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B Schultze

Publications and source records attributed to B Schultze.

11 recordsLinked to original sources
PubMed1979

Transit times through the cycle phases of jejunal crypt cells of the mouse. Analysis in terms of the mean values and the variances.

Mean transit times as well as variances of the transit times through the individual phases of the cell cycle have been determined for the crypt epithelial cells of the jejunum of the mouse. To achieve this the fraction of labelled mitoses (FLM) technique has been modified by double labelling with [3H] and [14C]thymidine. Mice were given a first injection of [3H]thymidine, and 2 hr later a second injection of [14C]thymidine. This produces a narrow subpopulation of purely 3H-labelled cells at the beginning of G2-phase and a corresponding subpopulation of purely 14C-labelled cells at the beginning of the S-phase. When these two subpopulations progress through the cell cycle, one obtains FLM waves of purely 3H- and purely 14C-labelled mitoses. These waves have considerably better resolution than the conventional FLM-curves. From the temporal positions of the observed maxima the mean transit times of the cells through the individual phases of the cycle can be determined. Moreover one obtains from the width of the individual waves the variances of the transit times through the individual phases. It has been found, that the variances of the transit times through successive phases are additive. This indicates that the transit times of cells through successive phases are independently distributed. This statistical independence is an implicit assumption in most of the models applied to the analysis of FLM curves, however there had previously been no experimental support of this assumption. A further result is, that the variance of the transit time through any phase of the cycle is proportional to the mean transit time. This implies that the progress of the crypt epithelial cells is subject to an equal degree of randomness in the various phases of the cycle.

Analysis of Variance↗
PubMed1978

Growth fraction and cycle duration of hepatocytes in the three-week-old rat.

The proliferation of hepatocytes in the liver of 3-week-old rats has been investigated by autoradiographic methods. This investigation is a continuation of earlier work on the same topic (Schultze & Maurer, 1972; 1973). 21 days after birth, 102 rats received a single injection of 3H-TdR. The percentage of labelled mitoses was then determined 1 hr later and at various times throughout the interval up to 12 days after application of 3H-TdR. In agreement with earlier work, a first peak of labelled mitoses was found 7 hr after 3H-TdR injection. The area under the peak indicates an S phase duration of 8 hr. In addition a second very broad peak of labelled mitoses was found between 2 and 12 days after pulse labelling. The analysis of the results leads to the conclusion that the hepatocytes of the 3-week-old rat have a growth fraction close to 1 and a doubling time of 6-7 days. This is at variance with earlier results of Post, Huang & Hoffman (1963) and Grisham (1969) who had derived a value of 21.5 hr for the duration of the cell cycle and a value of only 0.1-0.2 for the growth fraction of the hepatocytes.

Animals↗
PubMed1977

Autoradiographic demonstration of proliferating cells in cerebrospinal fluid.

The proliferative activity of cells, isolated from 82 human CSF specimens, was examined by 3H-thymidine autoradiography. High labelling indices (LI) were found in acute viral meningitis (up to 8 per cent) and radiculitis (up to 6 per cent). CSF cell proliferation was also shown in the subacute stages of viral diseases and in other inflammatory processes (LI ranging from 0.5 per cent to 3 per cent). Most of the cells labelled from these CSF specimens were large lymphocytes, "lymphoid cells" and plasmacytes. Their presence in CSF is presumed to indicate an immune reaction. By the demonstration of a proliferative activity of these cells, aseptic inflammatory processes can be differentiated from "unspecific" pleocytosis. Because of a correlation between the LI of CSF cells and the stages of some inflammations, this method is suggested for an assessment of pregression or remission of chronic processes, e.g. "chronic meningitis" and multiple sclerosis. It can also be used in experimental research: the same type of mononuclear cells was labelled after having been cultured for 23 hours prior to the incubation with 3H-thymidine. Proliferating tumor cells as well as proliferating non-neoplastic mononuclear cells were demonstrated in CSF from various neoplastic diseases. In the clinical diagnosis of these processes, the method is of limited value. It proved very useful, however, for an assessment of the therapeutic effects of intrathecal cytostatic therapy. CSF specimens from non-inflammatory and non-neoplastic diseases regularly contained very few proliferating cells (LI: less than 0.1).

Autoradiography↗
PubMed1977

In vivo cell synchrony in the L1210 mouse leukaemia studied with 5-fluorouracil or 5-fluorouracil followed by cold thymidine infusion.

[3H]-TdR and [3]-udR labelling indices and mitotic indices were followed in tumour-bearing mice after application of either 5-fluorouracil (FU) alone or of FU followed by cold TdR infusion. With FU alone, accumulation of cells at the beginning of S was found, but there was no indication of a synchronous passage of the accumulated cells further round the cycle. When FU injection was followed by cold TdR infusion, a synchronous passage of the accumulated cells through the cycle was observed. However, there was a large variation in the response of individual mice to this treatment.

Animals↗
PubMed1977

The effect of vincristine on mouse jejunal crypt cells of differing cell age: double labelling autoradiographic studies using 3H- and 14C-TdR.

The mechanism of action of the alkaloid vincristine (VCR) has been investigated in vitro on HeLa cells in culture and in vivo on jejunal crypt cells of the mouse. The in vitro experiments with HeLa cells show that VCR affects not only mitotic but also interphase cells. The VCR-affected cells first continue their passage through the cell cycle undisturbed but after reaching mitosis they are arrested in metaphase. This agrees well with the results obtained by Madoc-Jones & Mauro (1968) and Madoc-Jones (1973) on synchronized cell cultures. Until now there has been no investigation of the mechanism of action of VCR in vivo. This is due to the absence of a suitable technique for synchronization in vivo. The present study is based on a method which permits the assessment of the VCR sensitivity as a function of the cell age without synchronization in the usual sense. The jejunal crypt epithelium of the normal mouse was double labelled with 3H- and 14C-thymidine (TdR) in such a way as to produce a narrow subpopulation of crypt cells with a maximum age difference of 1 hr. On autoradiographs these cells can be distinguished by their characteristic labelling from other cells. As this 'pseudo'-synchronized subpopulation passes through the cycle the effect of VCR can be studied, i.e. one can analyse the effect in well-defined time intervals of the cycle. The results show that the effect of VCR is the same in vivo as in vitro. The crypt cells which are affected by VCR in interphase continue their passage through the cycle, but upon entering mitosis they are arrested in metaphase. VCR has, at the concentration used in the present study, no effect on the duration of the S and G2 phases. The necrotic cells seen after VCR application are formed from arrested metaphases.

Animals↗
PubMed1976

Synthesis of the glomerular basement membrane in the rat kidney. Autoradiographic studies with the light and electron microscope.

To study the origin and the formation of the glomerular basement membrane, autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin with semithin sections of the glomeruli of 42 male rats. The results of this study indicate that, of the three cell types of the glomerulus, the epithelial cells (=podocytes) synthesize the proline-rich scleroproteins of the glomerular basement membrane. Our autoradiographic studies have yielded no evidence for participation of the endothelial or mesangial cells in the formation of the basement membrane. The mesangial cells appear to be responsible for the synthesis of the mesangial matrix only.

Animals↗
PubMed1975

[Experiments and theoretical cell kinetic calculations on the problem of in vivo synchronization with vincristine in L 1210 ascites tumor cells and crypt cells of the mouse (author's transl)].

Experiments are described on synchronizing L 1210 ascites tumor cells and jejunal crypt cells of the mouse with vincristine. In both cases the percentage of mitoses increases to a peak value 4 hrs after application of vincristine and decreases during the following 8 hrs ("releasing time") to the level of the normal mitotic index. Following this first mitotic peak no futher peak of neither the mitotic nor the labeling index was observed during 48 hrs in L 1210 ascites tumor cells and during 38 hrs in crypt epithelia. Thus, in both cell types it was not possible to obtain a synchronizing effect by applying vincristine. Based on cell kinetic considerations it was examined whether peaks of the mitotic as well as the labeling index can be expected at all under the given circumstances. The results show that the theoretical course of the mitotic index coincides with the measured values. This means that no peak of the mitotic index can be expected from the theoretical point of view. In calculating the time course of the labeling index the theoretical curve proved to depend to a high degree on the variations of the cycle time which are not known in detail, especially not after application of vincristine. However, the theoretical conditions show that also in the case of the labeling index no peak can be expected. This agrees with the experimental results. The general significance of a long "releasing time" of 8 hrs or more for the lack of a synchronizing effect is discussed.

Animals↗
PubMed1975

Autoradiographic investigations of glial proliferation in the brain of adult mice. II. Cycle time and mode of proliferation of neuroglia and endothelial cells.

The cycle time of the proliferating glial cells outside the subependymal layer of the lateral ventricle as well as that of endothelial cells was studied autoradiographically in the brains of adult and untreated mice. To determine the mean cycle time two independent methods were used. A mean cycle time of about 20 hours was obtained for glial and endothelial cells from the decrease of the mean grain number/nucleus as a function of time after tritiated thymidine (3H-TdR) injection. Another group of experiments utilized the "method of labeled S phases". With this method the passage of labeled cells through successive S phases is observed. Passing through S phase following 3H-TdR injection the 3H-labeled cells are double labeled by an additional 14C-TdR injection. This method again resulted in a cycle time of 20 hours for glial and endothelial cells. From the present work and a former study (Korr et al., '73) the following cell cycle parameters were derived: Cycle time 20 hours; S phase 9.4 hours; G2 less than three hours; (G2+M) five hours; G1 five hours. The growth fraction of glial cells related to all glial cells is only 0.004. Furthermore, the present experiments show that in the case of glial cells 17% of the daughter cells after mitosis become pyknotic and are eliminated from the glial cell population. Apart from this cell loss, after mitosis about one-fourth of the daughter cells do not enter the next S phase. These cells leave the growth fraction and are replaced by a corresponding number of non-proliferating glial cells. There is a relatively extensive permanent exchange of cells between the growth fraction and non-growth fraction of glial cell.

Animals↗
PubMed1975

[Experimental and theoretical studies on the in-vivo production of a partially synchronous proliferating cell population with vincristine].

The problem of whether vincristine can be used to synchronize partially cells in vivo was investigated. After injection of 0,0045 mug vincristine/g body-weight into mice practically all L1210-ascites tumour cells entering mitosis were arrested in metaphase up to the fourth hour. However, no second peak of the mitotic index was observed within 48 hours. Calculation of the theoretical mitotic index to be expected under the present experimental conditions also shows no second peak. The reason for this lack of synchrony is the long releasing time of the arrested cells.

Animals↗
PubMed1975

[Proliferation kinetics of bile duct epithelia in the regenerating mouse liver after CCl4-poisoning].

Autoradiographic and morphometric methods were used in studying the proliferation of interlobular bile duct epithelia of adult NMRI mice after CC14-poisoning (1 ml/kg i.p.). DNA synthesis starts on the 2nd day after CC14 administration. The time course of the 3H-thymidine labelling index is biphasic, with a first maximum at 2.5 and a second one 5 days after CC14 injection. An S-phase of 5.8 h was measured by 3H plus 14C-TdR double-labelling experiments. Proliferation is completed 10 days after CC14-poisoning, coinciding with the restitution of the liver parenchyma. Bile-duct epithelia remain diploid during the whole proliferative period, which suggests that every S-phase leads to mitotic division. The number of duct cells in portal cross sections remains constant. A quantitative model of the CC14- induced proliferation of interlobular bile duct cells is presented after calculating the total number of S-phases, the increase in cell number, and the final percentage of 3H-labelled nuclei (continuous infusion of 3H-TdR) as a function of time: With regard to 100 bile duct cells at the onset of proliferation 20 per cent S-phases occur during the first maximum and an additional 26 per cent occur during the second maximum of DNA SYNTHESIS, WHICH LEADS TO A 1.46-FOLD INCREASE IN CELL NUMBER. As derived from continuous 3H-TdR labelling (48 per cent 3H-labelled nuclei at the 6th day) and autoradiographic grain density measurements, the second wave of S-phases is due to DNA synthesis in ductular cells that have been formed during the first proliferative maximum. It is not possible to determine whether the proliferative activity observed is induced by lethal damage to bile-duct cells in the early course of CC14-poisoning, followed by compensatory growth and replacement of degenerate cells, or by nonspecific growth stimulation, inducing hyperplastic growth and elongation of terminal bile ducts.

Animals↗