Tissue culture studies in Hodgkin’s disease morphologic, cytogenic, cell surface, and enzymatic properties of cultures derived from splenic tumors

Monolayer and suspension cell cultures prepared from Hodgkin's disease tumors in the spleen were examined microscopically and by cytogenetics, tested for lymphocyte and monocyte cell surface properties, and assayed for enzymes by histochemical and spectrophotometric techniques. Hodgkin's disease monolayer cultures were composed of rapidly proliferating round and polygonal cells that were capable of propagation in vitro for an indefinite period of time. Abnormal aneuploid chromosomes were found in short-term Hodgkin's disease monolayers that had been passaged 16-20 times, and in established cell lines carried in culture longer than 3 yr and passaged more than 200 times. Cells fromHodgkin's disease monolayers contained lysozyme (muramidase), fluoride-resistant alpha naphthol acetate esterase, acid and alkaline phosphatase, and chymotrypsin-like activity. The monolayers did not exhibit specific cell surface markers or phagocytosis. Suspension cultures derived from Hodgkin's disease monolayers were composed of cells with aneuploid karyotypes and similar enzymes. The Hodgkin's disease suspension culture cells had surface receptors for complement and IgGFc, lacked surface or cytoplasmic immunoglobulin, and did not form Erosettes, react with an antithymocyte serum, nor exhibit phagocytosis. Normal monolayer culture cells, derived from adult spleen and human fetal spleen and thymus, were composed of spindle cells with a diploid number of chromosomes that could be carried for only a finite period of time in vitro. Normal cultured cells contained similar esterases and phosphatases, but were devoid of lysozyme and chymotrypsin-like activity. The morphologic, cytogenetic, cell surface, and enzymatic findings indicate that our Hodgkin's disease monolayer and suspension cultures are composed of cells with many properties suggesting an origin from monocytes (macrophages) rather than lymphocytes or fibroblasts. The presence of aneuploid karyotypes is consistent with a neoplastic origin and derivation from a malignant cell of Hodgkin's disease.     

Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice.

AdmATF is a recombinant adenovirus encoding a secreted version of the amino-terminal fragment (ATF) of murine urokinase (uPA). This defective adenovirus was used in three murine models to assess the antitumoral effects associated with local or systemic delivery of ATF, a broad cell invasion inhibitor that antagonizes uPA binding to its cell surface receptor (uPAR). A single intratumoral injection of AdmATF into pre-established MDA-MB-231 human breast xenografts grown in athymic mice, or into pre-established C57/BL6 syngeneic Lewis lung carcinoma resulted in a specific arrest of tumor growth. Neovascularization within and at the vicinity of the injection site was also suppressed, suggesting that AdmATF inhibited primary tumor growth by targeting angiogenesis. AdmATF also interfered with tumor cell establishment at distant sites: (1) lung dissemination of Lewis lung carcinoma cells was significantly reduced following intratumoral injection at the primary site; and (2) systemic administration of AdmATF inhibited subsequent liver metastasis in a LS174T human colon carcinoma xenograft model. These data outline the potential of using a recombinant adenovirus directing the secretion of an antagonist of cell-associated uPA for cancer gene therapy.     

In vitro nanoparticle toxicity to rat alveolar cells and coelomocytes from the earthworm Lumbricus rubellus

Sensitivity of immune cells (coelomocytes) of Lumbricus rubellus earthworms was investigated for exposure to selected nanoparticles, in order to obtain further insight in mechanisms of effects observed after in vivo C₆₀ exposure. In the in vivo study, tissue damage appeared to occur without accompanying increased immune responses. Coelomocytes exposed in vitro to C₆₀ showed no decrease of their cellular viability, but demonstrated a decrease in gene expression of the cytokine-like protein CCF-1, indicating immunosuppression. Experiments with NR8383 rat macrophage cells and tri-block copolymer nanoparticles were used to compare sensitivity and to demonstrate the usefulness of coelomocytes as a test system for nano-immunotoxicity, respectively. Overall, the results imply that sensitivity towards nanoparticles differs between cell types and nanoparticles. Moreover, this study indicates that injuries in absence of an immune response, observed after in vivo C₆₀ exposure in our earlier work, are caused by immunosuppression rather than coelomocyte mortality.     

The coefficient of cyclic variation: a novel statistic to measure the magnitude of cyclic variation

Background

Periodic or cyclic data of known periodicity are frequently encountered in epidemiological and biomedical research: for instance, seasonality provides a useful experiment of nature while diurnal rhythms play an important role in endocrine secretion. There is, however, little consensus on how to analysis these data and less still on how to measure association or effect size for the often complex patterns seen.

Results

A simple statistic, readily derived from Fourier regression models, provides a readily-understood measure cyclic variation in a wide variety of situations.

Conclusion

The coefficient of cyclic variation or similar statistics derived from the variance of a Fourier series could provide a universal means of summarising the magnitude of periodic variation.

     

The landscape of forensic intelligence research

Criminology, forensic science and policing scholars have a significant role to play in exploring new developments and directions in modern policing. Yet while the concept of forensic intelligence has caught the attention of a number of policing agencies around the world, it has yet to become a mainstream undertaking. In part this is an artefact of a pragmatic policing culture that only institutes new practices based on demonstrable, research and practice-based effectiveness. Here, we seek to draw attention to efforts in the scholarly community to accumulate a body of evidence on the efficacy of forensic intelligence. The article describes the international landscape of research pertaining to the development of forensic intelligence. We outline the key use of digitised, triangulated data on biometrics, scene of crime and illicit substances. In doing so, we draw attention to the challenges remaining for scholars and professionals to further understand and advance the use of forensic intelligence in mainstream policing.     

The role of T cells in psoriasis

Evidence for a key role of T cells in the pathogenesis of psoriasis has come from both experimental and clinical data. Initially, generalized immunosuppressants, intended for use in transplant settings, were found to improve clinical signs and symptoms of psoriasis. Their efficacy attracted attention to the activated T cells that are a major component of the inflammatory infiltrate of psoriatic lesions. Further research determined that T cells from patients with psoriasis could transmit disease in animal models. These findings laid the groundwork for characterizing the pathogenesis of psoriasis as immune mediated with skin-directed T cells playing a central role. Once these pathogenic T cells have entered the skin, they become activated and release cytokines and chemokines to attract other immune cells to perpetuate the inflammatory cascade. As the role of the T cell in psoriasis has evolved and understanding of immunopathology has increased, a multitude of biologic targets have been revealed. Newer strategies for the treatment of psoriasis have therefore focused on modifying T cells in this disease through direct elimination of activated T cells, inhibition of T-cell activation, or inhibition of cytokine secretion or activity. The mechanisms by which these new biologic agents act on psoriasis will affect their profile of efficacy and safety. Important selection criteria for optimal antipsoriatic therapies include long-term safety and tolerability, ability to produce long-lasting remissions, and convenient dosing regimens.     

Increased incidence of indeterminate pancreatic cysts and changes of management pattern: Evidence from nationwide data

Background: Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions(PCLs) by analyzing large epidemiologic data. Methods: Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea. Results: The final number of patients with...     

A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

Background

The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia.

Design and Methods

Sixty patients received either continuous-infusion doxorubicin (12 mg/m²/day) and continuous-infusion vincristine (0.4 mg/day) on days 1–4 or pegylated liposomal doxorubicin (40 mg/m²) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors.

Results

Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm.

Conclusions

With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities.