Pronounced Stimulatory Effect Research Articles

The efficacy of recombinant thrombopoietin in murine and nonhuman primate models for radiation-induced myelosuppression and stem cell transplantation.

Radiation-induced pancytopenia proved to be a suitable model system in mice and rhesus monkeys for studying thrombopoietin (TPO) target cell range and efficacy. TPO was highly effective in rhesus monkeys exposed to the mid-lethal dose of 5 Gy (300 kV x-rays) TBI, a model in which it alleviated thrombocytopenia, promoted red cell reconstitution, accelerated reconstitution of immature CD34+ bone marrow cells, and potentiated the response to growth factors such as GM-CSF and G-CSF. In contrast to the results in the 5 Gy TBI model, TPO was ineffective following transplantation of limited numbers of autologous bone marrow or highly purified stem cells in monkeys conditioned with 8 Gy TBI. In the 5 Gy model, a single dose of TPO augmented by GM-CSF 24 h after TBI was effective in preventing thrombocytopenia. The strong erythropoietic stimulation may result in iron depletion, and TPO treatment should be accompanied by monitoring of iron status. This preclinical evaluation thus identified TPO as a potential major therapeutic agent for counteracting radiation-induced pancytopenia and demonstrated pronounced stimulatory effects on the reconstitution of immature CD34+ hemopoietic cells with multilineage potential. The latter observation explains the potentiation of the hematopoietic responses to G-CSF and GM-CSF when administered concomitantly. It also predicts the effective use of TPO to accelerate reconstitution of immature hematopoietic cells as well as possible synergistic effects in vivo with various other growth factors acting on immature stem cells and their direct lineage-committed progeny. The finding that a single dose of TPO might be sufficient for a clinically significant response emphasizes its potency and is of practical relevance. The heterogeneity of the TPO response encountered in the various models used for evaluation points to multiple mechanisms operating on the TPO response and heterogeneity of its target cells. Mechanistic mouse studies made apparent that the response of multilineage cells shortly after TBI to a single administration of TPO is quantitatively more important for optimal efficacy than the lineage-restricted response obtained at later intervals after TBI and emphasized the importance of a relatively high dose of TPO to overcome initial c-mpl-mediated clearance. Further elucidation of mechanisms determining efficacy might very well result in a further improvement, e.g., following transplantation of limited numbers of stem cells. Adverse effects of TPO administration to myelosuppressed or stem cell transplanted experimental animals were not observed.

Lipopolysaccharide-induced interleukin 8 production by human whole blood is enhanced by epinephrine and inhibited by hydrocortisone.

To determine the effect of epinephrine and hydrocortisone on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production, human whole blood was stimulated with LPS in the presence or absence of these stress hormones. Epinephrine caused a dose-dependent increase in LPS-induced IL-8 production, which was mediated exclusively via beta-adrenergic receptors, as reflected by the facts that beta (but not alpha) receptor blockade reversed the epinephrine effect and beta (but not alpha) receptor stimulation reproduced the epinephrine effect. Further, elevating cellular cyclic AMP (cAMP) concentrations, a known effect of beta-adrenergic stimulation, by addition of dibutyryl cAMP also enhanced LPS-induced IL-8 production. Epinephrine-induced upregulation of IL-10 production masked an even more pronounced stimulating effect of this hormone on IL-8 synthesis, as indicated by the finding that the extent of IL-8 upregulation was greater in the presence of anti-IL-10 than in the absence of anti-IL-10. Hydrocortisone dose-dependently inhibited LPS-induced IL-8 production and reversed epinephrine-induced enhancement of IL-8 production. Epinephrine and hydrocortisone have opposite effects on IL-8 production, which may be relevant for the understanding of endogenous and therapeutic stress hormone influences on IL-8 mediated inflammation.

THE EFFECT OF HUMAN ENDOTHELIAL CELL-DERIVED PROTEOGLYCANS ON HUMAN SMOOTH MUSCLE CELL GROWTH

Extracellular proteoglycans (PGs) purified from cultured human arterial endothelial cells were tested for their effects on the proliferation of human vascular smooth muscle cells (VSMC). Fractions containing perlecan, the basement membrane heparan sulphate (HS) PG, the large chondrotin sulphate (CS) proteoglycan from connective tissue and other immunoreactive CS did not inhibit the proliferation of human VSMC. Native endothelial extracellular matrix, which was shown to contain the same PGs, demonstrated a pronounced stimulatory effect on the proliferation of human VSMCs. This stimulatory effect was not removed by pre-incubation of the matrix with 1M NaCl, heparin, platelet extract or plasmin. These experiments demonstrate that PGs produced by human arterial endothelial cells do not inhibit the proliferation of VSMC. These data do not support the hypothesis that human endothelial cells,in vivocontrol the activation or proliferation of VSMCs directly by the secretion of a non-proliferative molecule. Instead they support the hypothesis that the endothelial cells counteract intimal hyperplasia of VSMC indirectly by providing a barrier from activating factors in the plasma.

Effect of lipid composition on lipoprotein lipase activity measured by a continuous fluorescence assay: effect of cholesterol supports an interfacial surface penetration model.

The breakdown of normal substrates by lipases requires an interfacial binding step prior to hydrolysis. Interfacial binding and subsequent hydrolysis will be affected by the lipid components and hence physical properties of the substrate surface. In order to investigate in detail the effect of lipid structure on the activity of lipoprotein lipase (LPL), triolein-containing emulsion particles of defined composition have been used as substrates. In addition, lipase activity has been measured using a continuous fluorescence displacement assay that monitors the release of long-chain fatty acids as an alternative to normal radiochemical assays. Using this fluorescence assay, rates of hydrolysis of triolein were the same as when using a standard radiochemical assay under identical conditions. Activation by apolipoprotein CII was very similar by both methods; however, the extent of activation (2-3-fold) was less than has been reported previously using different assay conditions. In order to investigate the effect of cholesterol on LPL activity, emulsion particles were prepared in which the cholesterol/egg-phosphatidylcholine ratio was increased up to a 1:1 molar ratio. A pronounced stimulatory effect of cholesterol was observed under these assay conditions, with up to a 5-fold increase in rate compared with emulsion particles without cholesterol. Since high molar ratios of cholesterol are reported to exclude triacylglycerol from the phospholipid surface [Spooner and Small (1987) Biochemistry 26, 5820-5825], these results are not consistent with a mechanism involving LPL hydrolysis of surface triacylglycerol. Instead, they support an interfacial penetration model, allowing the enzyme's active site direct access to triacylglycerol in the lipoprotein core. Perturbation of the surface phospholipid monolayer of the emulsion particle as a result of hydrolysis by Naja naja phospholipase A2 resulted in a 10-fold activation of LPL, providing further support for an interfacial penetration model. The stimulatory effect of apolipoprotein CII was not modulated by modification of the interface with cholesterol.

Demonstration of endothelial-activating properties of hypertensive sera

Sera from patients with hypertension were examined for their ability to influence endothelial cell function. Sera from 10 patients with hypertension and from 11 age-matched controls were incubated with endothelial cells and their effect on cell growth assessed by endothelial cell 3H-thymidine uptake. Sera from patients with hypertension had a more pronounced stimulatory effect on endothelial cell proliferation than control sera. In addition, hypertensive sera were also examined for their capacity to stimulate endothelial cell production of the vasoactive peptide endothelin. Confluent monolayers of endothelial cells were incubated with sera and the amount of endothelin generated in the supernatant measured by an immunoassay. Amounts of endothelin produced by the endothelial cells in response to hypertensive sera were significantly higher compared with the amounts produced in response to normal sera. The results of the studies suggest that a serum factor(s) in hypertensive patients may be of importance in modulating endothelial cell function. Such a factor(s) may have a significant role in the pathogenesis of hypertension.

Modulations of Elastin Expression and Cell Proliferation by Retinoids in Cultured Vascular Smooth Muscle Cells

Effects of retinoid derivatives (retinol, retinal, retinoic acid, and etretinate) on elastin expression and cell proliferation in chick embryonic vascular smooth muscle cells were compared. Retinoic acid and etretinate inhibited cell proliferation to a greater extent than retinol and retinal. Retinol showed no significant effect on cell proliferation or elastin synthesis. Retinoic acid exhibited the most pronounced stimulatory effect on elastin synthesis with a maximum stimulation of 2.8-fold at the concentration of 10(-6) M for 24-48 h treatment. A comparable increase in elastin mRNA level was observed in the case of retinoic acid treatment. When the cells were serially passaged to the third subcultivation, elastin synthesis declined with increasing number of cell passages. Retinoic acid reversed this decline of elastin synthesis. The results indicate that retinoic acid was potentially active and retinol was inactive for both inhibition of cell proliferation and stimulation of elastin synthesis. The inhibitory activities of the four compounds for cell proliferation appear to parallel the stimulatory activities for elastin synthesis. The stimulation of elastin expression by retinoids may thus be closely related to the inhibition of cell proliferation.

Lipid balance in HepG2 cells: active synthesis and impaired mobilization

The human hepatoma cell line HepG2 in culture medium synthesized fatty acids de novo (144 +/- 9 nmol fatty acid/mg protein per 24 h) at a rate similar to that observed in freshly prepared rat hepatocytes (192 +/- 8 nmol/mg per 24 h) and in primary cultures of rat hepatocytes (165.4 +/- 29.3 nmol/mg per 24 h). In HepG2 cells, fatty acid synthesis was inhibited by extracellular oleate (0.75 mM), and, to a lesser extent, by glucagon (10(-7) M). Insulin (7.8 x 10(-8) M) had a mild stimulatory effect. Fatty acid synthesis was not influenced by lipogenic precursors (lactate plus pyruvate), substances which, in rat hepatocytes, had pronounced stimulatory effects. Fatty acid synthesis rates were also unchanged in the presence of prostaglandin E2 (PGE2). In general, compared to rat hepatocytes, fatty acid synthesis in HepG2 cells was less sensitive to manipulation of the culture medium in vitro. HepG2 cells had a high capacity for triacylglycerol synthesis from extracellular oleate (469 +/- 43 nmol triacylglycerol/mg protein per 24 h) but phospholipid synthesis was relatively low (15.8 +/- 0.4% of total glycerolipids). Very little of the above newly synthesized triacylglycerol was secreted as lipoprotein (4.62 +/- 0.88 nmol triacylglycerol/mg protein per 24 h) resulting in a large intracellular accumulation of triacylglycerol. This was exacerbated by the absence of any detectable ketogenesis. The secretion of triacylglycerol produced from de novo synthesized fatty acids was also very low in HepG2 compared to that observed in primary cultures of rat hapatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of initial respiratory status on the short-and long-term activity of the trout red blood cell ?-adrenergic Na+/H+ exchanger

The effects of ambient O2 partial pressure and CO2 partial pressure on the intensity of rainbow trout (Oncorhynchus mykiss) red blood cell β-adrenergic Na+/H+ exchange were investigated. This was accomplished in vitro by continuously monitoring whole blood extracellular pH, partial pressures of O2 and CO2 and by measuring red blood cell water content and Na+ concentration before and 30 min after the addition of a catecholamine mixture (final nominal concentrations: 250 nmol·l-1 adrenaline and 20 nmol·l-1 noradrenaline). The experiments were performed under six different initial conditions combining two ambient partial pressures of CO2 (1.50 and 6.75 torr) and three ambient partial pressures of O2 (15, 30 and 150 torr). The activation of red blood cell Na+/H+ exchange (as indicated by marked reductions of whole blood pH) was followed by transient reductions in blood partial pressures of CO2 and O2 (2 min) resulting from the shift of the CO2/HCO3 - equilibrium within the cell and the subsequent binding of O2 to the haemoglobin. The initial reduction in blood CO2 partial pressure was followed by a rise reflecting the titration of plasma HCO3 - by extruded H+. At low partial pressure of CO2 (1.50 torr) there was a pronounced stimulatory effect of hypoxia on the initial intensity of the extracellular acidification (5 min), whereas at high CO2 partial pressure (6.75 torr) hypoxia actually lowered the extent of the initial acidification. In all cases, Na+/H+ exchange activation was accompanied by increases in cell water content and red blood cell Na+ levles when measured 30 min after addition of catecholamines. Both hypercapnia and hypoxia increased the magnitude of these changes although the largest changes in cell water content and Na+ levels were observed under hypercapnic conditions. Thus, the long-term activity (as determined by measuring cell water and Na+ levels) of the Na+/H+ exchanger was enhanced both by hypercapnia and hypoxia regardless of the initial CO2 partial pressure. The initial activity (5 min), on the other hand, although stimulated by hypercapnia was influenced by hypoxia in opposing directions depending upon the initial CO2 partial pressure of the blood.

Effects of various human interleukin-2 preparations and lymphokine-activated killer cells on the production of antibodies in micein vivo and of human immunoglobulinsin vitro

Comparison of the lymphocytic IL-2 (lIL-2, lymphokinin) and recombinant IL-2 (rIL-2) showed that lIL-2 is characterized by a more pronounced stimulating effect of low doses on antibody production in mice and on human immunoglobulin production. High doses of lIL-2, in contrast to rIL-2, do not cause hyperstimulation of antibody production or immunoglobulin production. Human lymphokine-activated killer (LAK) cells, induced by rIL-2in vitro during 7 but not 3 days, enhance the production of human immunoglobulins. Monocytes activated by rIL-2 suppress the stimulating effect of LAK cells on immunoglobulin production.

A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro

Estrogen/gestagen replacement therapy prevents excess bone loss in postmenopausal women. The mode of action by which these sex steroids exert their anabolic effects on bone has not been completely clarified yet. In this study, 17β-estradiol (E 2), as well as the progestins progesterone (P), dydrogesterone (DD), 20α-dihydroxydydrogesterone (DHD), medroxyprogesterone acetate (MPA), and cyproterone acetate (CPA) were able to stimulate the mitogenesis and differentiation of normal adult human osteoblast-like (HOB) cells harvested from female trabecular bone explants. The different progestins exerted a more pronounced stimulatory effect on HOB proliferation than E 2 did. The combination of E 2 with P, DD, or DHD did not result in a statistically significant further increase of HOB proliferation, as compared with the progestins alone. In general, E 2 showed a stronger differentiation-inducing effect than the progestins, as measured by histochemical staining of the HOB cells for alkaline phosphatase activity. Combining E 2 and the progestins did not result in a further increase of the number of alkaline phosphatase positive cells, compared with E 2 alone. The different progestins proved to be equally potent in stimulating HOB proliferation and differentiation. In conclusion, progestins as well as E 2 exerted anabolic but differential effects on normal adult human osteoblasts in vitro.

Colonization of Retama raetam seeds by fungi and their significance in seed germination

Examination by scanning electron microscopy and incubation on potato-dextrose agar medium showed that dry seeds ofRetama raetam were externally free of fungi. When planted in sandy loam soil, the seeds become colonized with eleven soil-borne fungal species. The fungi were isolated on cellulose agar, pectin agar and lignin agar media.Aspergillus flavus, A. niger, A. fumigatus, Penicillium capsolatum andFusarium oxysporum had broad occurrence and were recovered on all the three media. The production of hydrolytic enzymes by the isolated fungi depends on the substrate and species.Penicillium capsolatum, P. spinulosum andA. niger had wide enzymatic amplitude and they were able to produce cellulolytic, pectolytic and lignolytic activities on corresponding substrates as well as on seed-coat-containing media. The lignolytic activities of the isolated species exceptChaetomium bostrychodes andTrichoderma viride were enhanced by applying the seed-coat materials as C- source rather than lignin. SoakingR. raetam seeds in culture filtrates of most of the fungi grown on seed-coat-supplemented media induced a pronounced and distinct stimulating effect on seed germination. The most effective filtrates were those ofP. capsolatum, P. spinulosum andSporotrichum pulverulentum.

Tamoxifen stimulates in vivo growth of drug-resistant estrogen receptor-negative breast cancer.

An estrogen receptor-negative, multidrug-resistant MDA-MB-A1 human breast cancer cell line was grown in culture with and without a noninhibitory concentration (0.5 microM) of tamoxifen for 122 days. Tamoxifen-treated and control cells were inoculated into opposite flanks of nine nude mice, where they produced measurable tumors in every case. Six of the animals were treated with tamoxifen at 500 micrograms/day for 22 days. Although no inhibitory nor stimulatory effect of tamoxifen was seen in vitro, tamoxifen had a clear tumor-growth-stimulating effect in mice. The most pronounced stimulatory effects were observed in the cells that had been cultured with tamoxifen. Within 3 weeks of the start of tamoxifen therapy, the cells grown in the presence of tamoxifen produced tumors with a mean size of 380 mm2, whereas the cells not pretreated with tamoxifen had tumors of 220 mm2. In contrast, in mice not receiving tamoxifen, the sizes of the tumors were 190 and 140 mm2, respectively. These preliminary results suggest that prolonged in vitro tamoxifen exposure induces cellular changes that result in tumors that are stimulated to grow faster in mice following tamoxifen treatment.

Inhibition of herpes simplex virus replication and protein synthesis by non-smoked tobacco, tobacco alkaloids and nitrosamines

Inhibitory effects of snuff extract and the tobacco chemicals nicotine, anabasine, diethyl- N-nitrosamine (DEN), and the tobacco-specific nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on herpes simplex virus type 1 (HSV-1) replication in vitro and on HSV-1 protein synthesis in infected cells were analysed. Snuff extract and nicotine caused a significant reduction of HSV-1 attachment to cell membranes whereas anabasine, DEN, NNN and NNK did not affect adsorption of HSV-1. Virus production assays in the presence of snuff added after virus adsorption resulted in a significantly reduced production of virus at low multiplicities of infection (MOI), but at high MOI the inhibitory effect of snuff extract was less pronounced. DEN, NNN and NNK only affected virus production at toxic concentrations. Nicotine and anabasine reduced virus production in non-toxic doses but not at the concentrations present in snuff extract. In HSV-infected cells exposed to snuff extract, the immediate early (α-) infected cell proteins (ICPs) 4 and 27 (as well as the early (β-) ICPs 6 and 8) were markedly increased, whereas the late (γ-) ICPs 5, 11 and 29 were reduced. Nicotine had a less pronounced stimulating effect on the production of α-proteins but no detectable effect on production of β- or -γ-proteins. Anabasine, DEN, NNN and NNK did not affect HSV protein synthesis at non-toxic concentrations. Synthesis of thymidine kinase and DNA polymerase was significantly reduced by snuff extract. Also nicotine and anabasine affected thymidine kinase and DNA polymerase but only at toxic concentrations. The production of the cellular protein actin, which almost disappears a few hours after HSV-1 infection, remained at a significant level in HSV-infected cells exposed to snuff. Thus snuff extract blocks the replicative cycle of HSV at an early stage, which results in an increased production of α-proteins in the infected cells and in prolonged maintenance of cellular functions. This may be of importance for HSV-induced transformation and the development of HSV-associated tumours.

Fusicoccin action in cell-suspension cultures of Corydalis sempervirens Pers.

Mid-log-phase cell suspensions of Corydalis sempervirens Pers., when incubated in micromolar or submicromolar concentrations of fusicoccin, strongly acidified the culture medium. High-affinity fusicoccin-binding sites were found in microsomes prepared from these cells using the radioligand [(3)H]-9'-norfusicoccin-8'-alcohol. Binding was saturable with an apparent dissociation constant (K d) of 2.8 nM, a pH optimum of 6.0, a temperature optimum of 35° C and was rapid (t1/2 = 8 min). The site abundance was 0.76±0.17 pmol · (mg of protein)(-1). In the same membrane preparations, the K(+), Mg(2+)-ATPase (EC 3.6.1.3) was characterized. The enzyme was highly vanadate-sensitive (IC50=6.5 μM) and nucleotide-specific (ATP≫NTP), had a pH optimum of 6.2, an apparent K m for ATP of 0.23±0.12 mM, and V max of 10.6±1.8 nkat (mg of protein)(-1). Fusicoccin doubled V max and lowered, by a factor of 2, the apparent K m for ATP of the enzyme when the cells were incubated with the toxin for 30 min prior to homogenization of the cells. The stimulation of the enzyme was also pronounced when fusicoccin was added to the homogenization medium just prior to homogenization of the cells, but was slight to zero when the toxin was added at the microsomal stage. The pronounced stimulatory effect of fusicoccin on the ATPase was seen at pH 7.1, i.e. at a pH typical for the cytoplasmic compartment, but was not detectable at pH 6.2, the pH optimum of the enzyme. The implications of these findings for an understanding of fusicoccin action are discussed.

The stimulatory effect of soluble fibrin on plasminogen activation by tissue plasminogen activator as studied by the CDA-set fibrin monomer test

The stimulatory effect of various fibrin preparations on plasminogen activation by tissue plasminogen activator, was studied by the Coa-set Fibrin Monomer test (Kabi). Fibrin obtained by complete conversion of purified fibrinogen demonstrated a greater stimulatory effect on plasminogen activation than did equal amounts of fibrin obtained by partial conversion of fibrinogen. Soluble fibrin generated by treating human plasma with minute amounts of thrombin or bathroxobin, resembled partially converted purified fibrinogen. The plasminogen activating effect of completely converted fibrinogen was similar in thrombin and bathroxobin incubated samples. In preparations of partially converted fibrinogen and in plasma samples, bathroxobin digested fibrinogen expressed a more pronounced stimulatory effect on plasminogen activation than did thrombin digested specimens. The underlying mechanism for these differences are discussed.

Protein phosphorylation associated with the stimulation of neutrophils. Modulation of superoxide production by protein kinase C and calcium

Neutrophils and other phagocytic cells of the immune system possess a superoxide-generating oxidase system which is essential for the efficient killing of microbes. The system is activated by a wide variety of stimuli, some of which operate through pathways involving protein kinase C (PKC), while others appear not to. The PKC-dependent pathway is probably the major signal transduction route for most of the stimuli. Alterations in cellular Ca2+ and diglyceride levels can have a pronounced stimulatory effect on this pathway by their ability to synergistically activate PKC. This review discusses PKC, the different interactions of this kinase with the plasmalemma that are important in superoxide production, the synergy between Ca2+ and diglyceride, and the nature of the phosphoproteins involved. Evidence supporting the existence of the PKC-independent pathway is also reviewed.

Exogenous Polyamines Stimulate Ethylene Synthesis by Soybean Leaf Tissues

Exogenous supply of spermine (Spm) markedly stimulated ethylene evolution from intact soybean leaves of leaf discs, strongly increased the level of free 1-aminocyclopropane-1-carboxylic acid (ACC), and slightly stimulated ethylene forming-enzyme (EFE) activity Spm treatment also resulted in leaf epinasty and accelerated leaf senescence Ethylene stimulation was depressed, but not abolished, by light, and was suppressed by inhibitors of ACC synthase and EFE activity Spermidine had a less pronounced stimulatory effect on ethylene production whereas the diamines putrescine and diaminopropane were without effect These results contrast with other reports indicating that di- and polyamines inhibit ethylene biosynthesis in plants, and extend our previous results on detached tobacco leaves exogenously treated with polyamines

Involvement of a central nervous pathway in yohimbine-induced insulin secretion

Yohimbine hydrochloride, an α 2-adrenoceptor antagonist, was administered (3.3 mg/kg i.v.) to anesthetized normal dogs provided with a T-shaped catheter inserted in the pancreaticoduodenal vein. The effects on blood glucose levels and pancreatic hormones were investigated. We show that yohimbine induced an immediate and pronounced stimulatory effect on insulin secretion accompanied by a clear decrease in blood glucose levels. Yohimbine also stimulated the pancreatic secretion of somatostatin and glucagon. However, the secretion kinetics were not the same for the three hormones: the stimulation was rapid and immediate for insulin and somatostatin, whereas it was progressive for glucagon. All these stimulatory effects were suppressed by propranolol, thus implicating β-adrenergic mechanisms. Bilateral cervical vagotomy markedly reduced the immediate effect of yohimbine on insulin secretion, suggesting that a central neural pathway was implicated. In contrast, the progressive elevation in glucagon secretion was not decreased by vagotomy. Our results suggest thet yohimbine stimulates, at least in part, insulin secretion by blocking central α 2-adrenoceptors.

Substance immunologically cross-reactive with insulin (SICRI) stimulates cell division.

A substance immunologically cross-reactive with insulin (SICRI) was isolated and purified from murine melanoma B16. Biochemical and biological data provide evidence that SICRI and insulin are two distinct biologically active agents. In vitro, SICRI has stimulated the DNA and protein synthesis, cell growth or colony-forming ability of 19 normal and transformed cell lines of human and rodent origin. It indicates that SICRI is a potent nonspecific growth factor. The most pronounced stimulatory effect of SICRI on proliferative capacity of cells is observed with cells at G0/G1 point of the cell cycle.

Salt-induced enhancement of measles virus yields in cultured cells.

Supplementation of culture medium with MgSO4 or Na2SO4 in millimolar concentrations caused an enhanced measles virus (MV) yield from cultured quail embryo cells. MgSO4 at 25-50 mM concentrations exhibited the most pronounced and consistent stimulatory effect. MV infectivity increases ranged from 2- to 200-fold; the effect was highly reproducible for stationary monolayer, roller or microcarrier-grown cell culture types. MgSO4 also improved MV plaque development and caused MV plaque size enlargement on Vero cell monolayers. At mM concentrations MgSO4 was not operative as a MV thermostabilizing agent; rather, salt-induced enhancement of MV yields appeared to be due to intracellular events, e.g., augmented viral protein synthesis.