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Biomedical subjects

Michael Weiss

Publications and source records attributed to Michael Weiss.

At least 37 records · Page 2Linked to original sources
PubMed2005

Dryadomyces amasae: a nutritional fungus associated with ambrosia beetles of the genus Amasa (Coleoptera: Curculionidae, Scolytinae).

During surveys of woodlands in Taiwan a previously undescribed fungus Dryadomyces amasae gen. sp. nov., was found in the sapwood of dead angiosperm timbers in the gallery systems of the scolytine ambrosia beetle Amasa concitatus. The fungus grows predominantly in the immediate vicinity of the feeding beetle larvae and serves as a nutritional ambrosia fungus. The transmission of D. amasae to new breeding substrates is ensured by an oral mycetangium, a paired organ which was found in A. concitatus and A. aff. glaber near the mandibles and contained multiple cells of the fungus. Morphologically D. amasae resembles species of Ambrosiella. However, phylogenetic analysis based on partial nucSSU rDNA placed the fungus with certain species of the genus Ambrosiella within the Ophiostomatales, whereas the type species of Ambrosiella, A. xylebori, was assigned to the Microascales. A. xylebori, as well as A. ferruginea and A. hartigii, demonstrated phialidic conidial development, leading to an emendation of the description of the genus Ambrosiella. In contrast, Dryadomyces exhibited conidial development by apical, sympodial wall formation with prominent denticles bearing conidia. Other, previously described Ambrosiella species exhibited non-phialidic conidiogenesis, but lacked denticles on the conidiophores. Consequently, their classification needs further revision.

Ambrosia↗
PubMed2005

The systematic relevance of conidiogenesis modes in the gilled Agaricales.

Dikaryotic and haploid mycelia of more than 150 gilled species of euagarics were studied morphologically and by molecular phylogenetic methods. The morphological investigations revealed anamorphs in more than 90 species that were often specific at the genus or family level. Thallic conidiogenesis dominated and varied from fragmentation of normally branched hyphae to the formation of differentiated sympodially branched conidiophores. Secession modes, coiling of the conidiogenous hyphae or the swelling of the conidia were additional distinguishing features. Phylogenetic analysis of the D1-D3 domains of the nuclear gene for the ribosomal large subunit using a Bayesian Markov chain Monte Carlo approach resulted in several well-supported groups that are consistent with anamorph morphology. These results indicate that the anamorphs provide valuable characters for a natural classification of the Agaricales.

Agaricales↗
PubMed2005

High specificity generally characterizes mycorrhizal association in rare lady's slipper orchids, genus Cypripedium.

Lady's slipper orchids (Cypripedium spp.) are rare terrestrial plants that grow throughout the temperate Northern Hemisphere. Like all orchids, they require mycorrhizal fungi for germination and seedling nutrition. The nutritional relationships of adult Cypripedium mycorrhizae are unclear; however, Cypripedium distribution may be limited by mycorrhizal specificity, whether this specificity occurs only during the seedling stage or carries on into adulthood. We attempted to identify the primary mycorrhizal symbionts for 100 Cypripedium plants, and successfully did so with two Cypripedium calceolus, 10 Cypripedium californicum, six Cypripedium candidum, 16 Cypripedium fasciculatum, two Cypripedium guttatum, 12 Cypripedium montanum, and 11 Cypripedium parviflorum plants from a total of 44 populations in Europe and North America, yielding fungal nuclear large subunit and mitochondrial large subunit sequence and RFLP (restriction fragment length polymorphism) data for 59 plants. Because orchid mycorrhizal fungi are typically observed without fruiting structures, we assessed fungal identity through direct PCR (polymerase chain reaction) amplification of fungal genes from mycorrhizally colonized root tissue. Phylogenetic analysis revealed that the great majority of Cypripedium mycorrhizal fungi are members of narrow clades within the fungal family Tulasnellaceae. Rarely occurring root endophytes include members of the Sebacinaceae, Ceratobasidiaceae, and the ascomycetous genus, Phialophora. C. californicum was the only orchid species with apparently low specificity, as it associated with tulasnelloid, ceratobasidioid, and sebacinoid fungi in roughly equal proportion. Our results add support to the growing literature showing that high specificity is not limited to nonphotosynthetic plants, but also occurs in photosynthetic ones.

Base Sequence↗
PubMed2005

Russulaceae and Thelephoraceae form ectomycorrhizas with members of the Nyctaginaceae (Caryophyllales) in the tropical mountain rain forest of southern Ecuador.

* Three members of the Nyctaginaceae, two Neea species and one Guapira species, occurred scattered within a very species-rich neotropical mountain rain forest. The three species were found to form ectomycorrhizas of very distinctive characters, while all other tree species examined formed arbuscular mycorrhizas. * The ectomycorrhizas were structurally typified according to light and transmission electron microscope investigations. The internal transcribed spacer (ITS) rDNA and part of the nuclear large subunit (LSU, 28S) rDNA of the mycorrhiza forming fungi were amplified and sequenced. Phylogenetic analyses were carried out. * Neea species 1 was found to form typical ectomycorrhizas with five different fungal species, Russula puiggarii, Lactarius sp., two Tomentella or Thelephora species, and one ascomycete. Neea species 2 and the Guapira species were associated with only one fungus each, a Tomentella/Thelephora species clustering closely together in an ITS-neighbour-joining tree. The long and fine rootlets of the Guapira species showed proximally a hyphal mantle and a Hartig net, but distally intracellular fungal colonization of the epidermis and root hair development. The ectomycorrhizal segments of the long roots of Neea species 2 displayed a hyphal mantle and a Hartig net around alive root-hair-like outgrowths of the epidermal cells. * The distribution and the evolution of ectomycorrhizas in the predominantly neotropic Nyctaginaceae are discussed.

Ascomycota↗
PubMed2005

The high-affinity poplar ammonium importer PttAMT1.2 and its role in ectomycorrhizal symbiosis.

One way to elucidate whether ammonium could act as a nitrogen (N) source delivered by the fungus in ectomycorrhizal symbiosis is to investigate plant ammonium importers. Expression analysis of a high-affinity ammonium importer from Populus tremulax tremuloides (PttAMT1.2) and of known members of the AMT1 gene family from Populus trichocarpa was performed. In addition, PttAMT1.2 function was studied in detail by heterologous expression in yeast. PttAMT1.2 expression proved to be root-specific, affected by N nutrition, and strongly increased in a N-independent manner upon ectomycorrhiza formation. The corresponding protein had a K(M) value for ammonium of c. 52 microm. From the seven members of the AMT1 gene family, one gene was exclusively expressed in roots while four genes were detectable in all poplar organs but with varying degrees of expression. Ectomycorrhiza formation resulted in a strong upregulation of three of these genes. Our results indicate an increased ammonium uptake capacity of mycorrhized poplar roots and suggest, together with the expression of putative ammonium exporter genes in the ectomycorrhizal fungus Amanita muscaria, that ammonium could be a major N source delivered from the fungus towards the plant in symbiosis.

Base Sequence↗
PubMed2005

Intracellular T-cell cytokine levels are age-dependent in healthy children and adults.

Intracellular detection of cytokines via fluorescent antibody staining and flow cytometry has quickly become a standard method in experimental immunology. However, in pediatrics most studies have been hampered by the exclusion of healthy control individuals or have been skewed by neglecting to observe age-dependent differences in cytokine production. We therefore intended to establish normal values for different age groups and to describe the age-dependent development of cytokine profiles. Whole blood from 46 healthy children and 33 adults was analyzed by flow cytometry after stimulation with PMA, ionomycin and Mmonensin, and staining with anti-cytokine and surface antibodies. In the pediatric population, we found a significant positive correlation between age and intracellular cytokine levels of IFN-gamma, IL-2, IL-4 and TNF-alpha in CD4+ cells, as well as for IFN-gamma and TNF-alpha in CD8+ cells. In adulthood, no such striking trend could be detected, but significant correlation was found for IL-10 in CD4+ cells and IFN-gamma in CD8+ cells as well as for TNF-alpha in both cell subgroups. We present here the first systematic analysis of intracellular cytokine production in normal, healthy children between the ages of 0 to 18 years compared to results in adults. These data may provide a reference basis for the study of cytokine secretion patterns, and they also demonstrate a significant maturation of the T-cell cytokine production capacity from birth to adulthood.

Adolescent↗
PubMed2004

A stochastic differential equation model for drug dissolution and its parameters.

A stochastic differential equation describing the process of drug dissolution is presented. This approach generalizes the classical deterministic first-order model. Instead of assuming a constant fractional dissolution rate, it is considered here that the rate is corrupted by a white noise. The half-dissolution time is investigated for the model. The maximum likelihood and Bayes methods for the estimation of the parameters of the model are developed. The method is illustrated on experimental data. As expected, due to the nonlinear relationship between the fractional dissolution rate and the dissolution time, the estimates of the dissolution rate obtained from this stochastic model are systematically lower than the rate calculated from the deterministic model.

Algorithms↗
PubMed2004

Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943.

To gain more insight into the mechanistic processes controlling the kinetics of inotropic response of digoxin in the perfused whole heart, an integrated kinetic model was developed incorporating digoxin uptake, receptor binding (Na(+)-K(+)-ATPase inhibition), and cellular events linking receptor occupation and response. The model was applied to data obtained in the single-pass Langendorff-perfused rat heart for external [Ca(2+)] of 0.5 and 1.5 mM under control conditions and in the presence of the reverse-mode Na(+)/Ca(2+) exchange inhibitor KB-R7943 (0.1 microM) in perfusate. Outflow concentration and left ventricular developed pressure data measured for three consecutive doses (15, 30, and 45 microg) in each heart were analyzed simultaneously. While disposition kinetics of digoxin was determined by interaction with a heterogeneous receptor population consisting of a high-affinity/low-capacity and a low-affinity/high- capacity binding site, response generation was >80% mediated by binding to the high-affinity receptor. Digoxin sensitivity increased at lower external [Ca(2+)] due to higher stimulus amplification. Coadministration of KB-R7943 significantly reduced the positive inotropic effect of digoxin at higher doses (30 and 45 microg) and led to a saturated and delayed receptor occupancy-response relationship in the cellular effectuation model. The results provide further evidence for the functional heterogeneity of the Na(+)-K(+)-ATPase and suggest that in the presence of KB-R7943 a reduction of the Ca(2+) influx rate via the reverse mode Na(+)/Ca(2+) exchanger might become the limiting factor in digoxin response generation.

Animals↗
PubMed2004

Comparative molecular field analysis and comparative molecular similarity indices analysis of thalidomide analogues as angiogenesis inhibitors.

Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been shown to require metabolic activation for antiangiogenic activity. A series of 39 compounds, based upon the structure of some of these metabolites, was synthesized and tested for their ability to inhibit microvessel growth in the rat aortic ring assay. The results of this testing have been used as the basis for a three-dimensional quantitative structure-activity relationship (3D-QSAR) study, utilizing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) procedures. The best resulting CoMFA and CoMSIA models have conventional r(2) values of 0.924 and 0.996, respectively. The cross-validated q(2) values are 0.666 and 0.635, respectively. These models offer insight into the structural requirements for activity of thalidomide analogues as angiogenesis inhibitors, since there is only speculative knowledge of the target. Additionally, it appears as though there is more than one active site or mechanism of action.

Angiogenesis Inhibitors↗
PubMed2004

Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity.

OBJECTIVE: The autosomal-dominant form of the hyperimmunoglobulin E syndrome (AD-HIES) has been described as a multisystem disorder including immune, skeletal, and dental abnormalities. Variants of AD-HIES are known but not well defined. METHODS: We evaluated 13 human immunodeficiency virus-seronegative patients from six consanguineous families with an autosomal-recessive form of hyperimmunoglobulin E syndrome (AR-HIES) and 68 of their relatives. RESULTS: Persons affected with AR-HIES presented with the classical immunologic findings of hyperimmunoglobulin E syndrome, including recurrent staphylococcal infections of the skin and respiratory tract, eczema, elevated serum immunoglobulin E, and hypereosinophilia. In addition, severe recurrent fungal and viral infections with molluscum contagiosum, herpes zoster, and herpes simplex were noted. Autoimmunity was seen in two patients. Central nervous system sequelae, including hemiplegia, ischemic infarction, and subarachnoid hemorrhages, were common and contributed to high mortality. Notably, patients with AR-HIES did not have skeletal or dental abnormalities and did not develop pneumatoceles, as seen in AD-HIES. In lymphocyte proliferation assays, patients' cells responded poorly to mitogens and failed to proliferate in response to antigens, despite the presence of normal numbers of lymphocyte subpopulations. CONCLUSION: The autosomal-recessive form of hyperimmunoglobulin E syndrome is a primary immunodeficiency with elevated immunoglobulin E, eosinophilia, vasculitis, autoimmunity, central nervous system symptoms, and high mortality. AR-HIES lacks several of the key findings of AD-HIES and therefore represents a different, previously unrecognized disease entity.

Autoimmunity↗
PubMed2004

Sebacinales: a hitherto overlooked cosm of heterobasidiomycetes with a broad mycorrhizal potential.

Within the basidiomycetes, the vast majority of known mycorrhizal species are homobasidiomycetes. It was therefore surprising when molecular and ultrastructural studies revealed a broad diversity of mycorrhizal associations involving members of the heterobasidiomycetous Sebacinaceae, fungi which, due to their inconspicuous basidiomes, have been often overlooked. To investigate the phylogenetic position of the Sebacinaceae within the basidiomycetes and to infer phylogenetic relationships within the Sebacinaceae, we made molecular phylogenetic analyses based on nuclear rDNA. We present a well-resolved phylogeny of the main lineages of basidiomycetes which suggests that the Sebacinaceae is the most basal group with known mycorrhizal members. Since more basal taxa of basidiomycetes consist of predominantly mycoparasitic and phytoparasitic fungi, it seems possible that a mycorrhizal life strategy, which was transformed into a saprotrophic strategy several times convergently, is an apomorphic character for the Hymenomycetidae. Mycorrhizal taxa of Sebacinaceae, including mycobionts of ectomycorrhizas, orchid mycorrhizas, ericoid mycorrhizas, and jungermannioid mycorrhizas, are distributed over two subgroups. One group contains species with macroscopically visible basidiomes, whereas members of the other group probably lack basidiomes. Sebacina appears to be polyphyletic; current species concepts in Sebacinaceae are questionable. Sebacina vermifera sensu Warcup & Talbot consists of a broad complex of species possibly including mycobionts of jungermannioid and ericoid mycorrhizas. This wide spectrum of mycorrhizal types in one fungal family is unique. Extrapolating from the known rDNA sequences in Sebacinaceae, it is evident that there is a cosm of mycorrhizal biodiversity yet to be discovered in this group. Taxonomically, we recognise the Sebacinaceae as constituting a new order, the Sebacinales.

Basidiomycota↗
PubMed2004

Phylogenetic relationships of Plasmopara, Bremia and other genera of downy mildew pathogens with pyriform haustoria based on Bayesian analysis of partial LSU rDNA sequence data.

Bayesian and maximum parsimony phylogenetic analyses of 92 collections of the genera Basidiophora, Bremia, Paraperonospora, Phytophthora and Plasmopara were performed using nuclear large subunit ribosomal DNA sequences containing the D1 and D2 regions. In the Bayesian tree, two main clades were apparent: one clade containing Plasmopara pygmaea s. lat., Pl. sphaerosperma, Basidiophora, Bremia and Paraperonospora, and a clade containing all other Plasmopara species. Plasmopara is shown to be polyphyletic, and Pl. sphaerosperma is transferred to a new genus, Protobremia, for which also the oospore characteristics are described. Within the core Plasmopara clade, all collections originating from the same host family except from Asteraceae and Geraniaceae formed monophyletic clades; however, higher-level phylogenetic relationships lack significant branch support. A sister group relationship of Pl. sphaerosperma with Bremia lactucae is highly supported. Within Bremia lactucae s. l., three distinct clades are evident, which only partly conform to the published host specificity groups. All species of the genera Basidiophora, Bremia, Paraperonospora and Plasmopara included in the present study were investigated for haustorial morphology, and all had ellipsoid to pyriform haustoria, which are regarded as a diagnostic synapomorphy of the whole clade. Aspects of coevolution and cospeciation within the downy mildew pathogens with ellipsoid to pyriform haustoria are briefly discussed.

Bayes Theorem↗
PubMed2004

Inotropic effect of digoxin in humans: mechanistic pharmacokinetic/pharmacodynamic model based on slow receptor binding.

PURPOSE: The purpose of this study was to construct a mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for digoxin that describes the relationship between plasma concentration and inotropic response. METHODS: On the basis of results obtained in the isolated perfused rat heart, a PK/PD model for digoxin in humans was developed. In fitting the model to previously published bolus dose and concentration clamp data (shortening of electromechanical systole), the plasma concentration-time curves were used as forcing functions in the computer program ADAPT II. RESULTS: The mechanistic approach allowed a modeling of digoxin pharmacodynamics which is consistent with available inotropic response data. The estimates of the receptor binding parameters were in the same order of magnitude as those measured in vitro for ouabain. The mechanistic model explained the parameters of the empirical link model (EC50, Emax and delay time tau) in terms of the underlying processes, suggesting that the long equilibration half-time of 13 h is due to slow receptor binding. The empirical link model, in contrast, is not compatible with a noninstantaneous receptor binding process and led to estimates of the delay time tau that were dependent on the digoxin administration schedule. CONCLUSIONS: The new, mechanistic model may provide a rationale for better understanding of digoxin pharmacodynamics and could become a tool to bridge the gap between in vitro and in vivo studies.

Animals↗
PubMed2004

A novel CIAS1 mutation and plasma/cerebrospinal fluid cytokine profile in a German patient with neonatal-onset multisystem inflammatory disease responsive to methotrexate therapy.

The clinical features, the underlying CIAS1 mutation, and the results of cytokine analyses are described for a 10-year-old German boy with neonatal-onset multisystem inflammatory disease, whose condition improved with age. Disease onset occurred at 26 months of age with predominantly cutaneous (urticarial rash) and neurologic (headache, chronic meningitis) symptoms including early bilateral optic nerve atrophy, whereas articular manifestations were mild. Sequence analysis of exon 3 of the CIAS1 gene revealed heterozygosity for a novel missense mutation. A T515C transition led to the replacement of isoleucine by threonine at amino acid position 172 (I172T) in a region of cryopyrin flanking the PYRIN and NACHT domains. This mutation was not present in the parents or in 11 controls and therefore was considered to be a de novo mutation. Enzyme-linked immunosorbent assays were performed to determine interleukin-6 and soluble tumor necrosis factor receptor superfamily 1B levels in the patient's serum and cerebrospinal fluid (CSF). Concentrations were highly elevated in the CSF, whereas corresponding serum levels remained low. The strong cytokine activation in the CSF corresponded with the neurologic symptoms. Local activation of intrathecal macrophages may therefore be an important pathogenetic mechanism. CSF cytokine levels decreased to normal under corticosteroid and intrathecal methotrexate therapy. When the boy reached the age of 5.5 years, treatment was stopped, and he has remained relapse-free.

Arthralgia↗
PubMed2003

An integrated process for partial oxidation of alkanes.

The partial oxidation of alkanes via bromination followed by the reaction with solid metal oxide mixtures (MO) is shown to give an array of products that can be tuned by varying the MO and the reaction conditions.

Journal Article↗