Biomedical subjects

I Mueller

Publications and source records attributed to I Mueller.

11 recordsLinked to original sources

PubMed2003

Large-scale isolation of CD133+ progenitor cells from G-CSF mobilized peripheral blood stem cells.

We have evaluated the feasibility of large-scale isolation of CD133+ progenitors from healthy mobilized adult donors for potential clinical use in autologous and allogeneic transplantation. A total of 11 healthy volunteer adult donors were mobilized with G-CSF. CD133+ stem cells were isolated from a single leukapheresis using the Clinimacs method. The median percentage of CD133 before positive selection was 0.75% (range 0.39-2.03%). After selection, the median purity and recovery was 94% (range 85.2-98.0%) and 69% (range 44-100%), respectively. The median log10 T-cell depletion obtained by CD133+ positive selection was 4.2 (range 3.8-4.7). The CD133+ progenitors were highly enriched in colony-forming units (CFU) and transplantation into NOD/SCID mice resulted in a high engraftment rate. Transplantation of sorted CD133+/CD34+ cells into NOD/SCID mice showed a higher engraftment compared to CD133-/CD34+ cells. Mobilized peripheral CD133+ stem cells can be purified in large scale for potential clinical use. The biological function of the cells is not impaired. The majority of the NOD/SCID repopulating cells are within the CD133+/CD34+ subpopulation. Therefore, clinical studies using purified CD133+ stem cells can be envisoned to further clarify the role of CD133+ stem cells in hematopoietic reconstitution after transplantation.

AC133 Antigen↗

PubMed2002

A large-scale method for T cell depletion: towards graft engineering of mobilized peripheral blood stem cells.

We have investigated the feasibility and efficacy of large-scale T cell depletion from granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC). The method is based on the use of a CD3 antibody conjugated to magnetic microbeads and magnetic activated cell sorting (Clinimacs). A total of eight large-scale experiments were performed. In four experiments, CD3(+) T cells were depleted from PBSC obtained from volunteers mobilized with G-CSF whereas, in four experiments, T cells were depleted from PBSC from stem cell donors, in which the CD34(+) stem cells had been removed for allogeneic transplantation by positive selection prior to T cell depletion. The mean number of processed mononuclear cells (MNCs) was 3.3 x 10(10) (range 1.5 x 10(10)-5.1 x 10(10)) with a mean T cell proportion of 35.8% (range 16.7-64.0%). After T cell depletion, the percentage of contaminating T cells was 0.15% (range 0.01-1.01%) with a mean log(10) depletion of 3.4 (range 2.8-4.1). The mean recovery of CD3-negative MNCs after depletion was 76% (range 52-100%). The mean recovery of CD34(+) stem cells in the four evaluable experiments was 82% (range 75-92%). In vitro colony assays and in vivo NOD/SCID repopulation assays showed that this large-scale T cell depletion method has no negative impact on the function of the hematopoietic precursor cells. Therefore, we conclude that this T cell depletion method is a valuable tool for further graft engineering strategies involving mobilized PBSCs.

AC133 Antigen↗

PubMed2002

Stream-bank shade and larval distribution of the Philippine malaria vector Anopheles flavirostris.

The principal malaria vector in the Philippines, Anopheles flavirostris (Ludlow) (Diptera: Culicidae), is regarded as 'shade-loving' for its breeding sites, i.e. larval habitats. This long-standing belief, based on circumstantial observations rather than ecological analysis, has guided larval control methods such as 'stream-clearing' or the removal of riparian vegetation, to reduce the local abundance of An. flavirostris. We measured the distribution and abundance of An. flavirostris larvae in relation to canopy vegetation cover along a stream in Quezon Province, the Philippines. Estimates of canopy openness and light measurements were obtained by an approximation method that used simplified assumptions about the sun, and by hemispherical photographs analysed using the program HEMIPHOT. The location of larvae, shade and other landscape features was incorporated into a geographical information system (GIS) analysis. Early larval instars of An. flavirostris were found to be clustered and more often present in shadier sites, whereas abundance was higher in sunnier sites. For later instars, distribution was more evenly dispersed and only weakly related to shade. The best predictor of late-instar larvae was the density of early instars. Distribution and abundance of larvae were related over time (24 days). This pattern indicates favoured areas for oviposition and adult emergence, and may be predictable. Canopy measurements by the approximation method correlated better with larval abundance than hemispherical photography, being economical and practical for field use. Whereas shade or shade-related factors apparently have effects on larval distribution of An. flavirostris, they do not explain it completely. Until more is known about the bionomics of this vector and the efficacy and environmental effects of stream-clearing, we recommend caution in the use of this larval control method.

Animals↗

PubMed2001

Pseudomonas aeruginosa-induced apoptosis involves mitochondria and stress-activated protein kinases.

Pseudomonas aeruginosa, a gram-negative facultative pathogen, causes severe infections in immunocompromised and cystic fibrosis patients. However, the molecular details of the interaction between P. aeruginosa and mammalian cells are still largely unknown. Here we demonstrate that infection of human conjunctiva epithelial Chang cells with the well-characterized P. aeruginosa strain PAO-I results in rapid induction of apoptosis. Apoptosis was mediated by mitochondrial alterations, in particular mitochondrial depolarization, synthesis of reactive oxygen intermediates, and release of cytochrome c, as well as an activation of Jun N-terminal kinases (JNK). Stimulation of these events was dependent on upregulation of CD95 on infected cells, and a deficiency of CD95 or the CD95 ligand prevented mitochondrial changes, JNK activation, and apoptosis upon infection. Further, efficient apoptosis of Chang epithelial cells required infection with live P. aeruginosa, adhesion but not invasion of the bacteria, and expression of the type III secretion system in PAO-I. The data indicate a type III secretion system-dependent, sequential activation of several signaling pathways by P. aeruginosa PAO-I, resulting in apoptosis of the infected cell.

Animals↗

PubMed2001

A double-blind, placebo-controlled crossover study investigating the effect of porcine secretin in children with autism.

OBJECTIVES: A recent patient series reported the incidental findings of improved social and language skills in 3 children with autistic spectrum disorders after the administration of secretin, a peptide hormone. However, a subsequent study did not find evidence for a drug effect. Parents are seeking treatment with secretin despite the absence of empirical investigations demonstrating amelioration in autism symptomology. In order to more precisely measure the effects of secretin, this study investigated the effect of a single intravenous dose of porcine secretin on 12 autistic children through a randomized, double-blind, placebo-controlled, crossover study. Children were assessed on objective language and on social, neuropsychological, and gastrointestinal measures to evaluate drug effects. The study was conducted over a 16-week trial. The results indicated that significant differences were not observed on the majority of the dependent variables. Statistically significant differences were observed on measures of positive affect and activity level following secretin infusion. In general, the autistic children did not demonstrate the improvements described in the initial retrospective report.

Affect↗

PubMed2001

The Carter Center's assistance to river blindness control programs: establishing treatment objectives and goals for monitoring ivermectin delivery systems on two continents.

Periodic mass treatment with ivermectin in endemic communities prevents eye and dermal disease due to onchocerciasis. As part of an international global partnership to control onchocerciasis, The Carter Center's Global 2000 River Blindness Program (GRBP) assists the ministries of health in ten countries to distribute ivermectin (Mectizan, donated by Merck & Co.). The GRBP priorities are to maximize ivermectin treatment coverage and related health education and training efforts, and to monitor progress through regular reporting of ivermectin treatments measured against annual treatment objectives and ultimate treatment goals (e.g., full coverage, which is defined as reaching all persons residing in at risk villages who are eligible for treatment). Since the GRBP began in 1996, more than 21.2 million ivermectin treatment encounters have been reported by assisted programs. In 1999, more than 6.6 million eligible persons at risk for onchocerciasis received treatment, which represented 96% of the 1999 annual treatment objective of 6.9 million, and 78% of the ultimate treatment goal in assisted areas.

Africa↗

PubMed1999

Nonparametric analysis of the absorption profile of octreotide in rabbits from long-acting release formulation OncoLAR.

Octreotide (octreotide-acetate, Sandostatin(R)) is a somatostatin analogue, used in long-term treatment of acromegaly. The present study describes the absorption profile in rabbits of octreotide after release from the long-acting formulation OncoLAR (denoted as octreotide-LAR). In a first experiment, the disposition kinetics of octreotide was studied for 24 h in six rabbits after intravenous (i. v.) injection of 0.025 mg of a solution of octreotide. In a second experiment, release kinetics was studied in eight rabbits for 49 days after an i.m. injection of 5 mg/kg of octreotide-LAR. Concentrations were determined by radioimmunoassay. After i.v. injection of octreotide, one- and two-compartment models were compared for each rabbit. A typical disposition profile was computed using the mean parameters. After i.m. injection of octreotide-LAR, deconvolution was performed using the point-area method. Individual absorption profiles were characterised using natural splines. The number of breakpoints was selected using the generalised cross-validation criterion. The two compartment model was selected based on the i.v. study. After i.m. administration, octreotide exhibited a triphasic absorption profile, with large interindividual variability. A transient peak followed the initial burst phase. The third phase covered 85% of total drug released. The approach allows a model-independent description of the in vivo absorption profile of octreotide-LAR.

Absorption↗

PubMed1997

Biochemical analysis of p120/130: a protein-tyrosine kinase substrate restricted to T and myeloid cells.

T cell activation is mediated by a cascade of intracellular events involving protein-tyrosine kinases and their substrates. p56(lck) and p59(fyn) are protein-tyrosine kinases that associate with CD4/CD8 and the TCRzeta/CD3 complex, respectively. We previously reported the appearance of a protein doublet at 120 and 130 kDa that preferentially associates with p59(fyn) and undergoes tyrosine phosphorylation upon receptor ligation. In this paper, we demonstrate that p120/130 is a novel protein that is restricted in expression to T cells, thymocytes and myeloid cells. Internal peptide sequencing and immunoblotting using an anti-p120/130 antisera showed that p120/130 is a unique protein that is distinct from p130(cas) and p125(cbl). By contrast, p120 and p130 shared similar peptide patterns and are structurally related. Alkaline phosphatase digestion of precipitates showed that they are not related due to phosphorylation. p120/130 was found to associate constitutively with a 55-kDa protein of unknown identity, but which is distinct from p56(lck) and Shc. p120/130 also undergoes a unique kinetics of phosphorylation and associates with the Ag receptor in response to TCR ligation. In keeping with the association with p59(fyn), T cells from p59(fyn)-negative mice exhibit reduced phosphorylation of the protein. p120/130 therefore represents a novel TCR associated intracellular molecule with potential to play a role in T cell signaling.

Amino Acid Sequence↗

PubMed1969

[Not Available].

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Germany↗

PubMedDate not supplied

Spatial patterns of child growth in Papua New Guinea and their relation to environment, diet, socio-economic status and subsistence activities.

Anthropometric data from the 1982/83 Papua New Guinea (PNG) National Nutrition Survey were analysed to identify geographical patterns of child growth and investigate their relation to a wide range of environmental, dietary and socio-economic variables. Standardized growth scores for length-for-age (LAZ), weight-for-age (WAZ) and weight-for-length (WLZ) were calculated based on an internal PNG growth reference. Hierarchical Bayesian spatial models based on conditional autoregressive (CAR) priors were subsequently used to model spatial patterns in scores and their relation to different sets of covariates. The geographical differences were bigger for linear growth than for increases in weight. Growth was most reduced in parts of Milne Bay Province, Madang Province, the Torricelli/Prinz Alexander Ranges, and in the area occupied by Angan people. Socio-economic status was the most important factor determining variation in growth within populations. Differences in diet and, to a lesser extent, the physical environment were the main determining factor of differences among populations. Covariate adjustment accounted for more spatially structured variation in LAZ and WAZ than in WLZ. All variables indicating higher socio-economic status were correlated with better growth, as was a high consumption of imported and local high quality foods such as cereals, legumes, tinned fish/meat or fresh fish. This indicates that nutritional interventions in PNG should aim at promoting the consumption of such high energy and high protein foods as well as strengthening the general economic base of rural populations.

Analysis of Variance↗

PubMedDate not supplied

Patterns of child growth in Papua New Guinea and their relation to environmental, dietary and socioeconomic factors--further analyses of the 1982-1983 Papua New Guinea National Nutrition Survey.

Child growth and nutrition in rural Papua New Guinea vary widely among different environments. The 1982-1983 National Nutrition Survey (NNS) was re-analyzed in order to relate patterns of growth to a wide range of dietary, socioeconomic, agricultural and demographic variables. Anthropometric indices of growth were calculated based on an internal Papua New Guinean growth standard constructed from the children included in the NNS. Children were subsequently classified as stunted, wasted or underweight if they were more than 1 SD below the national mean. Regression analyses on 15,975 children show that variation in growth among environments can largely be accounted for by differences in diet, although significant differences in relation to altitude, relief and rainfall patterns persist. Other important predictors of child growth and nutrition included socioeconomic status, maternal education, marital status of the mother and father's occupation. Variance components analysis revealed that most of the geographical variation in child growth was accounted for by the environmental, dietary, socioeconomic, agricultural and demographic variables included in the regression analyses. Most of the factors which were found to be associated with child growth in this study are related in one form or another to differences in local subsistence agriculture, which may therefore be the main determinant of child growth and nutrition patterns in Papua New Guinea.

Anthropometry↗