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Biomedical subjects

M Tóth

Publications and source records attributed to M Tóth.

At least 145 records · Page 8Linked to original sources

Effect of estradiol and progesterone on the rate of incorporation of radiolabeled arachidonate into phospholipids and triglycerides of the rat uterus.

To obtain information on the effect of estradiol (E) and progesterone (P) on the overall rate of the acylation and deacylation reactions with [3H]arachidonate ([3H]AA) in the rat uterus, we investigated the effect of chronic treatment of ovariectomized rats with 2-200 micrograms/day E-dipropionate (EPP) and with 2 mg P alone or with the combination of these steroids on the extent and the time course of the in vitro incorporation of [3H]AA into various phospholipids (PLs) and the triacylglycerol fraction (TG). The results demonstrate that physiologic doses of E leads to a rapid equilibrium of the deacylation-acylation cycle only in the case of phosphatidylinositol (PI) whereas at high (200 micrograms/day) dose level it exerts the same effect on phosphatidylcholine (PC), phosphatidylethanolamine (PE) as well as on TG. P alone has no remarkable effects in the ovariectomized rat, but it decreases markedly the incorporation of [3H]AA into PI and TG in intact animals. Furthermore, P decreases the incorporation of [3H]AA into PI in the ovariectomized rat treated with 2 micrograms/day EPP as well as attenuating the enhanced labeling of PC, PE and PI caused by higher doses. Time-course studies provide evidence that all of these effects of progesterone can be accounted for by its ability to decrease the rate of deacylation and, therefore, to prolong the time needed to attain equilibrium in the rates of acylation and deacylation reactions of the various lipids with arachidonate. These data offer a novel outlook on the regulatory role of progesterone and estrogens in uterine function.

Acylation↗

Role of atrial natriuretic peptide in sodium homeostasis in premature infants.

To examine the possible involvement of atrial natriuretic peptide (ANP) in sodium homeostasis in premature infants, two groups of low birth weight infants with different dietary sodium regimens were studied. Sodium balance and plasma concentration of ANP were measured at weekly intervals for 5 weeks. At 1 week of age the study was started by dividing infants into two groups, group 1 with low and group 2 with increased sodium intake. Mean plasma concentrations of ANP were 47.7 +/- 7.6 and 51.4 +/- 9.5 fmol/ml, respectively. A steady decrease in plasma ANP concentration to 18.8 +/- 2.9 fmol/ml was observed in infants with sodium intake 1.5 mmol/kg/d (group 1), which was related to the decrease in serum sodium concentration in this group. In contrast, supplementation with NaCl 4.6 mmol/kg/d (group 2) was associated with a 30% increase in plasma ANP concentration, significantly different (P less than 0.025) from that in infants not given supplement, and was also higher than the values in full-term neonates. Our data suggest that altered sodium homeostasis induces regulatory changes in plasma ANP levels. ANP may provide a sensitive and important hormonal system for the control of sodium balance, even in premature neonates.

Atrial Natriuretic Factor↗

Classification of anabolic steroids using the method of competitive metabolism.

The effect of increasing concentrations of testosterone (T) and 19-nortestosterone (N) on the in vitro metabolism of [3H]N in minced tissue of the rat seminal vesicle indicates that T and N are equally appropriate substrates for the 5 alpha-reductase. Experiments in which increasing concentrations of 17-methyl-T (MT) or 1-ene-MT were incubated with [3H]T and vesicular mince have revealed that the formation of [3H]5 alpha-dihydro-T is suppressed markedly by MT while 1-ene-MT has no measurable effect. Since 5 alpha-dihydro-MT binds to the androgen receptor with a higher affinity than MT does and (relative to T) MT does not exhibit myotropic-androgenic (= M-A) dissociation, it can be concluded that MT is, whereas 1-ene-MT is not a substrate for the 5 alpha-reductase. Our present and previous data suggest that N exemplifies one class of anabolic steroids that become less androgenic due to 5 alpha-reduction, it shows high myotropic activity, M-A dissociation (= 7-30) and affinity to the androgen receptor. On the other hand, 1-ene-MT belongs to another class of anabolic steroids that are not substrates for the 5 alpha-reductase, exhibit a relatively small myotropic activity, M-A dissociation (= 2-3) and receptor affinity.

Anabolic Agents↗

Assignment of anabolic-androgenic and antiandrogenic properties to some chlorine-substituted steroids on the basis of their binding characteristics to the androgen receptor of the rat seminal vesicle.

In this study we investigated the affinity of several 4-chlorinated and 1-ene derivatives of 17 alpha-methyltestosterone (MT) and 17 alpha-methyl-5 alpha-dihydrotestosterone (MDHT) to the androgen receptor, and, additionally, the effect of a few MT-derived steroids on the activity of the 5 alpha-reductase enzyme present in the rat seminal vesicle. From our results we conclude, that delta 1 or/and delta 4 double bonds in ring A counteract the inhibition of receptor-binding caused by chlorine-substitution at C4; the dissociation of myotropic and androgenic effects [= M/A dissociation] of 4-chloro-MT (as compared to MT) is due to its inactivation by 5 alpha-reductase in androgen target organs and/or to the inhibition of the conversion of endogenous testosterone to DHT; the M/A dissociation of 1-ene-MT and 4-chloro-1-ene-MT may be explained by their inability to be activated by 5 alpha-reductase; for the same reason, M/A dissociation can be assigned to the effects of 4 alpha-chloro-1-ene-DHT. We determined the short-term and long-term competition of cyproterone acetate and chlormadinone acetate with [3H]DHT for receptor binding at 0 degrees C and showed, that the complexes formed by these antiandrogens with the androgen receptor have equally reduced stabilities compared to the DHT-receptor complex.

Anabolic Agents↗

Plant small nuclear RNAs. Nucleolar U3 snRNA is present in plants: partial characterization.

Nuclei, isolated from a number of plant species by either of two independent, newly developed methods, regularly contained a common set of low-molecular-mass RNAs. Partial characterization of these RNAs, based on cell fractionation, polyacrylamide gel electrophoretic and chemical sequencing techniques, as well as comparison with literature data, revealed that, in addition to tRNA, 5S RNA and 5.8S RNA, plant nuclei contain two families of low-molecular-mass RNAs, that are counterparts of vertebrate U1 and U5 RNAs respectively, and three individual low-molecular-mass RNA species. One of these may be related to vertebrate U6 RNA. The two others are true eukaryotic U2 and U3 RNAs, respectively, on the basis of the following lines of evidence obtained from analyses of broad bean nuclear RNAs. The 3'-end portion (121 nucleotides sequenced) of broad bean U2 RNA shows a nearly perfect sequence homology with that of authentic pea U2 RNA. Broad bean U3 RNA is localized in the nucleolus and its 3'-end portion (164 nucleotides sequenced) (a) shows sequence homology with that of both rat U3 RNA (48%) and Dictyostelium D2 RNA (39%), (b) has a secondary structure which fits perfectly that proposed for both rat U3 RNA and Dictyostelium D2 RNA, and (c) contains the specific sequence which, in a model based on the primary structure of rat U3 RNA, is supposed to be involved in the processing of eukaryotic 32S pre-ribosomal RNA. This is the first report on the occurrence in plants of nucleolar U3 RNA.

Animals↗

Human interferons alpha and beta have more potent priming activities than interferon gamma.

The priming activities of human IFN-alpha, IFN-beta and IFN-gamma were compared on the same antiviral basis using human buffy coat leukocytes stimulated with Sendai virus or concanavalin A (Con A) to produce IFN-alpha or IFN-gamma, respectively. Pretreatment of leukocytes with any type of IFN enhanced their IFN-alpha and IFN-gamma production, but IFN-alpha and IFN-beta had more potent priming activities than IFN-gamma. IFN-alpha and IFN-gamma did not potentiate the priming activity of each other in either the IFN-alpha or the IFN-gamma producing system. Pretreatment of leukocytes with relatively high doses of IFN-alpha or IFN-beta (1000 to 3000 IU/ml) resulted in a 40- to 50-fold increase in the IFN-gamma production of Con A-stimulated leukocytes. This observation will be of use in producing IFN-gamma with a high titre.

Humans↗

Prenatal diagnosis of cystic fibrosis by trehalase enzyme assay in amniotic fluid.

Amniocentesis and amniotic fluid trehalase enzyme assay were offered to 14 pregnant women at a 1 in 4 risk for a child with cystic fibrosis. Twelve of these pregnancies were screened at the 18th week of gestation; ten proceeded to term, seven following the finding of a normal trehalase activity and three despite the low enzyme level in amniotic fluid. In all ten cases prenatal diagnosis proved to be correct. In two cases with low enzyme activity parents opted for termination at the 19th week, and with PAS-Alcian Blue staining some slight histochemical lesions characteristic of cystic fibrosis were seen in the exocrine glands, including the pancreas and intestinal mucosa, of both fetuses. The total protein content in the meconium of these fetuses was significantly higher than in the controls. Results suggest that trehalase assay in the amniotic fluid is a potential prenatal test for cystic fibrosis and it appears that in fetuses with cystic fibrosis some histochemical and biochemical abnormalities can be observed as early as the 19th week of gestation. The role of ultrasound examination as an additional procedure for the prenatal diagnosis of cystic fibrosis is also discussed.

Amniotic Fluid↗

PGE2 binding, synthesis, and distribution in hen oviduct.

Prostaglandin E2 (PGE2) bound specifically to particulate fractions prepared from the vagina and uterus (shell gland) portions of the hen oviduct in a time and temperature dependent fashion. Scatchard analysis indicated a single class of high-affinity binding sites in the vagina (Kd congruent to 1 nM), whereas the myometrium exhibited two kinds of binding site populations (Kd1 congruent to 1 nM, Kd2 congruent to 20 nM). It is suggested that these binding sites represent specific PGE2 receptors mediating the effects of PGE2 in oviductal smooth muscle. Vaginal particulate fractions produced approximately four times more prostanoids from [3H]-arachidonate than did uterine preparations. In the presence of epinephrine both tissues synthesized mainly thromboxane (TxB2), PGE2, and significantly less prostaglandin F2 alpha (PGF2 alpha). Addition of glutathione (GSH) or cytosol prepared from the oviduct markedly increased the yield of PGE2 at the expense of TxB2. Of the five morphologically discrete regions of the oviduct the vagina, infundibulum, and uterus contained the highest amounts of PGE and PGF, whereas the magnum and isthmus portions contain the least. TxB2 and 6-keto PGF1 alpha could not be detected in significant quantities in either region. These studies support the notion that PGE2 play a key role in the physiology of oviposition.

Animals↗

Production of high titre human interferon-gamma in primed leukocyte cultures.

Con A-stimulated leukocytes previously treated with IFN-alpha (1500 IU/ml for 4 h) were very suitable for the production of IFN-gamma with a high titre even under large-scale conditions. The properties of the IFN produced under such conditions were identical to those of IFN-gamma. The IFN-gamma produced in primed cultures showed two peaks of antiviral activity corresponding to molecular weights of 51 000 and 23 000 daltons.

Carcinoma, Squamous Cell↗

Role of the NK reaction in the diagnostics of liver and pancreas tumours.

The NK (natural killer) and K (killer) activities of peripheral lymphocytes were determined. The peripheral blood was obtained from healthy individuals and from patients with liver and pancreas diseases. Examinations were performed preoperatively. The natural cell-dependent cytotoxicity (NK) was examined against the K-562 cell line, while the antibody-dependent cellular cytotoxicity (ADCC) was examined against human red blood cells. The NK and K cell activities of the 19 patients with malignant tumours were substantially lower than those of the 40 healthy subjects. In the 12 cases of benign diseases of the liver and pancreas, however, the mean percentage cytotoxicity expressing the NK and K activities (40 +/- 10%) agreed with, or was higher than, the value for the controls (32 +/- 12%). Low cytotoxicity levels (12.6 +/- 5%) were characteristic in the malignant processes; in the majority of these, exploration showed local metastases or metastases besides the primary lesion. Since the NK and K cells play an essential role in the defence of the organism against tumours, the decrease in activity of this cell population may be of diagnostic value. In vitro interferon treatment in the control and benign cases considerably stimulated the NK reaction, and in some of the malignant diseases it raised the cytotoxicity values close to the control level.

Adult↗

The left part of the viral genome is sufficient for interferon induction by adenovirus type 12.

Adenovirus type 12 is a potent interferon inducer on chick embryo cells. Incomplete particles induce similar levels of interferon as complete virions, even if they contain only the left 20 per cent of the genome. Empty capsids lacking DNA are not able to induce interferon, suggesting that part of the viral genome is required to trigger the cells to produce interferon.

Adenoviridae↗

Semi-crude human leukocyte interferon production in a simple medium.

Semi-crude human leukocyte interferon (specific activity at least 10(5) international units per mg protein) was produced by replacement of priming medium with protein poor medium before the production period. A simpler medium than Eagle's medium was suitable to obtain substantial quantities of interferon.

Blood↗

Turnover of lipid-bound arachidonate and biosynthesis of prostanoids in the endometrium and myometrium of the laying hen.

In vitro incorporation of [3H]arachidonate into various lipid fractions of minced avian endometrium and myometrium has shown that (i) phospholipids and triacylglycerols are labeled preferentially, whereas labeling of cholesteryl esters is only marginal; (ii) acylation reactions with arachidonoyl residues are very rapid in these tissues; (iii) incorporation of arachidonate into phosphatidylcholine and phosphatidylethanolamine seems to be a one-step reaction, whereas the transfer of arachidonate to phosphatidylinositol and phosphatidylserine proceeds after a time lag, suggesting that intermediate reaction steps are involved; and (iv) under conditions where tissue differences in free arachidonate levels are diminished by adding radioinert arachidonate to the incubation medium, endometrium incorporates more than twice as much [3H]arachidonate/unit of phospholipids than does the myometrium, whereas there is no such tissue-specific difference in the labeling of triacylglycerols. Furthermore, after a 90-min incubation phosphatidylserine and phosphatidylinositol not only are labeled markedly higher than either phosphatidylcholine or phosphatidylethanolamine in both tissues but the tissue-specific difference is also the highest (2.4- to 2.8-fold in the case of these phospholipids). Prostanoid synthesis from [3H]arachidonate in a crude membrane preparation in vitro has demonstrated that the myometrium possesses a significantly higher prostanoid-synthesizing capacity than the endometrium. This difference is particularly apparent (about 2.5-fold) in the case of prostaglandin E2. The results suggest that the endometrium is endowed with a special capacity to respond to signals with a rapid alteration of the level of free arachidonic acid, whereas the myometrium has the specific capacity to amplify its own contractions by an increased production of prostaglandins.

Animals↗