gain deeper insight into the chemical changes that occurred during the Salmonella/microsome test, the possible reactions were modelled in the laboratory by mixing predissolved diisocyanates with a defined surplus of water and monitoring the progress of the chemical reactions by analytical methods. Additionally, the quality of the model was checked by exposing solutions of 2,6-TDI and 4,4'-MDI to the real biological test environment. In both cases, the reaction patterns of TDI were different to those of MDI. Within 1 min, which is the maximum time needed to mix the predissolved compounds with water before they are poured onto the agar plate, the TDI content was reduced in favour of different ureas and TDA. In addition water was replaced by the complete set of test ingredients. While the TDA content remained more or less constant, the amount of residual TDI was reduced considerably. Reactions of MDI were markedly slower than those of TDI. More than 90% of the predissolved MDI remained intact when it was mixed with water. The biological test ingredients accelerated the reduction of the MDI content. Within 45 s, more than two thirds of the MDI disappeared. Evidently, the chemical reactions continue during incubation. It is assumed that the contrasting results of TDI and MDI in the Salmonella/microsome test are due to the different reaction patterns-and reaction products-of the predissolved diisocyanates created under the specific conditions of the test. These findings indicate that the chemical interactions between reactive test compounds and solvents or test media need to be considered in the interpretation of the relevance of test results.

Animals↗
PubMed1998

Schild regression analysis of antidepressant and bicuculline antagonist effects at the GABAA receptor.

We showed previously that antidepressants inhibit GABA-stimulated 36Cl- uptake in rat cerebral cortex. In this study Schild analysis was used to determine if antidepressants are competitive antagonists or allosteric modulators at GABAA receptors. GABA concentration-response curves for 36Cl- uptake in rat cerebral cortex were generated in the absence or presence of different concentrations of the following antidepressants: amitriptyline, amoxapine, mianserin, and also the GABAA receptor antagonist, bicuculline. The pA2 values for amitriptyline, amoxapine, mianserin, and bicuculline were 4.2 +/- 0.2, 5.5 +/- 0.3, 4.4 +/- 0.1 and 6.2 +/- 0.6, respectively. The respective Schild slope values were 0.7 +/- 0.1, 0.6 +/- 0.03, 0.7 +/- 0.2 and 1.0 +/- 0.3. All slope values for antidepressants differed from unity. The maximum effect produced by GABA to stimulate chloride influx was decreased by both antidepressants and bicuculline. It is concluded that neither the antidepressants studied nor bicuculline are pure competitive GABA antagonists at the GABAA receptor-chloride-ionophore complex in the rat cerebral cortex.

Animals↗
PubMed1998

[Prognostic significance of apoptosis inducers/inhibitors in stomach carcinoma with/without adjuvant intraoperative radiotherapy (IORT)].

Several studies have tried to improve the surgical results after resection for gastric cancer by different adjuvant therapy protocols, including intraoperative radiotherapy (IORT). Since 1990 we have performed a randomized, prospective trial comparing surgery alone and surgery plus adjuvant IORT to evaluate the role of adjuvant intraoperative radiotherapy in the treatment of curative resected gastric carcinomas. In the present study, p53, bcl-2 immunoreactivity and DNA fragmentation as a typical marker of apoptosis were determined to investigate the predictive value of apoptosis-related factors and the observed response to radiotherapy. Preliminary data indicate that patients with tumors containing increased numbers of apoptotic tumor cells might derive benefit from adjuvant IORT.

Adenocarcinoma↗
PubMed1996

[Choice of procedure in therapy of distal median nerve compression syndrome].

Endoscopic carpal tunnel release is frequently recommended. This technique allows only for division of the retinaculum flexorum, but does not enable the surgeon to address concommitant synovialitis or compression of the motor branch of the median nerve. In 67 patients, we attempted to differentiate the indications for procedures by endoscopic versus open carpal tunnel release. Beside an electrophysiological investigation, sonography of the wrist was performed to evaluate the extent of accompanying tenosynovialitis of the flexor tendons. A possible participation of the thenar branch was examined by electromyography. If there were no additional pathologic findings in the preoperative diagnostic work-up, a simple carpal tunnel release was performed. In all other cases, open surgical release was performed.

Adult↗
PubMed1992

Ganglioside-induced CD4 endocytosis occurs independent of serine phosphorylation and is accompanied by dissociation of P56lck.

Gangliosides induce a selective and complete modulation of CD4 from the surface of T cells. CD4 down-modulation occurs by CD4 endocytosis. This process is independent of serine phosphorylation of the cytoplasmic tail of CD4 and does not require the association between the tyrosine protein kinase p56lck and the cytoplasmic tail of CD4. Ganglioside-induced CD4 endocytosis is accompanied by the loss of p56lck activity associated with CD4. Sequential immunoprecipitation analysis using an anti-CD4 antibody and an anti-p56lck antiserum showed that this is caused by the dissociation of the enzyme from the cytoplasmic tail of CD4. The kinetics of p56lck dissociation after ganglioside treatment is identical to that of CD4 endocytosis, suggesting that p56lck is displaced in the process of endosome formation. The results indicate that CD4 endocytosis alone can cause the dissociation of the p56lck complex without the requirement for CD4 phosphorylation.

CD4 Antigens↗
PubMed1991

Altered protein kinase C activity in biopsies of human colonic adenomas and carcinomas.

Protein kinase C (PK-C) seems to be involved in the regulation of growth and differentiation of normal epithelial cells. Colonic adenomas and carcinomas show increased proliferation and decreased differentiation. We investigated the activity and subcellular distribution of PK-C in biopsies of normal, neoplastic, and malignant colonic epithelium to evaluate alterations in enzyme activity. In the control group (n = 7), the activity of PK-C was highest in the distal ileum (597 pmol/min/mg protein) and declined to the lowest amounts in rectal mucosa (225 pmol/min/mg protein). In patients with colonic adenomas (n = 16), total PK-C activity was significantly reduced as compared to adjacent mucosa (146 versus 336 pmol/min/mg protein, P less than 0.05) and to values determined in the control group (372 pmol/min/mg protein, P less than 0.01). The reduction of total PK-C activity in the adenoma group was even more evident in intraindividual comparison to paired adjacent mucosa (41.8% of adjacent mucosa, P less than 0.001). Specific activity of membrane-associated PK-C was equally decreased in colonic adenomas (36.3 pmol/min/mg protein) when compared to adjacent mucosa (102 pmol/min/mg protein, P less than 0.05) or to the control group (107 pmol/min/mg protein). In patients with colonic carcinomas (n = 10), the amount of total PK-C activity was also decreased (198 pmol/min/mg protein) when compared to adjacent mucosa or to the control group (P less than 0.05). In addition, the amount of membrane-associated PK-C activity (89.1 pmol/min/mg protein) was significantly reduced in carcinoma when compared to adjacent mucosa (P less than 0.05). The ratio of membrane-associated/total PK-C was not altered in adenomas, while in patients bearing carcinomas the relative fraction of membrane-associated PK-C activity was increased in samples from carcinomas and equally from adjacent colonic mucosa (45.0 and 44.6 versus 28.9%, P less than 0.05) when compared to controls. These results indicate that alterations within the protein kinase C pathway occur as early events in the adenoma-carcinoma sequence of intestinal mucosa, suggesting an important role of PK-C in epithelial differentiation and growth.

Adenoma↗
PubMed1991

Is initial (24 hours) lavage necessary in treatment of CAPD peritonitis?

A randomized trial was conducted to examine the influence of initial lavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty-six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including either initial 24 hours lavage before resumption of routine CAPD schedule (prior standard approach) or continued prolonged exchanges as in routine CAPD schedule. Median time to solved infection (normalization of white cell count in dialysis effluent) was identical (3 days) in the two groups. Treatment success rate was found to be 72% in the group with initial lavage and 89% in the group with prolonged exchanges. The difference in treatment success (17%) in favour of continued CAPD schedule was not found significant (95% confidence limits--1% to 35%). The results suggest lavage to be of no clinical benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock.

Acute Disease↗
PubMed1990

Suramin alters phosphoinositide synthesis and inhibits growth factor receptor binding in HT-29 cells.

Initiation of cell growth frequently involves activation of growth factor receptor-coupled tyrosine kinases and stimulation of the phosphoinositide second messenger system. The antitrypanosomal and antifiliarial drug suramin has been shown to exert antiproliferative activities by inhibition of growth factor receptor binding. We therefore investigated the effect of suramin on epidermal growth factor receptor-binding characteristics and, additionally, searched for effects on basal or cholinergically stimulated phospholipid metabolism in HT-29 cells. Suramin caused a dose-dependent and noncompetitive inhibition of 125I-epidermal growth factor binding (concentration producing 50% inhibition, 44.2 micrograms/ml) but did not alter muscarinic receptor binding. Suramin did not affect the basal 32P incorporation into phosphoinositides at concentrations of less than 200 micrograms/ml suramin. In contrast, the carbachol-stimulated enhancement of 32P incorporation into phosphatidic acid, phosphatidylinositol, and polyphosphoinositides was reduced by 48-95% in the presence of 100 micrograms/ml suramin. Thus, phosphoinositide and diacylglycerol kinases involved in basal and receptor-stimulated phosphoinositide metabolism may be localized in different subcellular compartments, which can be dissociated by the use of suramin. Direct measurements of phosphatidylinositol kinase and diacylglycerol kinase activities showed a potent inhibition when treated with suramin. Suramin did not affect the stimulation of phospholipase C by carbachol, determined by release of [3H]inositol phosphates in [3H]myoinositol-prelabeled cells. Our data indicate that suramin potently inhibits phosphoinositide resynthesis under stimulated conditions. Additionally, we confirm the inhibitory effects of suramin on epidermal growth factor receptor binding in a human intestinal cell line. The inhibitory effects of suramin on phospholipid metabolism may play a role in the antiproliferative actions of this drug.

1-Phosphatidylinositol 4-Kinase↗
PubMed1990

Agonist-induced desensitization of cholinergically stimulated phosphoinositide breakdown is independent of endogenously activated protein kinase C in HT-29 human colon carcinoma cells.

Activation of M3 muscarinic receptors in HT-29 cells by carbachol rapidly increases polyphosphoinositide breakdown. Pretreatment of these cells with carbachol (0.1 mM) for 5 h completely inhibits the subsequent ability of carbachol to increase [3H]inositol monophosphate ([3H]InsP) accumulation, paralleled by a total loss of muscarinic binding sites. In contrast, protein kinase C (PK-C)-mediated desensitization by incubation with phorbol esters [PMA (phorbol 12-myristate 13-acetate)], leading to a time- and dose-dependent inhibition of cholinergically stimulated InsP release (95% inhibition after 4 h with 0.1 microM-PMA), is accompanied by only a 40% decrease in muscarinic receptor binding, which suggests an additional mechanism of negative-feedback control. Neither carbachol nor PMA pretreatment had any effect on receptor affinity. Incubation with carbachol for 15 min caused a small increase of membrane-associated PK-C activity (15% increase, P less than 0.05) as compared with the potency of phorbol esters (PMA) (3-4-fold increase, P less than 0.01). Long-term incubation (4-24 h) with PMA resulted in a complete down-regulation of cytosolic and particulate PK-C activity. Stimulation of InsP release by NaF (20 mM) was not affected after a pretreatment with phorbol esters or carbachol, demonstrating an intact function of G-protein and phospholipase-C (PL-C) at the effector side. Determination of PL-C activity in a liposomal system with [3H]PtdInsP2 as substrate, showed no change in PL-C activity after carbachol (13 h) and short-term PMA (2.5 h) pretreatment, whereas long-term preincubation with phorbol esters (13 h) caused a small but significant decrease in PL-C activity (19%, P less than 0.05). Our results indicate that agonist-induced desensitization of phosphoinositide turnover occurs predominantly at the receptor level, with a rapid loss of muscarinic receptors. Exogenous activation of PK-C by phorbol esters seems to dissociate the interaction between receptor and G-protein/PL-C, without major effects on total cellular PL-C activity.

Carbachol↗
PubMed1990

Human gastric mucosa expresses glandular M3 subtype of muscarinic receptors.

Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 +/- 6 fmol/mg protein and the tritiated ligand N-methylscopolamine had an affinity of (KD) 0.39 +/- 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148 +/- 32 nM (n = 13) and 4043 +/- 1011 nM (n = 3) KD, respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities of KD 78 +/- 23 nM (n = 5) and 5.6 +/- 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type.

Carbachol↗
PubMed1990

Low diacylglycerol values in colonic adenomas and colorectal cancer.

The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis.

Adenocarcinoma↗
PubMed1989

Human HT-29 colon carcinoma cells contain muscarinic M3 receptors coupled to phosphoinositide metabolism.

Five different muscarinic receptor subtypes can be distinguished by the differences in their amino acid sequence, the coupled signal transduction system, pharmacological binding properties and activation of ionic fluxes. The present study served to characterize the binding profile of muscarinic receptors in human colon carcinoma cells (HT-29) using selective muscarinic antagonists. The affinities of the compounds were compared with their potency to inhibit cholinergically-activated phosphoinositide metabolism. Pirenzepine displaced [3H]N-methyl-scopolamine binding and inhibited inositolphosphate (IP) release with potencies typical of those of non-M1 receptors. The M3 subtype-selective antagonists sila-hexocyclium and hexahydro-sila-difenidol had high affinity to the muscarinic receptors in HT-29 cells (KD = 3.1 nM and 27 nM, respectively) and inhibited IP release at nanomolar concentrations. The M2 receptor antagonists, AF-DX 116 and methoctramine, had low antimuscarinic potencies. Our results demonstrate that HT-29 human colon carcinoma cells contain an apparently pure population of M3 receptors. These cells could serve as a model system for further investigations concerning regulatory and signal transduction mechanisms associated with glandular muscarinic M3 receptors.

Carbachol↗
PubMed1989

Stimulation of inositol phosphate and diacylglycerol production by RHC 80267, a diacylglycerol-lipase inhibitor, in rat gastric parietal cells: effects on hydrogen ion secretion.

RHC 80267, on inhibitor of diacylglycerol lipase, was used to investigate the role of diacylglycerol in acid secretion by isolated rat gastric parietal cells. Unexpectedly, RHC 80267 stimulated the production of inositol phosphates in [3H]inositol-prelabeled cells and increased levels of 32P-labeled phosphatidic acid to the same degree as did carbachol. RHC 80267 increased diacylglycerol to a greater extent than did carbachol, and additionally decreased levels of [3H]arachidonic acid. This suggests that RHC 80267 stimulated phospholipase C and inhibited diacylglycerol lipase in parietal cells. RHC inhibited [14C]aminopyrine uptake, a measure of acid secretion, stimulated by carbachol or by simultaneous addition of carbachol and dibutyryl-cAMP. These data support the model that the diacylglycerol/protein kinase C branch of the phosphoinositide system is inhibitory to acid secretion.

Aminopyrine↗