Differentiation of Normal and Malignant Human Squamous Epithelium in Vivo and in Vitro: A Morphologic Study

We would like to thank John Ellis for expert photographic assistance, Mervin Jones and Linda Lovell for expert animal husbandry, and Dr. Dorothy Easty for establishing the cell line LICR-LON-HN-5, without which this study would not have been possible.

We report a light microscopic and ultrastructural analysis of the comparative degrees of differentiation seen in keratinocytes derived from the tongue and epidermis with those of a well-differentiated human squamous carcinoma cell line (LICR-LON-HN5). When growing on plastic substrates, all cultures had a similar morphology, with multilayering and the production of cornified envelopes. When cultured on collagen gels the structure was more organized, with keratohyalin granules and keratin whorl formation in both the normal and the malignant cultures. Normal keratinocytes injected into athymic mice produced epidermal cysts, while cells from the cell line produced well-differentiated squamous cell carcinomas, which were partially solid and partially cystic. The tumor was well organized, with identifiable basal cells, spin-ous cells, keratohyalin granules, and a prominent basal lamina at the stromal/epithelial interface. This model is to be developed for comparative studies between normal and malignant cells, with particular reference to basement membrane production and to investigations of the relative importance of extrinsic and intrinsic factors in the control of squamous differentiation.     

Susceptibility of Anopheles quadrimaculatus (Diptera: Culicidae) to subperiodic Brugia malayi and Brugia pahangi (Nematoda: Filarioidea) adapted to nude mice and jirds

Anopheles quadrimaculatus and Aedes aegypti (Black-eyed Liverpool strain) were fed on jirds and nude mice (jird-jird infection, jird-mouse infection, and mouse-jird infection) infected with subperiodic Brugia malayi and B. pahangi. Microfilariae of B. malayi from jird-mouse and mouse-jird infections developed normally in An. quadrimaculatus, whereas those from jird-jird infections did not develop. Microfilariae of both species from jirds and nude mice developed normally in Ae. aegypti and those of B. pahangi developed normally in An. quadrimaculatus. It is suggested that microfilariae from nude mice are modified physiologically, immunologically, or both so that they can develop in refractory An. quadrimaculatus, thus indicating that susceptibility and refractoriness of An. quadrimaculatus to B. malayi also is influenced by factors relating to the vertebrate host in addition to mosquito genetic factors.     

Anti-Thy-1-mediated T cell activation. Role of soluble factors and expression of interleukin 2 receptors on T cells

Rabbit anti-Thy-1 antibody bound to T cells induces the appearance of T cell growth factor (interleukin 2, IL 2) receptors and the production of IL 2. IL2 receptors induction by this means occurs within a short time span, and independent of any demonstrable accessory cell. A source of exogenous or endogenous IL 2 is apparently the only requirement for proliferation after these receptors are expressed. IL 2 production, on the other hand, is accessory cell-dependent, and this help is mediated via Fc receptors on the accessory cell. IL 2 production in this model is demonstrable at 4–6 h, or earlier, and is proliferation-independent. X-irradiation actually augments apparent IL 2 production. The data are consistent with the hypothesis that a differentiated subset of T cells in any mixed population is responsible for IL 2 production.     

A comparison of three methods of scoring penile circumference changes

There are presently three widely used methods of scoring penile circumference data. The present experiment attempted to determine the ability of each method to explain the variance within a data set. A total of 19 subjects were presented with 20 photographic slides assigned to five categories: neutral, female adult, female adolescent, male adult, and male adolescent. Erectile responses to each slide were recorded and the data analyzed in terms of the raw scores, percentage of full erection, and a z-score transformation. Results indicated that the z scores captured the highest proportion of the variance (52.7%), followed by the percentage scores (32.5%), and the raw scores (30.1%). Findings are discussed in terms of their research and clinical implications.     

Temporal changes in cytoskeletal organisation within isolated chondrocytes quantified using a novel image analysis technique

This paper examines temporal changes in the organisation of the cytoskeleton within isolated articular chondrocytes cultured for up to 7 days in agarose constructs. Fluorescent labelling and confocal microscopy were employed to visualise microtubules (MT), vimentin intermediate filaments (VIF) and actin microfilaments (AMF). To quantify the degree of cytoskeletal organisation within populations of cells, a novel image analysis technique has been developed, and fully characterised. Organisation was quantified in terms of an Edge Index, which reflects the density of ‘edges’ present within the confocal images as defined by a Sobel digital filter. This parameter was shown to be independent of image intensity and, for all three cytoskeletal components, was validated statistically against a visual assessment of organisation. Both MT and VIF exhibited fibrous networks extending throughout the cytoplasm, while AMF appeared as punctate units associated with the cell membrane. The use of the Edge Index parameter revealed statistical significant temporal variation, in particular associated with VIF and AMF. These findings indicate the possibility of cytoskeletal mediated temporal variation in many aspects of cell behaviour following isolation from the intact tissue. Furthermore, the image analysis techniques are likely to be useful for future studies aiming to quantify changes in cytoskeletal organisation.     

The rheumatic poison: a survey of some published investigations of the immunopathogenesis of Henoch-Schönlein purpura

Laboratory studies of the pathophysiology of Henoch-Schönlein purpura (HSP) have become more numerous in recent years with the recognition of the disease's links with the mucosal immune system in general and IgA nephropathy in particular. There are weak genetic associations with C4 null phenotypes and with HLA B35 and DR4. Studies of plasma proteins in HSP patients show an increased IgA concentration, activation of the alternative pathway of complement and consumption of factor XIII. High molecular weight (polymeric) IgA has been detected in affected individuals, which some investigators have called immune complexes. Many patients synthesise an IgA rheumatoid factor in the acute phase, but other autoantibodies are largely absent. In vitro studies of lymphocytes from HSP patients have demonstrated an increased number of IgA-bearing and secreting B-cells, with altered T-cell regulation of antibody synthesis. While these observations point to immune dysregulation — primarily of IgA production — as a consistent feature of acute HSP, there is as yet insufficient information available to allow a consistent theory of pathogenesis to be formulated.     

Biokinetics of 237Pu citrate and nitrate in the rat: implications for Pu studies in man

Plutonium-237 decays mainly by electron capture with a half-life of 45 d. Alpha particles are emitted in only 5 x 10(-3)% of its disintegrations. This nuclide can now be produced with relatively small amounts of alpha-emitting contaminants so that, in principle, 237Pu can be used for studies of Pu biokinetics in man. However, because of its high specific activity, there was some doubt that its metabolism would be the same as that of the alpha- and beta-emitting isotopes of Pu normally encountered in the nuclear industry. In this study, the biokinetics of nearly "pure," high specific activity 237Pu are compared with those of lower specific activity, "impure" 237Pu containing significant amounts of alpha-emitting Pu, following administration to rats by intravenous injection as the citrate. Both the distribution and excretion of the "pure" and "impure" 237Pu used in the two studies were similar and also in good agreement with the results of previously reported studies using 239Pu and 241Pu citrate, thus validating the use of 237Pu for studies of Pu metabolism in man. Data on the biokinetics of 237Pu nitrate are also included.