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The development and teaching of contemporary issues courses provide unique opportunities for expanding influence, service to the university, and professional development. During the last decade, there has been a proliferation of such courses centered on the issue of human exploitation of animals. The Ohio State University's general education curriculum, initiated in 1990, includes a requirement that senior students complete a 5-credit course in the category Issues of the contemporary world. Currently, 28 courses are offered in this category, and 5 are from the College of Food, Agricultural, and Environmental Sciences. Our course, entitled Issues concerning the use of animals by humans, was the first from the college included in this category. The course has been offered continuously since 1990-4 quarters per year since 1992. Challenges included gaining approval of the course through a special oversight committee, enhancing visibility of the course outside the college, instructor education, and control of personal biases. The development of this type of course is, necessarily, a continuous process. Instruction of this course has been challenging, enlightening, and exceedingly rewarding. Instructors of similar courses at 11 other universities reported experiences similar to ours.

Heavy metals present in the soil get differently accumulated in organisms and show different rates of toxicity at different stages of the life cycle of any organism living there. To see whether such toxicants get accumulated during the embryonic development and/or change the normal developmental processes of organisms exposed to heavy metals, freshly laid eggs and egg pods of two acridids, Aiolopus thalassinus and Eyprepocnemis plorans, were tested against different concentrations of Hg2+, Cd2+, and Pb2+. At increasing Hg2+ concentration in the substrate, an increased egg mortality and reduced nymphal hatching in A. thalassinus were observed, yet no change in the normal duration for embryonic development was noticed. A higher hatching rate of E. plorans nymphs than that of A. thalassinus could possibly be due to the higher tolerance, contributed by larger egg volume and thicker foam around the egg pods of the former. Treated concentrations of Hg2+ could be of sublethal (0.121 &mgr;g Hg2+/g substrate) to lethal (0.605 &mgr;g and more Hg2+/g substrate) doses. The mortality of eggs did not always increase with increasing substrate concentration of Cd2+ and Pb2+, and the hatching rates of both grasshopper species in many cases were even higher than that in the control. Still, lower accumulation factors of Cd2+ and Pb2+ than that of Hg2+ were found coupled with not increased mortality. The tested concentrations of Cd2+ and Pb2+ in the substrates, thus, could be of subacute doses. The embryonic development was found prolonged due to Cd2+ and Pb2+. During parallel egg and egg pod treatments, higher metal concentrations were found in not developed eggs than that in fresh nymphs hatching from the same substrates. This indicated the role of foam around the egg pods as "protective filter" against the toxic substances in the soil.

Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.

Various toxicological symptoms were observed in Aiolopus thalassinus (Fabr.) adults which resulted from either contaminated soil or from being fed HgCl2-, CdCl2-, and PbCl2-treated diet. Many insects had abnormal wings which were present until the F3 untreated generation. Heavy metals were stored in different body parts, most of Cd2+ and Hg2+ were found in the testes, followed by the gut. Lead was enriched in all organs and body parts of the treated grasshoppers compared to the control. The highest lead concentrations were found in testes, wings, gut, and ovaries. In the treated generation ChE activity was reduced to about 23% compared to the untreated grasshoppers. In contrast to this, lead increased ChE activity to about 14%. In the following F2 untreated adults, ChE activity was normal; no long-term effect was found. In the supernatant of treated adults a Cd-type glycoprotein was found which can bind Cd ions; its MW was determined by electrophoresis and reference proteins at about 14,450 Da.

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)

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).

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.

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).

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.

The author critically examined removed implants, and found that the sac of both inflatable and gel mammary implants may perforate due to wear or erosion.

In Elasmucha grisea and E. fieberi we have confirmed parental care with a high effectiveness; in E. fieberi this behavior was still unknown. Two years of investigations revealed that a loss in the progeny was diminished during the egg stage by the defence behavior of the female, in 1972 from 92% to 9% and in 1974 from 81% to 4%. Because the 9% and 4% are not caused by external influences that can be eliminated by parental care, the effect of the defence behavior of the female amounts to about 100%. The eggs are particularly protected against entomophageous arthropods. Defence behavior against the male is not present. The female possesses no fungeous protection for the eggs, or if it does it is insignificant in view of the great threat posed by predators. No differences in social behavior between E. grisea and E. fieberi could be demonstrated.

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.

The mosaicism in aortic endothelium of mouse aggregation chimaeras is demonstrated using the lectin Dolichos biflorus agglutinin as a strain-specific marker. The general fragmentary appearance and considerable size range of patches suggests that endothelial cells do not proliferate in a highly coherent manner. The developmental significance of the observed patterns is investigated by means of a quantitative statistical analysis-the Greig-Smith analysis of variance. This method examines the spatial distribution of patches and is able to detect and characterize pattern at various scales. The results show that (1) patches are non-randomly distributed at all scales examined and (2) 'clusters of clusters' occur at one small and one large scale, defining territories of 'primary' and 'secondary' descendent clones, which arose respectively during early and late periods in the development of the endothelium. We conclude from this analysis that (1) cell mixing is never complete, even in the early embryo and (2) cell mingling is not uniform during development. A different pattern was previously demonstrated for intestinal epithelium (Schmidt, Wilkinson & Ponder, 1985c) indicating the potential value of the method for quantitative comparison of mosaicism between tissues and also different developmental stages. Our results suggest that the analysis of patch sizes is likely to be less informative in terms of developmental mechanisms, than the analysis of the spatial arrangement of patches.

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.

Adult intestinal epithelium consists of a sheet of single-cell thickness which is morphologically highly organized into tubular invaginations (crypts) and finger-like projections (villi). Proliferation of the cells is confined to the base of the crypts, from which cells migrate to the villi, where they are shed. The villi are formed during embryogenesis from a multilayered epithelium. In mice, crypts develop at about the time of birth from the epithelium between the villi, which by this stage is no longer multilayered. So far it has remained unknown how many progenitor cells contribute to each crypt, and whether they develop by the proliferation of already committed progenitors, or as a result of local inductive tissue interactions. Here, we have used mouse aggregation chimaeras as an experimental system to demonstrate immunohistochemically that the epithelium of individual crypts in small and large intestine of adult mice is always composed of cells of a single parental type. We have confirmed that this result is not an artefact of the chimaeric system by examining female mice that are mosaic for the X-linked alleles Pgk-1a and Pgk-1b. We conclude that the epithelium of each adult crypt is derived from a single progenitor cell.

One hundred-fifty diarymen in north-eastern Ohio, whose herds had a history of persistently high Wisconsin Mastitis Test scores, were invited to participate in this project, with 43 agreeing to do so. These dairymen were divided into two experimental groups and one control group to determine the effectiveness of two intensities of educational effort on adoption of mastitis control procedures and to demonstrate the effectiveness of mastitis control recommendations. A teat dipping and dry cow therapy program was adopted by more herds in the group with intense educational effort than in the intermediate or control group. Percents of herds in each group utilizing this program in 1977 (start of project), 1978, and 1979 were 8, 75, and 92 for the intense group; 30, 50, and 50 for the intermediate group; and 10, 27, and 27 for the control group. Prevalence of infection declined more rapidly in the intense group with 42, 28, and 24% of cows infected; 39, 25, and 30% in the intermedia, and 56, 35, and 42% in the control group in 1977, 1978, and 1979. Those herds adopting a teat dipping and dry cow therapy program had infection prevalence of 41, 25, and 20% of cows; bulk tank Wisconsin Mastitis Test scores of 15.5, 14.7, and 11.4; and milk production per cow per day of 18.4, 18.4, and 17.5 kg in 1977, 1978, and 1979.

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.

Blood oxytocin was determined on 10 Holstein cows during normal milking and during milking when epinephrine was injected intravenously before or after udder stimulation. The average peak oxytocin concentration during normal milking was 399.7 muU/ml plasma and was reached at 1 min after teat cup application. Oxytocin concentration in blood plasma declined rapidly after peak concentration and dropped to 30.5 muU/ml plasma within 4 min after the start of milking. By 5 min after removal of the teat cups, it had declined to less than 4 muU/ml plasma. The administration of epinephrine, either before or after udder washing, inhibited milk ejection as indicated by milk production and oxytocin concentrations. Peak oxytocin concentrations were 1.05 muU/ml plasma 1 min after teat cup application when epinephrine was injected before udder washing and 8.6 muU/ml plasma at teat cup application when epinephrine was injected after udder washing. These results and the use of a beta receptor blocker to inhibit the effect of epinephrine at the myoepithelial cell level indicated that epinephrine inhibited release of oxytocin from the neurohypophysis.

The advantages and disadvantages of the Ribeiro reduction mammaplasty are cited. It is a very good technique when used with the described modifications in properly selected patients.

The cell migration pathway in the intestinal epithelium of DDK in equilibrium C57BL/6JLac mouse chimeras is demonstrated using Dolichos biflorus agglutinin-peroxidase as strain-specific marker. Cell sheets of one genotype extend in relatively straight lines from crypt to villus apex. Narrow sheets are mostly interrupted in the distal two-thirds of duodenal but not ileal villi, suggesting that in the duodenum cell loss occurs below the apical extrusion zone. These differences between duodenum and ileum correspond to differences in villus shape. The pattern of cell migration in Peyer's patch epithelium is consistent with that of the duodenum. In chimeric colon, sharply demarcated territories of crypts with a narrow cuff of surface epithelium represent the counterpart of the villus/crypt unit of the small intestine.

Removing milker units as soon as milk flow stopped was compared to milking for a fixed time of 12 min in an 8-wk trial with 60 cows. Teats were dipped in broth culture of approximately 10(9) colony forming units per ml of Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus uberis for 4 wk. More new infections of quarters occurred in the 12-min group. In trials 2 and 3, 20 additional cows were milked with automatic milking machine detachers and 20 cows were milked with a flow control unit for 12 min each trial. New infection rates were highest in the two groups milked for 12 min. Age for lactation and cows were associated with most of the variation in the new infection rate. Cows with pointed teat ends had the highest rate of new infection. Effects of fixed-time milking on increased mammary infection and clinical mastitis were small.