Biomedical subjects

K Richter

Publications and source records attributed to K Richter.

At least 73 records · Page 4Linked to original sources

PubMed2000

Smokers eligible for a clinical trial. Correlates of not returning for randomization.

PURPOSE: Recruitment and retention of minority participants is often the rate-limiting step towards successful completion of clinical trials. Participants who are eligible, and express interest in, enrolling into a trial will sometimes not return for their randomization visit. Factors associated with failure to return for randomization are largely unknown.METHODS: We compared 287 eligible African American (AA) smokers who enrolled, but did not return for randomization (NR), to 500 AA smokers who returned and were randomized (R) to participate in a study comparing culturally sensitive educational materials to usual care materials for smoking cessation in AAs. An analysis was conducted on variables potentially associated with not returning for randomization.RESULTS:Table 1CONCLUSIONS: Potential NR participants differed in a number of ways from those who returned for randomization. Better understanding of these factors may allow researchers to target recruitment efforts, potentially resulting in enhanced accrual and retention, and therefore, generalizability.

Journal Article↗

PubMed2000

Some selective reactions of moenomycin A.

A number of new moenomycin A derivatives have been prepared. Their antibiotic properties highlight the very specific recognition of moenomycin A at the transglycosylase binding site which is the basis of the transglycosylase inhibiting property of moenomycin A (4a).

Anti-Bacterial Agents↗

PubMed2000

Membrane association of presynaptic cytomatrix protein bassoon.

Components of the specialized cytomatrix at active zones of presynaptic nerve terminals are thought to be involved in organizing synaptic events such as immobilisation or translocation of synaptic vesicles and assemblingactive zone components. The 420-kDa non-transmembraneprotein Bassoon is a specific componentof the presynaptic cytomatrix that shares features with both cytoskeleton-associated and peripheral-membrane proteins. Using immunogold electron microscopy we show here that synapse associated Bassoon is distributed in a subregion of active zones. Using a biochemical assay we show that a fraction of Bassoon is membrane associated. Electron microscopy performed on the same biochemical fraction further revealed that Bassoon is associated with vesicular structures. Together these data suggest that at least a fraction of Bassoon is associated with a membraneous compartment in neurons.

Animals↗

PubMed2000

Co-transplantation of donor-derived hepatocytes induces long-term tolerance to cardiac allografts in a rat model.

BACKGROUND: Liver allografts transplanted between MHC-disparate mice, rats, and swine are spontaneously accepted in most strain combinations without requirement for immunosuppression. The underlying mechanism has, however, remained elusive. Here, we demonstrate that co-transplantation of donor-derived hepatocytes protect Lewis (RT1.A1) cardiac allografts from acute and chronic rejection in DA (RT1.Aa) recipients indefinitely. METHODS: Livers of donor Lewis rats were harvested and the hepatocytes separated from hepatic leukocytes by collagenase digestion and gradient separation. DA recipient animals were transplanted Lewis cardiac allografts and simultaneously intraportally infused either Lewis-derived hepatocytes or hepatic leukocytes. Recipient animals were either not further treated or received a single dose of 15 mg/kg cyclosporine. RESULTS: Donor hepatocytes alone significantly protected syngeneic cardiac allografts from rejection, whereas hepatic leukocytes failed to influence graft survival. In combination with cyclosporine, recipient cardiac allografts were indefinitely protected from rejection. Graft-infiltrating cells in tolerant animals presented as clusters of CD4+ T cells and stained mostly positive for interleukin-4, whereas graft-infiltrating cells in rejected allografts were predominantly positive for interferon-gamma. Adoptive transfer of splenocytes derived from tolerant animals protected Lewis cardiac allografts from rejection in DA recipients without immunosuppression. In contrast, hepatic leukocytes protected only 50% of the allografts from rejection. CONCLUSION: We propose that donor hepatocytes induce permanent engraftment of syngeneic allografts by establishing a Th2 type alloresponse that is transferable to new graft recipients. The results of this study demonstrate that liver parenchymal cells significantly mediate spontaneously liver-induced tolerance.

Adoptive Transfer↗

PubMed2000

Sources and concentrations of indoor nitrogen dioxide in Hamburg (west Germany) and Erfurt (east Germany).

Here we report indoor and outdoor concentrations of NO2 for Erfurt and Hamburg and assess the contribution of the most important indoor sources (e.g. the presence of gas cooking ranges, smoking) and outdoor sources (traffic exhaust emissions). We examined the relative contribution of the different sources of NO2 to the total indoor NO2 levels in Erfurt and Hamburg. NO2 indoor concentrations in Hamburg were slightly higher than those in Erfurt (i.e. living room: 15 microg m(-3) for Erfurt and 17 microg m(-3) for Hamburg). A linear regression model including the variables, place of residence, season and outdoor NO2 levels, location of the home within the city, housing and occupant characteristics accounted for 38% of the NO2 variance. The most important predictors of indoor NO2 concentrations were gas in cooking followed by other characteristics, such as ventilation or outdoor NO2 level. Residences in which gas was used for cooking, or in which occupants smoked, had substantially higher indoor NO2 concentrations (41 or 18% increase, respectively). An increase in the outdoor NO2 concentration from the 25th to the 75th-percentile (17 microg m(-3)) was associated with a 33% increase in the living room NO2 concentration. Multiple regression analysis for both cities separately illustrated that use of gas for cooking was the major indoor source of NO2. This variable caused a similar increase in the indoor NO2 levels in each city (43% in Erfurt and 47% in Hamburg). However, outdoor sources of NO2 (motor vehicle traffic) contributed more to indoor NO2 levels in Hamburg than in Erfurt.

Air Pollution, Indoor↗

PubMed2000

Weak localization in antidot arrays: signature of classical chaos

We study, experimentally and theoretically, quantum weak localization (WL) corrections to the classical magnetoconductivity of two-dimensional ballistic systems with regular and disordered patterns of dense antidots. We analyze the observed temperature and flux dependences of the WL using different theoretical models for the chaotic dynamics and dephasing rates. The measured resistivity curves, which deviate from those of diffusive systems, reflect chaotic motion and correlations in the classical dynamics of electrons in the antidot landscape. The results support the significance of the Ehrenfest time as a relevant time scale for ballistic WL.

Journal Article↗

PubMed2000

Expression pattern of XIRG, a marker for non-neural ectoderm.

XIRG (for Xenopus IRG) was cloned by screening a cDNA library of UV-ventralized stage 13 Xenopus laevis embryos for specifically ventrally expressed mRNAs. Embryonic XIRG mRNA expression is restricted to non-neural ectoderm at the gastrula and neurula stages. In adult X. laevis, XIRG mRNA can be detected in skin and kidney. Extensive searches in nucleic acid and protein databases revealed homologous sequences in mouse, human and zebrafish. Mouse IRG1 mRNA is expressed in cultured macrophages as a response to bacterial lipopolysaccharide treatment.

Amino Acid Sequence↗

PubMed2000

The neuronal EF-hand calcium-binding protein visinin-like protein-3 is expressed in cerebellar Purkinje cells and shows a calcium-dependent membrane association.

Visinin-like protein-3 is a member of the family of intracellular neuronal calcium sensors belonging to the superfamily of EF-hand proteins. Members of this family are involved in the calcium-dependent regulation of signal transduction cascades. To gain insights into the characteristics of visinin-like protein-3, we have generated specific antibodies against visinin-like protein-3 and determined the developmental and tissue distribution of the protein and its exact cellular and subcellular localization. Expression of visinin-like protein-3 protein appeared late in development mainly in the cerebellum. It is strongly expressed in cerebellar Purkinje cells. The protein expression results were further confirmed by in situ hybridization and compared with hippocalcin messenger RNA localization. Native cerebellar visinin-like protein-3 was shown to bind calcium and to associate in a calcium-dependent manner with membrane fractions during subcellular fractionation. Recombinant wild-type visinin-like protein-3 was shown to be N-terminally myristoylated in transfected cells. The membrane association was strongly reduced for the non-myristoylated mutant of visinin-like protein-3 in transfected cells. These results suggest that visinin-like protein-3, which is mainly expressed in Purkinje cells in vivo, shows a calcium-dependent association with cell membranes which is mediated by a calcium-myristoyl switch.

Aging↗

PubMed2000

Urate attenuates oxidation of native low-density lipoprotein by hypochlorite and the subsequent lipoprotein-induced respiratory burst activities of polymorphonuclear leukocytes.

Oxidation converts native low-density lipoprotein (LDL) into a signal molecule promoting inflammatory processes during atherogenesis. The exact contribution of different antioxidants in prevention of LDL oxidation is not known. Uric acid efficiently scavenges oxidants including hypochlorite. We investigated the effect of different urate concentrations (25-500 micromol/l) on the oxidation of isolated native LDL by sodium hypochlorite (1000 micromol/l). While relative electrophoretic mobility declined continuously with increasing urate concentrations in the oxidation medium, lipid peroxidation as measured by TBARS was blunted only at high molar urate/NaOCl ratios. By decreasing oxidative modifications, urate dose-dependently (beginning with a urate/NaOCl ratio of 1:40) diminished stimulatory effects of oxidized LDL on the respiratory burst of resting polymorphonuclear leukocytes (PMNL). Protecting effects of urate against the proinflammatory action of oxidized LDL on activated cells were evident only at a molar urate/NaOCl ratio of 1:2 suggesting different sensitivities of PMNL to LDL oxidation state in dependence on their activity state.

Antioxidants↗

PubMed2000

Efficacy and duration of action of the antileukotriene zafirlukast on cold air-induced bronchoconstriction.

The objectives of the study were to assess the magnitude of the effect of the leukotriene receptor antagonist, zafirlukast, against cold air-induced bronchoconstriction following the first dose and to assess magnitude and duration after 5 days of dosing. Nineteen patients with asthma were included. In a randomized cross-over design, either zafirlukast 20 mg or 80 mg b.d. or placebo were given over 5 days. Challenges were performed 3 h post first dose and 3, 8, 12 and 24 h post last dose. The authors assessed the provocative ventilation rate necessary to achieve a 10% (PV10) and 20% (PV20) fall in forced expiratory volume in one second. The median PV20 3 h post first dose was 69.1 L x min-1 for zafirlukast 80 mg compared to 40 L x min-1 for placebo (p=0.004). The corresponding median value for zafirlukast 20 mg was 59.9 L x min-1 (p=0.06). At steady state the differences in PV20, between zafirlukast 80 mg and placebo were significant at 8 h and 12 h post last dose. The corresponding difference for zafirlukast 20 mg was statistically significant at 8 h post last dose. The analysis of PV10 yielded compatible results. There was no significant protection 24 h after last dose. This study has demonstrated that zafirlukast offers significant protection against cold air-induced bronchoconstriction in asthma. The degree and duration of protection were dose-dependent. However, there was a large interindividual variability for the protective effect of this leukotriene receptor antagonist.

Administration, Inhalation↗

PubMed2000

The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate.

Hydrogen peroxide (H2O2) is known to be detectable in exhaled air. The present study aimed to determine whether the concentration of exhaled H2O2 depends on expiratory flow rate in order to make inferences on the site of its production within the lung. Breath condensate was collected in cooled Teflon tubes, at three different expiratorv flow rates, in 15 healthy or mild asthmatic subjects. Tests were repeated 2-5 times to assess reproducibility. Mean+/-SEM concentrations of H2O2 at flow rates of 140, 69 and 48 mL.s(-1) were 0.12+/-0.02, 0.19+/-0.02 and 0.32+/-0.03 microM, respectively. These values differed significantly from each other (p<0.001). For comparison, average coefficients of variability within repeated measurements at each of the three flow rates were 68, 62 and 82%, respectively. These data demonstrate that the concentration of exhaled hydrogen peroxide depends on expiratory flow rate. Since flow dependence is an indicator of production within the airways, this result suggests that, to a large extent, the exhaled hydrogen peroxide originates within the airways. However, even under strictly controlled conditions, a high degree of variability persists, which may limit the usefulness of exhaled hydrogen peroxide as a marker of airway inflammation.

Adult↗

PubMed2000

A neuroendocrine releasing effect of melatonin in the brain of an insect, Periplaneta americana (L.).

Melatonin exists in nearly all organisms, but little is known of its function in non-vertebrates. Long-term perifusions as well as short-term batch incubations of brains and molting glands of the cockroach Periplaneta americana were used to test the influence of melatonin on the prothoracicotropic hormone, a glandotropic neuropeptide in the brain, which stimulates the production of the molting hormone ecdysone in the molting gland. Changes of ecdysteroid production in molting glands were determined by radioimmunoassay as ecdysone equivalents. Melatonin (10 nmol/L) was without effect on the prothoracic gland but stimulated the prothoracicotropic effect of brains in both in vitro investigations, long-term perifusions and short-term batch incubations. The effect was dose-dependent. The melatonin effect on the release of prothoracicotropic hormone in the brain was suppressed by luzindole (10 nmol/L), a pre-synaptic receptor antagonist of melatonin. The retro-cerebral complex (corpora cardiaca-corpora allata) did not seem to be involved in the effect of melatonin on the brain. Serotonin (10 nmol/L) suppressed the release of prothoracicotropic hormone. This is the first experimental evidence of a neurohormonal releasing effect of melatonin in the insect nervous system.

Animals↗

PubMed2000

Trends in bronchial hyperresponsiveness, respiratory symptoms and lung function among adults: West and East Germany. INGA Study Group. Indoor Factors and Genetics in Asthma.

Previous studies have shown higher prevalences of bronchial hyperresponsiveness (BHR), respiratory symptoms and atopic sensitization among adults in Western Germany than in Eastern Germany. One of the aims of the joint project INGA (INdoor Factors and Genetics in Asthma) is to assess incidence, prevalence and trends for asthma, BHR and atopic diseases over a time period of 11 years (1990-2001) in the former West (Hamburg) and East Germany (Erfurt), with special reference to indoor exposure. INGA was designed as a case-control study following a cross-sectional study performed from 1990 to 1992 within the European Community Respiratory Health Survey (ECRHS). The database consisted of 1159 subjects in Hamburg and 731 subjects in Erfurt from the ECRHS (age 20-44). In 1995-1996, 107 cases (diagnosed asthma, positive specific serum IgE, positive skin prick or PD20FEV1< or =2.0 mg methacholine at ECRHS) and 106 controls (none of the previous findings) participated in Hamburg (115 cases and 109 controls in Erfurt). The methodology was identical to the ECRHS and dose-response slopes (DRS) of the methacholine challenge were calculated as an index of responsiveness. In the control group, median values of DRS were 0.028% mg(-1) (1990-1992) and 0.044 (1995-1996) (P<0.01) in Erfurt. Corresponding values for Hamburg were 0.028 and 0.022 (NS). Corresponding values within the case groups were 0.041 and 0.049 (NS) for Erfurt, and 0.069 and 0.052 (P<0.05) for Hamburg. Thus, 4 years after the first survey, we found an increased BHR in the Erfurt control group while the bronchial responsiveness remained unchanged for the Hamburg group. These trends in BHR, which indicate the expected converging tendency between East and West Germany, have to be confirmed within the next INGA-survey in 2000-2001.

Adult↗

PubMed2000

ac-driven phase-dependent directed diffusion.

We study directed diffusion of a particle in a periodic symmetric potential under the influence of a time-periodic external field. The field lowers the symmetry of the phase space flow which results in directed diffusion even if the potential and the field are reflection symmetric. We analyze the interplay between broken symmetry and dynamical chaos.

Journal Article↗

PubMed2000

Role of Na(+)/H(+) exchanger NHE3 in nephron function: micropuncture studies with S3226, an inhibitor of NHE3.

Na(+)/H(+) exchanger NHE3 is expressed in the luminal membrane of proximal tubule and thin and thick ascending limb of Henle's loop. To further define its role, the novel NHE3 inhibitor S3226 was employed in micropuncture experiments in nephrons with superficial glomeruli of anesthetized rats. Microperfusion of proximal convoluted tubule with S3226 revealed a dose-dependent inhibition of reabsorption (IC(50) of 4-5 microM) with a maximum inhibition of 30% for fluid and Na(+). During microperfusion of Henle's loop (last superficial proximal to first superficial distal tubular loop), no effect of S3226 (10 or 30 microM) on the reabsorption of fluid or Na(+) was observed. Finally, S3226 (30 microM) left the tubuloglomerular feedback response unaltered as determined by the fall in proximal tubular stop-flow pressure in response to increasing loop of Henle perfusion rate. These studies indicate that NHE3 significantly contributes to fluid and Na(+) reabsorption in proximal convoluted tubule. NHE3 appears not to significantly contribute to fluid or Na(+) reabsorption in the loop of Henle (including the S3 segment of proximal tubule) or macula densa control of nephron filtration.

Absorption↗

PubMed2000

[Hepatocellular carcinoma in an additional pedunculated liver lobe in the lower abdomen: differential diagnosis problems].

The case described is that of a 36 years old patient with a known tumor in her lower abdominal cavity which has been observed to increase in size for the passed 16 years. Intraoperatively, one observed a very rare finding of an extra liver lobe of the left liver lobe and located in the lower abdominal cavity. Located within is a multifocal therapeutically treatable hepatocellular cancer.

Adult↗

PubMed1999

Sensitive method for the determination of the antiarrhythmic drug detajmium in serum by solid-phase extraction and high-performance liquid chromatography with fluorimetric detection.

The objective of this study was to develop a very sensitive and selective method for the determination of detajmium (4-3-diethylamino-2-hydroxypropyl-ajmaline), a sodium-channel-blocking drug with antiarrhythmic properties, in serum. A high-performance liquid chromatography (HPLC) method with solid-phase extraction and fluorimetric detection has been applied. Serum samples were diluted with phosphate buffer (pH 3.5) and the extraction of detajmium and ajmaline, which was used as an internal standard, was carried out with Oasis cartridges (Waters). The chromatographic separation was performed on a RP18 column. The limit of quantification for serum samples of detajmium was 1 ng/ml with good reproducibility (R.S.D. < 15%) and a linear response from 1 to 200 ng/ml. The described method is highly sensitive and specific for the determination of detajmium in serum of patients and volunteers.

Ajmaline↗

PubMed1999

Functional mapping of transsynaptic effects of local manipulation of inhibition in gerbil auditory cortex.

Cortical networks are under the tonic influence of inhibition which is mainly mediated by GABA. The state of inhibition of small neuronal populations in the auditory cortex (AC) field AI of gerbils was altered by local microinjection of GABA, of the GABA(A)-receptor agonist 4-piperidine-sulfonic acid (P4S) and the GABA(A)-receptor antagonists bicuculline methiodide (BMI) and SR-95531. In order to elucidate direct and transsynaptic effects of the alterations of inhibition produced by these substances we used the 2-fluoro-2-deoxy-D-[(14)C(U)] glucose (FDG) mapping method. The injection of GABA (10 mM) caused no significant changes in FDG labeling but P4S caused a marked decrease of local FDG uptake in a small region surrounding the injection site but in no other region. The injection of the GABA(A)-receptor antagonists caused massive increases of FDG uptake within the entire ipsilateral AC, whereas the contralateral AC was not significantly affected in spite of prominent callosal connections. However, disinhibited excitatory output from the ipsilateral AC is suggested by a strong increase in FDG labeling of the corticothalamic fiber tract and ipsilateral structures like medial geniculate nucleus, caudal striatum, and lateral amygdaloid nucleus and a structure at the caudoventral margin of the thalamic reticular nucleus, presumably the subgeniculate nucleus, a structure with hitherto unknown connections and function. No alteration of FDG uptake could be detected in the inferior colliculus, another main descending target structure of the AC. In summary, the effects resulting from microinjection of GABA(A)-receptor antagonists reflect a differential influence of the AC on its anatomically connected target regions. The findings demonstrate the potential of the method of focal application of neuroactive substances in combination with the FDG technique for mapping their transsynaptic influences which are hard to derive from anatomical tracing studies alone.

Animals↗