Biomedical subjects

M Keller

Publications and source records attributed to M Keller.

At least 19 recordsLinked to original sources

PubMed2006

Long-term field release of bioluminescent Sinorhizobium meliloti strains to assess the influence of a recA mutation on the strains' survival.

A field release experiment was carried out to study the fate of the isogenic, firefly luciferase (luc) gene-tagged Sinorhizobium meliloti strains L1 (RecA-) and L33 (RecA+) in the environment. Both strains were released at concentrations of approximately 10(6) cfu g(-1) soil in replicate and randomized field plots, which had been sown with alfalfa (Medicago sativa). The survival of both strains during the following 7 years could be subdivided into three phases: a sharp decline for more than two orders of magnitude within the first 4 months (phase I), followed by fluctuations around an average number of 10(4) cfu g(-1) soil for nearly 4 years (phase II), and a further decline to approximately 60 cfu g(-1) (phase III). At most sampling dates, no significant differences in the survival of both strains were detected, indicating that the recA gene function was dispensable under these environmental conditions. During the field inoculation, both strains were dispersed accidentally by wind in small numbers to noninoculated field plots. Strain L33 established at a concentration of more than 10(3) cfu g(-1) soil with subsequent seasonal fluctuations. Although strain L1 must have been disseminated to a similar extent, it could never be recovered from noninoculated field plots, indicating that the recA mutation interfered with the strain's capability to establish there. At the beginning of the field experiment, an indigenous alfalfa-nodulating population was below the limit of detection. In the following years, however, an indigenous population arose, which finally outcompeted both strains for saprophytic growth and alfalfa nodulation. RecA- strain L1 was outcompeted for alfalfa nodulation slightly faster than its RecA+ counterpart L33. The diversity of the indigenous population was characterized by employing the Enterobacterial Repetitive Intergenic Consensus polymerase chain reaction fingerprint method. Typing of 2731 root nodule isolates revealed a total of 38 fingerprint groups. More than 80% of the isolates could be grouped into six dominant fingerprint groups, indicating that a few dominant bacterial strain types had outcompeted the released strains.

Air Microbiology↗

PubMed2006

The estrogen-responsive B box protein: a novel enhancer of interleukin-1beta secretion.

The estrogen-responsive B box protein (EBBP) and Pyrin belong to a family of structurally related proteins. While mutations in the pyrin gene cause an autoinflammatory disease, the biological function of EBBP is unknown. In this study, we identified the proinflammatory cytokine interleukin-1beta (IL-1beta) as an EBBP-binding partner. Furthermore, caspase-1 and NACHT, LRR and Pyrin domain containing protein (NALP) 1, two components of the recently identified inflammasome, a platform for the activation of caspase-1, also interact with EBBP. These proteins bind to the RFP domain of EBBP, suggesting that this domain of so far unknown function is an important protein-binding domain. EBBP was secreted in a caspase-1-dependent manner from cultured cells, and its secretion was enhanced by IL-1beta. Vice versa, endogenous and overerexpressed EBBP increased IL-1beta secretion. These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1beta.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Animals↗

PubMed2006

[Open reduction and internal fixation of distal radius extension fractures in women over 60 years of age with the dorsal radius plate (pi-plate)].

PURPOSE: The goal of this study was to review the clinical and radiological results and to correlate them with the functional outcome score DASH in women over 60 years who underwent open reduction and internal fixation with a pi-plate for displaced distal radius fractures. METHOD AND CLINICAL MATERIAL: In this retrospective study, forty-nine women over 60 years old with mainly intra-articular distal radius fractures underwent open reduction and internal fixation with a pi-plate. The dorsal approach was used permitting an anatomical reduction of the articular surface under direct vision of the radio-carpal joint. Patient follow-up was for a minimum of twelve months with a mean of 32 months. RESULTS: For 71 % of patients, there were no limitations in their daily activities and only one patient complained of a major disability. Overall, the flexion of the wrist was reduced by 15 degrees compared to the opposite side (mean 50 degrees). The DASH score (14.4) was not higher than that of a comparable age controlled group without radius fracture. The pi-plate was demonstrated to be a stable implant in osteoporotic bone and there was only one secondary dislocation. Most patients were painfree with two patients describing tolerable pain, one because of a progressing radio-carpal osteoarthritis and the second due to a neuroma of the superficial branch of the radial nerve. The other major complication was a late rupture of the extensor tendon of the index finger in one of the twelve patients where the pi-plate had not been removed. CONCLUSION: We recommend anatomical reduction and internal fixation for displaced intra-articular distal radius fractures using a dorsal approach to achieve a good wrist function including painless load bearing with the implant removed four months after surgery.

Aged↗

PubMed2006

Sequence analysis of the 144-kilobase accessory plasmid pSmeSM11a, isolated from a dominant Sinorhizobium meliloti strain identified during a long-term field release experiment.

The genome of Sinorhizobium meliloti type strain Rm1021 consists of three replicons: the chromosome and two megaplasmids, pSymA and pSymB. Additionally, many indigenous S. meliloti strains possess one or more smaller plasmids, which represent the accessory genome of this species. Here we describe the complete nucleotide sequence of an accessory plasmid, designated pSmeSM11a, that was isolated from a dominant indigenous S. meliloti subpopulation in the context of a long-term field release experiment with genetically modified S. meliloti strains. Sequence analysis of plasmid pSmeSM11a revealed that it is 144,170 bp long and has a mean G+C content of 59.5 mol%. Annotation of the sequence resulted in a total of 160 coding sequences. Functional predictions could be made for 43% of the genes, whereas 57% of the genes encode hypothetical or unknown gene products. Two plasmid replication modules, one belonging to the repABC replicon family and the other belonging to the plasmid type A replicator region family, were identified. Plasmid pSmeSM11a contains a mobilization (mob) module composed of the type IV secretion system-related genes traG and traA and a putative mobC gene. A large continuous region that is about 42 kb long is very similar to a corresponding region located on S. meliloti Rm1021 megaplasmid pSymA. Single-base-pair deletions in the homologous regions are responsible for frameshifts that result in nonparalogous coding sequences. Plasmid pSmeSM11a carries additional copies of the nodulation genes nodP and nodQ that are responsible for Nod factor sulfation. Furthermore, a tauD gene encoding a putative taurine dioxygenase was identified on pSmeSM11a. An acdS gene located on pSmeSM11a is the first example of such a gene in S. meliloti. The deduced acdS gene product is able to deaminate 1-aminocyclopropane-1-carboxylate and is proposed to be involved in reducing the phytohormone ethylene, thus influencing nodulation events. The presence of numerous insertion sequences suggests that these elements mediated acquisition of accessory plasmid modules.

Agrobacterium tumefaciens↗

PubMed2006

Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

Administration, Oral↗

PubMed2005

Flow-cytometric detection of changes in the physiological state of E. coli expressing a heterologous membrane protein during carbon-limited fedbatch cultivation.

The key to optimizing productivity during industrial fermentations is the ability to rapidly monitor and interpret the physiological state of single microbial cells in a population and to recognize and characterize different sub-populations. Here, a flow cytometry-based method for the reproducible detection of changes in membrane function and/or structure of recombinant E. coli JM101 (pSPZ3) expressing xylene monooxygenase (XMO), was developed. XMO expression led to compromised but not permeabilized cell membranes. This was deduced from the fact that recombinant cells only stained with ethidium bromide (EB) and not with propidium iodide (PI). During the glucose-limited fedbatch cultivation, an increase from 25% to 95% of EB-stained cells was observed, occurring between 2 and 5 h after induction. Control experiments confirmed that this increase was due to the recombinant protein production and not caused by any possible effects of varying substrate availability, high cell density, plasmid replication or the presence of the inducing agent. We hypothesize that the integration of the recombinant protein into the cell membrane physically disrupted the functionality of the efflux pumps, thus resulting in EB-staining of the recombinant cells. This method enabled us to detect changes in the physiological state of single cells 2-4 h before other indications of partial cell damage, such as unbalanced growth, acetate accumulation and an increased CO(2) production rate, were observed. This method therefore shows promise with respect to the further development of an early-warning system to prevent sudden productivity decreases in processes with recombinant E. coli expressing heterologous membrane proteins.

Acetates↗

PubMed2005

Osteointegration of hydroxyapatite-titanium implants coated with nonglycosylated recombinant human bone morphogenetic protein-2 (BMP-2) in aged sheep.

Osteointegration of metal implants into aged organisms can be severely compromised due to reduced healing capacity of bone, lack of precursor cells for new bone formation, or osteoporosis. Here, we report on successful implant healing in a novel model of aged sheep in the presence of nonglycosylated bone morphogenetic protein 2 (BMP-2). Ewes of 8 to 12 years with significant radiologic and histologic signs of osteoporosis and adipocytic bone marrow received a cylindrical hydroxyapatite-titanium implant of 12 x 10 mm. BMP-2 has been produced as a bacterial recombinant fusion protein with maltose-binding protein and in vitro generation of mature BMP-2 by renaturation and proteolytic cleavage. A BMP-2 inhibition ELISA was developed to measure the in vitro release kinetics of bioactive human BMP-2 from immersed solid implant materials by using Escherichia coli expressed and biotinylated recombinant human BMP-2 receptor IA extracellular domain (ALK-3 ECD). The implants were placed laterally below both tibial plateaus, with the left leg implant carrying 380 microg BMP-2. Both implant types became integrated within the following 20 weeks. The control implant only integrated at the cortical bone, and little new bone formation was found within the pre-existing trabecular bone or the marrow cavity. Marrow fat tissue was partially replaced by unspecific connective tissue. In contrast, BMP-2-coated implants initiated significant new bone formation, initially in trabecular arrangements to be replaced by cortical-like bone after 20 weeks. The new bone was oriented towards the cylinder. Highly viable bone marrow appeared and filled the lacunar structures of the new bone. In mechanical tests, the BMP-2-coated implants displayed in average 50% higher stability. This animal model provided first evidence that application of nonglycosylated BMP-2 coated on solid implants may foster bone healing and regeneration even in aged-compromised individuals.

Aging↗

PubMed2005

Néel temperature of quasi-low-dimensional Heisenberg antiferromagnets.

The Néel temperature T(N) of quasi-one- and quasi-two-dimensional antiferromagnetic Heisenberg models on a cubic lattice is calculated by Monte Carlo simulations as a function of interchain (interlayer) to intrachain (intralayer) coupling J(')/J down to J(')/J approximately = 10(-3). We find that T(N) obeys a modified random-phase approximationlike relation for small J(')/J with an effective universal renormalized coordination number, independent of the size of the spin. Empirical formulas describing T(N) for a wide range of J(') and useful for the analysis of experimental measurements are presented.

Journal Article↗

PubMed2005

[Careers of women in academic surgery].

AIM: The aim of our national survey was to determine personal, working, and career conditions of women in academic surgery in Germany. METHODS: A questionnaire with 47 items was sent to 261 female surgeons working in 36 departments of general, abdominal, trauma, and vascular surgery. A total of 134 (51.3%) from all 36 surgical departments responded with completed surveys. RESULTS: The mean age of the women was 35.1 years (range 27 to 54). Seventy-eight percent of the surgeons worked in departments for general or abdominal surgery, 17% in trauma, and 5% in vascular surgery. 45% of the women had finished residency and 19% were in faculty positions. Eighty percent of those asked were mostly or always content with their working conditions. However, 79% perceived career obstacles in academic surgery. The most frequently addressed obstructions were: predominant male structures (80%), the absence of mentoring programs (70%), too few operative cases per month (67%), and no equality of career opportunities compared to male surgeons (60%). CONCLUSIONS: To reduce career obstructions, which were reported by 79% of the female surgeons, and to encourage those 33% who wanted to leave academic surgery, it seems necessary to improve cooperation between female surgeons, department chairs, and governmental institutions.

Adult↗

PubMed2005

Mapping of brain networks involved in consolidation of lamb recognition memory.

In sheep, ewes at parturition are responsive to any newborn lamb, but within less than 1 h, mothers learn to recognize the odor of their lamb and restrict maternal care to their own offspring (maternal selectivity). In a first experiment, we investigated the long-term retention of maternal selectivity after various mother-young contact and separation durations. After 4 h of contact, 36 h of separation leads to a total loss of selectivity. Increasing contact duration to 7 days prior to this separation maintains selectivity. These data suggest that lamb memory after going through an initial labile state after parturition, is consolidated over time into a more stable long-term memory. Fos immunohistochemistry reveals that reintroduction of the lamb after 4 h of mother-young contact and 3 h of separation activates different maternal brain regions than reintroduction of the lamb after 7 days of mother-young contact and 3 h of separation. While the piriform cortex shows an enhanced activation at both times, a selective enhancement of activation is observed in the frontal medial and orbitofrontal cortices only after 7 days of mother-young contact. These data suggest that as consolidation occurs, the neurobiological networks sustaining lamb memory involve different structures.

Animals↗

PubMed2004

Psychological problems of cancer patients: a cancer distress screening with a cancer-specific questionnaire.

The purpose of this study was to assess the psychological distress of cancer patients in a disease-specific manner as well as the demographic and medical variables that have an impact on the distress. Psychological distress was assessed with the Questionnaire on Stress in Cancer Patients revised version, which has been developed and psychometrically evaluated in Germany. It consists of items about 23 cancer-specific stress situations, which have to be answered in terms of relevance and amount of distress. A heterogeneous sample of 1721 cancer in- and outpatients was assessed. For the total group, the most important distress is the fear of disease progression. We consider between 23.4% (ca. of the upper gastrointestinal tract) and 40.9% (breast cancer patients) as highly distressed. The most distressed diagnostic subgroups are patients with soft tissue tumours and breast cancer patients. There are no global (general) stress factors, as the relevant demographic and medical 'risk factors' varied between the diagnostic subgroups. Cancer-specific distress questionnaires give a more precise insight into patients' experience than general or psychiatric questionnaires. They are not only used in large screening studies but also in routine medicine, particularly when the objective is to identify patients to whom psycho-oncological support is to be given.

Adult↗

PubMed2004

Mechanisms of Na+-Ca2+ exchange inhibition by amphiphiles in cardiac myocytes: importance of transbilayer movement.

The membrane lipid environment and lipid signaling pathways are potentially involved in the modulation of the activity of the cardiac Na(+)-Ca(2+) exchanger (NCX). In the present study biophysical mechanisms of interactions of amphiphiles with the NCX and the functional consequences were examined. For this purpose, intracellular Ca(2+) concentration jumps were generated by laser-flash photolysis of caged Ca(2+) in guinea-pig ventricular myocytes and Na(+)-Ca(2+) exchange currents ( I(Na/Ca)) were recorded in the whole-cell configuration of the patch-clamp technique. The inhibitory effect of amphiphiles increased with the length of the aliphatic chain between C(7) and C(10) and was more potent with cationic or anionic head groups than with uncharged head groups. Long-chain cationic amines (C(12)) exhibited a cut-off in their efficacy in I(Na/Ca) inhibition. Analysis of the time-course, comparison with the Ni(2+)-induced I(Na/Ca) block and confocal laser scanning microscopy experiments with fluorescent lipid analogs (C(6)- and C(12)-NBD-labeled analogs) suggested that amphiphiles need to be incorporated into the membrane. Furthermore, NCX block appears to require transbilayer movement of the amphiphile to the inner leaflet ("flip"). We conclude that both, hydrophobic and electrostatic interactions between the lipids and the NCX may be important factors for the modulation by lipids and could be relevant in cardiac diseases where the lipid metabolism is altered.

Animals↗

PubMed2004

Olfactory regulation of maternal behavior in mammals.

In mammals, olfactory cues are extensively used in many aspects of maternal care to ensure the coordination of mother-infant interactions and consequently the normal development of the offspring. Outside the period of parturition and lactation, when the young are not a behavioral priority, olfactory cues play an inhibitory role on maternal responsiveness since in most mammalian species studied so far, nonpregnant females find the odor of young aversive. On the contrary at the time of parturition, a shift in the hedonic value of infantile odors occurs so that the young now become a very potent stimulus and this sensorial processing constitutes an important part of the maternal motivational system. Moreover, infants' odors provide a basis for individual recognition by their mothers and some species (ungulates) have developed highly specialized mechanisms for processing of the infant signals. Perception of the smell of the young also regulates various aspects of maternal behavior. Dodecyl propionate, a compound released by of pup's preputial glands, has been shown to influence anogenital licking behavior, a fundamental pattern of maternal behavior in rodents. While there is no functional specificity of either the main or the accessory olfactory systems in the development of maternal behavior amongst species, it appears that only the main olfactory system is implicated when individual odor discrimination of the young is required. Neural structures, such as the main olfactory bulb, undergo profound changes when exposed to offspring odors at parturition. These changes in synaptic circuitry contribute both to maternal responsiveness to these odors, to their memorization, and to effects of long-term maternal experience.

Animals↗

PubMed2004

Association of T-786C eNOS gene polymorphism with increased susceptibility to acute chest syndrome in females with sickle cell disease.

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). A retrospective study was performed to evaluate the role of endothelial nitric oxide synthase (eNOS) gene polymorphisms (E298D and T-786C) in African-American SCD patients. The D298 allele showed no association; the C-786 allele showed a statistically significant association (P = 0.0061) in female ACS cases. Multiple logistic regression analysis showed that relative risk of ACS was 8.695 (P = 0.0076, 95% confidence interval 1.761-42.920) for female carriers of C-786. eNOS T-786C is a gender-specific genetic modifier that is associated with increased susceptibility to ACS in female SCD patients.

Acute Disease↗

PubMed2004

Third ventriculostomy in communicating hydrocephalus in adult patients -- the role of lumbar and cranial cerebrospinal fluid outflow measurement.

OBJECTIVE: To evaluate the value of CSF outflow resistance testing as a criterion for endscopic treatment in case of communicating hydrocephalus. METHODS: 12 patients with communicating hydrocephalus were integrated in a prospective study from 1999 - 2001. Under the assumption of different hydromechanical properties of both spinal and cerebral CSF compartment the resorption capacity was measured. V.-p. shunting, ventriculostomy or conservative treatment were performed dependent on the results and clinical outcome was evaluated. RESULTS: Six patients with pathological lumbar testing underwent primary ventriculo-peritoneal shunting. In 6 of the 12 cases the lumbar CSF resorption capacity was found to be normal and cerebral testing was accomplished. Two patients with normal spinal and cerebral resorption capacity were not operated. In the remaining 4 patients cerebral testing was found to be pathological and ventriculostomy was performed. An improvement of clinical symptoms was observed in patients operated with a v.-p. shunt and in the VCS group as well. CONCLUSIONS: This study demonstrates that there is a subgroup of patients with morphological communicating hydrocephalus that is characterized by a functional dissociation of hydromechanical properties of intracranial and spinal CSF compartment. In cases of regular CSF resorption but restricted CSF outflow from the ventricular system to the subarachnoid space ventriculo-peritoneal shunting may be an efficient therapy, but VCS was proved to be an efficient alternative.

Aged↗

PubMed2004

Recognition of distress and psychiatric morbidity in cancer patients: a multi-method approach.

BACKGROUND: This study aimed to determine the prevalence of psychiatric morbidity and distress among 189 consecutively recruited cancer patients upon admission to surgical oncology wards, and to investigate the recognition of distressed patients by medical staff. PATIENTS AND METHODS: Assessment consisted of a diagnostic psychiatric interview (SCID, DSM-IV), patient-reported distress using a standardised questionnaire (Hospital Anxiety and Depression Scale), and physicians' and nurses' estimates of patients' distress. Twenty-eight per cent of patients were assigned a psychiatric diagnosis, with adjustment disorder predominating. RESULTS: Surgeons accurately recognised marked distress in 77% of patients with a psychiatric disorder and nurses did so in 75%. Because of low specificity, the positive predictive value was only 39% in surgeons and 40% in nurses. However, recognition of distress translated into referral to the psychosocial liaison service for only a minor proportion of distressed patients. CONCLUSIONS: Since a remarkable proportion of distressed patients remained unrecognised by the medical staff, only systematic screening of patients upon admission allows timely support to those who are most in need.

Adult↗

PubMed2003

Biodiversity meets the atmosphere: a global view of forest canopies.

The forest canopy is the functional interface between 90% of Earth's terrestrial biomass and the atmosphere. Multidisciplinary research in the canopy has expanded concepts of global species richness, physiological processes, and the provision of ecosystem services. Trees respond in a species-specific manner to elevated carbon dioxide levels, while climate change threatens plant-animal interactions in the canopy and will likely alter the production of biogenic aerosols that affect cloud formation and atmospheric chemistry.

Animals↗