Investigation of a substance of renal origin which inhibits the growth of renal cortex explant in vitro

Development ◽  
1974 ◽  
Vol 31 (3) ◽  
pp. 655-665
Author(s):  
S. E. Dicker ◽  
Christine A. Morris
Keyword(s):  
Chick Embryo ◽  
Guinea Pig ◽  
Inhibitory Activity ◽  
Renal Cortex ◽  
Renal Medulla ◽  
Immune Serum ◽  
Supernatant Fluid ◽  
Serum Samples ◽  
Growth Inhibitory

(1) Explants of renal cortex from 7-day mice or 5-day rats were reared on plasma clots, in the presence or absence of chick embryo metanephros. (2) The size of outgrowth, estimated after 48 h, was similar for renal cortex of both species. When reared in chick embryo extract in the presence or absence of metanephros, the out-growth estimated after 48 h was 2·08±0·092 greater than that of the initial explant. (3) Addition of supernatant fluid from a homogenate of renal cortex of adult mouse, rat, guinea-pig, rabbit or pig inhibited the outgrowth of renal cortex explant from neonate mouse or rat. The supernatant fluid from a homogenate of adult renal medulla had no significant effect. (4) The inhibitory activity of the supernatant fluid from a homogenate of renal cortex from adult animals was destroyed by heating at 99 °C. (5) The compound with growth-inhibitory activity appeared to be cortex-specific but not species-specific. Extracts of liver, spleen, duodenum, and heart muscle of adult animals had no significant effect on the outgrowth of renal explants of neonate animals; and extracts from renal cortex of adult mammals had no significant effect on the growth of other tissues from neonate mice or rats. (6) The degree of growth inhibition was related to the amount of protein in the extract of renal cortex. Maximum inhibition was observed with extracts of renal cortex containing 2·5 mg protein/0·5 ml. (7) Immune serum samples were obtained from rabbits and guinea-pigs immunized against extracts of renal cortex and medulla and liver from rats and mice. Only the serum from either rabbit or guinea-pig immunized against extracts of renal cortex blocked the growth-inhibitory action of renal cortex extracts.

scholarly journals Plasmodium falciparum Line-Dependent Association ofIn VitroGrowth-Inhibitory Activity and Risk of Malaria

2012 ◽  
Vol 80 (5) ◽  
pp. 1900-1908 ◽  
Author(s):  
Josea Rono ◽  
Anna Färnert ◽  
Daniel Olsson ◽  
Faith Osier ◽  
Ingegerd Rooth ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Content Type ◽  
Phenotypic Differences ◽  
Erythrocyte Invasion ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Control Study

ABSTRACTPlasmodium falciparum's ability to invade erythrocytes is essential for its survival within the human host. Immune mechanisms that impair this ability are therefore expected to contribute to immunity against the parasite. Plasma of humans who are naturally exposed to malaria has been shown to have growth-inhibitory activity (GIA)in vitro. However, the importance of GIA in relation to protection from malaria has been unclear. In a case-control study nested within a longitudinally followed population in Tanzania, plasma samples collected at baseline from 171 individuals (55 cases and 116 age-matched controls) were assayed for GIA using threeP. falciparumlines (3D7, K1, and W2mef) chosen based on their erythrocyte invasion phenotypes. Distribution of GIA differed between the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.96;P= 0.04), whereas GIA to K1 and W2mef was not. These results show that GIA, as well as its association with protection from malaria, is dependent on theP. falciparumline and can be explained by differences in erythrocyte invasion phenotypes between parasite lines. Our study contributes knowledge on the biological importance of growth inhibition and the potential influence ofP. falciparumerythrocyte invasion phenotypic differences on its relationship to protective immunity against malaria.

scholarly journals Anti-Trypanosomal Alkaloids from Xymalos Monospora

2006 ◽  
Vol 1 (8) ◽  
pp. 1934578X0600100
Author(s):  
Dieudonne Ngamga ◽  
Pierre Tane ◽  
Donna Rattendi ◽  
Cyrus Bacchi ◽  
Christopher C. Okunji ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Stem Bark ◽  
Aporphine Alkaloid ◽  
African Trypanosomes ◽  
Benzylisoquinoline Alkaloids ◽  
Benzylisoquinoline Alkaloid ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

From an extract of the stem bark of Xymalos monospora, a bis-benzylisoquinoline alkaloid (1), three benzylisoquinoline alkaloids (mollinedine, 1-(p-methoxybenzyl)-6,7-methylenedioxyisoquino-line, doryafranine), and an aporphine alkaloid (N-methyllaurotetanine) were isolated. These compounds were tested for growth inhibitory activity against bloodstream forms of three strains of African trypanosomes. In vitro IC50 values starting from 1.8 μg /mL were obtained.

THE EFFECTS OF GR32191, A NEW THROMBOXANE RECEPTOR BLOCKING DRUG,ON PLATELETS AND VASCULAR SMOOTH MUSCLE IN VITRO

1987 ◽  
Author(s):  
P Lumley ◽  
E W Collington ◽  
P Hallett ◽  
E J Hornby ◽  
p PA Humphrey ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Vascular Smooth Muscle ◽  
Inhibitory Activity ◽  
Whole Blood ◽  
Blocking Drug ◽  
Receptor Blocking ◽  
Thromboxane Receptor ◽  
Induced Aggregation

The effect of a new thromboxane receptor blocking drug GR32191 ([1R-[1α(Z),2β,3β,5α]]-(+)-7-[5-[[(1,1"-biphenyl)-4-yl]methoxy] -3-hydroxy-2-(l-piperidinyl)cyclopentyl]-4-heptenoic acid,hydrochloride) has been examined upon platelets and vascular smooth muscle. In human platelet-rich plasma (PRP), aggregation to thromboxane(Tx) A2, PGH2, arachidonic acid, collagen andU-46619 was antagonised by GR32191 (IC50 range 2-36 nM).Primary aggregation (PRP treated with aspirin 10 pM) to ADP, 5-HT and adrenaline were unaffected by concentrations of GR32191 up to 10 pM. In human PRP, U-46619-induced aggregation and 5-HT release were antagonised by GR32191(10-100 nM). In contrast, in theabsence of aspirin, ADP-induced 5-HT release,but not aggregation, was antagonised by the compound implicating a role for TXA2 in the release process. In human PRP GR32191 (up to 30μM) did not itself induce aggregation or, in the presence of EGTA (4 mM), induce detectable shape change. Up to 10 μM GR32191 was without effect upon the inhibitory activity of PGI2 or PGD2 and at 1μMhad no significant inhibitory activity upon fatty acid cyclooxygenase, thromboxane synthase, prostacyclin synthase, 12-lipoxygenase orphosphodiesterase. The effect of GR32191was quantified further in human platelets suspended in whole blood or physiological salt solution. Aggregation to U-46619 was antagonised byGR32191 with a pA2 (slope of the Schild regression) of 8.2 (1.3) in whole blood and 8.8 (1.3) in resuspended platelets. The compound competitively and specifically antagonised the contractions of strips of human isolatedpulmonary blood vessels and rat and guinea-pig aortic strips produced by U-46619 with pA2 (slope) values of 8.2 (1.1), 7.9 (0.9) and 8.7(0.9) respectively. In contrast contractions induced by KC1 and 5-HT (rat) orKC1and histamine (guinea-pig) were unaffectedbyconcentrations of GR32191 up to 30 μM.Thus GR32191 is a potent and specific thromboxane receptor blocking drug on platelets and vascular smooth muscle in vitro. It is orally active and long lasting in man (Thomas, M et al.,this meeting).

scholarly journals In Vitro Growth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

2009 ◽  
Vol 78 (2) ◽  
pp. 737-745 ◽  
Author(s):  
Peter D. Crompton ◽  
Kazutoyo Miura ◽  
Boubacar Traore ◽  
Kassoum Kayentao ◽  
Aissata Ongoiba ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Vaccine Development ◽  
Critical Role ◽  
Malaria Risk ◽  
Activity Level ◽  
Asexual Blood Stage ◽  
Growth Inhibition Assay ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

ABSTRACT Immunity to the asexual blood stage of Plasmodium falciparum is complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a corresponding in vitro correlate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth of P. falciparum in vitro. In humans, naturally acquired and vaccine-induced P. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95; P = 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85; P = 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as an in vitro correlate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity.

scholarly journals Specific growth inhibitory sequences in genomic DNA from quiescent human embryo fibroblasts.

1987 ◽  
Vol 7 (5) ◽  
pp. 1894-1899 ◽  
Author(s):  
R Padmanabhan ◽  
T H Howard ◽  
B H Howard
Keyword(s):  
Dna Sequences ◽  
Hela Cells ◽  
Human Embryo ◽  
Inhibitory Activity ◽  
Genomic Dna ◽  
Molecular Mechanisms ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Embryo Fibroblasts

We used HeLa cells as recipients in a gene transfer assay to characterize DNA sequences that negatively regulate mammalian cell growth. In this assay, genomic DNA from quiescent human embryo fibroblasts was more inhibitory for HeLa replication than was DNA from either Escherichia coli or HeLa cells. Surprisingly, growth inhibitory activity depended on the growth state of the cells from which genomic DNA was prepared; it was strongest in DNA prepared from serum-deprived, quiescent embryo fibroblasts. This latter observation implies a role for DNA modification(s) in regulating the activity of the inhibitory sequences detected in our assay. The level of the observed growth inhibitory activity was sometimes high, suggesting that the relevant sequences may be abundantly represented in the mammalian genome. We speculate that these findings may provide new insights into the molecular mechanisms involved in cellular quiescence and in vitro senescence.

Synthesis of new oxathiazinane dioxides and their in vitro cancer cell growth inhibitory activity

2010 ◽  
Vol 20 (17) ◽  
pp. 5353-5356 ◽  
Author(s):  
Françoise Borcard ◽  
Matthias Baud ◽  
Claudia Bello ◽  
Giovanna Dal Bello ◽  
Francesco Grossi ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
Cancer Cell Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

scholarly journals STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION

1924 ◽  
Vol 40 (4) ◽  
pp. 467-485 ◽  
Author(s):  
Oswald H. Robertson ◽  
Richard H. P. Sia
Keyword(s):  
Growth Inhibition ◽  
Protective Action ◽  
Immune Serum ◽  
Rabbit Serum ◽  
In Vitro Test ◽  
High Dilution ◽  
Protective Properties ◽  
Growth Inhibitory ◽  
Vitro Test

Using the method described in an earlier publication for testing the growth-inhibitory and bactericidal activity of serum-leucocyte mixtures for the pneumococcus, a study has been made of the action of antipneumococcus serum added to the serum and leucocytes of the rabbit, which alone lack the power to inhibit pneumococcus growth. It was found that the additiori of relatively small quantities of immune serum to a mixture of rabbit serum and washed rabbit leucocytes conferred on this mixture marked growth-inhibitory and pneumococcidal powers. The effect of the immune serum was found to be quantitative in nature. Beyond a certain point progressive dilution of the serum resulted in a corresponding decrease in the degree of growth inhibition, but this property of the immune serum did not disappear until a high dilution was reached. The leucocytes were also found to exert their effect quantitatively. Within certain limits the number of pneurnococci killed was dependent on the quantity of them present. Tests comparing the action of immune serum in the rabbit serum-leucocyte tubes with their protective action in mice showed a close parallelism between these two effects; that is to say, an immune serum showing marked protective properties for mice was likewise effective in high dilution in the in vitro test, and vice versa.

scholarly journals BACTERICIDAL EFFECT OF HUMAN SERUM ON BORRELIA MIYAMOTOI, CAUSATIVE AGENT OF IXODES TICK-BORNE BORRELIOSIS (ITBB-BM)

2018 ◽  
pp. 58-67 ◽  
Author(s):  
A. E. Platonov ◽  
J. .. Koetsveld ◽  
O. A. Stukolova ◽  
A. S. Dolgova ◽  
N. M. Kolyasnikova ◽  
...  
Keyword(s):  
Human Serum ◽  
Protein Microarray ◽  
Bactericidal Effect ◽  
Dark Field ◽  
Immune Serum ◽  
Heat Inactivation ◽  
Borrelia Miyamotoi ◽  
Serum Samples ◽  
Variable Major Proteins

Aim. Our aim was to study the bactericidal effect of human serum on Borrelia miyamotoi in vitro. Materials and methods. B. miyamotoi spirochetes (strains HT31 and LB-2001) were incubated in non-immune serum of healthy donors (SHD) and in heat inactivated complement-depleted SHD, as well as in serum samples of the patients recovered from ITBB-BM. The viability, that is motility, of borrelia after incubation was investigated by dark-field microscopy. The levels ofserum antibody to B.miyamofoi-specificproteins (GlpQ enzyme and four variable major proteins Vlpl5/16, Vlpl8, Vspl, and Vlp5) were measured by specially designed plane protein microarray. Results. Borrelia fully retain their viability in non-immune SHD, but their motility is partially or completely suppressed by the addition of serum from ITBB-BM convalescents or rabbit antibodies to Д. miyamotoi. The immobilizing effect of the immune serum is substantially inhibited by its heat-inactivation, which indicates that immobilizing effect is mediated by the complement system. Conclusion. Antibody-dependent complement-mediated bactericidal action ofhuman blood serum is probably not the only and 100% effective mechanism for human defense against B. miyamotoi infection, but requires support from cellular immunity.

scholarly journals Evaluation of Immunoglobulin A1 (IgA1) Protease and IgA1 Protease-Inhibitory Activity in Human Female Genital Infection with Neisseria gonorrhoeae

1998 ◽  
Vol 66 (12) ◽  
pp. 5826-5832 ◽  
Author(s):  
Spencer R. Hedges ◽  
Matthew S. Mayo ◽  
Lisa Kallman ◽  
Jiri Mestecky ◽  
Edward W. Hook ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Inhibitory Activity ◽  
Genital Tract ◽  
Protease Activity ◽  
Cervical Mucus ◽  
Serum Samples ◽  
Iga1 Protease ◽  
Significant Difference ◽  
Protease Inhibitory Activity

ABSTRACT Immunoglobulin A1 (IgA1) protease, an enzyme that selectively cleaves human IgA1, may be a virulence factor for pathogenic organisms such as Neisseria gonorrhoeae. Host protection from the effects of IgA1 protease includes antibody-mediated inhibition of IgA1 protease activity, and it is believed that the relative balance between IgA1 protease and inhibitory antibodies contributes to the pathogenesis of disease caused by IgA1 protease-producing organisms. We have examined the levels of these two opposing factors in genital tract secretions and sera from women with uncomplicated infection withN. gonorrhoeae. When IgA1 in cervical mucus was examined by Western blotting, no evidence of cleavage fragments characteristic of IgA1 protease activity was seen in gonococcus-infected or control patients. Cleavage fragments typical of IgA1 protease were detected, however, after the addition of exogenous IgA1 protease to cervical mucus. Degraded IgA1 was detected in some vaginal wash samples, but the fragment pattern was not typical of IgA1 protease activity. AllN. gonorrhoeae isolates from the infected patients produced IgA1 protease in vitro. All but two serum samples and 16 of 65 cervical mucus samples displayed inhibitory activity against gonococcal IgA1 protease, but there was no significant difference in the level of inhibitory activity between gonococcus-infected and noninfected patients in either cervical mucus or serum. There was no difference in the levels of IgA1 protease-inhibitory activity in serum or cervical mucus collected from patients at recruitment and 2 weeks later. These results suggest that cleavage of IgA1 by gonococcal IgA1 protease within the lumen of the female lower genital tract is unlikely to be a significant factor in the pathogenesis of infections by N. gonorrhoeae.

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