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L Lehmann

Publications and source records attributed to L Lehmann.

At least 19 recordsLinked to original sources
PubMed2007

The evolution of trans-generational altruism: kin selection meets niche construction.

A cornerstone result of sociobiology states that limited dispersal can induce kin competition to offset the kin selected benefits of altruism. Several mechanisms have been proposed to circumvent this dilemma but all assume that actors and recipients of altruism interact during the same time period. Here, this assumption is relaxed and a model is developed where individuals express an altruistic act, which results in posthumously helping relatives living in the future. The analysis of this model suggests that kin selected benefits can then feedback on the evolution of the trait in a way that promotes altruistic helping at high rates under limited dispersal. The decoupling of kin competition and kin selected benefits results from the fact that by helping relatives living in the future, an actor is helping individuals that are not in direct competition with itself. A direct consequence is that behaviours which actors gain by reducing the common good of present and future generations can be opposed by kin selection. The present model integrates niche-constructing traits with kin selection theory and delineates demographic and ecological conditions under which altruism can be selected for; and conditions where the 'tragedy of the commons' can be reduced.

Adaptation, Biological↗
PubMed2006

The evolution of cooperation and altruism--a general framework and a classification of models.

One of the enduring puzzles in biology and the social sciences is the origin and persistence of intraspecific cooperation and altruism in humans and other species. Hundreds of theoretical models have been proposed and there is much confusion about the relationship between these models. To clarify the situation, we developed a synthetic conceptual framework that delineates the conditions necessary for the evolution of altruism and cooperation. We show that at least one of the four following conditions needs to be fulfilled: direct benefits to the focal individual performing a cooperative act; direct or indirect information allowing a better than random guess about whether a given individual will behave cooperatively in repeated reciprocal interactions; preferential interactions between related individuals; and genetic correlation between genes coding for altruism and phenotypic traits that can be identified. When one or more of these conditions are met, altruism or cooperation can evolve if the cost-to-benefit ratio of altruistic and cooperative acts is greater than a threshold value. The cost-to-benefit ratio can be altered by coercion, punishment and policing which therefore act as mechanisms facilitating the evolution of altruism and cooperation. All the models proposed so far are explicitly or implicitly built on these general principles, allowing us to classify them into four general categories.

Altruism↗
PubMed2006

An evolutionary analysis of the relationship between spite and altruism.

We investigate the selective pressures on a social trait when evolution occurs in a population of constant size. We show that any social trait that is spiteful simultaneously qualifies as altruistic. In other words, any trait that reduces the fitness of less related individuals necessarily increases that of related ones. Our analysis demonstrates that the distinction between "Hamiltonian spite" and "Wilsonian spite" is not justified on the basis of fitness effects. We illustrate this general result with an explicit model for the evolution of a social act that reduces the recipient's survival ("harming trait"). This model shows that the evolution of harming is favoured if local demes are of small size and migration is low (philopatry). Further, deme size and migration rate determine whether harming evolves as a selfish strategy by increasing the fitness of the actor, or as a spiteful/altruistic strategy through its positive effect on the fitness of close kin.

Altruism↗
PubMed2005

SAK/PLK4 is required for centriole duplication and flagella development.

BACKGROUND: SAK/PLK4 is a distinct member of the polo-like kinase family. SAK-/- mice die during embryogenesis, whereas SAK+/- mice develop liver and lung tumors and SAK+/- MEFs show mitotic abnormalities. However, the mechanism underlying these phenotypes is still not known. RESULTS: Here, we show that downregulation of SAK in Drosophila cells, by mutation or RNAi, leads to loss of centrioles, the core structures of centrosomes. Such cells are able to undergo repeated rounds of cell division, but display broad disorganized mitotic spindle poles. We also show that SAK mutants lose their centrioles during the mitotic divisions preceding male meiosis but still produce cysts of 16 primary spermatocytes as in the wild-type. Mathematical modeling of the stereotyped cell divisions of spermatogenesis can account for such loss by defective centriole duplication. The majority of spermatids in SAK mutants lack centrioles and so are unable to make sperm axonemes. Finally, we show that depletion of SAK in human cells also prevents centriole duplication and gives rise to mitotic abnormalities. CONCLUSIONS: SAK/PLK4 is necessary for centriole duplication both in Drosophila and human cells. Drosophila cells tolerate the lack of centrioles and undertake mitosis but cannot form basal bodies and hence flagella. Human cells depleted of SAK show error-prone mitosis, likely to underlie its tumor-suppressor role.

Animals↗
PubMed2005

Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells.

The mycotoxin alternariol (AOH) is found in food and beverages infected by Alternaria alternata. Because consumption of foodstuffs contaminated with A. alternata has been implicated in an elevated incidence of esophageal carcinogenesis, we have investigated the estrogenic potential, the effect on cell proliferation, and the genotoxic effect of AOH in cultured mammalian cells. AOH replaced E2 from isolated human estrogen receptors alpha and beta and increased the level of alkaline phosphatase (ALP) mRNA and the enzymatic activity of ALP in a human endometrial adenocarcinoma cell line (Ishikawa cells). The estrogenicity of AOH was about 0.01% of that of E2. The effects in Ishikawa cells were reversed by the ER antagonist ICI 182,780. Analysis of cell proliferation by flow cytometry and microscopy of Ishikawa and Chinese hamster V79 cells revealed that AOH inhibited cell proliferation by interference with the cell cycle. The genotoxic potential was assessed by the micronucleus (MN) assay and immunochemical differentiation between MN containing whole chromosomes (kinetochore-positive) and DNA fragments (kinetochore-negative) in Ishikawa and V79 cells. AOH induced kinetochore-negative MN in both cell lines. This is the first report on the estrogenic potential, inhibition of cell proliferation and clastogenicity of AOH in Ishikawa and V79 cells in vitro.

Adenocarcinoma↗
PubMed2005

Estrogenic and genotoxic potential of equol and two hydroxylated metabolites of Daidzein in cultured human Ishikawa cells.

The soy isoflavone daidzein (DAI) is known to undergo metabolism to equol (EQO) and to 3'-hydroxy-DAI (3'-HO-DAI) and 6-hydroxy-DAI (6-HO-DAI) in humans. In order to better understand the implications of soy diets for human health, the hormonal and genotoxic activities of these DAI metabolites were studied in cultured human endometrial carcinoma cells. When the estrogenicity was tested by cell-free binding to recombinant human estrogen receptor (ER) alpha and beta as well as by the induction of enzyme activity and gene expression of alkaline phosphatase (ALP) in Ishikawa cells, the ranking order was EQO>DAI>3'-HO-DAI>6-HO-DAI. All compounds had a higher affinity to ERbeta than to ERalpha. No significant anti-estrogenic effects of the DAI metabolites were observed in the cells at non-cytotoxic concentrations. The in vitro genotoxicity was assessed by analyzing effects on cell cycle distribution and cell morphology as well as the induction of micronuclei (MN). EQO caused a slight increase in G1 and decrease in S phase of the cell cycle, and slightly but significantly induced kinetochore-positive as well as kinetochore-negative MN and an elevated proportion of abnormal mitotic spindles. 3'-HO-DAI, but not 6-HO-DAI, induced kinetochore-negative MN. The observation that major human metabolites of DAI exhibit estrogenic and genotoxic potential may be of relevance for the safety evaluation of diets containing soy isoflavones.

Adenocarcinoma↗
PubMed2005

Determination of the heat stability profiles of concentrated milk and milk ingredients using high resolution ultrasonic spectroscopy.

In the present work, we used high resolution ultrasonic spectroscopy for the analysis of heat coagulation process in milks. Two skim milks recombined from powder samples differing by their preheating treatments as well as dairy ingredients (phosphocasein, whey protein isolate, and a milk model) were monitored while submitted to a temperature of 120 degrees C. Three stages in the precoagulation and coagulation processes can be distinguished in the ultrasonic velocity and attenuation profiles. The first stage shows a very sharp decrease in ultrasonic velocity and increase in ultrasonic attenuation. This could be attributed to fast denaturation and aggregation of whey proteins and precipitation of calcium phosphate. In the second stage, small changes in ultrasonic velocity are observed, the rate of which depends on the nature and pH of the samples. In the third stage, a sharp decrease in ultrasonic velocity and attenuation is recorded for all samples, which corresponds to the coagulation and formation of the gel network. After coagulation, a very small change in ultrasonic velocity and attenuation was observed. From the ultrasonic measurements, we determined the heat stability vs. pH profiles of the different samples studied. The observed ultrasonic attenuation profiles were also interpreted in terms of changes in the size of casein micelles and coagulation processes.

Animals↗
PubMed2004

Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein.

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15-1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16-0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13-0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35-5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann-Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152-1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94-445) for patients with fever of unknown origin, 177 pg/ml (IR, 142-208) for patients with non-microbial fever and 942 pg/ml (IR, 181-2,807) for patients with bacteremia. Using the Mann-Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.

Adult↗
PubMed2004

[Pain symptoms of osteoarthritis-aspects of etiology and therapy].

Due to demographic changes and associated socioeconomic problems osteoarthritis is of increasing value. Simultaneously there are more and more older people who want to practice sports. Pain symptoms of osteoarthritis can be positively influenced by paracetamol and NSAR, in combination with orthopedic aids and physical therapy in early stages. Apart from these established pain-therapeutic procedures as well as first evident results of osteoarthritis modifying drugs, gene-therapy offers promising approaches that will have to be confirmed in further studies. In case of failure of conservative treatment there are several surgical options. Arthroscopic surgery mostly offers pain reduction only for a short period of time. A slower progression of osteoarthritis in the long run can only be achieved by osteotomy provided the right indication. Ultimately joint replacement exists as a reliable and successful treatment option in hip, knee and shoulder surgery.

Analgesics↗
PubMed2004

New type of Sesiidae sex pheromone identified from the hornet moth Sesia apiformis.

Two components of the female-produced sex pheromone of the hornet moth, Sesia apiformis, were identified as (3Z,13Z)-octadeca-3,13-dien-1-ol (3Z,13Z-18:OH) and (2E,13Z)-octadeca-2,13-dienal (2E,13Z-18:Al), a pheromone structure new in Sesiidae. Pooled gland extracts showed the two major compounds in a proportion of ca. 2:3, while SPME-investigations on single calling females revealed a ratio of ca. 1:7. Although the single compounds were not attractive, a 2:3 mixture proved to be highly active towards males in field tests. Small amounts of (2E,13Z)-octadecadienol (2E,13Z-18:OH) were found in the sex pheromone gland of females, however, the biological significance of the compound remains unclear. Methyl sulfide was found to readily react with 2-alkenals, providing an effective new method for the characterization of this type of compound upon GC/MS. The derivatives, 1,1,3-tris(methylthio)alkanes, are the products of the addition of methyl sulfide to the double bond and the transformation of the carbonyl group into the corresponding bis(methylthio)acetal. The mass spectra of these compounds are characterized by diagnostic signals at m/z 107 and/or m/z 121. These fragments represent the first carbon unit or the first two carbon units of the derivative, respectively. The parent signal in the spectra of thiomethyl derivatives of 2-alkenals showing no other double bonds is represented by m/z M+ - 121, formed upon loss of the first two carbon units. By employing a solution of methyl sulfide in dimethyl sulfide, the double bond positions in 2E,13Z-18:Al could be fully characterized by GC/MS.

Aldehydes↗
PubMed2004

Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood.

The optimal therapy for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We therefore reviewed our institutional outcomes for children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for advanced APL. Between 1986 and 2003, 12 allogeneic HSCTs (five related donor, seven unrelated donor) were performed for 11 patients (median age, 13 years) with relapsed (n = 8) or refractory (n = 3) APL. All patients engrafted, after a median of 18.5 days. Grade B-D acute graft-versus-host disease (GVHD) developed after five transplants (42%; 90% CI, 18-68%), and the cumulative incidence of chronic GVHD was 45% (90% CI, 19-71%). The cumulative incidence of overt relapse post-HSCT was 10% (90% CI, 0-28%). The overall 5-year survival was 73% (90% confidence interval (CI), 51-95%), with a median post-HSCT follow-up of 64 months. The Lansky/Karnofsky performance scores are 100% in six of eight survivors. In view of the low risk of subsequent relapse and favorable survival suggested by other reports and our own experience, we continue to recommend allogeneic HSCT for children with advanced APL for whom a suitably HLA-matched donor is identified.

Acute Disease↗
PubMed2002

Hormonal and genotoxic activity of resveratrol.

Resveratrol (RES) is a natural polyphenol present in red wines and various human food items. The estrogenic activity of RES was demonstrated in two in vitro assay systems, i.e. binding to human estrogen receptor alpha and stimulation of MCF-7 cell proliferation. To investigate the inhibition of cell proliferation observed at high concentrations of RES, we analyzed the compound for genotoxic potential. RES induced cellular toxicity, micronuclei, and metaphase chromosome displacement in L5178Y mouse lymphoma cells. Likewise, the induction of micronuclei was observed in Chinese hamster V79 cells. Determination of kinetochore signals in micronuclei and cell cycle analysis suggested that RES did not cause a direct disturbance of mitosis. In support of this notion, cell-free tubulin polymerization studies indicated no direct effect of RES on microtubule assembly. According to an estimation of daily intake and bioavailability, concentrations that were found genotoxic in vitro might be reached in human exposure. On the other side, the estrogenic acitivity might be beneficial. Therefore, further investigations of mechanisms, possibly including animal models, would be desirable to clarifiy a potential risk for humans.

Animals↗
PubMed2001

Effects of microemulsions on the stratum corneum and hydrocortisone penetration.

We tested a high-water-content hydrophilic microemulsion (ME 1) and a low-water-content lipophilic microemulsion (ME 2) for their suitability for use in dermatology, in general, and as alternative hydrocortisone (HC) vehicles, in particular. The lipophilic component of both study products was isopropyl myristate. The surfactant/cosurfactant system of ME 1 consisted of two sucrose esters and that of ME 2 was a mixture of Tagat S and Plurololeat. Both MEs showed no in vitro irritability in the hen's egg test on chorioallantoic membranes. In 14 subjects, stratum corneum water content was determined by corneometry and transepidermal water loss (TEWL) by the Tewameter before and after 3 days use of ME 1 or ME 2 as well as on two untreated control sites. ME 1 produced dehydration and increased TEWL as evidence of barrier compromise. ME 2 also produced an increase in TEWL but had no dehydrating effect. Subjects then underwent standardized washing with a surfactant solution. Under these conditions, pretreatment with ME 2 also produced dehydration, but to a lesser extent than did pretreatment with ME 1. In the same subjects, the impact of the two MEs on HC penetration (0.5%, 24h occlusion) was evaluated in terms of the chromameter-determined blanching effect compared with that on a site treated only with an occlusive film dressing. The comparator was an ambiphilic cream (Basiscreme (BC) Deutscher Arzneimittel Codex (German Formulary)). Irritative skin redness produced by ME 1 was significant and that produced by ME 2 was slight but visible, compared with BC. HC penetration was demonstrable from all the study products via the blanching effect and was significantly greater from ME 1 and slightly greater from ME 2 than from BC. However, neither ME would improve HC therapy because the irritative effects were so great that the blanching effect of HC formulated in ME 1 was significantly smaller and that of HC in ME 2 slightly smaller than that of HC formulated in BC.

Adult↗
PubMed2000

[Rotator cuff tears: diagnosis and therapy].

Since the life span of our society is increasing and the expectation of high functional demands is growing more and more older people take part in sports activities emphasises the necessity of early diagnosis of rotator cuff lesions and their correct treatment. The goal of any diagnostic means should be a proper treatment of rotator cuff lesions according to the detected pathology. New arthroscopic techniques to surgically reconstruct rotator cuff tears have brought the operative repair techniques another step further. In cases of large and complex cuff tears the surgeon can individually select an adequate reconstruction procedure which includes anatomical-, partial-, tendon-transfer and muscle-transfer repairs. In cases of irreparable tears with cuff-tear arthropathy and consecutive superior migration of the humeral head hemiarthroplasty or the inverse deltoid prosthesis have to be considered. Based on clinical, radiological and arthroscopic findings we developed algorithms that will lead to the best suited procedure for a given lesion.

Algorithms↗
PubMed1999

Cytogenetic changes in radiation-induced tumors of the thyroid.

Thyroid carcinoma incidence is increased significantly after ionizing irradiation; however, the possible mechanisms have not yet been identified. To provide clues for an understanding of the radiation-induced transformation of thyroid epithelium, we analyzed the karyotypes of 56 childhood thyroid tumors that appeared in Belarus after the Chernobyl nuclear accident in 1986. We also studied eight secondary thyroid tumors that developed after radiotherapy. Metaphase preparations obtained from primary cultures were analyzed by G-banding. Clonal structural aberrations were found in 13 of 56 Belarussian cases and in 6 of 8 secondary tumors that developed after radiotherapy. Furthermore, we detected multiple chromosomal aberrations as well as complex rearrangements in some of these tumors and performed a detailed analysis of marker chromosomes from a single case using spectral karyotyping and comparative genomic hybridization in a childhood tumor from Belarus with a near-triploid karyotype. Both comparative genomic hybridization and spectral karyotyping analysis revealed structural alterations affecting identical chromosomes 1, 2, 9, and 13, among others. In addition to the known hot spots of alterations in papillary thyroid carcinomas on chromosomes 1q and 10q, a comprehensive breakpoint analysis in the pooled data set revealed novel breakpoints on chromosomes 4q, 5q, 6p, 12q, 13q, and 14q. The chromosomal aberrations in these tumors may provide suitable starting points for the positional cloning of genes involved in radiation-induced tumorigenesis.

Adolescent↗
PubMed1999

Drug resistance testing of acute myeloid leukemia in adults using the MTT assay.

OBJECTIVE: We want to evaluate the MTT in vitro assay for newly diagnosed AML in adults, in particular its prognostic significance. METHODS: MTT tests were performed according to Pieters et al., Blood 76: 2327, 1990. Up to 18 cytostatic drugs were tested in a wide range of concentrations over 4 days and compared with controls. If necessary, blasts were enriched > 80% by negative selection with dynabeads (Kaspers et al., Br. J. Cancer 70: 1047, 1994). Percent S-phase was measured at begin of assay and after 4 days. RESULTS: Technical success rate was 80-85% and the assay took about one day of work. IC50 values as a measure for drug resistance were highly reproducible with an interassay CV (range) of 28% (13-47) between days. Median cell viability of controls after 4 days was 80% (44-97);% S-phase at begin of assay was 3% (0.1-15) and after 4 days 9% (1-39). Leukemic blasts from 57 adult AML patients were prospectively tested in vitro at diagnosis. Large interindividual differences in drug resistance were observed (over 1000 fold on average). There was a trend for greater IC50 with higher cytogenetic risk and nonresponders to induction. Other clinical prognostic factors such as patient age, initial WBC, FAB subtype, prior MDS and % S-phase did not show a relationship with the in vitro data. There was a high correlation between the topoisomerase II related drugs regarding in vitro resistance. CONCLUSION: In vitro sensitivity tests like the MTT assay may provide a valuable tool for prediction of individual therapy outcome in combination with cytogenetics. However, longer follow-up is required.

Adolescent↗