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Biomedical subjects

G H Schmidt

Publications and source records attributed to G H Schmidt.

At least 19 recordsLinked to original sources
PubMed1992

Long-term effects of heavy metals in food on developmental stages of Aiolopus thalassinus (Saltatoria: Acrididae).

Newly hatched F1 nymphs of Aiolopus thalassinus (Fabr.) were fed on food treated with various concentrations of HgCl2, CdCl2, and PbCl2 until the end of adult life. Toxicological observations were followed in the F1 generation and in the F2 generation derived from the heavy metal-loaded F1 parents. The highest concentration of the heavy metal caused 100% mortality of the F1 adults within four weeks. The nymphal duration of the F1 and F2 generations was significantly prolonged after Hg and Cd exposure, but the F1 of the group treated with lead was not affected. The fresh body weight of adults was significantly reduced in the F1 generation of most treatments and in the resulting untreated F2. The lifespan of the F1 adults was shortened. In the F2 generation, although the lifespan was somewhat longer, generally it was still shorter than that of the control adults. The mean egg number laid by F1 adults fed on food contaminated with Hg or Cd was decreased. This decrease was more pronounced in the case of Cd than Hg. In the females fed on food treated with Pb the reduction of the number of egg pods was not remarkable. The hatchability of the eggs laid by F1 females was significantly reduced as compared to the control. The viability of the eggs laid by F2 adults was somewhat decreased due to either a reduced number of egg pods or to a lower rate of hatchability, especially in the case of Cd. The treated adults frequently displayed weakness in their legs, difficulties in walking, tremors, and nervous movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Expression of SV-40 T antigen in the small intestinal epithelium of transgenic mice results in proliferative changes in the crypt and reentry of villus-associated enterocytes into the cell cycle but has no apparent effect on cellular differentiation programs and does not cause neoplastic transformation.

The mouse intestinal epithelium represents a unique mammalian system for examining the relationship between cell division, commitment, and differentiation. Proliferation and differentiation are rapid, perpetual, and spatially well-organized processes that occur along the crypt-to-villus axis and involve clearly defined cell lineages derived from a common multipotent stem cell located near the base of each crypt. Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene were used to establish three pedigrees of transgenic mice that expressed SV-40 large T antigen (TAg) in epithelial cells situated in the uppermost portion of small intestinal crypts and in already committed, differentiating enterocytes as they exited these crypts and migrated up the villus. T antigen production was associated with increases in crypt cell proliferation but had no apparent effect on commitment to differentiate along enterocytic, enteroendocrine, or Paneth cell lineages. Single- and multilabel-immunocytochemical studies plus RNA blot hybridization analyses suggested that the differentiation programs of these lineages were similar in transgenic mice and their normal littermates. This included enterocytes which, based on the pattern of [3H]thymidine and 5-bromo-2'-deoxyuridine labeling and proliferating nuclear antigen expression, had reentered the cell cycle during their migration up the villus. The state of cellular differentiation and/or TAg production appeared to affect the nature of the cell cycle; analysis of the ratio of S-phase to M-phase cells (collected by metaphase arrest with vincristine) and of the intensities of labeling of nuclei by [3H]thymidine indicated that the duration of S phase was longer in differentiating, villus-associated enterocytes than in the less well-differentiated crypt epithelial cell population and that there may be a block at the G2/M boundary. Sustained increases in crypt and villus epithelial cell proliferation over a 9-mo period were not associated with the development of gut neoplasms--suggesting that tumorigenesis in the intestine may require that the initiated cell have many of the properties of the gut stem cell including functional anchorage.

Animals↗
PubMed1992

Studies of intestinal stem cells using normal, chimeric, and transgenic mice.

The mouse intestinal epithelium represents a continuous developmental system. Its four principal differentiated cell types--enterocytes, goblet, enteroendocrine, and Paneth cells--are derived from a common multipotent stem cell located near the base of monoclonal crypts. Members of these four lineages undergo rapid and perpetual renewal along an anatomically well-defined pathway. The gut epithelium provides a unique mammalian model for studying the biological features of stem cells (e.g., their ability to undergo asymmetric division, their enormous proliferative potential, their capacity for functional anchorage in a niche), examining how stem cell hierarchies are established and maintained in renewing cell populations, analyzing the relationships between passage through the cell cycle and lineage allocation (commitment), and defining the mechanisms that give stem cells a "positional address" along the cephalocaudal axis, allowing them to generate regional differences in the differentiation programs of their derived lineages (axial pattern formation).

Animals↗
PubMed1991

Toxicological studies on the long-term effects of heavy metals (Hg, Cd, Pb) in soil on the development of Aiolopus thalassinus (Fabr.) (Saltatoria: Acrididae).

Long-term effects of soil treated with 0.12-12 ppm HgCl2, 2-100 ppm CdCl2 and 25-500 ppm PbCl2 on the development, reproductive capacity and viability of Aiolopus thalassinus (Fabr.) (grasshoppers) during two successive generations were studied. The hatching rate of nymphs developed from eggs laid in treated soil was significantly reduced. Mercury was the most effective in reducing the hatching rate followed by cadmium and lead. The newly hatched nymphs, which developed in the heavy-metal-treated soil, were transferred to and reared in separate cages in order that toxicological effects could be followed through the next two generations without any further treatment. No significant increase was observed in percent mortality during both the F1 and F2 nymphal stages resulting from Hg, Cd and Pb treatment. The nymphs were more tolerant than the eggs and adults to the cumulative effect of heavy metals. The mean durations of the F1 and F2 nymphal stages were prolonged in all Hg and Cd treatments, but such a prolongation in the Pb treatments was found only in F1 nymphs, those developed from the two highest soil PbCl2 concentrations (250 and 500 ppm). The adult fresh weight of the F1 and F2 generations was significantly low in the case of the Hg and Cd treatments. The lifespan of the F1 and F2 adults developed from eggs laid in Hg-, Cd- and Pb-treated soil was significantly shortened and thus the number of egg pods was reduced in comparison with the control. The hatchability of nymphs developed from eggs laid by the F1 generation was significantly lower than that of the untreated control. No significant decrease in the hatching rate was found for the eggs laid by the F2 generation, except at the highest soil concentrations of the three metals. The metal content of eggs laid by the F1 generation increased significantly with increasing soil concentrations of the three metals. In the F2 generation eggs the heavy metal content was reduced in all cases; this indicates a dilution of the metal concentration in successive generations if no further exposure takes place.

Animals↗
PubMed1990

On the clonal origin of tumours--lessons from studies of intestinal epithelium.

Clonal studies of adult chimaeric mouse epithelium have demonstrated the monoclonal composition of crypts of Lieberkühn. In neonatal life, however, polyclonal crypts have been found, indicating that crypts are of polyclonal origin. We here relate these findings to studies of mosaic tissues which have addressed the question whether solid tumours are of monoclonal or polyclonal origin. The issues has so far remained unresolved because the expected frequencies of polyclonal tumours, given polyclonal origins, have not previously been estimated. A general approach for the calculation of such expected values is suggested. The consistent reports of tumours with polyclonal components suggest that autocrine or paracrine mechanisms play an important role during tumorigenesis.

Animals↗
PubMed1990

Ethylnitrosourea-induced mutations in vivo involving the Dolichos biflorus agglutinin receptor in mouse intestinal epithelium.

A mutagenesis assay system is introduced based on the induction of mutations in somatic cells of mouse small intestine using ethylnitrosourea (ENU). F1 mice heterozygous for the Dolichos biflorus agglutinin (DBA) locus (Dlb-1a/Dlb-1b) encoding the DBA cell surface receptor, were treated in utero on either day 7, day 9 or day 11 post coitum. Mutant intestinal cell populations of adult mice were visualised in whole-mount preparations by the absence of histochemical staining using peroxidase-labelled Dolichos biflorus agglutinin. Loss of staining is attributed to mutagenesis of the Dlb-1b allele in the heterozygote. This system allows one to evaluate mammalian mutagenesis in vivo at a single locus. Mutant cell populations appeared as discrete groups of 'striped' villi, each stripe comprising cells derived from unstained crypt stem cells (cf. Schmidt et al., 1985a). A spontaneous mutation level was noted in untreated controls which was found to differ significantly from that recorded in mice treated with the mutagen (P less than 0.01). The mutation scores were highly consistent among mice and a small number of animals (i.e., 16) were sufficient to detect mutagenic effects of ENU. Thus, the advantages which accrue from the assay are (1) the ability to detect small clones of mutant cell populations in the intestine (i.e., cells derived from a single mutated crypt); (2) a small number of tested mice are required to generate a conclusive result, especially when compared to the mammalian spot test (Fahrig, 1978).

Analysis of Variance↗
PubMed1989

Economics of using bovine somatotropin in dairy cows and potential impact on the US dairy industry.

Budgets with a microcomputer spreadsheet were developed to evaluate the economics of bovine somatotropin use and to estimate the impact on US dairy cow numbers. Income over feed and variable costs increased with somatotropin use and low feed prices. With high feed prices, income responses were less favorable, and when combined with low milk prices, somatotropin use resulted in less income than from control cows. Price of somatotropin did not have a major effect on production costs. The number of cows needed to meet US milk requirements is primarily influenced by per capita consumption and production per cow. With continuing yearly increases in per capita consumption of 2 kg of milk equivalent and cow milk yields of 114 kg, the number of milk cows needed through 1992 remains at the 1987 figure of approximately 10.3 million. In the scenario of a 15% increase in milk yield due to somatotropin, 20% of cows receiving the hormone, and cows receiving the hormone being 10% above the national average of all cows; the number needed in 1992 is 9.77 million, or a drop of 5.4% from 1987. Somatotropin use will have a less drastic effect on cow numbers than originally predicted.

Animals↗
PubMed1988

Development of the pattern of cell renewal in the crypt-villus unit of chimaeric mouse small intestine.

We have previously shown that the epithelium of each adult intestinal crypt in chimaeric mice is derived from a single progenitor cell. Whether the crypts are monoclonal from the outset-that is, are formed by the proliferation of a single cell-or whether their formation is initiated by several cells was not known. Here we report that many crypts contain cells of both chimaeric genotypes in the neonatal period indicating a polyclonal origin at this stage of morphogenesis. The cellular organization of the early neonatal crypt is therefore different from that of the adult crypt, which includes a zone of 'anchored' stem cells above the crypt base. Within 2 weeks, however, the crypt progenitor cell and its descendants displace all other cells from the crypt and the crypt attains monoclonality. The distribution of enterocytes on chimaeric villi in the neonate shows a mottled pattern of mosaicism which is progressively replaced by coherent sheets of cells from the crypts, and within two weeks the orderly adult clonal pattern is established.

Animals↗
PubMed1987

Calculating numbers of tissue progenitor cells using chimaeric animals.

Experimental chimaeras have been used to estimate the number of tissue progenitors from the variation in the proportions of cells of each genotype that can be found in a given tissue. However, because of a failure to appreciate the importance of assessing the extent of agreement required between the predictions made by a specific mathematical model and the actual data, we believe that the statistical procedures were inappropriate and have led to unjustified conclusions. We illustrate our argument by reference to published data on the number of progenitor cells in the facial nerve nucleus of the mouse (K. Herrup, T. Diglio, A. Letsou, (1984). Dev. Biol. 103, 329-336).

Animals↗
PubMed1987

Immunochemical demonstration of the clonal organization of chimaeric mouse epidermis.

The clonal organization of chimaeric mouse epidermis was demonstrated by in situ staining of whole-mount preparations using monoclonal antibodies directed against H-2k and H-2b antigens. A striking pattern of transversely oriented stripes or patches was found which extended from mid-dorsum to the flank region. The orientation of these patches indicates a preferred directional expansion of clones during the development of dorsal/lateral epidermis. The clonal pattern of the belly region differed in that stripes were not found, but a marked ventral midline boundary was observed. This demarcation line may be due to a physical effect, i.e. isolation of the left and right ventral halves of the epidermis during early embryogenesis with relatively little cell mingling following closure of the abdominal wall. The obvious nonhomogenous distribution of chimaeric components in dorsal/lateral and ventral epidermis contradicts assumptions of homogenous, fine-grained patchiness derived from electrophoretic analysis of tissue samples and used in studies of skin carcinogenesis. The observation that hair follicles may contain cells of both parental genotypes implies a polyclonal origin. Epidermal proliferative units as described by Potten (1974) were not revealed by the pattern of mosaicism at the cellular level in these chimaeric tissue sheets. This indicates that the proliferative compartment of each putative epidermal unit is polyclonal.

Animals↗
PubMed1986

Immunohistochemistry in the analysis of mouse aggregation chimaeras.

We have used cellular mosaicism in chimaeric mice to study the clonal organization of normal tissues. The mosaicism has been demonstrated in sections and in whole mounts of intestinal epithelium, aortic endothelium and retinal pigment epithelium using H2 antigens and a carbohydrate polymorphism recognized by Dolichos biflorus lectin as strain-specific markers. The results show that the epithelium of each adult intestinal crypt is derived from a single progenitor cell. Because crypts of differing genotype may contribute cells to the same villus, the pathways of cell migration up the villi can be demonstrated. The ability to stain mosaic patches in two dimensions in large intact sheets of epithelium has permitted a more satisfactory analysis in terms of clonal development than was previously possible with data from tissue sections. We have adapted statistical procedures from plant ecology to examine the scale of clustering of patches of like genotype, and thence to recognize 'descendent' clones, i.e. groups of cells which are not contiguous, but are related by descent from a common ancestor in embryogenesis.

Animals↗
PubMed1986

Non-random spatial arrangement of clone sizes in chimaeric retinal pigment epithelium.

Clonal analysis of whole-mount preparations of entire retinal pigment epithelium (RPE), using SWR in equilibrium C57BL/6JLac and DDK in equilibrium C3H/Bi mouse aggregation chimaeras in which one of the two parental components predominated, revealed a markedly non-random spatial arrangement of patch (clone) sizes. Single-cell and small patches predominated in an area around the optic nerve head while large patches occurred most frequently near the periphery. Mechanisms are discussed which may explain these results. Patch size frequency distributions were concave and skewed. Singletons were the most frequent size class, but a wide range of sizes and a smaller number of much larger patches were also always found. The results preclude the use of statistical methods previously employed to calculate clone sizes from the geometric means of observed patch sizes. Instead, the median and interquartile range may provide the best summary of the observed patch size frequency distributions. Our findings support a stochastic model of tissue growth.

Animals↗