Anticardiolipin antibodies in Grave's disease: relationship with thrombin activity in vivo.
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Biomedical subjects
Publications and source records attributed to M Conti.
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We performed a retrospective study of 57 HIV-positive pregnant women and their children to look for maternal parameters related to rates of vertical transmission of HIV. Sixteen (28%) infants were HIV-infected. There was no positive correlation between maternal risk factors for HIV and vertical transmission of HIV. Multiparity seemed to be related to a higher prevalence of vertical transmission, whereas neither preterm delivery nor cesarean section resulted in different rates of vertical transmission, although they tended to have some protective effect. Maternal beta 2-microglobulin and serum neopterin levels were not related to different rates of vertical transmission of HIV. CD4+ cell counts did so only when cut-off values of 400/mm3 were taken. All the women in CDC group IV and all the HIV p24 antigen-positive transmitted the infection to their infants, whereas only 7/48 women in CDC groups II and III (P = 0.000006) and 9/48 HIV p24 antigen negative women (P = 0.00006) gave birth to infected infants. No other maternal characteristics were associated with different rates of vertical transmission in a multivariate analysis restricted to women in CDC groups II and III and with HIV p24 antigen negativity.
Upon exposure to follicle-stimulating hormone (FSH), the gonadotropin-responsive Sertoli cell expresses increased rolipram-sensitive cAMP-specific phosphodiesterase (cAMP-PDE) activity. To understand the mechanisms leading to this activation, the cAMP-PDEs present in the Sertoli cell were characterized and their regulation studied. Comparison of the conceptual translates of two groups of PDE cDNA clones isolated from a Sertoli cell cDNA library (ratPDE3 and ratPDE4) showed that the encoded proteins were structurally similar, containing a core region of 455 amino acids with a sequence identity of 87%. The amino and carboxyl termini were divergent. Expression of these cDNAs in Escherichia coli and monkey COS-7 cells demonstrated that the encoded cAMP-PDEs had similar affinities for the cAMP substrate and were equally sensitive to a number of PDE inhibitors (rolipram greater than Ro 20-1724 greater than cilostamide). FSH stimulation of the Sertoli cell produced an increased rate of transcription of the ratPDE3 gene and elevated mRNA levels for ratPDE3 and to a lesser extent of ratPDE4. The increase in mRNA levels was detected after 1 h of stimulation. Forskolin, cholera toxin, and N6, O2'-dibutyryl cAMP produced a similar increase in rate of transcription and elevated mRNA levels, indicating that this activation is mediated by an increase in intracellular cAMP. RatPDE4 mRNA levels were maximal upon exposure to 10 ng of FSH/ml, whereas ratPDE3 mRNA levels could be further elevated, with higher FSH concentrations. The intensity of an immunoreactive band with characteristics identical to a purified cAMP-PDE, correlated with the increased cAMP hydrolytic activity after FSH or dibutyryl cAMP treatment, demonstrating that changes in cAMP-PDE protein levels are involved in this regulation. These data provide evidence that multiple cAMP-PDE forms are expressed in the rat Sertoli cell. Although differences in the pattern of activation of these forms were observed, these data show, that in the rat Sertoli cell, the cAMP-PDE activity is regulated by hormones via a novel mechanism that involves a cAMP-dependent activation of transcription of a PDE gene.
In order to assess the effect of increased cAMP degradation on the responsiveness on an endocrine cell, we have obtained stable transfectants of MA-10 Leydig tumor cells that overexpress a mammalian cAMP-phosphodiesterase. Two novel cell lines, designated MA-10(P+8) and MA-10(P+29), that express high levels of the transfected enzyme were characterized. Although the basal levels of cAMP in the mutant cell lines are comparable to those of the wild-type cells, the increase in cAMP accumulation elicited by human choriogonadotropin (hCG) is severely blunted. Further studies with MA-10(P+29) show that the ability of hCG to stimulate adenylyl cyclase activity is normal. The failure of MA-10(P+29) cells to accumulate cAMP in response to hCG can be correlated with a similar reduction in hCG-stimulated steroidogenesis. On the other hand, the maximal steroidogenic response of MA-10(P+29) cells to dibutyryl cAMP, a cAMP analogue that is fairly resistant to phosphodiesterase degradation, is normal. We also show that the ability of these cells to respond to hCG with increased cAMP accumulation and steroid synthesis can be restored with a specific phosphodiesterase inhibitor. These results demonstrate that overexpression of a cAMP-phosphodiesterase in MA-10 cells limits the levels of cAMP attained under hCG stimulation and supresses the steroidogenic response of these cells to hCG. Since gonadotropins increase the cAMP-phosphodiesterase activity in their target cells, these findings also provide evidence that this regulation plays a major role in the modulation of cell responsiveness. Last, these new cell lines should be valuable in the study of the actions of cAMP because they express a conditional and reversible cAMP-resistant phenotype.
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Pretreatment of rat FRTL-5 thyroid cells with thyrotropin (TSH) markedly potentiated the mitogenic response to insulin-like growth factor I (IGF-I) (Tramontano, D., Moses, A. C., Veneziani, B. M., and Ingbar, S. H. (1988) Endocrinology 122, 127-132; Takahashi, S.-I., Conti, M., and Van Wyk, J. J. (1990) Endocrinology 126, 736-745). The present study was undertaken to determine whether this synergism between TSH and IGF-I in FRTL-5 cells was correlated with changes in tyrosine phosphorylation of intracellular proteins. Tyrosine phosphorylation in intact cells was determined by gel electrophoresis and immunoblotting using monospecific anti-phosphotyrosine antibodies. Cells were preincubated for up to 24 h with TSH, dibutyryl cAMP, forskolin, or cholera toxin and then incubated for an additional 1 min in the absence or presence of IGF-I. As reported by others, IGF-I rapidly increased tyrosine phosphorylation of a 175-kDa protein as well as a less intense band of 90-100 kDa. Pretreatment for 6-12 h with either TSH or other agents that elevate intracellular cAMP potentiated the IGF-I-dependent tyrosine phosphorylation of the 175-kDa substrate by 3-5-fold. Since TSH did not increase IGF receptor number of kinase activity, the effect of TSH is assumed to be exerted at a step distal to IGF receptor tyrosine kinase. Surprisingly, IGF-I-independent tyrosine phosphorylation was also increased by pretreatment with TSH. When intact cells were analyzed TSH produced a time- and concentration-dependent increase in tyrosine phosphorylation of a prominent 120-125-kDa substrate and less prominent 100- and 80-kDa substrates. Assays using Triton X-100-soluble extracts incubated with MgCl2, ATP, and orthovanadate demonstrated that TSH pretreatment increased tyrosine phosphorylation over that observed in untreated cells. In this cell-free assay, TSH pretreatment enhanced the phosphorylation of multiple substrates. These studies suggest that a cAMP stimulus that initiates a trophic effect can be propagated indirectly through multiple pathways including enhancement of tyrosine phosphorylation.
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We studied blood coagulation and fibrinolysis activities in hyperthyroidism before and after methimazole or 131I. Fibrinopeptide A and B beta 15-42, in vivo indicators of thrombin and plasmin activity, were measured by RIA, while fibrinogen by the Clauss method. We studied 50 patients, affected by toxic diffuse goiter. We evaluated 21 of them before and after treatment. Fibrinogen, fibrinopeptide A, and B beta 15-42 were higher in patients than in controls (p less than 0.0001). There was no difference in fibrinopeptide A nor in B beta 15-42 before or after treatment. In euthyroidism fibrinogen returned to normal values. Inflammation of the thyroid gland secondary to autoimmunity may activate blood coagulation by release of tissue factor. High fibrinogen before treatment may be explained as an aspecific response. Since it persists in euthyroidism, autoimmunity could account for high fibrinopeptide A and B beta 15-42 aftertreatment.
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The authors report on the use of interventional radiology modalities in the treatment of some gastrointestinal diseases (intussusception, stenosis, hemorrhage, etc). The results are compared with literature data relative to both interventional radiology and conventional therapeutic procedures. In our series, hydrostatic reduction of ileocolic intussusception was successful in 60% of cases. Transluminal dilatation with a balloon catheter was attempted in 108 patients with alimentary tract stenosis and was successful in 93. Hemorrhage and ischemia can be treated by means of transcatheter therapy (vasopressin, embolization) and percutaneous angioplasty. Percutaneous gastrostomy appears to be an effective alternative to surgical gastrostomy. Tapeworm infections can be cured by intraduodenal injection of "Gastrografin" (Schering). The success achieved in the different applications is such as to suggest a wider use of interventional radiology procedures, for they offer a more favorable cost/benefit ratio and often yield better results than conventional techniques.
The authors report on the diagnostic role of radiological imaging in the study of the patients who underwent gastric surgery. This kind of intervention is often followed by postoperative complications, so that accurate clinical-instrumental investigations are required. Routine controls both in the immediate postoperative period and during follow-up are useful especially when a neoplastic lesion was the underlying condition leading to surgery. Radiological imaging plays a fundamental role especially in evaluating such postoperative conditions as afferent and efferent loop syndromes. Radiology is thought to be essential to demonstrate the syndrome and to identify the mechanical/functional nature of the factors causing the disease, all of which are essential to an appropriate and safe therapy. Both the duration of follow-up (early and late controls) and the choice of contrast (water-soluble contrast medium or double contrast enema) are very important factors depending on the time of surgery and the clinical indication.
Ergometric tests (ET) were used to study 900 patients undergoing surgical myocardial revascularisation during the period between January 1983 and December 1989. ET was carried out without medical therapy between the 30th and 35th day post surgery. The test was positive in 193 subjects (21%); in 42 of the latter (5% of the total and 229 of positive subjects) symptoms of effort angina were found to persist. ET was negative in 557 patients (62%); 150 subjects (17%), although not positive, did not attain a sufficient heart rate to enable a 100% negative diagnosis to be made. No major complication was observed. Maximal short-term ET is a reliable and safe test for checking the efficacy of myocardial revascularisation and to assess functional recovery. In view of the relatively high percentage of positive tests due to ischemia but with the complete absence of symptoms, the authors affirm that the mere onset of anginous symptoms alone cannot be considered indicative of the success of cardiosurgery.
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1-Phenylalkylindole-3-carboxylic acids 1-4, indole-1-acetic acids/esters 5-10 and the hydrazones 11-15 were prepared and submitted to the rat paw edema test using carrageenin. In the first two groups of compounds, the 2-chloro indoles were more active than the corresponding indole derivatives. In the third group the activity seemed to be determined largely by the substituent at the 1-position.
Lipoperoxidation is implicated in various pathological conditions. Malonaldehyde (MDA) is the most commonly used marker of this process. We propose simple modifications to Yagi's fluorometric assay for MDA determinations, to avoid long and tedious manipulations by eliminating the first precipitation and washing steps, analogous to HPLC methods, and to increase both the sensitivity and the specificity of the assay by measuring synchronous fluorescence. The proposed technique is easier, faster, and more sensitive than Yagi's method (Academic Press, 1982: Lipid peroxides in biology and medicine). The results obtained with the novel method correlate with those from the HPLC method described by Therasse and Lemonnier (J Chromatogr Biomed Appl 1987;413:237-41).