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Biomedical subjects

R Jansen

Publications and source records attributed to R Jansen.

At least 55 records · Page 3Linked to original sources
PubMed1998

LU 302 872 and its racemate (LU 224 332) show balanced endothelin-A/B receptor affinity, high oral activity, and inhibit human prostate tissue contractions.

LU 302 872 (racemate LU 224 332) is a new glycerinic acid derivative related to the selective ETA receptor antagonist LU 135 252. LU 302 872 exhibits high and balanced affinity to ETA and ETB receptors (Ki 2.2 and 5.8 nmol/L), whereas LU 135 252 is ETA-selective (Ki 1.4 and 184 nmol/L). Two hours after oral treatment of rats with 10 mg/kg of LU 302 872 or of LU 135 252, the big ET-1-induced (20 micrograms/kg i.v.) blood pressure increase is inhibited by 59 +/- 8% or 52 +/- 2% (n = 6-8; p < 0.05 vs. control), whereas bosentan is without effect (-6 +/- 7%; n = 6). In guinea pigs, 10 mg/kg p.o. of LU 302 872 inhibited the big ET-1 (20 micrograms/kg i.v.)-induced bronchospasm (reduction in respiratory volume) by 78 +/- 7% (n = 6; p < 0.05), whereas the ETA antagonist LU 135 252 was ineffective (0.2 +/- 37%; n = 6). Hence, a high oral effectiveness of the new ETA/B antagonist could be demonstrated in two species for both an ETA- or an ETB-mediated response. In human prostate tissue (excised during cystectomy in bladder cancer patients), ET-1 and in most cases, the ETB agonist sarafotoxin 6c (S6c) caused contractions of similar magnitude but more sustained than that of norepinephrine (10(-6) mol/L). A high concentration (10(-5) mol/L) of the ETA antagonist LU 135 252 only moderately attenuated ET contractions. The ETA/B antagonist LU 302 872 or its racemate, LU 224 332, dose-dependently inhibited ET-1-induced contractions. S6C dose-response curves, too, were shifted to the right or suppressed by the combined ETA/B antagonist (10(-6) mol/L LU 224 332). LU 302 872 may be a suitable candidate for testing in benign prostate hyperplasia (BPH).

Animals↗
PubMed1998

Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): production, physico-chemical and biological properties.

A novel macrolide, apicularen A, was produced by several species of the genus Chondromyces. Initially it was discovered by bioassay-guided RP-HPLC-fractionation of culture extracts of Chondromyces robustus, strain Cm a13. Apicularen A showed no antimicrobial activity, but was highly cytotoxic for cultivated human and animal cells, with IC50 values ranging between 0.1 and 3 ng/ml. A cometabolite of apicularen A, the N-acetylglucosamine glycoside apicularen B, was distinctly less cytotoxic with IC50 values between 0.2 and 1.2 microg/ml, and showed weak activity against a few Gram-positive bacteria. Apicularen A is chemically closely related to the salicylihalamides A and B from the marine sponge Haliclona sp.

Animals↗
PubMed1997

Median power frequency of the surface electromyogram and blood lactate concentration in incremental cycle ergometry.

The electromyogram (EMG) median power frequency of the vastus lateralis and flexor digitorum superficialis muscles was measured in 12 subjects during cycle ergometry with step-wise increasing exercise intensities up to 100% of VO2max. Blood lactate concentration was measured to investigate the relationship between changes in lactate concentration and shifts in the EMG median power frequency of exercising vastus lateralis and non-exercising flexor digitorum superficialis muscles. The results indicated that lactate concentration did not systematically affect median frequency: in spite of a considerable increase in blood lactate concentration, no systematic decrease of the median frequency during exercise was found, either for the vastus lateralis or for the flexor digitorum superficialis muscles. Instead of a decrease of the median frequency during exercise, as seen in isometrical protocols, an increase was seen in most subjects. An interesting finding was a decrease of the median frequency of vastus lateralis muscle during recovery in 8 subjects. The present findings showed that the relationship between EMG frequency decrease, lactate accumulation and fatigue, as observed in isometric protocols, cannot be simply applied to dynamic exercise.

Adult↗
PubMed1997

Multicenter feasibility study of a new coaxial falloposcopy system.

We compared falloposcopy employing a new coaxial system with traditional laparoscopic chromotubation and hysterosalpingography in a prospective, multicenter clinical trial at five tertiary infertility centers. Based on findings at hysterosalpingography or laparoscopic chromotubation, the 16 women (22 tubes) in group 1 had a presumed diagnosis of proximal tubal obstruction, and the 4 (7 tubes) in group 2 had unexplained infertility. Cannulation was successfully achieved in 83.3% of tubes. In group 1, 85% (17/20) of visualized tubes were patent and 35% (7/20) were normal. In group 2, 40% (2/5) of visualized tubes were abnormal. Management was changed in 52.4% of women as a result of falloposcopic findings. Falloposcopy with this new coaxial system allows improved visualization with less bulky and less traumatic instruments. The system provides valuable information regarding the fallopian tube lumen that correlates poorly with that obtained with more traditional techniques.

Adult↗
PubMed1997

Nervous control of male sexual drive in the hermaphroditic snail

We studied the role of the prostate gland in determining the level of male sexual drive in the hermaphroditic pond snail Lymnaea stagnalis. Male sexual drive is high after a period of social isolation and decreases after copulation as a male. A positive correlation exists between the level of male sexual drive and the volume of the prostate gland. Like male sexual drive, the volume of the prostate gland increases during a period of social isolation and decreases after copulation as a male. Behavioural experiments demonstrated that animals with a lesion of the nerve that innervates the prostate gland (NP1) have a lower level of male sexual drive after social isolation than control animals. However, lesion of NP1 did not affect the increase in the volume of the prostate gland caused by social isolation. Extracellular recordings from NP1 in a semi-intact preparation show a change in firing pattern during an experimentally induced increase in prostate gland volume. The results indicate that NP1 serves as a nervous pathway for the male sexual drive. We propose a simple motivational model for male sexual behaviour in L. stagnalis in which the volume of the prostate gland sets the level of male sexual drive.

Journal Article↗
PubMed1996

Identification of S-(2,3-dihydroxypropyl)cystein in a macrophage-activating lipopeptide from Mycoplasma fermentans.

Mycoplasmas are capable of stimulating monocytes and macrophages to release cytokines, prostaglandins, and nitric oxide. The aim of this study was to characterize the chemical nature of the previously isolated [Mühlradt, P. F., & Frisch, M. (1994) Infect. Immun. 62, 3801-3807] macrophage-stimulating material "MDHM" from Mycoplasma fermentans. Mycoplasmas were delipidated, and MDHM activity was extracted with octyl glucoside and further purified by reversed-phase HPLC. Macrophage-stimulating activity was monitored by nitric oxide release from peritoneal macrophages from C3H/HeJ endotoxin low responder mice. HPLC-purified MDHM was rechromatographed on an analytic scale RP 18 column before and after proteinase K treatment. Proteinase treatment did not diminish biological activity but shifted MDHM elution toward higher lipophilicity, suggesting that the macrophage-stimulating activity might reside in the lipopeptide moiety of a lipoprotein. Proteinase K-treated MDHM was hydrolyzed, amino groups were dansylated, and the dansylated material was isolated by HPLC. Dansylated S-(2,3-dihydroxypropyl)cystein (glycerylcystein thioether), typical for Braun's murein lipoprotein, and Dns-Gly and Dns-Thr were identified by tandem mass spectrometry. These amino acids were isolated from biologically active but not from the neighboring inactive HPLC fractions. IR spectra from proteinase K-treated, HPLC-purified MDHM and those from the synthetic lipopeptide [2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-CysSerSer AsnAla were very similar. The data, taken together, indicate that lipoproteins of a nature previously detected in eubacteria are expressed in M. fermentans and that at least one of these lipoproteins and a lipopeptide derived from it constitute the macrophage-activating principle MDHM from these mycoplasmas.

Animals↗
PubMed1996

Phagocytosis and intracellular killing of serum-opsonized Staphylococcus aureus by mouse fibroblasts expressing human Fcgamma receptor type IIa (CD32).

Phagocytes bear more than one class of receptors for the Fc domain of IgG (FcgammaR). In addition the same ligand can interact with different classes of FcgammaR. This complexity makes it difficult to study the contribution of the various classes of FcgammaR to antimicrobial functions. To circumvent this difficulty, in the present study mouse 3T6 fibroblasts transfected with cDNA encoding for human FcgammaR type IIa (FcgammaRIIa-expressing cells) were used to determine the role of this receptor in phagocytosis and intracellular killing of serum-opsonized Staphylococcus aureus. Experiments using microbiological and fluorescent techniques to discriminate between cell-adherent and intracellular bacteria revealed that serum-opsonized bacteria are phagocytized by FcgammaRIIa-expressing cells, but not by parental fibroblasts. Non-opsonized bacteria were poorly internalized by FcgammaRIIa-expressing as well as parental fibroblasts. Furthermore, incubation of FcgammaRIIa-expressing cells with opsonized bacteria at 4oC and incubation of FcgammaRIIa-expressing cells with cytochalasin E prior to addition of opsonized bacteria inhibited the phagocytosis of these bacteria almost completely. Phagocytosis of opsonized bacteria by FcgammaRIIa-expressing cells was partly inhibited by selective inhibition of protein tyrosine kinases (PTK). FcgammaRIIa cross-linking initiated transient tyrosine phosphorylation of various proteins in FcgammaRIIa-expressing cells. These data indicate that activation of PTK is involved in the FcgammaRIIa-mediated phagocytosis of opsonized S. aureus by transfected fibroblasts. Human serum from normal individuals and agammaglobulinemic patients triggered the intracellular killing of S. aureus by FcgammaRIIa-expressing fibroblasts. Surprisingly, heat-inactivated human serum, IgG and incubation with anti-FcgammaRII antibodies followed by a bridging secondary antibody did not stimulate the killing process. The possibility that these ligands did not interact with FcgammaRIIa on the cells can be excluded since they induced tyrosine phosphorylation of cellular proteins. The serum factor that stimulates the intracellular killing of bacteria by FcgammaRIIa-expressing cells is not yet identified. Oxygen-independent mechanisms are thought to be responsible for the killing of intracellular bacteria by these cells since the NADPH oxidase inhibitor diphenylene iodonium did not affect the serum-stimulated intracellular killing of S. aureus and no reactive oxygen and nitrogen intermediates were produced by FcgammaRIIa-expressing cells after appropiate stimulation. Taken together, these data show that phagocytosis but not intracellular killing of S. aureus is mediated via FcgammaRIIa on cells expressing this receptor.

Animals↗
PubMed1996

Synthesis and antiviral activity of 2'-deoxy-4'-thio purine nucleosides.

A series of 2'-deoxy-4'-thioribo purine nucleosides was prepared by trans-N-deoxyribosylase-catalyzed reaction of 2'-deoxy-4'-thiouridine with a variety of purine bases. This synthetic procedure is an improvement over methods previously used to prepare purine 4'-thio nucleosides. The compounds were tested against hepatitis B virus (HBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV-1 and HSV-2), varicella zoster virus (VZV), and human immunodeficiency virus (HIV-1). Cytotoxicity was determined in a number of cell lines. Several compounds were extremely potent against HBV and HCMV and had moderate to severe cytotoxicity in vitro. The lead compound from the series, 2-amino-6-(cyclopropylamino)purine 2'-deoxy-4'-thioriboside, was the most potent and selective agent against HCMV and HBV replication in vitro; however, this analogue was nephrotoxic when tested in vivo.

Antiviral Agents↗
PubMed1996

Introduction of a New Coaxial Falloposcopy System

Coaxial falloposcopy is a transcervical approach to visualizing the entire fallopian tubal lumen from the uterotubal ostium (UTO). To eliminate bulky camera attachments and poor image quality, a new falloposcopy system was developed with a small articulating-tip hysteroscope, stabilizing device to maintain UTO alignment, flexible coaxial catheter and guidewire, and 0.4-mm outer diameter falloposcope with enhanced fiberoptics. We used the instrument in 23 women with a diagnosis of proximal (PTO) or distal (DTO) tubal obstruction (group 1, 16 patients, 30 tubes) or unexplained infertility (group 2, 4 patients, 7 tubes) after previous hysterosalpingogram or laparoscopy. Successful cannulation was achieved in 31 (83.3%) of 37 tubes. Fibrosis of the UTO prevented access to two tubes. In group 1, 14 of 23 tubes with presumed PTO were patent and normal at falloposcopy. In group 2, pathology was present in two of seven tubes. A false positive diagnosis was made in 61% of tubes with presumed PTO and false negative diagnosis in 29% of presumably normal tubes. Coaxial falloposcopy is an effective means of assessing the tubal lumen and should become a more routine part of infertility evaluations.

Journal Article↗
PubMed1995

The CAMP effect of Actinobacillus pleuropneumoniae is caused by Apx toxins.

Actinobacillus pleuropneumoniae shows synergistic haemolysis when cocultured with Staphylococcus aureus on blood agar plates. This CAMP effect has been attributed to a discrete CAMP factor, but also to the A. pleuropneumoniae-RTX-toxins I, II, and III. We examined the CAMP effect of recombinant Escherichia coli strains that secreted each of these toxins, and of A. pleuropneumoniae mutant strains that were devoid of one or more these toxins. We found that the E. coli strains were CAMP positive, whereas the A. pleuropneumoniae strain devoid of functional toxin genes was CAMP negative. This demonstrated that the CAMP effect of A. pleuropneumoniae is caused by the toxins and that no CAMP factor per se exists.

Actinobacillus pleuropneumoniae↗
PubMed1995

Isobutyramide therapy in patients with sickle cell anemia.

We have administered Isobutyramide as a suspension over a period of 3 months, from a starting dose of 50 mg/kg/day up to 150 mg/kg/day, to four adult sickle cell (SS) anemia patients. The maximum dose was maintained for 3 weeks. The blood counts remained stable and the Hb F levels decreased slightly. The G gamma levels increased at the end of the trial, suggesting activation of the G gamma gene at the highest dose of Isobutyramide. Three patients showed a stable rate of hemolysis, while in one patient, an increase of lactate dehydrogenase occurred. None of the patients experienced pain crisis or organ-specific crisis, but all four complained about mild epigastric burning and a bitter taste. After the first month of treatment one patient complained about intolerable epigastric discomfort which was relieved by Omeprazole. Another patient complained about increasing dyspepsia in the 12th week leading to the termination of the trial. Oral Isobutyramide administration does not qualify as an effective treatment of SS patients.

Adult↗
PubMed1995

Molecular investigation of the role of ApxI and ApxII in the virulence of Actinobacillus pleuropneumoniae serotype 5.

The extracellular hemolytic toxins (ApxI and ApxII) of Actinobacillus pleuropneumoniae are thought to be important factors in this microorganism's virulence and the pathogenesis of swine pleuropneumonia. Using the polymerase chain reaction, the apxI locus of a non-hemolytic, avirulent mutant of A. pleuropneumoniae serotype 5 (mIT4-H) generated by chemical mutagenesis (Inzana T. J., Todd J., Veit H. P. Microb Pathog 1991; 10: 281-96) was found to contain deletions that affected major parts of the entire apxICABD operon, thus inactivating each gene in the operon. The apxII locus was not affected. Monoclonal antibodies to ApxI and ApxII were used to confirm that ApxI was not synthesized, and that ApxII was synthesized but not secreted from the cell. The apxICABD genes and apxIBD genes were cloned into a broad host range vector to obtain plasmids pJFF800 and pJFF801, respectively. Each recombinant plasmid was electroporated into strain mIT4-H to obtain strain mIT4-H/pJFF800 and strain mIT4-H/pJFF801, respectively. Strain mIT4-H/pJFF800 exported ApxI and ApxII, and produced hemolytic activity comparable to or exceeding that of wild type strain J45. Strain mIT4-H/pJFF801 exported only ApxII and produced weak hemolytic activity. Strain mIT4-H/pJFF800 was virulent in mice, and had an LD50 of about 2 x 10(6) colony forming units. In contrast, mIT4-H/pJFF801 and mIT4-H were essentially avirulent in mice, and LD50s for these strains could not be calculated. Strain mIT4-H/pJFF800 was virulent in pigs and caused lethal pleuropneumonia, whereas parent strain mIT4-H was avirulent. Strain mIT4-H/pJFF801 was also able to induce pleuropneumonia in pigs, although a higher dose was required to induce lesions similar to those caused by mIT4-H/pJFF800. Thus, A. pleuropneumoniae strains that produce ApxI and ApxII require ApxI for full virulence and toxic activity in pigs. However, other factors including ApxII contribute to the virulence of A. pleuropneumoniae in pigs.

Actinobacillus Infections↗
PubMed1995

Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides in rabbits receiving single and repeated doses of morphine.

The pharmacokinetics of morphine in plasma and the distribution of morphine and its glucuronidated metabolites within the cerebrospinal fluid were investigated in rabbits. After single morphine dosage, the plasma AUC ratio of morphine-3- glucuronide/morphine was 11.1 compared with 0.14 for morphine-6-glucuronide/morphine. The similar elimination half-lives of morphine (107 min), morphine-3-glucuronide (122 min), and morphine-6-glucuronide (105 min) suggested the glucuronidation to be the rate-limiting step, which was substantiated by the observation that morphine-3-glucuronide becomes eliminated four times faster when applied intravenously. Both after single and repeated morphine administration, the ratios of CSF and plasma levels of the parent drug were higher than those of morphine-3-glucuronide or morphine-6-glucuronide. These data demonstrate a poor penetration of the glucuronides across the blood-brain barrier and do not support the previously postulated accumulation of morphine-6-glucuronide in the central nervous system during chronic morphine treatment.

Animals↗
PubMed1995

Knockout mutants of Actinobacillus pleuropneumoniae serotype 1 that are devoid of RTX toxins do not activate or kill porcine neutrophils.

The Actinobacillus pleuropneumoniae RTX-toxins ApxI, ApxII, and ApxIII are important virulence factors of this swine pathogen. It is hypothesized that the Apx toxins are deleterious to defense cells of the host, enabling the bacterium to infect the host. To confirm this, we studied the effect on porcine polymorphonuclear neutrophils of mutant strains of A. pleuropneumoniae that were devoid of Apx toxins. For this purpose, we developed a system for targeted mutagenesis of A. pleuropneumoniae based on the conditionally replicating plasmid pVE6063 and insertional mutagenesis by homologous recombination. Employing this system on the reference strain of serotype 1, a strain that secretes ApxI and ApxII, we generated mutant strains that were devoid of ApxI and/or ApxII. We compared the ability of the parent strain and the mutant strains to provoke an oxidative burst in porcine neutrophils and to kill these cells. The parent strain and mutants that secreted either ApxI or ApxII provoked an oxidative burst and killed the neutrophils, whereas mutant strains that were devoid of ApxI and ApxII did not. These experiments indicate the importance of ApxI and ApxII to these profound effects on neutrophils and emphasize the importance of ApxI and ApxII in pathogenesis.

Actinobacillus pleuropneumoniae↗
PubMed1995

Chondramides A approximately D, new antifungal and cytostatic depsipeptides from Chondromyces crocatus (myxobacteria). Production, physico-chemical and biological properties.

Novel depsipeptides, named chondramides were produced at levels up to 4.3 mg/liter by several myxobacteria of the genus Chondromyces. The compounds are structurally closely related to jaspamide/jasplakinolide from marine sponges of the genus Jaspis. Initially the chondramides were detected in acetone extracts of the biomass of Chondromyces crocatus, strain Cm c2. So far, four structural variants could be characterized, the chondramides A approximately D. They inhibited the growth of a few yeasts and showed high cytostatic activity against cultivated human and animal cells.

Animals↗