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A case report of a 33-year-old woman with progressive systemic sclerosis and polymyositis is presented. Admitted with a beta-hemolytic Streptococcus infection of the right knee joint, she had progressive systemic sclerosis with small intestinal involvement, which is rare. This led to more serious complications, malabsorption, pneumoperitoneum, and pneumatosis cystoides intestinalis, which forced a decision to treat her with home total parenteral nutrition. The diagnostic as well as treatment problems encountered in this patient illustrate the importance of nursing care in the overall management of patients with this disease.

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Primary sclerosing cholangitis is characterized by inflammation and fibrotic strictures of the intra- and extrahepatic bile ducts. The diagnosis is confirmed by cholangiography, either endoscopic or percutaneous. An association between primary sclerosing cholangitis and chronic ulcerative colitis has been recognized by physicians for years. To date, there is no known cure for this disease. Several drugs are currently being utilized for symptomatic relief. Therapeutic radiologic and endoscopic procedures are performed to relieve obstruction of the bile ducts and reduce the back pressure on the liver. Surgical procedures are also designed to relieve biliary obstruction and to protect hepatic function. Recently, liver transplantation has become an option for some patients.

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Ligamentous injuries of the ankle are usually benign and may be managed satisfactorily by nonoperative measures. This is not true, however, of the Maisonneuve variant. In this paper we present a case report of a high school athlete who sustained a Maisonneuve fracture dislocation of the ankle. The diagnosis was missed initially, because of an incomplete examination. The subsequent physical and radiographic examination revealed the proper diagnosis. Guidelines for the evaluation and appropriate treatment are discussed.

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Biliary obstruction can prohibit therapeutic endoscopic stent placement. For patients with this condition, percutaneous transhepatic biliary catheters can provide an alternative method to drain the obstructed system. The biliary catheter presents nurses with several challenges: assessment of the patient for potential complications, home care teaching and supportive care.

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The somatic cell hybrid C121, with chromosome 7 as its sole human component, arose when mouse macrophages SV40 genomes are integrated at 7q31-7q35. We show that hybrids with a reduced chromosome 7 component, but which retain markers linked to the cystic fibrosis locus, can be generated by direct in vivo tumor selection or following chromosome-mediated gene transfer and SV40-mediated cellular transformation. Our methods for chromosome fragmentation and fine-structure mapping can now be applied to the substantial number of SV40-transformed human cell lines, with independent chromosomal integration sites, already available. Our results also suggest that expression of human epidermal growth factor receptor augments the tumorigenic potential of the SV40-transformed C121 hybrid.

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The development of therapeutic endoscopic procedures over the past 20 years has been phenomenal. From the visualization of bile and pancreatic ducts years ago, technology has progressed to complex sphincterotomies, stenting and removal of common duct stones. Nurses working with these patients after these procedures need physical assessment skills and a knowledge base of both the therapeutic endoscopic procedures and the complications associated with the procedures.

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Fusion of human EJ bladder carcinoma cells to mouse C127 cells, with direct selection for tumor growth, gave rise to hybrid cells in which the human chromosome complement had been reduced dramatically, while selectively retaining the activated HRAS1 at chromosome band 11p15. A single-component hybrid retaining only part of human chromosome 11 is described in detail. Our results suggest a novel and general approach for investigating the chromosomal basis of neoplastic change and for subchromosomal mapping of and enrichment cloning for the human genome.

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This paper reports further study of the identity and function of a protein shown to be elevated in serum from cystic fibrosis (CF) patients and clinically normal heterozygotes. Monoclonal antibodies, specifically recognizing the tentatively named cystic fibrosis antigen (CFAg), were produced. Immunoaffinity purification of CFAg from several sources revealed two components: 11 x 10(3) and 14 x 10(3) Mr protein. cDNA clones corresponding to each protein have been isolated. Data-base comparisons of the deduced amino acid sequences suggest that both genes encode related but distinct calcium-binding proteins. We propose the name calgranulin A and B, for the 11 x 10(3) and 14 x 10(3) Mr components, respectively. It is clear from the assignment of the calgranulin genes to chromosome 1 that neither is the product of the mutant CF gene, which maps to chromosome 7. We have used the monoclonal antibodies to study the tissue distribution of the two proteins in a wide-ranging immunohistological survey. Where possible the pattern of expression was confirmed by RNA blot analysis. Strong calgranulin expression in granulocytes was confirmed. In addition to myeloid cells, a restricted subset of normal stratified squamous epithelia were found to be calgranulin-positive. These included tongue, oesophagus and buccal cells, the last of which has been shown to have altered calmodulin activity in CF patients. Using indirect alkaline phosphatase staining, tissue sections of lung, pancreas and skin (normally considered sites where the CF defect is expressed) were not calgranulin-positive. However, by indirect immunofluorescence, nasal polyp sections showed weak patchy calgranulin expression in some epithelial cells, and stronger, higher frequency expression when such cells were briefly cultured.(ABSTRACT TRUNCATED AT 250 WORDS)

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The clonal composition of neoplastic foci was examined in histological sections of the colonic epithelium of azoxymethane (CAS: 25843-45-2)-treated CBA/Ca----C57BL/6J mouse aggregation chimeras, with the use of H-2 antigens as markers of cellular genotype. Each of 55 early neoplastic foci occurring at a mosaic patch boundary was composed of cells of a single genotype. Our results provide direct evidence that these foci arise from single crypts. In contrast, the epithelium of 5 of 17 larger adenomas was of mixed genotype: In 3, one genotype was represented only by a rim of cytologically normal epithelium derived from adjacent crypts, but in the other 2 the epithelium of both genotypes was dysplastic. One of these was probably a "collision" tumor arising from adjacent but independent foci; in the other, the minority component may have been derived from entrapped non-neoplastic crypts.

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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.

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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.

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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.

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The mosaic pattern of patches of crypts of Lieberkühn in chimaeric C57BL/6JLac (B6)----DDK mouse small intestine, demonstrated using Dolichos biflorus agglutinin as strain-specific marker, is quantitatively examined using the Greig-Smith analysis of variance. This analysis, widely used in ecological research, provides a method to detect and characterize pattern at various scales. The analysis demonstrates that B6 patches are non-randomly distributed at all scales examined. A consistent increase in the intensity of pattern at one particular scale over all replicate samples identifies 'clusters of clusters' which probably are territories of 'descendent' clones. The sizes of descendent clones, either in terms of numbers of patches or total numbers of crypts, are highly variable. A steady reduction in the strength of pattern from proximal to distal is found. The Greig-Smith analysis of variance provides a valuable method for the analysis of pattern in chimaeric tissue.

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We used staining of tissue sections by lectin conjugates to screen inbred strains of mice for polymorphisms which could be used as histological markers of chimaerism. We found one polymorphism, which involves reciprocal patterns of expression of binding sites for the N-acetyl-galactosamine-binding lectins from Dolichos biflorus (DBA), Helix pomatia (HPA) and Wisteria floribunda (WFA) on intestinal epithelium and vascular endothelium. The polymorphism is due to alleles at a single locus, designated D1b-1 (for Dolichos lectin binding). Of 29 inbred strains examined, 3 are D1b-1a (type strain RIII-ro; gut epithelium-ve, vascular endothelium + ve), and 26 are D1b-1b (type strain C57BL/6J; gut epithelium + ve, vascular endothelium-ve). In RIII-ro and C57BL/6J embryos, the polymorphic difference is not clearly present until day 11 of gestation. Before then, embryos of both strains express binding sites on gut epithelium and on endothelium. The temporal and tissue-specific patterns of expression of lectin-binding sites may result from differences in expression of an N-acetyl galactosaminosyl transferase. If so, elucidation of the genetic basis of the polymorphism might provide an insight into the mechanisms of developmental regulation of glycosyltransferase activity.

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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.

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The epithelium of each individual intestinal crypt in adult mouse aggregation chimaeras is composed of cells of a single parental genotype (Ponder et al. 1985). Using a carbohydrate polymorphism recognized by Dolichos biflorus agglutinin as a strain-specific marker on entire sheets of intestinal mucosa, we have analysed the two-dimensional mosaic patterns of patches of the chimaeric intestinal crypt population. The relative proportions of each genotype varied greatly along the length of any one intestine. In chimaeras with highly unbalanced proportions, the minority component occurred as discrete patches. Patches of single or a few crypts were most frequent, but a smaller number of much larger patches was always present. The size frequency distribution of discrete patches was highly concave and departed significantly from a geometric distribution (a model for non-differential proliferation), but fitted the more skewed negative binomial model. The data are consistent with the interpretation that most progenitor crypts never or rarely divide, while a minority proliferate to a greater extent. We discuss ways in which our system could be analysed further to examine this interpretation. Our results also support Whitten's (1978) conclusion from a computer simulation that the mean patch size, as it has previously been used in statistical analyses of chimaeric tissue, 'is not a reliable statistic on which to judge mosaicism'.

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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.

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A technique for the preparation of entire intestinal mucosal sheets is described that renders the population of crypts accessible for two-dimensional study. We have applied the technique to demonstrate the mosaic crypt populations in the intestinal epithelium of mouse aggregation chimeras, using the lectin Dolichos biflorus agglutinin (DBA) as a strain-specific histochemical marker.

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We describe an immunohistochemical method, using monoclonal anti-H-2 antibodies, for demonstrating H-2 antigens in cryostat sections of a variety of mouse tissues. Double staining allows simultaneous demonstration of both cell populations in tissue sections from H-2b in equilibrium H-2k aggregation chimaeras.

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