Thrombocyte substitution in acute leukemia. Effect of histocompatibility on the clinical efficacy

Thrombocyte substitution is an essential prerequisite for intensive cytoreductive therapy in acute leukemia. Evaluating 228 thrombocyte transfusions in 17 patients shows that the clinical effectiveness of thrombocyte concentrates can be increased by making the coordination of HLA antigens of donor and receiver as good as possible. When measured in the corrected increment (CI) 24 hours after transfusion, the effectiveness of A3/B1 match preparations (CI = 7.0 +/- 1.6) is significantly higher than that of random preparations (CI = 3.0 +/- 0.5). With the presence of HLA antibodies an effective substitution (CI24 greater than or equal to 4.5) can only be achieved by A3/B1 match thrombocytes. This can only be realized by applying the fourfold thrombapheresis of single donors.     

Plasma membrane of a murine T cell lymphoma: surface labelling, membrane isolation, separation of membrane proteins and distribution of surface label amongst these proteins.

Two established techniques for analysis of plasma membranes, namely, lactoperoxidase catalyzed surface radioiodination of intact cells and bulk membrane isolation following disruption of cells by shear forces, were applied in studies of membrane proteins of continuously cultured cells of the monoclonal T lymphoma line WEHI-22. It was found that macromolecular 125I-iodide incorporated into plasma membrane proteins of intact cells was at least as good a marker for the plasma as was the commonly used enzyme 5'-nucleotidase. T lymphoma plasma membrane proteins were complex when analysed by polyacrylamide gel electrophoresis in sodium dodecylsulphate-containing buffers and more than thirty distinct components were resolved. More than fifteen of the components observed on a mass basis were also labelled with 125I-iodide. Certain bands, however, exhibited a degree of label disproportionate to their staining properties with Coomassie Blue. This was interpreted in terms of their accessibility to the solvent in the intact cells.     

Immunologic reactivity to incompatible blood group substances of the ABO system in scleroderma.

The immunization with incompatible blood groups substances of the ABO system yielded distinct increases in the isohemagglutinin titers and their scores in 16 patients suffering from systemic sclerosis (scleroderma) and in 16 controls. The difference between these two groups was not statistically significant, which suggests an intact humoral immunological reactivity of these antigens. However, investigations with further antigens would be necessary to judge the immunological factors supposed to be involved in the pathogenesis of systemic sclerosis. The method may be recommended for testing the humoral immunological response in similar problems.     

An unusual presentation of a malignant jejunal tumor and a different management strategy

BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients.     

Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1

Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). This study investigates the role of intercellular adhesion molecule-1 (ICAM-1) within this action. In the lung cancer cell lines A549, H358, and H460, cannabidiol (CBD; 0.001-3 μM) elicited concentration-dependent ICAM-1 up-regulation compared to vehicle via cannabinoid receptors, transient receptor potential vanilloid 1, and p42/44 mitogen-activated protein kinase. Up-regulation of ICAM-1 mRNA by CBD in A549 was 4-fold at 3 μM, with significant effects already evident at 0.01 μM. ICAM-1 induction became significant after 2 h, whereas significant TIMP-1 mRNA increases were observed only after 48 h. Inhibition of ICAM-1 by antibody or siRNA approaches reversed the anti-invasive and TIMP-1-upregulating action of CBD and the likewise ICAM-1-inducing cannabinoids Δ(9)-tetrahydrocannabinol and R(+)-methanandamide when compared to isotype or nonsilencing siRNA controls. ICAM-1-dependent anti-invasive cannabinoid effects were confirmed in primary tumor cells from a lung cancer patient. In athymic nude mice, CBD elicited a 2.6- and 3.0-fold increase of ICAM-1 and TIMP-1 protein in A549 xenografts, as compared to vehicle-treated animals, and an antimetastatic effect that was fully reversed by a neutralizing antibody against ICAM-1 [% metastatic lung nodules vs. isotype control (100%): 47.7% for CBD + isotype antibody and 106.6% for CBD + ICAM-1 antibody]. Overall, our data indicate that cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent decreased cancer cell invasiveness.     

Species loss of stoneflies (Plecoptera) in the Czech Republic during the 20th century

1. Rapid expansion and intensification of anthropogenic activities in the 20th century has caused profound changes in freshwater assemblages. Unfortunately, knowledge of the extent and causes of species loss (SL) is limited due to the lack of reliable historical data. An unusual data set allows us to compare changes in the most sensitive of aquatic insect orders, the Plecoptera, at some 170 locations in the Czech Republic between two time periods, 1955–1960 and 2006–2010. Historical data (1890–1911) on assemblages of six lowland rivers allow us to infer even earlier changes. 2. Regional stonefly diversity decreased in the first half of the 20th century. Streams at lower altitudes lost a substantial number of species, which were never recovered. In the second half of the century, large‐scale anthropogenic pressure caused SL in all habitats, leading to a dissimilarity of contemporary and previous assemblages. The greatest changes were found at sites affected by organic pollution and a mixture of organic pollution and channelisation or impoundment. Colonisation of new habitats was observed in only three of the 80 species evaluated. 3. Species of moderate habitat specialisation and tolerance to organic pollution were most likely to be lost. Those with narrow specialisations in protected habitats were present in both historical and contemporary collections. 4. Contemporary assemblages are the consequence of more than a 100 years of anthropogenic impacts. In particular, streams at lower altitude and draining intensively exploited landscapes host a mere fragment of the original species complement. Most stonefly species are less frequently present than before, although their assemblages remain almost intact in near‐natural mountain streams. Our analyses demonstrate dramatic restriction of species ranges and, in some cases, apparent changes in altitudinal preference throughout the area.     

The Oligopoly of Academic Publishers in the Digital Era

The consolidation of the scientific publishing industry has been the topic of much debate within and outside the scientific community, especially in relation to major publishers’ high profit margins. However, the share of scientific output published in the journals of these major publishers, as well as its evolution over time and across various disciplines, has not yet been analyzed. This paper provides such analysis, based on 45 million documents indexed in the Web of Science over the period 1973-2013. It shows that in both natural and medical sciences (NMS) and social sciences and humanities (SSH), Reed-Elsevier, Wiley-Blackwell, Springer, and Taylor & Francis increased their share of the published output, especially since the advent of the digital era (mid-1990s). Combined, the top five most prolific publishers account for more than 50% of all papers published in 2013. Disciplines of the social sciences have the highest level of concentration (70% of papers from the top five publishers), while the humanities have remained relatively independent (20% from top five publishers). NMS disciplines are in between, mainly because of the strength of their scientific societies, such as the ACS in chemistry or APS in physics. The paper also examines the migration of journals between small and big publishing houses and explores the effect of publisher change on citation impact. It concludes with a discussion on the economics of scholarly publishing.     

Immunoglobulin of T lymphoma cells. Biosynthesis, surface representation, and partial characterization.

Four cloned continuously cultured mouse T lymphoma cell lines, WEHI-22.1, WEHI-7.1, S49.1, and EL-4.1, were examined for immunoglobulin biosynthesis and the presence of immunoglobulin on the cell surface. Incorporation of [-3H]leucine into cellular proteins followed by serological analysis showed that immunoglobulin constituted between 0.1 and 1.1 percent of protein synthesized by the different cell lines during a 6-hr period. Under the same conditions cultured cells of nonlymphoid origin, the mastocytoma P-815 X-2.1, did not synthesize any detectable immunoglobulin. Lactoperoxidase-catalyzed radioiodination was used to label proteins on the surface of viable lymphoma and mastocytoma cells. Although the lymphoma lines lacked immunoglobulin as assessed by fluorescent antibody staining, immunoglobulin was detected in surface proteins of all four lymphoma lines. Estimates of the number of immunoglobulin molecules on the cell surface were 1.1 times 10-4/cell for S49.1 and EL-4.1, 1.7 times 10-4 for WEHI-7.1, and 4.3 times 10-4 for WEHI-22.1. Electrophoretic mobilities in sodium dodecyl sulfate polyacrylamide gel indicated that intact cell surface immunoglobulin was slightly larger than IgG, and on disulfide bond reduction to dissociate into two components, one with the mobility of serum immunoglobulin light chain, the other with a mobility similar to that of mu heavy chain. The heavy chain from the T lymphoma cells possessed an apparent molecular weight of about 65,000 compared with 70,000 for mu chain, although both chains shared antigenic determinants characteristic of mu chains. These findings are interpreted as support for other reports that T lymphocytes carry immunoglobulin on their surface and as direct evidence that thymus-derived lymphoid cells synthesize an immunoglobulin resembling the 7S subunit of IgM.