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Biomedical subjects

E Krause

Publications and source records attributed to E Krause.

At least 91 records · Page 5Linked to original sources

Inhibition of adenosine deaminase activity of aortic endothelial cells by extracts of garlic (Allium sativum L.).

Aqueous extracts of fresh garlic (Allium sativum L.) inhibited efficiently the activity of adenosine deaminase (ADA) of cultivated endothelial cells. The IC50 value (range between 6 and 120 micrograms per ml) depended on the origin and storage time of the fresh garlic. The aqueous extraction of dried garlic powder showed also an inhibition if ADA activity, but the IC50 value was in the range of 2.5 mg per ml indicating that parts of the active principle were lost during the preparation of the garlic powder. The inhibition of endothelial ADA by garlic extracts seems to contribute to the hypotensive activity and vessel protective effects of A. sativum L.

Adenosine Deaminase Inhibitors↗

Determination of peptide hydrophobicity parameters by reversed-phase high-performance liquid chromatography.

The log kw values of fourteen potential fibrinogen receptor antagonist peptides (RGDX) determined by reversed-phase HPLC were correlated to hydrophobic parameters of the amino acid side-chain log P in position X of the tetrapeptides. Comparing the polymer columns with LiChrosorb RP-8, the correlation coefficient using a polyethylene column is higher (0.94) than that for RP-8 (0.88), which demonstrates the importance of a homogeneous hydrophobic surface and makes this method very suitable for the determination of the overall hydrophobicity of shorter peptides. The hydrophobicity parameters log kw of the RGDX peptides (-1.15 to 2.19) were used to investigate the influence of molecular parameters of X on the potency of RGDX in inhibiting platelet aggregation. The results confirm the importance of hydrophobicity for the contribution of X to the biological activity of RGDX.

Amino Acid Sequence↗

Cloning of a VLP-protein coding gene from a parasitoid wasp Venturia canescens.

Virus-like particles (VLPs) that are bound to the egg surface of a parasitic wasp Venturia canescens are void of nucleic acid and unable to infect host tissue but instead provide a passive protection against the host's immune recognition. To investigate evolutionary and functional properties of Venturia particles, we isolated cDNAs coding for a VLP-protein by screening an expression library of the wasp, using antibodies against purified VLPs. The corresponding coding DNA is present in the wasp genome as a single-copy gene.

Animals↗

Structural organization and differential expression of three stilbene synthase genes located on a 13 kb grapevine DNA fragment.

A 13 kb DNA fragment was isolated from a grapevine (Vitis var. Optima) genomic library by hybridizing with elicitor-induced stilbene synthase cDNA as a probe. After fragmentation with Eco RI, subcloning and sequencing, two full-size stilbene synthase genes (Vst1 and Vst2) and the 3' end of a third stilbene synthase gene (Vst3) were located within the 13 kb fragment. Vst1 and Vst2, differing only slightly in the coding region, are distinguished in the intron size and in the structure of the promoter region. The 5' flanking region of gene Vst1 contains a TATAA box at nucleotide -48. The substantial structural differences found for the promoters of the two genes are paralleled by a striking difference in the expression of the two genes in elicitor-treated cells. Moreover, the accumulation upon elicitation of six different stilbene synthase mRNAs was studied and found to differ by two orders of magnitude.

Acyltransferases↗

Postoperative antiarrhythmic effects of diltiazem in patients undergoing coronary bypass grafting.

Hemodynamic problems resulting from cardiac arrhythmias often occur in patients undergoing coronary bypass grafting in the early postoperative period. Therefore, in this study the antiarrhythmic effects of the calcium channel antagonist diltiazem were evaluated in coronary bypass grafting. Forty patients were randomly assigned either to a therapy with diltiazem or nitroglycerin. Hemodynamic measurements were established by Swan-Ganz catheter, and long-term ECG analyses were performed preoperatively and 1, 3 and 5 days after operation. There were significantly fewer ventricular arrhythmias (Lown class IV) in the diltiazem groups than in the nitroglycerin groups (p < 0.05). Supraventricular tachycardias were significantly more often observed in the nitroglycerin groups on all 3 days (p < 0.05). As a result, the calcium channel antagonist diltiazem is recommended as a standard adjunct to perioperative medication in cardiac surgery.

Aged↗

Inhibition of K+ channels by chlorpromazine in rat ventricular myocytes.

Isolated rat ventricular myocytes were investigated with the whole-cell patch-clamp technique. Chlorpromazine inhibited inward-rectifying K+ currents (IC50 = 6.1 microM), time-independent outward currents (IC50 = 16 microM) and transient outward K+ currents. In the latter case, 100 microM of chlorpromazine reduced the amplitude of the peak current recorded at a clamp potential of 50 mV from 2.14 +/- 0.59 nA to 1.38 +/- 0.20 nA (n = 4) and decreased the time course of fast inactivation from 8.29 +/- 1.17 msec to 4.01 +/- 0.90 msec (n = 4). In addition, chlorpromazine blocked the ATP-dependent K+ current, which was activated either by the channel opener rilmakalim (10 microM) or by metabolic inhibition with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP, 500 nM; IC50 for rilmakalim = 2.5 microM; IC50 for FCCP = 11.5 microM). The drug caused marked depolarization of the resting potential at higher concentrations (50 microM) from -79 +/- 3 mV to -27 +/- 11 mV (n = 4). The reversibility from channel block was slow and only partial for time-independent currents, especially inward-rectifying K+ currents, but it was relatively fast and complete for time-independent currents. Thus chlorpromazine blocks a variety of K+ channels in heart muscle cells. Inasmuch as the potency of inhibition is less than the previously reported use-dependent block of Na+ channels, the cardiovascular adverse effects of chlorpromazine are probably caused mainly by the latter effect.

Animals↗

Disease resistance results from foreign phytoalexin expression in a novel plant.

Although phytoalexins have long been inferred to be important in the defence of plants against fungal infection, there are few reports showing that they provide resistance to infection. Several plants, including grapevine, synthesize the stilbene-type phytoalexin resveratrol when attacked by pathogens. Stilbenes with fungicidal potential are formed in several unrelated plant species, such as peanut (Arachis hypogaea), grapevine (Vitis vinifera) and pine (Pinus sylvestris). Stilbene biosynthesis only specifically requires the presence of stilbene synthase. Furthermore, the precursor molecules for the formation of hydroxy-stilbenes are malonyl-CoA and p-coumaroyl-CoA, both present in plants. To investigate the potential of stilbene biosynthetic genes in a strategy of engineering pathogen resistance, we isolated stilbene synthase genes from grapevine, where they are expressed at a high level, and transferred them into tobacco. We report here that regenerated tobacco plants containing these genes are more resistant to infection by Botrytis cinerea. This is, to our knowledge, the first report of increased disease resistance in transgenic plants based on an additional foreign phytoalexin.

Acyltransferases↗

Serial evaluation of left ventricular function by radionuclide ventriculography at rest and during exercise after orthotopic heart transplantation.

Discrepant results have previously been reported concerning long-term left ventricular function in the human transplanted heart as assessed by radionuclide ventriculography. In this study, radionuclide ventriculograms were obtained at rest and during exercise in 19 patients < 6 months, 7-12 months, 13-24 months and > 24 months after transplantation. Ejection fraction decreased significantly from < 6 months to 13-24 months after transplantation (rest: 69.1% +/- 9.7% to 56.7% +/- 8.3%, P < 0.05; exercise: 70.4% +/- 11.3% to 59% +/- 8%, P < 0.05). Heart rate increased significantly during exercise after > 2 years (90.2 +/- 10.5 beats/min to 103.5 +/- 15 beats/min, P < 0.05) but not within 6 months after transplantation (98.5 +/- 12.8 beats/min to 99.07 +/- 15.8 beats/min). Left ventricular end-diastolic volume remained unchanged. Peak filling rate at rest decreased significantly from 4.2 +/- 0.96 edv/s < 6 months after transplantation to 3.3 +/- 0.66 edv/s (P < 0.05) 13-24 months and 3.3 +/- 0.64 edv/s (P < 0.05) > 24 months after cardiac transplantation. Exercise peak filing rate did not change significantly. It is concluded that radionuclide ventriculography demonstrates a decrease in systolic left ventricular function in the long-term course after cardiac transplantation. A significant increase in exercise peak heart rate may be due to autonomic reinnervation. Differences in the literature concerning left ventricular function may be due to different observation intervals following cardiac transplantation.

Erythrocytes↗

A comparison of serotonin (5-HT) blood levels and activity of 5-HT2 antagonists in adjuvant arthritic Lewis and Wistar rats.

The total plasma 5-HT levels of adjuvant arthritic rats were increased in animals of both strains in comparison to healthy controls. The exception was day 1, when the 5-HT plasma level in arthritic Lewis rats was decreased by 77%, but only by 17% in Wistar rats. Treatment with the 5-HT2 receptor antagonist ritanserin caused a significant inhibition of macroscopic arthritis at day 14 in Lewis but not in Wistar rats. The total plasma 5-HT level was significantly decreased by the 5-HT2 antagonists in both strains at various times. 5-HT as an autacoid with effects on the T-lymphocytes and on delayed hypersensitivity reactions might be responsible, at least in part, for strain differences regarding the incidence of secondary lesions in rat adjuvant arthritis.

Animals↗

Spontaneous chemical degradation of substance P in the solid phase and in solution.

The instability of the undecapeptide substance P (SP), a neuropeptide implicated in several physiological processes, was occasionally observed when the peptide was stored in the solid state or in solution. The aim of the present study was to identify the decomposition products of SP stored as lyophilized peptide or in aqueous neutral solution. The main pathway of the decomposition of SP acetate consists of the subsequent release of N-terminal dipeptides via their diketopiperazines, cyclo(Arg-Pro) and cyclo(Lys-Pro). In contrast to the decomposition of the acetate of SP, the hydrochloride and trifluoroacetate salts were found to be considerably more stable. Under the studied conditions the release of N-terminal dipeptides dominates over other possible routes of spontaneous modifications, such as S-oxidation and deamidation.

Amino Acid Sequence↗

Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high-risk heterosexual population.

A group of 58 heterosexual female partners (FP) of human immunodeficiency virus type 1 (HIV-1)-seropositive hemophiliacs was studied by conventional diagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot analysis to examine whether any had acquired HIV-1 infection through sexual transmission. A subset of 29 FP were asked to answer a detailed questionnaire concerning their health, use of "safer sex" techniques, and other risk factors for HIV-1 infection. They also had additional blood drawn for CD4 cell analysis, viral cultures, nef, gag, and env immunoblots, and polymerase chain reaction (PCR) analysis to assess the occurrence of "silent" HIV-1 infection in a high-risk seronegative population. Among the 58 FP, three were found to be HIV-1-seropositive on first testing, with no new seroconversions occurring with subsequent testing in the remaining 55. Two seropositive FP had the additional testing and were found to have positive viral cultures, as well as positive PCR results. All of the seronegative FP (n = 24) who had additional testing were negative in viral culture, had negative immunoblots, and had no HIV-1 nucleic acid sequences detected by PCR. Thus, in this population, silent HIV-1 infection appears to be a rare occurrence and antibody testing seems to correlate with the more sensitive techniques of PCR and viral cultures.

Acquired Immunodeficiency Syndrome↗

Right ventricular volumes and hemodynamics after successful orthotopic heart transplantation. A comparison to coronary artery disease using thermodilution.

Only few data exist concerning right ventricular function in the chronic stage after cardiac transplantation. Therefore, we investigated hemodynamic and right ventricular volumetric data by a computerized thermodilution Swan-Ganz catheter in 17 patients (median age: 53, range: 18-63 yr) at a median of 24 (4 to 44) months after cardiac transplantation during rest and supine bicycle exercise. Myocardial biopsy showed grade one or less according to the classifications of Billingham. Sixteen patients with coronary artery disease, but without prior myocardial infarction, served for comparison. While angiographic left ventricular ejection fraction was nearly identical in transplant recipients [77 (60-92)%, median (range)] and in patients with coronary artery disease [78 (64-94)%], right ventricular ejection fraction was lower (p < 0.001) in patients after cardiac transplantation [37 (16-58)%] as compared to patients with coronary artery disease [56 (46-62)%]. In transplant recipients right atrial pressure was significantly higher both at rest [10 (2-18) mmHg] and exercise [18 (8-30) mmHg] than in patients with coronary artery disease [5 (1-11) and 8 (3-18) mmHg]. Pulmonary capillary wedge pressure behaved similar in both groups. To further evaluate reasons for right ventricular impairment, a correlation analysis was performed. This showed a negative correlation between right ventricular ejection fraction and the time interval after transplantation (p < 0.0002). However, there was no correlation between right ventricular ejection fraction and acute rejection or a rejection score. In conclusion, right ventricular function may be severely altered in transplant recipients, in contrast to an only slight impairment of left ventricular function.

Adolescent↗

[Rheumatoid factors].

Rheumatoid factors (RF), which are auto-antibodies recognising the Fc fragment of IgGs, are the commonest auto-antibodies in man. They are present in polyclonal form in a large number of auto-immune disorders as well as in certain inflammatory states. In monoclonal form, they are frequently the product of "mature" malignant (chiefly Waldenström's macroglobulinemia and chronic lymphoid leukemia) and allegedly benign (such as cryoglobulinemias) lymphoid proliferations. In addition, RF account for a significant part of the normal antibody repertory, notably during the fetal and neonatal periods, suggesting that they may play an important role in the development and regulation of the immune system. As a result, RF are an excellent model for the analysis of auto-immunity in man. Thus many indirect (analysis of antigens recognised and of idiotopes carried) and, more recently, direct (protein or nucleotide sequencing of their various regions) studies have now provided the following conclusions. RF are coded by a very limited repertory of V genes. These genes are present in the normal genome and appear to be highly preserved in the human species. They are used with very few somatic mutations by monoclonal B proliferations (which opens up valuable therapeutic possibilities) as well as probably by RF producing B lymphocytes in normal individuals. In contrast, in the context of auto-immune disorders, these same genes have many somatic mutations suggesting maturation governed by the antigen and/or escape from idiotype control.

Autoimmune Diseases↗

Chymotrypsin-catalyzed fragment coupling synthesis of GnRH-analogs.

D-Xaa6-GnRH analogs (Xaa: Ala, Nal1), Phe, Ser(tBu), Trp) were prepared by chymotrypsin catalyzed 3 + 7 fragment coupling synthesis with conversion rates of the amino component in the range from 90.3 to 97.4%. For D-Phe6-GnRH the method was scaled up to production level.

Catalysis↗

[Experiences with the application of monoclonal Indium-111 antimyosin scintigraphy in the diagnosis of rejection episodes following orthotopic heart transplantation].

Indium-111-labeled Fab fragment imaging using a murine antimyosin monoclonal antibody (Myoscint, Centocor, Leiden) was evaluated for efficacy in detecting cardiac allograft rejection. Diagnosis of rejection was made by endomyocardial biopsy with four to five samples taken for each procedure. Eighty-one studies were performed in 25 patients (21 men, four women, mean age 50 +/- 9 years) from 2 weeks to 45 months after cardiac transplantation. 0.5 mg of the monoclonal antibody labeled with 60 MBq Indium-111 (Antimyosin-Fab-DTPA) was administered i.v. Planar scintigraphic images were obtained in LAO 45 and anterior projections as well as "half-body-scintigrams" 48 h after injection. Using the regions-of-interest-(ROI)technique the relative uptake over the lung and the heart was determined and an index of In-111 uptake was calculated. A heart-to-lung ratio of 1.5 or higher was considered indicative for moderate to severe rejection. Specificity was 86% (nine false-positive In-111 studies in 68 negative biopsy studies), sensitivity was 85% (two false-negative In-111 studies in 13 pathological biopsy studies). It is concluded that the In-111 method has a high sensitivity and specificity in detecting heart transplant rejection and may be useful in the monitoring of patients in the chronic phase after heart transplantation. The 48-h delay in establishing the diagnosis limits the applicability in acute severe rejection.

Adult↗