Australasian bryogeography: fact, fallacy and fantasy

It is claimed that possible mechanisms leading to the present patterns of distribution of Australasian bryophytes cannot be rigorously deduced from the patterns themselves, and that the distribution data are all imperfect and rapidly changing. Possible causes of the major disjunctions are discussed. There are serious deficiencies in discussions of endemism.     

The AT2 receptor: fact, fancy and fantasy.

The angiotensin AT2 receptor subtype was recently cloned and pharmacologically characterized but its function still remains elusive and controversial. It is a member of the G-protein coupled receptor superfamily with a minimal sequence homology with the AT1 receptor, responsible for the known effect of angiotensin II. The AT2 receptor displays a totally different signaling mechanisms from the AT1 receptor and involves various phosphatases. It is expressed at low density in adult tissues but up-regulated in pathological circumstances. Clearly, the AT2 receptor has antiproliferative properties and therefore opposes the growth promoting effect linked to the AT1 receptor stimulation. It is also reported that the AT2 receptor regulates ionic fluxes, affects differentiation and nerve regeneration, has anti-angiogenic and anti-fibrotic properties and stimulates apoptosis. However, the results, although suggestive, are sometimes equivocal. Obviously, the AT2 receptor plays a role in the pathogenesis and remodeling of cardiovascular and renal diseases. A more extensive knowledge of the AT2 receptor could therefore contribute to the understanding of the clincial beneficial effects of the AT1 receptor antagonists.     

The Croonian Lecture 2004 risk: food, fact and fantasy

We all take risks, but most of the time we do not notice them. We are generally bad at judging the risks we take, and in the end, for some of us, this will prove fatal. Eating, like everything else in life, is not risk free. Is that next mouthful pure pleasure, or will it give you food poisoning? Will it clog your arteries as well as filling your stomach? This lecture weaves together three strands-the public understanding of science, the perception of risk and the role of science in informing government policy-as it explains how food risks are assessed and managed by government and explores the boundaries between the responsibilities of the individual and the regulator. In doing so, it draws upon the science of risk assessment as well as our attitudes to risk in relation to issues such as bovine spongiform encephalopathy, dioxins in salmon and diet and obesity.     

Human lung cancer cell lines in our laboratory: establishment of three large cell carcinoma cell lines and their biological characterization]

Three large cell carcinoma cell lines were established from tumors of lung cancer patients. The cell lines were named NUTLC-2, NUTLC-4 and NUTLC-5 and they were found to have the following biological characterization. 1) By chromosomal analysis, the tumor cells of two of the cell lines (NUTLC-2 and NUTLC-5) were human-origin cells. Numbers of chromosomes of these cells ranged from 52 to 59 in NUTLC-2 and from 68 to 75 in NUTLC-5, with the modal numbers of 56 and 71, respectively. 2) Primary tumor resected from the patient with lung cancer was heterotransplanted into the subcutis of a nude mouse. NUTLC-4 cell line was established in vitro from the tumor in nude mouse and the tumor cells were found to be mouse-origin cells by chromosomal analysis. Human DNA was not detected by Alu analysis. 3) The tumor cells of three cell lines could be heterotransplanted subcutaneously into nude mice. However, no natural distant metastasis in nude mouse was observed. 4) Drug sensitivity to NUTLC-2, NUTLC-4 and NUTLC-5 tumor cells differed individually according to MTT colorimetric assay, and characteristic drug sensitivity was not noted in histological types of lung cancer.     

Human cancer cell lines: Experimental models for cancer cells in situ? For cancer stem cells?

Established human cancer cell lines are routinely used as experimental models for human cancers. Their validity for such use is analyzed and discussed, with particular focus on thyroid tumors. Although cell lines retain some properties of the cells of origin, from the points of view of their genetics, epigenetics and gene expression, they show clear differences in these properties compared to in vivo tumors. This can be explained by a prior selection of initiating cells and a Darwinian evolution in vitro. The properties of the cell lines are compared to those of the postulated cancer stem cells and their use as models in this regard are discussed. Furthermore, other proper and possible uses of the cell lines are discussed.     

Human B-lymphoid cell lines.

The collective efforts during almost three decades by hematologists, tumor biologists and immunologists have provided a collection of established human hematopoietic cell lines, representing most of the hematopoietic cell lineages. The representativity of cell lines derived from the B cell differentiation lineage, however, is the most impressive. Human B-lymphoid cell lines are extensively used world wide as models in studies of various aspects of B cell biology and as tools in research on the etiology, pathogenesis and the biology of leukemia and lymphoma. Lymphoblastoid cell lines (LCL) carrying the Epstein-Barr Virus (EBV) are of particular importance. These lines can be established spontaneously from blood and lymphoid tissue from any EBV positive individual by special techniques, and from all individuals by EBV infection of peripheral blood B cells by EBV infection in vitro. At spontaneous establishment B cells, latently infected by EBV in vivo, will release EBV which subsequently infects normal EBV-negative B cells and immortalizes them into LCL cells, but direct outgrowth of the latently infected B cells as LCLs has also been documented. The target B cells for the EBV infection in vitro are not fully defined-most are mature B cells but also pro-B and pre-B and some B-blasts can be infected. Apart from their capacity for infinite growth, LCL cells have non-malignant properties, e. g. they are diploid, do not grow in agarose and do not form tumors upon inoculation subcutaneously in nude mice. LCLs have a phenotype corresponding to activated B cells (B-blasts) and have been used as "the E. Coli" of eukaryotic cells for about two decades. LCLs are derived at a high frequency also from tumor biopsies of EBV positive patients with leukemia and lymphoma. However, tumor cell lines are available from most of the B cell lineage-derived leukemias, B-lymphomas and myeloma. The frequency of successful establishment has been particularly high from EBV positive Burkitt's lymphoma (BL). From EBV genome negative BL and other B-lymphoma and B-leukemia biopsies the frequency of successful, spontaneous establishment is low (5-10%), and such lines have, with rare exceptions, been derived from pleural effusions and ascitis of patients with advanced, chemotherapy resistant, disease. Many of the cell lines therefore do not represent the clinically most common types of leukemia and lymphoma. No authentic malignant cell lines have been established from chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL) and Waldenstr?m's disease.(ABSTRACT TRUNCATED AT 400 WORDS)     

Human embryonic stem cell and embryonic germ cell lines

Undifferentiated human embryonic stem (ES) cells and embryonic germ (EG) cells can be cultured indefinitely and yet maintain the potential to form many or all of the differentiated cells in the body. Human ES and EG cells provide an exciting new model for understanding the differentiation and function of human tissue, offer new strategies for drug discovery and testing, and promise new therapies based on the transplantation of ES and EG cell-derived tissues.     

Human lymphoid cell lines: Models for immunological analysis

Summary Investigations with human long term lymphoid cell lines have amply demonstrated the versatility of these tissue culture systems for the detection, definition, and solution of current problems in cell biology, biochemistry, genetics, and immunology. These systems are contributing much to our understanding of the multiple functions of lymphoid cells in the immune response. Human lymphoid cell lines produce, in large quantities, the putative extracellular mediators of cell-mediated immunity, including migration inhibitory factor (MIF), lymphotoxin, interferon, and a specific, reversible inhibitor of lymphocyte biosynthetic activity. The MIF released by human lymphoid cell lines is similar to that produced by phytomitogen- or antigen-stimulated human peripheral lymphocytes. Human lymphoid cells from lines producing MIF mimic the capillary migration patterns of guinea pig peritoneal macrophages, and are more sensitive than the guinea pig cells to human MIFs. Studies with these migrating cells indicate that MIF is not solely a lymphoid cell product, but is synthesized by a wide variety of activated cell types. Extracts of cultured human lymphoid cells inhibit the synthesis of RNA, protein, and DNA by established lymphoid cell lines and by phytomitogen-stimulated human peripheral lymphocytes, but have no inhibitory effects on human nonlymphoid cells. The reversible inhibition is produced with physiological quantities of extract, suggesting a functional immunoregulatory activity for this material in lymphocyte-mediated immunological reactions. Initial findings indicate that these mediators are multiple and distinct molecular species. The remarkable proliferative and synthetic potential of human lymphoid cell systems provides a most useful resource for the purification and characterization of these immunological substances. This invited paper was presented at the Hematopoietic Systems Sessions in Depth section of the 24th Annual Meeting of the Tissue Culture Association, Inc., Boston, June 4, 1973. The work was supported by Grants RO1-AI10422 and TO1-AI00445 from the National Institute of Allergy and Infectious Diseases and PO1-GM19443 from the National Institute of General Medical Sciences of the National Institute of Health, United States Public Health Service. Recipient of Research Career Development Award AI46371 from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health.     

Human breast cancer cell lines and tissues express tartrate-resistant acid phosphatase (TRAP)

Tartrate-resistant acid phosphatase (TRAP) is expressed by osteoclasts, macrophages and dendritic cells. TRAP has been identified in a wide variety of tissues, however, its biological function is not fully understood. Serum TRAP is a marker of diseases involving excessive bone resorption including metastatic bone disease in breast cancer patients and can be used to monitor responses to treatment. Our aim in this study was to determine whether TRAP is expressed by human breast tumours. Four breast cancer cell lines were assayed for TRAP activity. MDA-MB-435, the most tumourigenic line, had an activity twofold higher than the other cell lines. Immunohistochemistry using a TRAP specific antibody confirmed that both cell lines and human breast tumours express TRAP. Expression was absent in benign tissues and abundant in more aggressive tumours. This work suggests that tumour derived TRAP contributes to the raised enzyme activity found in the serum of breast cancer patients.     

Human embryonic stem cell lines: socio-legal concerns and therapeutic promise

Stem cell lines would be very valuable for the repair of diseased or damaged organs. Stem cells derived from adult tissues raise few ethical problems, and would not be rejected if derived from the patient. They show considerable plasticity and might be appropriate for some clinical conditions, but they tend not to grow well in culture. Stem cells derived from the early human embryo proliferate indefinitely in culture and can give rise to many different tissues, but their derivation requires destruction of the embryo, which is not ethically acceptable in some countries. Other countries allow strictly regulated destructive research on human embryos, usually those that have been produced for infertile couples in infertility clinics. Embryos that are no longer required for the couple's own reproductive project could be donated for research rather than just discarded. Different approaches are being developed to avoid immunological rejection of embryonic stem cells used for therapy. Derivation of embryonic stem cell lines by somatic cell nuclear transfer ('cloning') from the patients themselves might be one possible approach, but is unlikely to be used in routine clinical practice if more cost-effective methods are available.     

The significance of scirrhous gastric cancer cell lines: the molecular characterization using cell lines and mouse models

Scirrhous gastric cancer (SGC) exhibits aggressiveness of the rapid infiltrating tumor cells with abundant fibroblasts. Experimental studies using SGC cell lines have obtained useful information about this cancer. Our literature search divulged a total of 18 SGC cell lines; two cell lines were established from primary SGC and the other lines were established from a metastatic lesion of SGC. Fibroblast growth factor receptor 2 (FGFR2) and transforming growth factor-beta receptor (TβR) are linked to the rapid development of SGC. Cross-talk between the cancer cells and cancer-associated fibroblasts (CAFs) has been shown to contribute to the progression of SGC. Chemokine (C-X-C motif) receptor 1 (CXCR1) from SGC cells might be associated with the abundant CAFs in cancer microenvironments. The in vivo models established using SGC cell lines are expected to serve as a useful tool for the development of drugs such as FGFR2 inhibitors, TβR inhibitors, and CXCR1 inhibitors, which might be promising as SGC treatments. However, the number of available SGC cell lines is insufficient for the clarification of the entire biologic behavior of SGC. Since the mechanisms responsible for the characteristic aggressiveness of SGC are not fully elucidated, the establishment of new SGC cell lines could help clarify the biological behavior of SGC and contribute to its treatment.