Preliminary characterization of a placental factor inhibiting breathing in fetal sheep

1997 ◽  
Vol 9 (6) ◽  
pp. 641 ◽  
Author(s):  
Ruben E. Alvaro ◽  
May Robertson ◽  
Saad Al-Saedi ◽  
Robert P. Lemke ◽  
Don B. Cates ◽  
...  

Previous studies have revealed a placental extract that inhibits breathing in fetal sheep. In the present study of 29 chronically instrumented sheep at 132±1 days of gestation, infusion of the 1-10 kDa extract inhibited breathing in 76% of the experiments whereas Krebs’ solution inhibited it in 24%. It retained this activity after 6 months of freezing, after lyophilization, and upon lowering the pH during purication from 8·0 to 4·0, but it inhibited breathing in only 35% when the pH was lowered to 2·0. A signicant dose-dependent effect was observed from a 16-fold dilution to a 4-fold concentration. Treatment of the extract with proteinase K or boiling reduced the activity to 30% or 26% inhibition, respectively. The activity was not adsorbed to an ion-exchange column at pH 7·0 or 8· 0, but it was at pH 9· 0 and it eluted with increasing NaCl concentrations. On a polyacrylamide gel the activity was eluted at a Kav of 0· 66 (82% inhibition), corresponding to between 2·5 and 4·5 kDa. These ndings suggest that a peptide produced by the placenta, with a molecular mass between 2· 5 and 4·5 kDa, inhibits fetal breathing.

1996 ◽  
Vol 8 (3) ◽  
pp. 423 ◽  
Author(s):  
RE Alvaro ◽  
V Rehan ◽  
Almeida V de ◽  
Z Haider ◽  
M Robertson ◽  
...  

We have found previously that the infusion of a placental extract inhibits breathing induced by 100% O2 plus umbilical cord occlusion in the fetal sheep, suggesting that a placental factor is responsible for the inhibition of fetal breathing. To test whether this factor is specific to the placenta and whether it also inhibits spontaneous fetal breathing (occurring in the absence of cord occlusion), we administered extracts from the placenta, muscle and liver of the pregnant ewe, extracts of fetal liver, and Krebs solution to 16 chronically instrumented fetal sheep at 135 +/- 5 days of gestation. Infusions were made during low-voltage electrocortical activity, 5 to 15 min after a switch from high voltage, when breathing was well established. Within 90 s of the infusion of the placental extract in the carotid artery of the fetus, breathing decreased in 79% (33/42) of the experiments and was completely abolished in 71% (30/42) of them (P < 0.0001 compared with the other infusates). No apnoeas were observed with the Krebs solution (0/19) and the maternal muscle (0/20). Extracts of maternal and fetal liver abolished breathing in only 17% (4/23) and 21% (6/29) of the experiments respectively (NS compared with Krebs solution). There were no significant changes in blood gas tensions, pH, blood pressure and heart rate associated with the infusion of the extracts. The electrocortical activity (ECoG) switched from low to high voltage in 50% of the experiments using placental extract compared with 0% with Krebs solution and maternal muscle, and with 9% and 17% with maternal and fetal liver respectively (P < 0.005). Breathing output (integral of EMGdi x f) during and after the infusions significantly decreased only with the placental extract. These findings indicate the presence of a factor produced by the placenta which inhibits fetal breathing and may be responsible for the normal inhibition of breathing observed in fetal life.


Author(s):  
Shiva Naseri ◽  
Gabriele Griffanti ◽  
William C. Lepry ◽  
Vimal B. Maisuria ◽  
Nathalie Tufenkji ◽  
...  

2011 ◽  
Vol 91 (2) ◽  
pp. 520-525 ◽  
Author(s):  
Salima Mithani ◽  
Michael Kuskowski ◽  
Yelena Slinin ◽  
Areef Ishani ◽  
Edward McFalls ◽  
...  

Author(s):  
Alina Alshevskaya ◽  
Olga Koneva ◽  
Irina Belomestnova ◽  
Julia Lopatnikova ◽  
Irina Evsegneeva ◽  
...  

<b><i>Introduction:</i></b> Modulating specific biological effects through the changes in cytokine receptors’ expression level remains poorly understood. This study aimed to investigate the influence of the dose-dependent effect of TNF on the balance between proapoptotic and proliferation response depending on the parameters of TNFR1/2 expression density. <b><i>Methods:</i></b> Tumor cell lines (HEp-2, K-562, MCF-7, ZR-75/1, MOLT-4, IM-9, and Raji) were characterized for TNFR1/2 co-expression using flow cytometry and were studied to reveal the dose-dependent effect of rhTNF on cell cycle and apoptosis parameters. The associations among the studied parameters were estimated by correlation and regression analysis. <b><i>Results:</i></b> It was found for ZR-75/1 cells (the cell line characterized by high expression of both types) that a dose-dependent increase in expression of both types of TNF-α receptors on cells reduces the proliferative activity of cells. For MOLT-4 cells (which are characterized by lower expression), an increase in proliferative response of cells was positively associated with the percentage of both TNFR1<sup>+</sup> and TNFR2<sup>+</sup> cells. However, opposite effects on the cells were shown for the K-562 and MCF-7 lines having a similar expression profile. A similarity (a large percentage of double-positive cells) was revealed for the lines having similar effects (K-562 and ZR-75/1). <b><i>Conclusions:</i></b> High expression of TNF receptor type 1 is not always associated with predominant activation of proapoptotic pathways. However, in the case of simultaneous high expression of both types of receptors, the proportion of double-positive cells is crucial for the activation of either the proapoptotic or proliferation pathways.


2006 ◽  
Vol 24 (11) ◽  
pp. 2072-2079 ◽  
Author(s):  
Chun Wai Chan ◽  
Ling Qin ◽  
Kwong Man Lee ◽  
Wing Hoi Cheung ◽  
Jack Chun Yiu Cheng ◽  
...  

1997 ◽  
Vol 49 (1) ◽  
pp. 17-21 ◽  
Author(s):  
A. Bertoli ◽  
R. Magnaterra ◽  
P. Borboni ◽  
M.A. Marini ◽  
A. Barini ◽  
...  

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