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Biomedical subjects

T Koch

Publications and source records attributed to T Koch.

At least 127 records · Page 7Linked to original sources
PubMed1999

Identifying strategies for managing urinary incontinence with women who have multiple sclerosis.

The aim of this pilot project was to identify strategies for managing incontinence with women who have multiple sclerosis (MS). The project used the formation of a group in which eight women with MS and four Continence Nurse Advisers (CNAs) and the first author were brought together. In the course of the research process, the women found a voice on a topic previously thought of as taboo. When they realized that they had suffered alone and in silence they felt empowered to act. In this way, the methodology evolved from group work into a participatory action research process (PAR), as the group initiated action. Participants formed a self-help group, and continued to meet with each other after the research had run its course.

Activities of Daily Living↗
PubMed1999

Women living with type II diabetes: the intrusion of illness.

This study is part of a larger research project which aimed to create an understanding of how people with type II diabetes incorporated chronic illness into their lives. We aimed to find wellness in the context of a chronic illness. The participatory action-orientated research (PAR) approach is consumer based and managed, and six women with diabetes and the research team met for eight two-hour sessions in August and September 1998. The objectives were to contribute to understanding of the health of adults who live with chronic illness by providing greater insight and understanding into the worlds of people who live with a chronic illness and allowing the voices of people with diabetes to be clearly heard in relation to their health. There was a wellness theme around taking time out, but considering the other dominant negative experiences, this study can only be considered as an attempt to find wellness in the context of chronic illness. The PAR process, built upon sharing, listening and reconstructing stories, worked toward the women being heard and having a voice for the first time. Listening and acting upon the voices of the women has implications for the practice of health care professionals.

Activities of Daily Living↗
PubMed1999

Pancreatitis-associated protein protects the lung from leukocyte-induced injury.

BACKGROUND: Severe pancreatitis is often complicated by shock and acute lung failure. Little is known about the pathophysiologic impact of the 16.6-kD lectine, named pancreatitis-associated protein (PAP), which is expressed during pancreatitis and which reduces mortality in a rat model with severe pancreatitis. Therefore, the aim of this study was to investigate the effects of PAP on the pulmonary vasculature after leukocyte activation with N-formyl-Met-Leu-Phe (fMLP). METHODS: The experiments were performed in buffer-perfused isolated rabbit lungs. Mean pulmonary artery pressure, weight gain, and thromboxane A2 synthesis of the lungs were monitored. PAP was obtained by affinity chromatography of pancreas juice from pancreatitic rats. The authors tested whether treatment with PAP (260 microg/l, n = 9; or 500 microg/l, n = 6) before fMLP injection (10(-6) M) influences mean pulmonary artery pressure and edema formation. Lungs that were treated only with fMLP (n = 6) served as controls. Additional experiments in which PAP was applied were performed to study whether PAP (260 microg/l, n = 3; 500 microg/l, n = 3; 1,000 microg/l, n = 3) itself effects lung vasculature. RESULTS: Application of fMLP resulted in an increase of mean pulmonary artery pressure (+/- SD) from 8 +/- 2 mmHg up to 26 +/-13 mmHg (P < 0.01) at a flow of 150 ml/min. Pretreatment with PAP reduced the peak pressure developed after fMLP to 15 +/- 7 mmHg (PAP 260 microg/l; P < 0.05) and to 9 +/- 4 mmHg (PAP 500 microg/l), respectively. In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration. In parallel to the attenuated pressure increase, thromboxane A2 release was significantly suppressed in the 260-microg/l (200 +/- 220 pmol x ml(-1) x min(-1); P < 0.01) and 500-microg/l (285 +/- 70 pmol x m(-1) x min(-1); P < 0.05) PAP groups compared with controls (1,138 +/- 800 pmol x ml(-1) x mi(-1)). Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release. CONCLUSION: Clinically relevant concentrations of PAP prevented fMLP-induced vasoconstriction and edema formation in the lung. These findings point toward a protective effect of PAP on polymorphonuclear neutrophil leukocyte-mediated lung injury.

Acute-Phase Proteins↗
PubMed1999

Pentoxifylline improves bacterial clearance during hemorrhage and endotoxemia.

OBJECTIVE: The aim of this study was to investigate whether the methylxanthine-derivative pentoxifylline (PTX) affects bacterial clearance of the organism in states of hemorrhage and endotoxemia. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Fifty-four female chinchilla rabbits. INTERVENTIONS: To quantify the clearance process, defined numbers (10(7) CFO) of Escherichia coli bacteria were injected intravenously into anesthetized rabbits, 60 mins after induction of hemorrhage (n = 9 + 3) or infusion of endotoxin (lipopolysaccharide [LPS]; 40 microg/kg/hr; n = 9 + 3) and after saline infusion (control; n = 9), respectively. Hemorrhage was induced by bleeding, standardized by defined reduction of mean arterial pressure (30% of baseline value). To evaluate the potential effects of PTX on bacterial elimination and killing, in states of hemorrhage and endotoxemia, blood clearance of E. coli and colonization of different organs were investigated after pretreatment with PTX (30 mg/kg) as a bolus injection followed by continuous infusion of PTX (50 mg/kg/hr) in hemorrhagic (n = 9) and endotoxemic rabbits (n = 9). Three additional experiments were performed to evaluate the effects attributable to PTX itself. MEASUREMENTS AND MAIN RESULTS: Parameters monitored were rates of bacterial and LPS elimination from the blood, arterial blood pressure, blood gases, and serum lactate concentrations. Additionally, flow cytometric analysis of respiratory burst activity was performed. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, kidney, spleen, and lung were collected for bacteriologic examinations. Compared with the controls, hemorrhage and endotoxemia resulted in a significantly prolonged elimination of injected E. coli from the blood. The delayed blood clearance was associated with a significantly (p < .01) higher bacterial colonization of all organs, which was most pronounced in the lung. Pretreatment with PTX slightly enhanced blood clearance of E. coli as well as of LPS, and significantly reduced (p < .05) the colonization of lung and kidney after hemorrhage and endotoxemia. Furthermore, PTX suppressed polymorphonuclear neutrophil respiratory burst activity. CONCLUSIONS: Hemorrhage and endotoxemia induce impaired bacterial clearance from blood and tissue. Treatment with PTX may reduce the risk of bacterial infections by attenuating bacterial colonization of organs in states of hemorrhage and endotoxemia.

Animals↗
PubMed1999

Characterization and distribution of endothelin receptors in the pulmonary circulation: investigation of isolated, perfused, and ventilated rabbit lungs.

The aim of the study was to investigate the distribution of 2 subtypes of endothelin-receptors, mediating the effects of endothelin-1 (ET-1) in the pulmonary circulation. Until now, it is still unclear, whether ET(A) receptors or ET(B) receptors or even both are localized in pulmonary vessels. The experiments were performed on 72 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. The arterial pressure and the lung weight gain were continuously registered. Intermittently perfusate samples were taken for determination of thromboxane A2 (TXA2) and prostacyclin (PGI2). The injection of ET-1 (10(-8) M, n = 6) resulted in a biphasic increase in pulmonary arterial pressure (PAP) that was accompanied by the generation of TXA2 and PGI2. Pretreatment with the ET(A)-receptor antagonist LU135252 (10(-6) M, n = 6) suppressed the pressure response after ET-1 application (P < 0.01 at 120 min) and reduced the generation of TXA2 (P < 0.05 at 120 min) and PGI2 (P < 0.05 at 120 min). Pretreatment with the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6) also reduced the PAP increase after ET-1 injection. In contrast to this, the pulmonary vascular pressure reaction after ET-1 application was elevated, when ET(B)-receptor antagonist BQ788 (10(-6) M; n = 6) was given. Furthermore, the PGI2 to TXA2 ratio was shifted from 2.3 to 0.9, reflecting a predominance of vasoconstrictive TXA2. The simultaneous application of LU135252 and BQ788 significantly reduced the PAP increase after ET-1 application, but no beneficial effects were observed compared with the application of LU135252 solely. The injection of the ET(B)-receptor agonist sarafotoxin S6c (S6c; 10(-8) M, n = 6) also induced an increase in PAP that was not attenuated by pretreatment with the ET(B)-receptor antagonist BQ788 (10(-6) M, n = 6). LU135252 (n = 6) as well as the application of LU135252 in combination with BQ788 (n = 6) failed to suppress the pressure response after S6c, whereas the cyclooxygenase inhibitor diclofenac (10 microg/mL, n = 6) alone and in combination with LU135252 and BQ788 (n = 6) was able to prevent the PAP increase after S6c injection (P < 0.001). The results demonstrate that the ET-1-induced increase in pulmonary vascular resistance is mainly mediated via ET(A) receptors, whereas ET(B) receptors seem to mediate vasodilation, which was shown by an imbalance of TXA2 and PGI2 generation. On the other hand, the ET(B)-receptor agonist S6c induced vasoconstriction, which was only attenuated by the cyclooxygenase inhibitor diclofenac. From the current results we conclude that, apart from vasoconstrictor ET(A) receptors, at least 2 ET(B)-receptor subtypes are expressed in the pulmonary circulation, one mediating vasoconstriction, which was not blocked by BQ788, and one mediating vasodilation, which was influenced by BQ788.

Animals↗
PubMed1999

Differential induction of plant volatile biosynthesis in the lima bean by early and late intermediates of the octadecanoid-signaling pathway.

Plants are able to respond to herbivore damage with de novo biosynthesis of an herbivore-characteristic blend of volatiles. The signal transduction initiating volatile biosynthesis may involve the activation of the octadecanoid pathway, as exemplified by the transient increase of endogenous jasmonic acid (JA) in leaves of lima bean (Phaseolus lunatus) after treatment with the macromolecular elicitor cellulysin. Within this pathway lima bean possesses at least two different biologically active signals that trigger different biosynthetic activities. Early intermediates of the pathway, especially 12-oxo-phytodienoic acid (PDA), are able to induce the biosynthesis of the diterpenoid-derived 4,8, 12-trimethyltrideca-1,3,7,11-tetraene. High concentrations of PDA result in more complex patterns of additional volatiles. JA, the last compound in the sequence, lacks the ability to induce diterpenoid-derived compounds, but is highly effective at triggering the biosynthesis of other volatiles. The phytotoxin coronatine and amino acid conjugates of linolenic acid (e.g. linolenoyl-L-glutamine) mimic the action of PDA, but coronatine does not increase the level of endogenous JA. The structural analog of coronatine, the isoleucine conjugate of 1-oxo-indanoyl-4-carboxylic acid, effectively mimics the action of JA, but does not increase the level of endogenous JA. The differential induction of volatiles resembles previous findings on signal transduction in mechanically stimulated tendrils of Bryonia dioica.

Amino Acids↗
PubMed1999

Replacement of threonine 394 by alanine facilitates internalization and resensitization of the rat mu opioid receptor.

Signaling of G protein-coupled receptors is terminated by phosphorylation of intracellular serine and threonine residues. Resensitization of these receptors requires internalization and subsequent dephosphorylation. We have recently shown that the resensitization rate of the rat micro opioid receptor (MOR) isoforms MOR1 and MOR1B is mainly determined by the amino acid composition of their alternatively spliced C-terminal tails. Upon agonist stimulation, MOR1B passes through an accelerated cycle of receptor endocytosis and reactivation, which in turn promotes a greater resistance to agonist-induced desensitization, as compared with MOR1. Given the fact that MOR1B lacks only one putative phosphorylation site (T394 of MOR1), we replaced this threonine by an alanine and stably expressed the wild-type MOR1 and its T394A mutant in mouse neuroblastoma Neuro2a cells. We show that during prolonged [D-Ala2, MePhe4, Gly5-ol]enkephalin exposure (5 h), the T394A receptor mutant desensitized at a slower rate than MOR1. In contrast, T394A is more rapidly removed from the cell surface than MOR1, as determined by flow cytometry using epitope-tagged receptors. This fast internalization was followed by immediate resensitization of T394A during 20 min of agonist removal while the wild-type MOR1 remained inactive. Similar to MOR1B, rapid internalization and reactivation of T394A may explain its delayed desensitization. These findings suggest that T394 represents a negative regulatory signal for MOR1 internalization. Furthermore, phosphorylation of this threonine residue may influence the time course of micro opioid receptor resensitization.

Alanine↗
PubMed1999

Detection of the factor V Leiden mutation by direct allele-specific hybridization of PCR amplicons to photoimmobilized locked nucleic acids.

BACKGROUND: Individuals carrying the factor V Leiden mutation have been shown to have an increased risk of developing venous thromboembolism. Our aim was to develop an ELISA-like assay to detect the mutation in PCR-amplified genomic DNA using novel, high-affinity DNA analogs, termed locked nucleic acids (LNAs). METHODS: LNA octamer probes complementary to the factor V wild-type or mutated sequence were covalently attached to individual wells of a microtiter plate. Biotinylated factor V amplicons were added, and hybridization to the immobilized LNA probes was scored colorimetrically using a horseradish peroxidase-anti-biotin Fab conjugate and tetramethylbenzidine substrate. RESULTS: In a prospective study of 53 patients, the assay reproducibly scored both factor V homozygotes and heterozygotes with excellent sensitivity and specificity. All results were in complete agreement with the results obtained with the conventional PCR-restriction fragment length polymorphism technique. CONCLUSIONS: The simplicity of the assay and its procedural relatedness to the widely used ELISA format should make it useful for routine factor V testing in the clinical laboratory.

Alleles↗
PubMed1999

Understanding what is important for women who live with multiple sclerosis.

In this pilot-project eight women with multiple sclerosis (MS), four Continence Nurse Advisers (CNAs) and one researcher formed a participatory action research (PAR) group. Ten group sessions were held in 1997. The CNAs found that 80 of their referrals for continence management were women with MS and they wanted to explore the way in which women manage their incontinence. Although the group was brought together to discuss incontinence, other emergent themes were raised by the women. These themes were: women's ad hoc experience with community services, their problems concerning access to toilets for the disabled, concern with health professionals' lack of knowledge about MS, their formidable experiences of hospitalisation and respite care admissions, their individual efforts in maintaining wellness in the context of chronic illness and the effect of MS on sexual relationships.

Adaptation, Psychological↗
PubMed1998

Enzymatic reaction with unnatural substrates: DNA photolyase (Escherichia coli) recognizes and reverses thymine [2+2] dimers in the DNA strand of a DNA/PNA hybrid duplex.

Peptide nucleic acids (PNA) are mimics with normal bases connected to a pseudopeptide chain that obey Watson-Crick rules to form stable duplexes with itself and natural nucleic acids. This has focused attention on PNA as therapeutic or diagnostic reagents. Duplexes formed with PNA mirror some but not all properties of DNA. One fascinating aspect of PNA biochemistry is their reaction with enzymes. Here we show an enzyme reaction that operates effectively on a PNA/DNA hybrid duplex. A DNA oligonucleotide containing a cis, syn-thymine [2+2] dimer forms a stable duplex with PNA. The hybrid duplex is recognized by photolyase, and irradiation of the complex leads to the repair of the thymine dimer. This finding provides insight into the enzyme mechanism and provides a means for the selective repair of thymine photodimers.

Base Sequence↗
PubMed1998

Olanzapine-induced Fos expression in the rat forebrain; cross-tolerance with haloperidol and clozapine.

Acute administration of the atypical antipsychotic drug olanzapine (5 mg kg(-1 i.p.) increased the number of Fos-positive cells moderately in the prefrontal cortex and the striatum; more pronounced were the effects in the nucleus accumbens, the lateral septum, the hypothalamic paraventricular nucleus and the amygdala. The acutely-induced Fos responses of olanzapine were significantly reduced in all brain areas investigated after a 3-week treatment period, indicating the development of tolerance. Through evaluation of cross-tolerance we investigated whether the effects of olanzapine, haloperidol and clozapine on Fos expression and on plasma corticosterone are mediated by the same or by different mechanisms. Cross-tolerance between olanzapine and either haloperidol or clozapine was assessed by the administration of a challenge dose of olanzapine to rats, that were pretreated for 3 weeks with either the same drug, with saline (1 ml kg(-1) day(-1), haloperidol (1 mg kg(-1) day(-1) or clozapine (20 mg kg(-1) day(-1). A competitive dose of olanzapine in long-term haloperidol-treated rats showed cross-tolerance in the rostral part of the cingulate cortex, the dorsomedial and the dorsolateral striatum, the nucleus accumbens and the lateral septum. Cross-tolerance between olanzapine and clozapine, however, was limited to limbic nuclei, including the prefrontal cortex, the lateral septum, the hypothalamic paraventricular nucleus and the amygdala, with minor effects in the mid- and caudal parts of the cingulate cortex. Interesting are the common effects in the lateral septum, possibly an important target for antipsychotic efficacy. Olanzapine administration induced elevated levels of plasma corticosterone and cross-tolerance was seen in haloperidol- and clozapine-pretreated rats.

Animals↗
PubMed1998

Hairpin-forming peptide nucleic acid oligomers.

A series of partially self-complementary peptide nucleic acid (PNA) oligomers was prepared. Examination of their melting behavior, circular dichroism spectra, and fluorescence properties reveals that these PNA oligomers exist as stem-loop ("hairpin") structures. Fluorescence is readily observed in hairpins containing a covalently linked, emissive acridine derivative which is, at least partially, intercalated in the duplex region of the PNA hairpin. The acridine fluorescence is quenched when an anthraquinone derivative is covalently attached to the PNA so that it is bound near the acridine in the hairpin structure. Acridine fluorescence is restored in hairpins containing both the anthraquinone and the acridine by increasing the temperature and melting the structure to its linear form or by opening the hairpin through formation of a hybrid duplex with complementary DNA. The latter process may form the basis for development of selective and sensitive DNA assays.

Aminacrine↗
PubMed1998

Inhibition of PNA triplex formation by N4-benzoylated cytosine.

The synthesis of N-((N4-(benzoyl)cytosine-1-yl)acetyl)- N -(2-Boc-aminoethyl)glycine (CBz) and the incorporation of this monomer into PNA oligomers are described. A single CBzresidue within a 10mer homopyrimidine PNA is capable of switching the preferred binding mode from a parallel to an antiparallel orientation when targeting a deoxyribonucleotide sequence at neutral pH. The resulting complex has a thermal stability equal to that of the corresponding PNA-DNA duplex, indicative of a strong destabilization of Hoogsteen strand PNA binding due to steric interference by the benzoyl moieties. Accordingly, incorporation of the CBz residue into linked PNAs (bis-PNAs) results in greatly reduced thermal stability of the formed PNA:DNA complexes. Thus, incorporation of the CBz monomer could eliminate the stability bias of triplex-forming sequences in PNA used in hybridization arrays and combinatorial library formats. Furthermore, it is shown that the benzoyl moiety does not severely interfere with Watson-Crick hydrogen bonding, thereby presenting an interesting route for novel cytosine modifications.

Benzoates↗
PubMed1998

Carboxyl-terminal splicing of the rat mu opioid receptor modulates agonist-mediated internalization and receptor resensitization.

The rat mu opioid receptor is alternatively spliced into two isoforms (MOR1 and MOR1B) which differ in length and amino acid composition at the carboxyl terminus. When stably expressed in HEK 293 cells, both splice variants bind the mu receptor agonist [D-Ala2,N-Me-Phe4,-Gly-ol5]enkephalin (DAMGO) with similar affinity and exhibit functional coupling to adenylyl cyclase with similar efficiency. However, the shorter isoform, MOR1B, desensitized at a slower rate during prolonged DAMGO exposure (4 h) but resensitized at a faster rate than MOR1 during agonist withdrawal (20 min). Immunocytochemical analysis revealed that DAMGO-induced internalization of MOR1B proceeded much faster than that of MOR1 followed by rapid recycling of the receptor to the cell surface. In addition, the greater resistance of MOR1B to homologous desensitization compared with MOR1 as well as MOR1B resensitization was abolished when receptor reactivation/recycling was blocked with monensin, an inhibitor of endosomal acidification. It is concluded that the sequence at the cytoplasmic tail of MOR1B facilitates clathrin-coated vesicle-mediated endocytosis which, in turn, promotes accelerated receptor reactivation. Taken together, our findings suggest that carboxyl-terminal splicing of the rat mu opioid receptor modulates agonist-induced internalization and receptor resensitization.

Alternative Splicing↗
PubMed1998

Methylazoxymethanol acetate-induced abnormalities in the entorhinal cortex of the rat; parallels with morphological findings in schizophrenia.

It has been suggested repeatedly that the non-heritable factors in the pathogenesis of schizophrenia involve abnormalities of prenatal neurodevelopment. Furthermore, post-mortem studies show neuropathology of apparently developmental origin in the entorhinal cortex and other brain regions of schizophrenic subjects. In an attempt to model a developmental defect of the entorhinal region in the rat, cerebrocortical proliferation was briefly interrupted during its earliest stages, when the entorhinal area is thought to undergo major cell division. Specifically, the experimental set-up involved the administration of methylazoxymethanol acetate (MAM) on 1 of 4 consecutive days of embryonal development, from E9 to E12. Analysis of the forebrain in adult animals shows reduction of the entorhinal cortex in rats treated on each of these days. This effect shifts from lateral to medial divisions of the entorhinal cortex with later administration of MAM, following a known developmental gradient. Morphological consequences of MAM administration appear to be largely confined to the entorhinal cortex in the groups treated on E9 to E11, although slight reductions of the frontal and occipital neocortex were also observed in these animals. MAM treatment on E12 produces relatively more widespread damage, as reflected among other in a small reduction of brain weight. The described brain abnormalities are not accompanied by obvious phenotypical changes in any, but the E12-treated group. They, moreover, involve cortical thinning, disorganised cortical layering, and abnormal temporal asymmetries. These finding bare some similarity to observations in brains of schizophrenic subjects. The possible relevance of this approach in modeling neurodevelopmental aspects of schizophrenia is discussed.

Animals↗