Biomedical subjects

M Loeffler

Publications and source records attributed to M Loeffler.

117 records · Page 7Linked to original sources

PubMed1984

The kinetics of granulopoiesis in long-term mouse bone marrow culture. Part I.

The spontaneous stratification in long-term bone marrow cultures was illustrated and quantified. The cultures were separated into three hematopoietic layers: nonadherent cells in the supernatant medium, lightly adherent cells on top of the stromal layer, and remaining cells buried within the stromal layer. The cells of each layer were subcultured for 10 days in plastic tubes that inhibit the formation of a stromal layer. Daily samplings with absolute and differential cell counts were obtained. We identified three families of cell disappearance curves and cell types: CFU-s, hemocytoblasts, myeloblasts, and promyelocytes (G1, 2); myelocytes (G3); and postmitotic granulocytes (G4). Also, the numbers of mitotic and necrotic cells were determined. The longest half-time of CFU-s was 2.5 days. Lacking stromal support, CFU-s disappeared faster than other differentiated cells. Generally, these cells maintained their numbers for the first week of subcultures, which was attributable to a temporarily maintained balance of cell death and fresh cell production. After more than 7 days, there was a rapid decline of all differentiated cell types.

Animals↗

PubMed1984

The kinetics of granulopoiesis in long-term mouse bone marrow culture. Part II.

A mathematical model of mouse granulopoiesis in long-term bone marrow culture was constructed, based on established in vivo cell kinetic parameters. We applied the model to the cell kinetic experiment presented in Part I. Comparing model-predicted cell kinetics with the experimental data led to iterative testing of several hypotheses. In the final model, the cell kinetics of intact tissue culture flasks were reconstructed, using the experimental data from 10 days of tube culture. Among other things, our analysis suggests that the parameters of normal in vivo granulopoiesis apply to bone marrow culture.

Animals↗

PubMed1984

The kinetics of hematopoietic stem cells during and after hypoxia. A model analysis.

A previously described mathematical model of the hematopoietic stem cell system has been extended to permit a detailed understanding of the data during and after hypoxia. The model includes stem cells, erythroid and granuloid progenitors and precursors. Concerning the intramedullary feedback mechanisms two basic assumptions are made: 1) The fraction "a" of CFU-S in active cell cycle is regulated. Reduced cell densities of CFU-S, progenitors or precursors lead to an accelerated stem cell cycling. Enlarged cell densities suppress cycling. 2) The self renewal probability "p" of CFU-S is also regulated. The normal steady state is described by p = 0.5, indicating that on statistical average each dividing mother stem cell is replaced by one daughter stem cell, while the second differentiates. Diminished cell densities of CFU-S or enlarged densities of progenitors and precursors induce a more intensive self renewal (p greater than 0.5), such that the stem cell number increases. The self renewal probability declines (p less than 0.5) if too many CFU-S or too few progenitors and precursors are present. The model reproduces bone marrow data for CFU-S, BFU-E, CFU-C, CFU-E, 59 Fe-uptake and nucleated cells in hypoxia and posthypoxia. Although the ratio of differentiation into the erythroid and granuloid cell lines is kept constant in the model, a changing ratio of CFU-E and CFU-C results. The model suggests that stem cells and progenitor cells are regulated by a regulatory interference of erythropoiesis and granulopoiesis.

Cell Differentiation↗

PubMed1983

[Mathematical models in hematology].

The use of mathematical models in haematology is shown by some examples concerning stem cell kinetics, erythropoiesis and thrombopoiesis. At first, model assumptions are formulated which include the biological knowledge and some regulatory hypotheses. Then, the reaction of the model on stimulation and suppression is calculated. Finally, by comparison with experimental or clinical data one can evaluate how far the model assumptions are sufficient to understand the measurements. Thus one can exclude wrong hypotheses and identify the important regulatory influences.

Blood Platelets↗

PubMed1983

Comparisons of different assays for the thyroid-stimulating antibody of Graves' disease.

Various current methods for the assay of the thyroid-stimulating antibody of Graves' disease (TSAb) were assessed for comparative sensitivity and specificity. Five procedures were examined in detail: I) increase in cAMP in human thyroid slices; II) inhibition of [125I]TSH binding to human thyroid membranes, particulate or III) solubilized; IV) inhibition of [125I]TSH binding to guinea pig fat cell membranes, particulate or V) solubilized. The minimum effective concentration of TSH (microunits per ml) in these assays was: I) 5; IV) 12.5; V) 25 and II and III) 100. The guinea pig fat systems (IV and V) were more sensitive than the human thyroid assays (II and III) in terms of the concentration of TSH required for 50% inhibition of binding. Five preparations of TSAb-immunoglobulin G were found in general to have constant relative potency in the five assay systems, but individual immunoglobulins G were variable in their effects when data in the five procedures were compared directly. It is probable that, in addition to TSAb, other antibodies, more or less specific for the human thyroid, influenced the TSH binding inhibition assays to a variable extent. The above TSH binding inhibition assays were carried out with solutions or suspensions of receptor preparations. Solid phase systems, using microtiter plates for TBI assays, were assessed in less detail. Human thyroid, particulate or solubilized, was ineffective (little specific binding of [125I]TSH), but a particulate preparation of guinea pig fat cell membranes was an efficient basis for a solid phase TBI system. Solid phase assessment with [125I]staphylococcal protein A of binding of thyroid autoantibodies to human thyroid membranes was not specific for TSAb.

Adipose Tissue↗

PubMed1982

Evidence for discrete cell kinetic subpopulations in mouse epidermis based on mathematical analysis.

Continuous (repeated) labelling studies in mouse epidermis indicate that nearly all cells are labelled after about 100 hr. Percentage labelled mitoses studies ([3H]TdR at 15.00 and 03.00 hours) have a first peak that does not reach 100% and has a half-width of about 10 hr. Small second and third peaks can be detected at about 90 and 180 hr. respectively. The changes with time in the number of labelled cells show a difference dependent on the time of day of [3H]TdR administration. Both curves show an early doubling in labelled cells which then decline, forming a peak of labelled cells. A second peak occurs at about 120 hr. This is followed by a progressive decline with no further peak until values of about 1% labelling are obtained at 340 hr. These experiments have been investigated mathematically. A computer programme has been devized that permits all three types of experiments to be analyzed simultaneously. More importantly, it can analyse situations with a heterogeneity in cell cycle parameters in all proliferative subpopulations. Various models for epidermal cell replacement have been considered. The data as a whole can best be explained if the basal layer contains at least two distinct subpopulations of cells and an exponentially decaying post-mitotic population with a half-life of about 30 hr. The proliferative sub-populations must be characterized by near integer differences in the length of cycle, the precursor (stem) compartment having the longer cycle. An inverse relationship is required for the length of S, i.e. the shortest time for the stem cells. A full range of cell kinetic parameters can be calculated and are tabulated for the most appropriate model system which is one involving three transit proliferating subpopulations.

Animals↗

PubMed1982

A solution to the controversy on stem cell regulation.

Supplementary to the discussion in Blood Cells 7 (1981) pp. 417-443 concerning regulatory mechanisms of stem cell proliferation and differentiation, the consequences of the two proposed hypotheses of Blackett and Botnick and Lord have been calculated. It can be shown that their equations are equivalent and can be transformed into each other. However, their verbally described regulatory mechanisms are different and turn out to be more important than the equations. The assumptions of Blackett and Botnick lead to an unstable behaviour of the stem cell system with cyclic cell numbers while the hypothesis of Lord leads to stable recovery curves.

Animals↗

PubMed1980

A comprehensive mathematical model of stem cell proliferation which reproduces most of the published experimental results.

On the basis of experimental knowledge about haemopoietic stem cells a catalogue of fundamental statements is formulated. From this a simple mathematical model of haemopoietic regulation mechanisms is developed. The functional net effects of regulatory processes which are still unknown or unmeasurable are estimated using evolution arguments. The model is developed in three steps. It allows description of the self-replication of stem cells after direct destruction as well as their reaction to increased or reduced needs in the erythropoietic system. The most important experimental data about changes in CFUs, BFUe and CFUe after acute or chronic irradiation, anaemia, hypoxia, hypertransfusion or direct erythropoietic stimulation can be reproduced within the model. The model allows us to understand most of the results of experimental stem cell research. Furthermore, it can be applied for a more precise analysis of the existing data. Predictions about the results of certain experiments can be made.

Animals↗

PubMedDate not supplied

Contrast sensitivity letter charts as a test of visual function in amblyopia.

Anisometropic and strabismic amblyopes were studied using the Regan Contrast Sensitivity Charts. At all levels of contrast, the amblyopic eyes of both the strabismic and anisometropic patients scored significantly lower than did their fellow normal eyes, which were used as controls. In comparing the differences between the normal and amblyopic eyes of both groups, we noted a normalization of the visual function of strabismic amblyopes at low contrast. This feature was not observed in the anisometropic amblyopes who consistently scored poorly when viewing either the high or low contrast chart.

Adolescent↗