Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
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The maternal deaths occurring in the Kilimanjaro Christian Medical Center (KCMC), which serves as a supraregional reference hospital for the 5 regions of Northern and Central Tanzania, are reviewed for the 1971-1977 period and avoidable factors are discussed. All deaths occurring within the hospital during pregnancy or the first 6 weeks of the puerperium were included in this survey. Postmortem examination was performed in 35% of the cases. In the remaining cases the diagnosis was made on clinical grounds. During the period under review, there were 10 deaths among 83 cases, a mortality of 12%. The major cause of rupture was obstructed labor associated with a contracted pelvis or abnormal lie. 25% of the patients had had a previous cesarean section scar give way. 2 other deaths were attributed to anesthetic accidents and 1 was probably due to pulmonary embolism. The primary cause of death in the 7 remaining cases was hemorrhage (4) and sepsis (3). If deaths from ruptured uterus are to be avoided, early diagnosis is essential. 1044 cases of moderate and severe EPH gestosis (preeclampsia) were treated in KCMC during the period under review together with 54 cases of eclampsia. There were 5 deaths among the patients with eclampsia, a mortality of 9%. In addition to the 11 sepsis deaths there were 3 others included among the cases of ruptured uterus. There were 4 cases of septic abortion and 3 of those admitted to criminal interference. Preexisting anemia was a complicating factor in 5 cases, all of whom died within 15 minutes of arrival. There were 4 deaths among 251 cases of ruptured ectopic pregnancy. There were 10 deaths associated with cesarean section among 1271 sections peformed during the period under review. Deaths from associated diseases included the following: enterocolitis (12 deaths); renal and hypertensive disease (4 deaths); cardiac disease (2 deaths); anemia (2 deaths); malaria (2 deaths); tuberculous meningitis (2 deaths); and miscellaneous associated conditions (11 deaths).
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PMID:Maternal deaths in the Kilimanjaro region of Tanzania. 47 24

The digital estimation of utero-placental circulation by means of nuclear-medical examinations with help of 113 m In-Cl and regarding to the "region of interest" gives no depositions in cases with an intrauterine retardation. This concerns the activity as well in the placenta as in the uterus too. Exceptions represents intrauterine retardations on the base of heaviness EPH-gestosis and placenta previa. Herewith the rise of activity corresponds with the thickness in the III. trimester of pregnancy. A treatment about several weeks with Hepain under bed conditions leads to no proofed influence of the uteroplacental circulation, on the contrary to a rise of estriol and HPL-values, meaning a improvement of placental performance. The estimation of the utero-placental circulation by means of nuclear-medical examinations is situated to the problem of fetal condition by EPH-gestosis, placenta previa and other.
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PMID:[Performance of uteroplacental perfusion in contrast to hormone-analytic investigations in intrauterine retardation and under the influence of intravenous long-term application of heparin (author's transl)]. 60 45

1 The in vivo actions of the oestrogen antagonists, MER-25 and tamoxifen upon the cytosol oestrogen receptors prepared from amygdala, hypothalamus, pituitary and uterus of rats were studied 24 h after drug administration. 2 There was a dose-related depletion of cytosol oestrogen receptors. However, the uterine and pituitary receptors were consistently affected at a lower dose than were those from the brain. 3 The ratios of the combined central ED50 to the combined peripheral ED50 were clomiphene 169 greater than MER-25 19.2 greater than tamoxifen 2.13. 4 The receptor changes were not related to biological activity monitored by serum luteinizing hormone levels and uterotrophic response. 5 The possible role of these drug effects in the induction of ovulation and future developments are discussed.
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PMID:Differential depletion of cytoplasmic high affinity oestrogen receptors after the in vivo administration of the antioestrogens, clomiphene, MER-25 and tamoxifen. 65 95

The estrogenic effects of MER-25, an antiestrogen, on eating and body weight were studied in rats. As evidenced by its failure to cause an habitual aversion to saccharin and failure to alter spontaneous activity, MER-25 inhibited weight gain and eating. Estradiol benzoate (EB) and MER-25 both had similar effects in gonadectomized rats, and produced a transient decrease in food consumption and a permanent decrease in body weight. Progesterone ameliorated the effect of both agents on eating and body weight. MER-25 and EB were both more active in females than males. MER-25 did not markedly alter the effects of EB on body weight and eating, but did antagonize the effects of EB on the uterus, vagina, and sex behavior. The results indicate biochemical differences between the effects of estrogens on eating and body weight and other estrogen-dependent processes.
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PMID:Estrogenic effects of an antiestrogen, MER-25, on eating and body weight in rats. 94 84

In experiments with animals it was investigated the endurance of the myometrial and the blood flow of the renal cortex during endogenous pressure substances. At the same time it was tested, if treatment with sexual hormones or a pregnancy had the tested principles and changes through pressure substances, and that the changes were significant. The investigations were conducted on three groups of female rabbits. The blood changes in myometrial and in the uterine were measured and continually registered with the special heated thermistor, from the principle of the thermoclearance. The success of the blood pressure was intraarterial measured with an electric mechanism. Precisely the same doses (in relativity of the animals weight) of pressure substances were applied with an infusions pump intravenously. And pressure substances Angiotensin II, Norepinephrine and Epinephrine, and their actions on the blood pressure and blood flow through the myometrium and through the renal cortex were examined. Altogether 131 values were registered. The results of the study that were statistically secure were as follows: a) The uterine blood flow pro tissue volume unit stays constant also by pregnancy or pseudopregnancy. b) The blood flow of the kidney is perhaps twice as high as the myometrial. c) The myometrial blood flow is with the arterial systolic blood pressure tightly correlated. Blood pressure increases through Angiotensin-infusion and also recovery of the uterine blood flow. d) An autoregulation of the uterine blood flow is not observed. e) The decrease of the renal blood flow after the giving of pressure substances was not modified through pregnancy. f) In quality the behaviour of the organ blood flow is the same after applied infusion of the pressure substances. Quantity differences exist however between Angiotensin II, Norepinephrine and Epinephrine. The method of measuring the blood flow through the uterus and in the kidney was placed in one view there. The finding of another examination groups for the problem of the organ blood flow in pregnancy was under critical consideration the methods combined and in connection with the proper examinations discussed. Till now in the theory over the cause of EPH-syndrom the predominate recently compiled comprehensive summary was; the proper body pressure substances--especially from the renin Angiotensin system--after chronical invoices it was decides diminished uterus blood flow appeared. After the earlier results were not all secure. The proper examination speech was therefore, that regarding the kidney function relevant alterations, also unter the conditions of pregnancy, are to be observed. The pressure dependant regulation of myometrial blood flow without proving autoregulation required however another test of the predominante gestose theory.
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PMID:[The experimental examination of the effect on the uterine blood flow of angiotensin II during pregnancy (author's transl)]. 99 65

The distribution of alpha- and beta-type receptors for PDGF was studied immunohistochemically in the uterus of cycling and pregnant pigs with well-documented hormonal status in order to determine a possible steroid hormone-dependence of its expression. Peroxidase-antiperoxidase (PAP) labelling at light microscopical level was done with rabbit polyclonal antisera recognizing either both alpha- and beta-type receptors (PDGFR-1), or selectively beta-type (PDGFR-3). Immunoreactivity to the PDGF-receptors of alpha- and beta-type (PDGFR-1) was present in all endometrial samples examined, being located principally on subepithelial stromal and endothelial cells, the wall of endometrial blood vessels and in the fetal placenta (trophoblast and adjoining blood capillaries). In the myometrium, the major reactive cells were the non-vascular smooth muscle cells, and to some extent, also those of the tunica media of major uterine vessels. No dramatic variations in the intensity of the reaction were noticed during the oestrous cycle. A very intense immunoreactivity was present at early pregnancy and at term, i.e. under major oestrogenic influence. The immunoreactivity to the PDGF-receptor antiserum R-3 (against beta-type) was similarly localized as that showed for R-1 antiserum, while of a weaker intensity. The results indicate the presence of PDGF receptors (alpha- and beta-type) in the endo- and myometrium of cycling and pregnant pigs, and that their expression seems to be accentuated under oestrogenic influence.
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PMID:Immunohistochemical localization of platelet-derived growth factor receptors in the porcine uterus during the oestrous cycle and pregnancy. 131 97

The pregnant rat uterus contains a membrane-bound metalloendopeptidase that is biochemically and immunologically similar to kidney enkephalinase (E.C.3.4.24.11). The uterus enzyme readily cleaved specific neutral endopeptidase substrates and oxytocin as well as the synthetic elastase substrate, Suc(Ala)3-pNA, yet did not digest native elastin. Using specific inhibitors, the uterus endopeptidase was identified as a metallopeptidase and not a serine protease, having an absolute requirement for zinc and perhaps calcium for maximal activity. The uterus endopeptidase cross-reacted with polyclonal antiserum to kidney microvillar endopeptidase and a monoclonal antibody to common acute lymphocytic leukemia antigen. Immunohistochemical localization of the enzyme in a 17 day pregnant uterus indicated that the enzyme was localized on the smooth muscle bundles of the myometrium and the endometrial epithelium. Total enzyme activity was 25 times higher in the late-term pregnant uterus (17th day of pregnancy) than in the nonpregnant uterus. Enzyme levels dropped rapidly prior to parturition and within 4 days after delivery the enzyme activity had returned to control levels. Inhibition of NEP in uterine strips with phosphoramidon resulted in a marked potentiation of oxytocin-induced contractions. Our results suggest that the uterine endopeptidase may have an important role in regulating uterine smooth muscle cell contraction during the later stages of pregnancy through its action on oxytocin and perhaps other biologically active peptides.
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PMID:Neutral metalloendopeptidase associated with the smooth muscle cells of pregnant rat uterus. 204 32

Two monoclonal antibodies against the receptor for platelet-derived growth factor (PDGF) were obtained by immunizing mice with pure PDGF receptor preparations derived from porcine uterus. The antibodies, denoted PDGFR-B1 and PDGFR-B2, both bound to the external domain of the receptor, as demonstrated by indirect immunofluorescence and binding of 125I-labeled antibodies to intact human fibroblasts. Both antibodies precipitated pure 175-kDa 32P-labeled autophosphorylated porcine PDGF receptor as well as a Mr 175,000 glycoprotein from metabolically labeled cells. The monoclonal antibodies did not inhibit binding of 125I-PDGF to human fibroblasts and did not stimulate these cells to undergo mitosis. Both antibodies induced clustering and down-regulation of their antigen. However, this resulted in only a partial loss of cell surface binding sites for PDGF itself, consistent with the conclusion that the monoclonals recognized only one of two or several receptors for PDGF. Clustering and down-regulation were not seen when the cells were incubated with monovalent Fab' fragments of the PDGFR-B2 antibody. The antibodies also stimulated autophosphorylation of pure PDGF receptor, and PDGFR-B2 was shown to stimulate phosphorylation of phosphofructokinase, an exogenous substrate for the PDGF receptor kinase. High concentrations of PDGFR-B2 antibody, or Fab' fragments thereof, failed to enhance the PDGF receptor kinase activity, compatible with the possibility that dimerization was of importance in the antibody-stimulated kinase activity of purified PDGF receptors.
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PMID:Characterization of two monoclonal antibodies reactive with the external domain of the platelet-derived growth factor receptor. 245 16

Beraprost sodium (sodium (+/-)-(1R*,2R*,3as*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its general pharmacological effects on peripheral organs were studied. 1. In isolated organs, beraprost sodium relaxed the trachea and increased atrial beating rate (2.4 x 10(-5) mol/l). It also dose-dependently contracted the stomach, aorta, ileum and uterus (2.4 x 10(-7)-2.4 x 10(-4) mol/l). These effects of beraprost sodium were similar, but inferior to those of PGI2 and PGE1. 2. Intravenous administration of beraprost sodium produced a dose-related decrease in blood pressure (BP), its potency being about 1/3 times that of PGI2 in anesthetized rats and dogs. Beraprost sodium and PGI2 had no effects on heart rate (HR), and enhanced respiration in conjugation with a decrease in BP. Oral administration of beraprost sodium in high doses (1-3 mg/kg in rats and 0.3 mg/kg in dogs) caused a decrease in BP. A compensatory tachycardia and an elevated plasma renin activity (PRA) occurred after low doses (0.1-0.3 mg/kg) in rats. In contrast, a change of HR and PRA in rabbits and dogs was mild. 3. Beraprost sodium produced suppression of digestive organs: markedly, gastric motility and secretion and intestinal transport; slightly, but significantly, biliary secretion. On the other hand, it enhanced ileal motility at a high dose (300 micrograms/kg i.v.). 4. Oral administration of beraprost sodium caused a decrease in urinary volume and electrolyte excretion in rats. 5. Oral administration of beraprost sodium prolonged bleeding time in mice, while it had no effect on the blood coagulation system in vitro. In addition, beraprost sodium had no hemolytic action. 6. The other effects of beraprost sodium were weak. Beraprost sodium had no local anesthetic activity and no effect on salivation, pupil size and neuromuscular transmission in the skeletal muscle. Beraprost sodium slightly contracted the uterus of non-pregnant rats in situ and dose-independently inhibited carrageenin-induced paw edema. In conclusion, beraprost sodium produced various effects on the autonomic, cardiovascular, and gastrointestinal systems. Probably, these effects may be based on its own action like PGI2.
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PMID:General pharmacology of beraprost sodium. 2nd communication: effect on the autonomic, cardiovascular and gastrointestinal systems, and other effects. 251 Jul 43

It was the aim of this study to conduct simultaneous qualitative analysis of blood flow spectra of uteroplacental and foetal vessels in normal pregnancy, in growth retardation and in EPH gestosis using the pulsed Doppler method. In 237 women who had delivered we performed 291 measurements in uteroplacental vessels, 318 in the umbilical artery, 339 in the foetal aorta and 130 in the foetal common carotid artery. The blood flow spectra were evaluated with the help of the resistance and pulsation index ratio (RI/PI) as a measure of the resistance of the subsequent vascular system. We observed in uteroplacental vessels in EPH gestosis and retardation a significant elevation of the index values in the wall of the uterus outside or inside the placental margin. In foetal vessels we noted a highly significant increase of RI and PI in the umbilical artery and the foetal aorta--simultaneously, however, a drop in the index values in the foetal common carotid artery. These changes point on the one hand to the increased resistance in the capillary net of the placenta and a possible vascular constriction in the region of the lower abdominal organs and extremities, whereas on the other hand they point towards a compensatory lowering of the vascular resistance in the cerebral circulation--possibly as an expression of the risk of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pathophysiologic and clinical aspects of measuring blood flow in utero-placental vessels, the umbilical artery, the fetal aorta and the fetal common carotid artery]. 296 May 86


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