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Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy., Graphical Abstract, Highlights • Apoptotic lymphoma cells promote tumor growth, angiogenesis, and TAM accumulation • Unbiased “in situ transcriptomics” analysis shows TAMs promote pro-tumor pathways • Apoptotic tumor cells express and process matrix remodeling proteins • The oncogenic potential of apoptotic tumor cells extends beyond lymphoma, Apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. Ford et al. demonstrate apoptotic lymphoma cells can promote tumor growth, angiogenesis, TAM accumulation, and TAM activation to potentiate cancer progression. These results have important implications for apoptosis-inducing anti-cancer therapies.

Achlorophyllous plants that are dependent on an association with fungi linked to photosynthetic plants for their carbon source are known as mycoheterotrophs. Arachnitis uniflora Phil., a monotypic member of the monocotyledonous family Corsiaceae, fits this category, as it relies on a glomalean fungus belonging to Glomus Group A for carbon acquisition. Although basic structural features of root colonization have been reported for A. uniflora, the nutrient exchange interface has not been studied. This is the first study to use confocal microscopy, transmission electron microscopy, and cytochemical procedures to study the interface between a glomalean fungus and the roots of a mycoheterotrophic species. Results showed that arbuscules are never formed, and that the “vesicles in bundles” reported earlier are unlike typical glomalean vesicles, in that they form in clusters by the enlargement of hyphal branches and have a complex multilayered wall. The thick inner wall layer consists primarily of ß-1,3-glucans (callose) and is surrounded by a thin outer layer of chitin. Each structure is surrounded by host cell wall material and a perifungal membrane, suggesting an involvement in nutrient exchange. The cytoplasm contains a complex of small ß-1,3-glucan-containing vacuoles, lipid bodies, endobacteria, and many nuclei. These structures enlarge to occupy most of the cortical cell volume and then degrade, releasing lipids and other materials into the host cell. We suggest that these structures should not be equated with typical glomalean vesicles but are unique structures that may be involved, along with the hyphal coils, in nutrient acquisition by the host.

SUMMARY To investigate husbandry-disease associations in farmed crocodiles 7 farms in Queensland and the Northern Territory were visited and details of past and present farm design and husbandry practices were recorded. In addition pathological examination of 300 (mostly young) crocodiles was carried out (85 necropsied, one biopsied and 214 examined retrospectively). Mortality rate and occurrence of disease, especially opportunistic infections with bacteria and fungi, were highest during winter months and in farms located at greater latitudes. A difference in the presence and prevalence of disease between the initial establishment phase of Northern Territory crocodile farms (1984–87) and currently (1988–91) was apparent; parasitic infections are now relatively infrequent and bacterial septicaemias and mycoses less common as a result of some provision of artificial heating for juveniles. Gross and microscopic changes observed in visceral and periarticular gout, bacterial hepatitis/septicaemia, deep and superficial mycosis, pentastomiasis and other parasitic infections are described.

The clinical course of 130 patients treated for malignant parotid tumors at the three institutions have been reviewed. Fifty-six of these 130 patients developed recurrences following their primary treatment by a surgical procedure. There were a total of 109 recurrences among these 56 patients. The average number of recurrences was two per patient. The average survival from first recurrence was 3.7 years, with the median survival 2 years. The range of survival was 0.5 to 17 years. Once recurrence developed, treatment was by surgery, radiation therapy, chemotherapy, or a combination. Of 56 patients with recurrence, 33 are dead and 9 patients are alive with disease. Fourteen patients are alive and well with no evidence of disease. These NED patients had an average number of 1.6 recurrences and a median survival to date of only 3 years. Our study indicates that for the majority of patients who develop recurrence, survival is relatively short and treatment is usually ineffective in three of four patients. The authors conclude that after a surgical procedure for malignant salivary gland tumors, a trial of wide field postoperative radiation therapy to high dose should be considered as part of the initial treatment.

Relatively unique data on the costs of public services for local governments in Victoria, Australia, are used to estimate a system of demand equations and to test alternative specifications of the underlying preferences using a translog model. Symmetry conditions are rejected so the data are not consistent with constrained utility maximization. A nonparametric test confirms that result. Conditional on symmetry, tests reject homogeneity and the additivity of preferences and also the separability of personal and property services. Copyright 1988 by MIT Press.

Given the spatial character of many local “public” goods, the traditional recommendations for internalizing benefits–either rejurisdiction or grants–appear insufficient to achieve the optimal levels of output. This analysis indicates that frequently both rejurisdiction and grants are necessary. Contrary to the conventional opinion, the economically optimal constitution may allow spillovers, and such internalization as is required can be more appropriately accomplished not by the extension of boundaries, but by their restriction and the addition of more jurisdictions.

CONCLUSIONS (1) So small a per cent of the increasing incidence of lung cancer is resectable that efforts must be made to improve the treatment of inoperable lesions. (2) Improved equipment and technics of radio-therapy may increase palliation and survival times. (3) Internal irradiation with radio-active isotopes is a modality whose usefulness is to be explored.

The concept of total-body irradiation goes back many years. In 1905, Dessauer (1) described a set-up which would employ multiple x-ray tubes distributed around a room to achieve uniform irradiation of a whole body centrallyplaced. This was theoretical only; it did not become a reality for several years. In 1927, Krause (2) suggested total-body irradiation for the treatment of disseminated neoplasms, and in the same year, Werner Teschendorf (3) described the use of the procedure in leukemia. He administered a dose of 200 to 250 R with but one x-ray tube placed at some distance from the body; a unit functioning at 180 kvp at a distance of 150 em. In 1932, Heublein (4) in a preliminary report described a specially designed room at the Memorial Hospital for total-body irradiation. Twenty patients had been treated in this chamber, receiving doses from 37.5 to 225 R. Some improvement resulted in the lymphomas treated, no response was elicited in the leukemia patients, and slight improvement was noted in patient...

Teletherapy sources such as cobalt 60 and cesium 137 have been used for localizing studies in conjunction with radiation therapy for some time. In fact, one of the few references in the literature (1) points out that, under certain circumstances, radiography with these high-energy sources can provide diagnostic information beyond that provided by routine radiography. In view of the obvious advantages to using the teletherapy source for radiographic localization, it is surprising that so little has appeared concerning the procedure in the literature. This may well be due to the equally obvious limitation imposed on a radiographic system in which the energy of the radiation results in practically 100 per cent Compton interaction with the subject. Since Compton interactions are essentially independent of atomic number, the resulting differentials in absorption for the various structures in the human body are not very large and contrast, therefore, is at a minimum. In high-energy radiography, the proper filmi...

Scanning electron microscopy (SEM) has added considerably to an understanding of the morphology of ectomycorrhizae. Features of the mantle of mature ectomycorrhizae have been studied most frequently. There is considerable variation in arrangement of hyphae and therefore in the appearance of the outer mantle. This variation is due primarily to the fungal symbiont although the host genome may also influence this feature. The Hartig net has been studied from fractured ectomycorrhizal roots and, in the present study, from fractured cryopreserved specimens; general features of the interaction between Hartig net hyphae and contiguous root cells have been described. There are few published accounts of using SEM techniques to study the ontogeny of ectomycorrhizae. This study demonstrates the usefulness of such techniques in studying the initial interaction of hyphae with root hairs and root surfaces, including the extramatrical phase which is normally very difficult to study using other techniques.

A comparative study of ectomycorrhiza formation between the host species Dryas integrifolia and four fungal species belonging to the Basidiomycotina ( Laccaria bicolor, L. laccata, Hebeloma cylindrosporum, Paxillus involutus) and one species in the Ascomycotina (Cenococcum geophilum) showed that patterns in ectomycorrhizal development were distinctive enough to characterize each fungal symbiont. Several aspects of hyphal growth on the plant root during colonization were studied in order to demonstrate the usefulness of SEM in observing the ontogeny of ectomycorrhizae. Each fungal species had a different rate of colonization, and varying root and root hair interactions. As a consequence mantle morphology and the overall appearance of mature ectomycorrhizal apices were also characteristic for each fungal species. Results indicate that the mycobiont plays a major role in determining the morphology of mature ectomycorrizae.

In the past few years there has been a rapidly growing interest in the problems of radiation protection in cases of exposure of large areas of the human body. In addition, much work has been done in the field of organ transplants, particularly with respect to the management of leukemia with bone-marrow transplants. It is of interest to note that more success has attended the studies on experimental animals than on man. It is postulated that one of the problems in evaluating the efficacy of total-body irradiation of man has been the difficulty of obtaining a fairly uniform dose of radiation throughout the entire volume of a patient. Certainly a system which provided such a uniform energy deposition would eliminate a variable in the ultimate evaluation of total-body irradiation. It is the object of this paper to describe a physical system designed and constructed with this in view and to report the initial results of the dosimetry connected with it, as well as the problems encountered. The irradiation chamb...

The treatment of lymphoma has, over the past half century, steadily improved, and survival rates have risen. The authors believe that this is due primarily to better radiotherapy. The advent of high-energy radiation, either from high-voltage generators or isotopes, i.e., cobalt 60 and cesium 137, has made possible higher dose irradiation to demonstrable or palpable lesions. The purpose of this paper is to explore the relationship between the quantity of radiation delivered to localized areas and the recurrences in those fields. The publications in 1958 of Peters and Middlemiss (8) gave encouragement to therapists whose observations indicated inadequate control by low dosage patterns. In the early part of this century, it was customary to employ 1,000 r or less to separate areas. Some regressions did result; however, many recurrences were noted after such limited quantities of irradiation. Peters and Middlemiss, as well as Kaplan (11, 13) have lucidly described the rationale for irradiating not only the in...

A total-bcdy gamma irradiation chamber is described for studies on small laboratory animals. The chamber uses four 300c Cs/sup 137/ sources. Diagrammatic sketches are included. (C.H.)

Chromic radiophosphate, Cr P 32 0 4 , was injected intrathoracically in 41 patients with pleural effusion and intraabdominally in 16 with ascites. In every case there was proof that the lesion was neoplastic and its location was known. The chromic radiophosphate was in the form of a colloidal supension with mean particle-size of 4μ and a concentration of 1 mc. of P 32 per milliliter. Good results, in the sense of relief of symptoms and cessation of the effusion, were obtained in 25 of the first group and 5 of the second group of patients. Four case histories illustrate the completeness and duration of relief so obtained, and P 32 is shown to have certain advantages over Au 198

Air embolism is not an uncommon complication when diagnostic or therapeutic measures using air under pressure are employed. Air embolism also occurs when the air is not under pressure. In either instance there must be a break in the continuity of a vessel, either artery or vein, and the open vessel must contain blood under less pressure than the surrounding air. Of particular interest and concern to the obstetrician are those situations involving the female genital tract that may give rise to air embolism during or shortly following pregnancy. Forbes 1 reported the case of a woman dying suddenly at three months pregnancy apparently after a self-administered douche. Autopsy revealed the right side of the heart and the pulmonary artery to be filled with frothy blood. Deadman 2 reported four cases of fatal air embolism in women anywhere from three and one-half to seven months pregnant. In three of these

Gap junctions provide pathways for direct communication between cells in almost all animal tissues. The junctional channels are freely permeable to small ions and molecules but not to macromolecules. A coupled cell population is as a consequence a partial syncytium, within which metabolites, cofactors, small control molecules and inorganic ions can all diffuse freely through the combined cytoplasmic compartment, while intracellular macromolecules remain relatively fixed in space, in the cells where they are synthesized. Little is known about the extent and distribution of these communication compartments in tissues. To further understand their significance, we have mapped the patterns of junctional communication in skin by intracellular injection of the tracer dye Lucifer Yellow. Cells in the dermal layer are widely coupled, with dye spreading through hundreds of cells in a few minutes. Dye spread in the epidermis is much more restricted, passing in the same time into only a few cells. Dermal-epidermal coupling is not normally detected but is occasionally seen in new-born mouse skin when hair follicles are starting to invaginate. Dermal cells are coupled to a band of follicular cells near the base of mature hair follicles, whereas sebaceous glands appear to be coupled units, isolated from surrounding cells.