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Biomedical subjects

G Werner

Publications and source records attributed to G Werner.

At least 19 recordsLinked to original sources
PubMed1992

Immune response to tumor antigens in a patient with colorectal cancer after immunization with anti-idiotype antibody.

An active vaccination protocol was performed on one patient with colon carcinoma as a pilot to a prospective randomized double-blind clinical trial with the vaccine SDZ SCV 106. This vaccine is an anti-idiotype goat antibody to the monoclonal antibody 17-1A, which is directed against the tumor antigen 17-1A. To study the effect of the therapy on the immune reactivity, several tests were performed to detect anti-tumor antibodies in the serum as well as in eluates of metastatic tissue. Furthermore metastases removed from the lung were examined by immunohistochemistry. The results suggest that the humoral and cellular immune reactivity against the tumor are enhanced.

Adult↗
PubMed1992

Intervascular and stimulus selectivity of nitrendipine and related derivatives in KCl and prostaglandin F2 alpha precontracted porcine arteries.

1. Dihydropyridine-type calcium entry blockers exhibit a different vasodilator potency depending on the arterial tissue (intervascular selectivity) as well as on the precontracting stimulus used (stimulus selectivity). In addition, the structure of their ester side chains seems to influence their activity. 2. Vascular activity of nitrendipine and six related 3-ester side chain derivatives was investigated in isolated coronary, ulnar and basilar arteries of the pig following precontraction with KCl or prostaglandin F2 alpha (PGF2 alpha). 3. After depolarization, all dihydropyridines exhibited a weak preferential action on coronary arteries. Bay E 6927 produced the strongest effect in all vessel types. By contrast, precontraction with PGF2 alpha resulted in a marked preferential action in basilar arteries, although higher concentrations of the dihydropyridines were required for half maximal vasorelaxation. In each case, ulnar arteries were less sensitive. 4. Except with Bay O 5572, the most bulky substituted and least active derivative, only moderate differences were observed within the dihydropyridines studied. On the other hand, there was a pronounced increase in the ratios of the half maximal active concentrations required after precontraction of the vessels with PGF2 alpha compared to KCl (stimulus selectivity) following a limited prolongation of the 3-ester side chain up to an isopropyl-group. 5. It is suggested that the observed shift in the intervascular selectivity after precontraction with PGF2 alpha is a consequence of different contractile mechanisms in the three vessel types studied. The degree of the stimulus selectivity may also depend on the structure of the dihydropyridines.

Animals↗
PubMed1991

Sialic acid removal modulates the myocardial and vascular activity of calcium channel ligands.

Selective removal of sialic acid from isolated guinea pig left atrial strips and rabbit thoracic aortic ring segments was performed by neuraminidase prepared from Clostridium perfringens and was controlled electron microscopically. Preincubation of these organs (2 units/mL; 2 hr) resulted in enzyme mediated hydrolysis of total tissue sialic acid; 55.2% for atria and 60.9% for aorta. Contractile force of atria and arterial diameter of thoracic aorta were measured isometrically and isotonically by means of a force displacement transducer. Pretreatment of both organs with neuraminidase (2 units/mL; 2 hr) in a carbogen saturated organ bath caused a moderate left-hand shift of the cumulative concentration response curves for the dihydropyridine type calcium antagonist nisoldipine, the phenylalkylamine derivative gallopamil and the benzothiazepine diltiazem. EC50 values were significantly lower (P less than 0.05), particularly in the atrial muscle, when compared to untreated preparations. There was no effect of neuraminidase on the negative inotropic and vasodilator potency of the calcium channel modulator fendiline. Conversely, neuraminidase induced a right-hand shift in the concentration response curves shown by the pure calcium agonist (-)-S-Bay K 8644 leading to significantly higher EC50 values in both organs. Similarly, the contractile potency of calcium chloride (atria) and potassium chloride (aorta) was attenuated upon neuraminidase treatment. From the results obtained it is concluded that sialic acid removal may modulate the action of calcium channel ligands through an inhibitory effect on transmembrane calcium fluxes and/or by decreasing the external calcium availability. Whether the present results suggest a functional role for sialic acid in the regulation of calcium channels warrants further investigation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Initial clinical results with the Wiktor stent: a new balloon-expandable coronary stent.

The Wiktor stent, a new coronary balloon-expandable tantalum stent, was implanted in 17 patients for other wise nonmanageable occlusion after balloon angioplasty (n = 11) and for recurrent restenosis (n = 6). Stents of 3.0 to 4.0 mm were implanted (right coronary artery: n = 10, left anterior descending artery: n = 4, left circumflex artery: n = 2, venous graft: n = 1). All patients were fully anticoagulated initially with heparin followed by coumadin for 3 months and were treated with acetylsalicylic acid indefinitely. Due to its good radiopacity, the device could be placed easily without complications. Early occlusion occurred in one patient after 8 h probably due to friable atheromatous material prolapsing between the meshes of the stent. Late occlusion occurred in another patient who was admitted in cardiogenic shock after pre-hospital reanimation and was stented after occlusive disection following balloon angioplasty of an occluded right coronary artery. In this patient with severe hypoxic brain damage, reocclusion and reinfarction to which the patient finally succumbed occurred following cessation of anticoagulation. Histology demonstrated occlusive thrombosis without evidence of a neointimal covering of the stent. Another thrombotic occlusion due to inadvertent omission of anticoagulation occurred in another patient two weeks after stenting. Control angiography after 6 months in 12 patients revealed restenosis in two patients (50% and 80%). The patient with 80% restenosis of the right coronary artery and pathologic results during stress testing underwent surgical revascularization. The other patient with a 50% restenosis of the right coronary artery was managed medically as he was asymptomatic and without evidence of ischemia during stress testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

The influence of 3-ester side chain variation on the cardiovascular profile of nitrendipine in porcine isolated trabeculae and coronary arteries.

It has been reported that the lipophilicity of dihydropyridine-type calcium entry blockers may influence both their negative inotropic and their vasodilator activities. The action of nitrendipine and six related 3-ester side-chain derivatives with increasing alkyl and aryl substituents have been investigated in isolated porcine trabecular muscles and coronary artery rings. The lipophilicity of the drugs was determined by high-pressure liquid chromatography. In addition, some sterical parameters of the ester derivatives were considered. For the drugs tested, an increase in 3-ester side chain volume correlated well with increasing lipophilicity. Compared to nitrendipine, vascular selectivity of the ester side-chain derivatives, as expressed by the ratio of their negative inotropic and vasodilator activities, was much reduced. Neither vasodilator nor negative inotropic activity was directly related to the corresponding lipophilicity. Based on these results, earlier suggestions about the influence of the ester side-chain in dihydropyridines on their cardiovascular profile are extended.

Animals↗
PubMed1991

Hydrophobic properties of novel dihydronaphthyridine calcium antagonists and biological activity in porcine isolated cardiac and vascular smooth muscle.

Dihydronaphthyridine calcium antagonists are structurally related to the well known dihydropyridines and act in a similar manner. In order to establish the vascular selectivity of these compounds contractile force was evaluated in porcine isolated ventricular trabeculae and right coronary arteries. The dihydropyridine derivatives nisoldipine and nitrendipine as well as the structurally different compounds gallopamil and flunarizine were included for comparison purpose. All compounds studied exhibited dose-dependent negative inotropic and vasodilator activities. The negative inotropic potency of all dihydronaphthyridines, especially of the highly lipophilic bulky ester-variated derivatives (Goe 5584-A, Goe 5806-A) was comparable to that of flunarizine but was considerably less pronounced than that of nisoldipine, nitrendipine or gallopamil. By contrast, half-maximal vasodilator responses of the dihydronaphthyridines studied in coronary arteries being in the nanomolar concentration range were comparable to the dihydropyridines nisoldipine and nitrendipine, whereas the activity of gallopamil and flunarizine was less marked. On the other side the dihydronaphthyridines, especially the more hydrophilic 3-ethylester-4-(2-cyanophenyl) derivative Goe 5606, exerted an obvious biphasic concentration-response behaviour in coronary arteries leading to a high affinity relaxant process in subnanomolar concentrations, whereas the low affinity response could be observed at rather high concentrations (mostly greater than 1 microM). Mainly due to their relative uneffectiveness in cardiac muscle, vascular selectivity of the dihydronaphthyridines was considerably higher than that of the structurally related dihydropyridines nisoldipine resp. nitrendipine increasing in the following order: nitrendipine less than nisoldipine less than Goe 5606 less than Goe 5438 less than Goe 5584-A less than Goe 5806-A. By contrast, gallopamil exerted a slight cardiac preference, whereas the vascular selectivity of flunarizine was also pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Biologically active protease 3C of human rhinovirus 1A is expressed from a cloned cDNA segment in Escherichia coli.

We produced the putative protease 3C of human rhinovirus 1A (HRV-1A), a minor group rhinovirus, by Escherichia coli expression of a segment of HRV-1A cDNA coding for 3A, 3B, 3C, and parts of 2C and 3D (delta 2C3ABC delta 3D). The protease 3C was expected to be processed by intramolecular Q-G cleavages from the virus-specific precursor polypeptide. While the N-terminal 3B-3C site was correctly cleaved, the C-terminal Q-G site of 3C was not processed. Western blotting with a site-specific polyclonal antipeptide antibody showed that not the mature 3C polypeptide, but the 3C-containing precursor 3C delta 3D was the only rhinovirus-specific protein. Mature 3C was obtained by introducing two stop codons at positions glycine-1 and glutamine-2 of 3D by site-specific mutagenesis. This mutant produced the mature 3C protease of HRV-1A. In contrast to poliovirus, the mature 3C protease of HRV-1A is a minor peptide in virus-infected HeLa cells. The 3C protein can be detected only by Western blotting with a polyclonal antipeptide 3C antibody but not by radiolabeling the viral polypeptide.

3C Viral Proteases↗
PubMed1991

Excimer laser angioplasty in coronary artery disease.

The results of coronary excimer laser angioplasty were evaluated in 70 patients. Forty-five patients had laser angioplasty of coronary stenoses. Twenty-five patients in a total of 35 attempts had wire-guided laser recanalization of chronic coronary occlusions, resulting in a success rate of 71%. Immediate results in both groups demonstrated the efficacy of this technique without serious side-effects. Stenoses were reduced from 90 +/- 5% to 48 +/- 18% diameter reduction (mean +/- standard deviation) by excimer laser angioplasty. Residual stenosis in recanalized vessels after laser angioplasty was 52 +/- 19%. In slightly more than half of the patients with a residual stenosis greater than 50% after excimer laser angioplasty, subsequent balloon angioplasty was performed for further stenosis reduction. While satisfactory immediate results were achieved by excimer laser angioplasty intermediate follow-up revealed a restenosis rate in the same range as with balloon angioplasty.

Aged↗
PubMed1991

The fine structure of testicular interstitial cells in the mouse. A comparison after conventional double fixation versus rapid freezing followed by freeze substitution.

The interstitial cells in the testis of the mouse have been studied both after conventional double fixation with glutaraldehyde followed by osmium tetroxide and after rapid freezing and cryosubstitution with osmium tetroxide-acetone by light, scanning and transmission electron microscopy. Differences have been found especially concerning the preservation of lipids and the appearance of mitochondria. Varying proportions and different aspects of rough and smooth endoplasmic reticulum were observed corresponding after both preparation methods thus confirming their real existence. Numerous specific contacts are found between macrophages and Leydig cells, indicating a functional interdependence between these two cell types. Though structural preservation is superior after freeze substitution in the outermost zone, artifacts caused by the initial impact, by ice crystal formation, and during substitution must be considered.

Animals↗
PubMed1990

[Basic programs in internal medicine--pro and contra their justification].

Reasons for and against the justification of basis programs in medicine are under world-wide discussion. Due to the different use of relevant terms there are no definite statements in special literature. In this paper an attempt is made to prove the legitimacy of basis programs in internal medicine. The main purpose is to describe the course of actions in medical workday routine. Methodic aspects of the approach to related problems are explained, too.

Clinical Competence↗
PubMed1990

Simultaneous determination of creatine, uric acid and creatinine by high-performance liquid chromatography with direct serum injection and multi-wavelength detection.

An isocratic high-performance liquid chromatographic separation of creatine, uric acid and creatinine with direct on-column application of the serum sample has been developed. The pre-column, used for sample clean-up, is switched out of the eluent flow after a definite time. Simultaneous three-wavelength detection with a diode array detector allows a very precise quantitation of the three compounds at the optimum wavelength for each (210, 234 and 290 nm) with a coefficient of variation of less than 2% (creatine 3-5%). Good linearity and 100% recovery are obtained over a wide range of concentration in biological material. No interferences are observed caused by medication with lidocaine or dobesilate (Ca), or high bilirubin concentrations. This makes the method useful for clinical purposes or even as a reference for other methods.

Bilirubin↗
PubMed1990

Malignant restenosis after primary successful excimer laser coronary angioplasty.

In a series of 20 coronary excimer laser angioplasties, two patients presented with a peculiar type of malignant restenosis 6 and 8 weeks after a successful laser angioplasty procedure. One patient had a successful recanalization of an occluded left anterior descending (LAD) coronary artery and the second patient had a successful angioplasty of a subtotal proximal stenosis of the left anterior descending coronary artery. After the procedure, no ischemia could be demonstrated by exercise ECG and thallium scintigraphy. Both patients were free of angina until the sudden development of nocturnal angina several hours before reangiography, which showed subtotal restenosis in both cases. One patient had a mammaria graft on the LAD and the second patient underwent a successful balloon angioplasty. This uncommon sudden and malignant development of restenosis seems to be related to the excimer laser angioplasty procedure and warrants some caution with the indiscriminative use of this new angioplasty procedure.

Aged↗
PubMed1990

Voltammetric behaviour of immunoglobulin G at stationary mercury electrodes.

A.c. voltammetric measurements have shown that bovine and human immunoglobulin G are adsorbed at a mercury electrode over a broad potential range and at open circuit. A current signal at ca. -0.55 V was identified as being due to an interfacial process connected with reversible protein re-orientations in the adsorption layer and, possibly, with fast faradaic reactions of both adsorbed redox states of the immunoglobulin.

Animals↗
PubMed1989

Genome structure of adenovirus 12 host range mutants adapted to growth in simian Vero cells.

Mutants of adenovirus type 12 adapted to growth in Vero cells were studied by restriction enzyme and sequence analysis. Plaque-purified mutants were isolated either after long-term passage of the virus in Vero cells (CS-1, CL-1) or from Vero cells transfected with viral DNA (11-g, 12-k). The plaque-forming activity of these mutants was equal or even slightly higher in Vero cells than in HeLa cells, whereas the activity of wild-type virus in HeLa cells exceeded that in Vero cells by about one to two orders of magnitude. All mutants tested had an insertion of variable length consisting of adenoviral sequences at the right end of the viral genome. Sizes of the insertions were determined to be 294 bp (CS-1, 12-k), 560 (11-g), or 180 bp (CL-1). Additional insertions of multiple size and less than equimolar amount were detected and seem to exist in some of the viral particles. Furthermore, all four mutants tested showed an identical 69-bp deletion in the first exon of the E1a gene.

Adenoviridae↗
PubMed1989

[Differential pulse-voltametric determination of dopamine using pretreated electrochemical electrodes].

The electroanalytical method proposed permits a sensitive and selective determination of dopamine in the presence of ascorbic acid applying a fast galvanostatic pretreatment of the carbon electrodes. The effect of the electrochemical pretreatment at glassy carbon electrode (A = 0.8 mm2) was compared with that of carbon fibre array electrode (A = 0.15 mm2). Both types of electrodes showed approximately the same detection limit for dopamine of about 1.10(-7) mol/l dopamine. In comparison to the polished electrodes the sensitivity is improved by a factor of 100. The galvanostatic pretreatment led also to a drastic improvement of selectivity by cathodic shift of the ascorbic acid peak potential.

Carbon↗