The use of primary cultures of adult rat hepatocytes to study induction of enzymes and DNA synthesis: effect of nafenopin and electroporation

Primary cultures of adult rat hepatocytes maintained in a well-differentiated state, in a chemically defined medium containing 2% DMSO, have been utilized to study the effect of non-mutagenic hepatocarcinogens such as the peroxisome proliferator nafenopin. The parameters chosen in this in vitro system were those that paralleled the major in vivo effects of nafenopin on the liver, mainly: the proliferation of the endoplasmic reticulum and induction of cytochrome P-452, the proliferation of the peroxisome compartment and the induction of cyanide-insensitive beta-oxidation of fatty acids and the stimulation of liver growth as measured by the DNA synthetic activity of the hepatocytes. In this review, we also describe the morphology of hepatocyte cultures prepared from previously electroporated hepatocytes and the potential for the use of electroporation to introduce growth related genes into hepatocyte cells to study the mechanisms of hepatocyte growth at the molecular level. In addition we describe the formation of endoplasmic reticulum whorls in these cultures as a consequence of nafenopin treatment. 'Whorl formation' by hepatotrophic chemicals has been previously shown to occur in vivo; in this report, it is described for the first time in vitro.     

Forecasts and expectations: Some evidence for the U.K.

Forecasts from econometric models have been given a lot of publicity in the U.K. This paper examines the performance of five major models in forecasting inflation and the rate of growth. Two types of forecast are considered: the annual pre-budget ones and a quarterly series. It is suggested that public forecasts provide a cheap method of implementing economically rational expectations.     

Mutants of Escherichia coli deficient in 4-thiouridine in which growth is insensitive to illumination at 365 nm]

Thirteen different mutants of E coli K12 selected for a reduced near ultra-violet induced growth delay have been isolated. The t-RNAs extracted from these clones have all a depressed content of 4-thiouridine. One of these mutants, called Nop has an almost negligible growth delay and completely lacks 4-thiouridine in its t-RNAs. Thus we provide genetic proofs that 4-thiouridine is the chromophore for growth delay.     

Regulation of B and T cell development by anterior pituitary hormones

Hormones produced by the anterior pituitary gland have been implicated in the regulation of primary lymphocyte development. In order to identify endocrine factors involved in that process, several strains of mice with genetic defects resulting in a selective impairment in the production of one or more anterior pituitary-derived hormones have been analysed. This study has resulted in the classification of endocrine hormones into the following four categories (i) hormones such as prolactin with no apparent effects on primary lymphopoiesis; (ii) anabolic hormones such as growth hormone and insulin-like growth factor-I whose stimulatory effects on primary lymphopoiesis are non-lineage-specific and related to their actions as systemic mediators of growth and/or differentiation; (iii) hormones such as thyroid hormones that have an obligate role in primary B lymphopoiesis; and (iv) hormones such as oestrogens that act as negative regulators of lymphopoiesis.     

Forecasting US GNP growth: The role of uncertainty

A large number of models have been developed in the literature to analyze and forecast changes in output dynamics. The objective of this paper was to compare the predictive ability of univariate and bivariate models, in terms of forecasting US gross national product (GNP) growth at different forecasting horizons, with the bivariate models containing information on a measure of economic uncertainty. Based on point and density forecast accuracy measures, as well as on equal predictive ability (EPA) and superior predictive ability (SPA) tests, we evaluate the relative forecasting performance of different model specifications over the quarterly period of 1919:Q2 until 2014:Q4. We find that the economic policy uncertainty (EPU) index should improve the accuracy of US GNP growth forecasts in bivariate models. We also find that the EPU exhibits similar forecasting ability to the term spread and outperforms other uncertainty measures such as the volatility index and geopolitical risk in predicting US recessions. While the Markov switching time‐varying parameter vector autoregressive model yields the lowest values for the root mean squared error in most cases, we observe relatively low values for the log predictive density score, when using the Bayesian vector regression model with stochastic volatility. More importantly, our results highlight the importance of uncertainty in forecasting US GNP growth rates.     

Vascular endothelial growth factors (VEGFs) and stroke

Vascular endothelial growth factors (VEGFs) have been shown to participate in atherosclerosis, arteriogenesis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair, and the effects of transplanted stem cells in experimental stroke. Most of these actions involve VEGF-A and the VEGFR-2 receptor, but VEGF-B, placental growth factor, and VEGFR-1 have been implicated in some cases as well. VEGF signaling pathways represent important potential targets for the acute and chronic treatment of stroke.     

Growth and longevity of Wistar rats receiving a diet whose protein content is rapidly lowered in relation to aging]

Growth and longevity of the Rats were the same when: (i) the diet was rich in casein (21%), from weaning to death: (ii) the casein content of this diet (without B12) was progressively lowered from weaning to 200 days of age, and thereafter was 7%. When the casein level had been too rapidly lowered, inducing retardation of growth after 75 days, maximal growth was lowered and life span was increased.     

Galectins in cell growth and apoptosis

Fourteen members of the galectin family, proteins with conserved carbohydrate-recognition domains that bind β-galactoside, have been cloned and more are expected to be discovered in the near future. Many aspects of galectin biology have been thoroughly explored, and functional studies have implicated these proteins in cell growth, differentiation and apoptosis, in addition to cell adhesion, chemoattraction and cell migration. In some cases a galectin can either promote or suppress cell growth, depending on the cell types and doses used. Galectin-3 is the only member known so far to inhibit apoptosis, while galectin-1, -7 and -9 promote this cellular process. Galectins can act either extracellularly or intracellularly to exert effects on cell growth and apoptosis. RID="*" ID="*"Corresponding author.     

Enhancement of virus growth produced by thiols and disulphides

Summary Several thiols and disulphides have been found able both to shorten the latency phase and to increase the growth of several virus strains in cell cultures.This work has been supported by a grant of Consiglio Nazionale delle Ricerche, Roma (Italy).     

Dual action of the active oxygen species during plant stress responses

Adaptation to environmental changes is crucial for plant growth and survival. However, the molecular and biochemical mechanisms of adaptation are still poorly understood and the signaling pathways involved remain elusive. Active oxygen species (AOS) have been proposed as a central component of plant adaptation to both biotic and abiotic stresses. Under such conditions, AOS may play two very different roles: exacerbating damage or signaling the activation of defense responses. Such a dual function was first described in pathogenesis but has also recently been demonstrated during several abiotic stress responses. To allow for these different roles, cellular levels of AOS must be tightly controlled. The numerous AOS sources and a complex system of oxidant scavengers provide the flexibility necessary for these functions. This review discusses the dual action of AOS during plant stress responses.     

Enhancement of virus growth produced by thiols and disulphides.

Several thiols and disulphides have been found able both to shorten the latency phase and to increase the growth of several virus strains in cell cultures.     

Heterotransplantation of human glioblastoma in the brain of newborn mice]

7 human multiform glioblastoma have been transplanted into the brain of 100 new born Mice. Electron microscopy and chromosome analysis confirm the growth of a human tumor showing malignant features of glioblastoma.     

Phosphate mediated regulation of some of the enzymes of carbohydrate metabolism inNeurospora crassa

Summary The levels of FDP aldolase, isocitrate lyase, isocitrate dehydrogenase, malate dehydrogenase and glucose-6-P dehydrogenase were found to be rugulated by inorganic phosphate in the growth medium. The possible regulatory aspects have been discussed.     

Transgenic and knock-out mice for deciphering the roles of EGFR ligands

Generation of genetically engineered mice with either gain-of-function or loss-of-function mutations is the most popular technique for determining gene functions and the interrelationship between molecules in vivo. These models have provided a wealth of information about the developmental and physiological roles of oncogenes and growth factors. To date, transgenic techniques have been used extensively to study the functions of the epidermal growth factor (EGF) family. This review highlights some of the major recent findings pertinent to the EGF receptor (EGFR) and its ligands with special reference to elucidating how EGF and its related growth factors work together to regulate reproduction, growth and development. Finally, future investigations on ligand-ligand communications, EGFR and its ligands in neural stem cell research, and the mechanisms of EGFR signaling and trafficking in cells are also suggested. Received 24 May 2002; received after revision 15 July 2002; accepted 16 July 2002     

The use of primary cultures of adult rat hepatocytes to study induction of enzymes and DNA synthesis: Effect of nafenopin and electroporation

Summary Primary cultures of adult rat hepatocytes maintained in a well-differentiated state, in a chemically defined medium containing 2% DMSO, have been utilized to study the effect of non-mutagenic hepatocarcinogens such as the peroxisome proliferator nafenopin. The parameters chosen in this in vitro system were those that paralleled the major in vivo effects of nafenopin on the liver, mainly: the proliferation of the endoplasmic reticulum and induction of cytochrome P-452, the proliferation of the peroxisome compartment and the induction of cyanide-insensitive -oxidation of fatty acids and the stimulation of liver growth as measured by the DNA synthetic activity of the hepatocytes.In this review, we also describe the morphology of hepatocyte cultures prepared from previously electroporated hepatocytes and the potential for the use of electroporation to introduce growth related genes into hepatocyte cells to study the mechanisms of hepatocyte growth at the molecular level. In addition we describe the formation of endoplasmic reticulum whorls in these cultures as a consequence of nafenopin treatment. Whorl formation by hepatotrophic chemicals has been previously shown to occur in vivo; in this report, it is described for the first time in vitro.     

Developmental actions of natriuretic peptides in the brain and skeleton

The concept that atrial natriuretic peptide (ANP) and the closely related peptides BNP and CNP might be involved in the ontogeny of several organ systems emerged in the late 1980s. While many of the reported in vitro actions have not been examined in the context of organ development in vivo, recent studies demonstrate that mice which lack or overexpress natriuretic peptides or receptors exhibit pronounced skeletal growth defects. This article discusses how natriuretic peptides and other factors appear to regulate bone growth as an example of how natriuretic peptides might participate in the ontogeny of other organ systems. Evidence indicating that natriuretic peptides regulate neural development is then reviewed. Natriuretic peptides and receptors exhibit complex expression patterns in the developing nervous system, where they have been shown to act on neural cells as early as at the embryonic neural tube stage. Interestingly, both bone and brain growth appear to utilize primarily CNP and the CNP-specific type B receptor, and perhaps the type C receptor. In vitro data indicate that CNP may act on developing neurons, astrocytes and Schwann cells like a classical growth factor, regulating proliferation, patterning, phenotypic specification, survival and axonal pathfinding. Natriuretic peptides might also have roles in the vascularization of the embryonic brain, establishment of the blood-brain and blood-nerve barriers, and perhaps in nerve regeneration.Received 13 April 2004; received after revision 20 May 2004; accepted 27 May 2004     

Activity of soluble factors produced by Epstein-Barr virus-transformed human B lymphocytes on different cell lines.

Self-stimulatory growth factors, produced by a human Epstein-Barr virus (EBV)-positive lymphoblastoid B cell line, named BA-D10-4, have been tested for the capacity to induce DNA synthesis in various human and animal cell lines, including lymphoid, either EBV-positive or EBV-negative, and non-lymphoid cell lines. It has been found that BA-D10-4 cells produce growth factors which seem to be essential for their sustained proliferation in vitro, and which increase DNA synthesis in different primate lymphoid cells, independently of the presence of the EBV genome and of the lymphocyte lineage.     

Activity of soluble factors produced by Epstein-Barr virus-transformed human B lymphocytes on different cell lines

Summary Self-stimulatory growth factors, produced by a human Epstein-Barr virus (EBV)-positive lymphoblastoid B cell line, named BA-D10-4, have been tested for the capacity to induce DNA synthesis in various human and animal cell lines, including lymphoid, either EBV-positive or EBV-negative, and non-lymphoid cell lines. It has been found that BA-D10-4 cells produce growth factors which seem to be essential for their sustained proliferation in vitro, and which increase DNA synthesis in different primate lymphoid cells, independently of the presence of the EBV genome and of the lymphocyte lineage.     

Extraordinary levels of cadmium and zinc in a marine sponge,Tedania charcoti Topsent: inorganic chemical defense agents

The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria.     

Analysis of the immune system with transgenic mice: B cell development and lymphokines

Over the last decade transgenic mice expressing genes relevant for the immune system have been generated. Transgenic expression of immunoglobulin heavy and/or light chain genes of different isotypes and different specificities have helped to better understand phenomena relevant to B cell development such as allelic exclusion of immunoglobulins and B cell tolerance. Transgenic mice expressing interleukin genes have also been used to study the ways of action of these important growth and differentiation factors in the context of the mouse immune system.