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Biomedical subjects

H Meyer

Publications and source records attributed to H Meyer.

At least 37 records · Page 2Linked to original sources
PubMed2004

[[1]Benzothieno[3,2-b]pyridin-4-yl-amine--synthesis and investigation of activity against malaria].

The ethyl 4-chlorobenzothieno[3,2-b]pyridine-3-carboxylate (2) reacted with the hydrochlorides of the mono- and bis-phenol Mannich bases 6 to yield the amodiaquine and pyronaridine analogues 9. The chloroquine analogue 10 was formed by melting 2 with the novaldiamine base (7) in phenol. The stability of the 4-aminophenols 9 was investigated by anodic oxidation using the rotating platinum electrode by means of difference pulse voltammetry. The half wave potentials were measured giving E(1/2) approximately 1.05 V. Compound 9g displayed the highest activity against the growth of the malaria parasite Plasmodium falciparum. Testing against the chloroquine sensitive 3D7 and the chloroquine resistant Dd2 strain resulted in IC50 values of 150 nM and 210 nM, respectively. Surprisingly, the 3-carbinol 4 and the 3-chloromethyl derivative 5, synthesized from the 3-carboxylic acid ester 2, reacted with the phenol Mannich base 6a and the novaldiamine base (7), respectively, to yield the 4-pyridone 8.

Amines↗
PubMed2004

[Chloroquine analogues from benzofuro- and benzothieno[3,2-b]-4-pyridone-2-carboxylic acid esters].

The amides 7 were synthesized from the annulated methyl 4-pyridone-2-carboxylates 4 via the carboxylic acids 5 and their acid chlorides by reacting with the novaldiamine base 6. The alcohol 8b, obtained from DIBAH reduction of the ester 4b, was transformed to the chloromethyl derivative 9 which reacted with 6 and 18-crown-6 leading to the 2-novaldiaminomethyl-4-pyridone 10. Compound 10 was obtained with higher yield from DIBAH reduction of the amide 7b. The substances 7 and 10 were inactive when tested against the chloroquine resistant Plasmodium falciparum strain Dd2.

Animals↗
PubMed2004

[Bisbenzofuro[3,2-b: 2',3'-e]pyridines].

Heating the potassium 3-enaminobenzo[b]furan-2-carboxylate 3 in acetic acid on 110 degrees C yielded the pentacyclic acetate 6. The acetic acid 7, formed by hydrolysis of the ester 6, decarboxylated easily giving 6-methyl-bis[1]benzofuro[3,2-b: 2',3'-e]pyridine (8).

Antimalarials↗
PubMed2004

[Bisbenzothieno[3,2-b: 2',3'-e]pyridines].

Heating potassium 3-aminobenzo[b]thiophene-2-carboxylate (1) with ethyl propiolate or ethyl 3-ethoxyacrylate in acetic acid yielded the ethyl 2-(6,12-Dihydro-bis[1]benzothieno[3,2-b:2',3'-e]pyridin-6-yl)acetate (3) as main product and 1,4-dihydro-[1]benzothieno[3,2-b]-4-pyridone (2) as by-product. The dihydropyridine (DHP) 3 was dehydrogenated with ammonium cerium nitrate (CAN) to give the pyridine (Py) 4. The half wave potential E(1/2) = 1.64 V showed that 3 was much more stable against oxidizing agents than the reference compound nifedipine with E(1/2) = 1.15 V. Alkaline saponification of the acetic acid ester 4 did not yield the corresponding acetic acid, because decarboxylation took place to form the methylpyridine 5.

Acetates↗
PubMed2004

[Pigs led by rope].

Up to the midth of the 20th century in central europa single pigs were led by a rope, fixed on a hindleg. This technique can be proved back by pictures to antique. As shown by several illustrations this form was customary during Middle Ages and later.

Animal Husbandry↗
PubMed2003

Convection in a very compressible fluid: comparison of simulations with experiments.

The time profile DeltaT(t) of the temperature difference, measured across a very compressible fluid layer of supercritical 3He after the start of a heat flow, shows a damped oscillatory behavior before steady-state convection is reached. The results for DeltaT(t) obtained from numerical simulations and from laboratory experiments are compared over a temperature range where the compressibility varies by a factor of approximately 40. First the steady-state convective heat current j(conv) as a function of the Rayleigh number Ra is presented, and the agreement is found to be good. Second, the shape of the time profile and two characteristic times in the transient part of DeltaT(t) from simulations and experiments are compared, namely (1) t(osc), the oscillatory period, and (2) t(p), the time of the first peak after starting the heat flow. These times, scaled by the diffusive time tau(D) versus Ra, are presented. The agreement is good for t(osc)/tau(D), where the results collapse on a single curve showing a power-law behavior. The simulation hence confirms the universal scaling behavior found experimentally. However for t(p)/tau(D), where the experimental data also collapse on a single curve, the simulation results show systematic departures from such a behavior. A possible reason for some of the disagreements, both in the time profile and in t(p), is discussed.

Journal Article↗
PubMed2003

Bcl-x(L) antisense oligonucleotides radiosensitise colon cancer cells.

Advanced colon cancer is a malignancy with poor response to various treatment modalities including ionising radiation (IR) and chemotherapy. Both IR and chemotherapeutic agents have been shown to act by inducing apoptosis, a type of cell death antagonised by the Bcl-x(L) gene product. Since approximately 60% of human colon cancers express Bcl-x(L), it was the aim of this study to explore the potential of Bcl-x(L) antisense oligonucleotides as a novel radiosensitisation strategy. Caco-2 colon cancer cells were treated with Bcl-x(L) antisense oligonucleotides in combination with IR or cisplatin, and Bcl-x(L) protein expression, apoptosis, cell viability and clonogenic survival were examined. Bcl-x(L) antisense oligonucleotide specifically reduced the Bcl-x(L) protein level by almost 50% in Caco-2 cells. The decreased threshold for the induction of apoptosis resulted in a 300% increase of apoptosis after IR or cisplatin treatment and led to a 60% reduction of cell proliferation beyond response rates achieved with IR. These data suggest that Bcl-x(L) is an important factor contributing to the treatment resistance of human colon cancer. Specific reduction of Bcl-x(L) protein levels by antisense oligonucleotides qualifies as a promising therapeutic strategy for colon cancer that may help overcome resistance and improve clinical outcome in this malignancy.

Antineoplastic Agents↗
PubMed2003

[Coronary heart disease in childhood in familial hypercholesteremia. Maximum therapy with LDL apheresis].

In children with familial hypercholesterolemia, coronary heart disease requires both medical theraphy and LDL apheresis. We report a case of verified occlusion of the anterior descending branch of the left coronary artery in a 10-year-old patient. The pathological findings revealed by ergometry established the diagnosis. The goal was to achieve the greatest possible reduction of lipid parameters and fibrinogen by lowering plasma viscosity employing LDL apheresis. It is astonishing that this treatment is also well tolerated by children. The basic vascular approaches suffice and shunt operations are not absolutely necessary. The efficacy of this method became vividly apparent by the changes in the skin lesions. Additional angiographic follow-up and further clinical course wil provide information on the usefulness of this treatment strategy with maximum lipid theraphy and the expected improvement in prognosis.

Anticholesteremic Agents↗
PubMed2003

Alpha2A and alpha2C-adrenoceptor regulation in the brain: alpha2A changes persist after chronic stress.

Stress-induced activation of the central nervous noradrenergic system has been suspected to induce depressive disorders. As episodes of depression often occur some time after a stress experience we investigated whether stress-induced changes in the alpha2-adrenoceptor (alpha2-AR) system persist throughout a post-stress recovery period. Brains of male tree shrews were analysed after 44 days of chronic psychosocial stress and after a subsequent 10-day recovery period. Expression of RNA for alpha2A and alpha2C-adrenoceptors was quantified by in situ hybridization, and receptor binding was determined by in vitro receptor autoradiography. Activities of the sympathetic nervous system and of the hypothalamo-pituitary-adrenal axis were increased during chronic stress but normalized during recovery. Alpha2A-AR RNA in the glutamatergic neurons of the lateral reticular nucleus was elevated significantly after stress and after recovery (by 29% and 17%). In the dorsal motor nucleus of the vagus, subtype A expression was enhanced after recovery (by 33%). In the locus coeruleus, subtype A autoreceptor expression was not changed significantly. Subtype C expression in the caudate nucleus and putamen was elevated by stress (by 5 and 4%, respectively) but normalized during recovery. Quantification of 3H-RX821002 binding revealed receptor upregulation during stress and/or recovery. Our data therefore show: (i) that chronic psychosocial stress differentially regulates expression of alpha2-adrenoceptor subtypes A and C; (ii) that subtype A heteroreceptor expression is persistently upregulated whereas (iii), subtype C upregulation is only transient. The present findings coincide with post mortem studies in depressed patients revealing upregulation of alpha2A-ARs.

Animals↗
PubMed2003

[Socioepidemic analysis of sources of information and medical care for a subpopulation of female and male participants in a nationwide informative campaign in Germany on "Danger Signal: Heartburn"].

Whilst the prevalence of gastroesophageal reflux is increasing, most people are unaware of its possible consequences. Therefore, in Autumn 2000 a nationwide information campaign was launched on the symptoms of gastroesophageal reflux and its possible treatments. One part of the information campaign was a telephone hotline which was followed by an interview by phone or a mailed questionnaire. The objective of this was to find out more about the people concerned and their complaints. The subjects of both data sets were on average 53 respectively 57 years old, half of them were female and over 60 % had had heartburn for more than two years. The interview showed that 53 % took notice of the hotline by a press release. The interviewed persons gathered information in general about health-related issues primarily from newspapers and TV reports and from their physician. 81.7 % of the questionnaire sample had already at least one gastroscopy. Another 9.5 % made use of medical services because of their complaints in the last year. 8.8 % used exclusively over-the-counter medication for relief from their complaints. These three groups of different degrees of utilisation differed in respect of age, intensity and duration of the symptom heartburn and lifestyle-factors such as smoking. Those who had a gastroscopy were older, symptoms were more prolonged, more severe, more often and comprised a wider range of symptoms and less cigarette consumption. The analysis of both samples showed that the telephone hotline was used mainly by people who had had their symptoms for a long time and had already been in medical care. The chosen means of information stated by the sample indicate that media are prominently involved in disseminating information and educating the public.

Age Factors↗
PubMed2003

Structure formation of supercooled polymers in confined geometries--a molecular-dynamics simulation study.

Molecular-dynamics simulations of thin polymer films are performed with a recently introduced coarse-grained model. This model reproduces many features of polymer crystallization from the melt. In this work, we show how confining walls influence the structure formation depending on the degree of supercooling. Already in the melt at high temperature a preorder is induced near the walls. On lowering the temperature, crystalline order nucleates at the walls, from which it propagates into the film. We show how this growth can be influenced by prestructuring the wall.

Journal Article↗
PubMed2002

L-H transition in the mega-amp spherical tokamak.

H-mode plasmas have been achieved on the MAST spherical tokamak at input power considerably higher than predicted by conventional threshold scalings. Following L- H transition, a clear improvement in energy confinement is obtained, exceeding recent international scalings even at densities approaching the Greenwald density limit. Transition is accompanied by an order-of-magnitude increase in edge-density gradient, a marked decrease in turbulence, the efficient conversion of internal electron Bernstein waves into free space waves, and the onset and saturation of edge poloidal rotation.

Journal Article↗
PubMed2002

[Exercise recommendation and catecholamines in patients with coronary artery disease].

Exercise training for patients with coronary artery disease (CAD) is recommended in a wide range between 40-85% of maximum functional capacity (MFC) or 55-90% of maximum heart rate (HR). During exercise, high levels of catecholamines and metabolic acidosis could induce arrhythmia and ischemia. But catecholamines have never been determined in CAD during constant load exercise in the upper range of recommended intensities. In 11 CAD patients (age 58+/-8 years, BMI 26.1+/-4.0 kg x m(-2), NYHA I n=7, II n=4) we tested the maximum functional capacity (MFC), norepinephrine (NE), epinephrine (E) and blood lactate ([Lac(-)](B)) in a symptom-limited incremental ergometer test. Related to the exercise recommendation, the kinetics of NE, E and [Lac(-)](B) were determined in two 30 min constant load tests in randomized order: one was performed at the anaerobic lactate threshold (CTAT), a second was performed 10% above the individual threshold intensity (CT+10%). In the incremental tests maximum workload and VO(2) were 141+/-54 W and 1766+/-532 ml x min(-1), respectively (85+/-22% of normal; [Lac(-)](B) 5.7+/-1.9 mmol x l(-1), HR 138+/-28 b x min(-1), NE 11.7+/-5.1, E 1.6+/-1.4 nmol x l(-1)). In CTAT the anaerobic threshold (63+/-7% of MFC) represented the mean range of recommended exercise intensity for CAD (40-85%) and could be validated as steady-state intensity because catecholamines and [Lac(-)](B) concentrations remained constant after the initial increase (workload 88+/-35 W, [Lac(-)](B) 3.3+/-1.4 mmol x l(-1), HR 117+/- 23 b x min(-1), NE 8.3+/-3.5, E 0.8+/- 0.7 nmol x l(-1)). In all patients CT+10% (71+/-7% of MFC) led to a continuous rise in [Lac(-)](B), to a NE overload and to earlier exhaustion, although the intensities were in the recommended training range (workload 100+/-38 W, [Lac(-)](B) 5.8+/- 1.9 mmol x l(-1), HR 129+/- 29 b x min(-1), NE 13.9+/-6.9, E 1.5+/- 1.7 nmol x l(-1); p<0.01 against CTAT for all except E). Conclusions In the upper range of recommended training intensity for CAD patients, norepinephrine and lactate were higher during endurance exercise than at MFC in incremental tests. Endurance exercise with intensities >70% of MFC could overload the cardiac patient and increase the risk of arryhthmia and ischemia. Therefore, endurance exercise should be performed below 70% of MFC or below 85% of maximum HR, respectively, whereas higher intensities should apply to interval exercise.

Aged↗
PubMed2002

Orthologs of the vaccinia A13L and A36R virion membrane protein genes display diversity in species of the genus Orthopoxvirus.

Alignment of vaccinia and variola virus genomes has highlighted some targets that display diversity. We have investigated the sequence diversity of two viral membrane protein genes from 36 different orthopoxvirus (OPV) strains to evaluate the suitability of these loci to differentiate between OPV species. Orthologs of the vaccinia virus Copenhagen A13L gene were all predicted to have functional genes that ranged between 201-213 bps in length. Whereas the N- and C-termini of each protein were relatively well conserved within the genus, a central proline-rich domain displayed characteristic species-specific amino acid motifs. Orthologs of the A36R gene displayed considerable sequence variation between species and strains. The majority of variation was localised to the last 100 bps of the gene. Multiple-alignment of these sequences identified the presence of gaps, insertions or frame-shift mutations among the samples examined. Nearly all strains of cowpox virus contained different nucleotide sequences at this locus. Phylogenetic analysis of the aligned sequences showed that variola and camelpox viruses shared a common ancestry with cowpox virus, whereas ectromelia viruses were divergent from all the other OPVs examined. Phylogeny generated with A13L sequences distributed the OPV species in a manner that correlated to their known properties.

Acinonyx↗
PubMed2002

Amplification of 'variola virus-specific' sequences in German cowpox virus isolates.

In 1995 a polymerase chain reaction (PCR) protocol describing the specific detection of variola virus, the causative agent of smallpox, was published by Knight and others. Virulent variola major strains could be differentiated from less virulent variola minor strains because of the distinct amplicon sizes. Here, we applied this PCR protocol to DNA from various orthopoxvirus isolates. There was no amplification with the orthopoxvirus species vaccinia, monkeypox, mousepox, or camelpox viruses. However, amplification was observed in six out of 15 cowpox virus strains investigated. The size of the amplicons corresponded exactly with the size described for variola minor strains and the nucleotide sequence identity accounted for 97%. Findings are discussed with respect to the evolution of orthopoxvirus species assuming that variola virus most probably stems from a rodent-transmitted cowpox virus-like progenitor.

Animals↗
PubMed2002

[Late complications in the aorta and iliac artery following open aortic surgery].

Late complications following conventional repair of abdominal aortic surgery were measured in 304 patients. Further operations were necessary in 4.6 % of the patients after an average time of 8 years. Indications for further operation were: Suture line aneurysms (6), endoleak (2), kinking of the prosthesis (2), occlusion (2), infection (2). In one of these cases an aortoduodenal fistula was observed. There was no lethality in the redo operations. It can be shown that vascular follow up operations are necessary after conventional aortic surgery. In comparison to endovascular surgery, however, they are less frequent and can be performed with acceptable security for the patient.

Aged↗