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Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 163 records · Page 9Linked to original sources
PubMed1994

Follicle-stimulating hormone regulation of AP-1: inhibition of c-jun and stimulation of jun-B gene transcription in the rat Sertoli cell.

The proto-oncogenes c-fos and c-jun and the related jun-B encode the components of transcription factor, AP-1, a heterodimeric DNA-binding protein that mediates hormone and growth factor-regulated gene expression. In the rat Sertoli cell, FSH rapidly inhibited c-jun gene expression while it stimulated c-fos and jun-B as well as the expression of the more slowly responding, tissue plasminogen activator (tPA) and inhibin alpha-subunit. These early effects of FSH were not inhibited by cycloheximide. Nuclear run-off analyses demonstrated that the FSH-dependent decline in c-jun and increases in c-fos, jun-B, tPA and inhibin alpha-subunit mRNAs were regulated at the transcriptional level. The rates of degradation of c-fos, c-jun and jun-B mRNAs were unaffected by FSH while tPA and inhibin alpha-subunit mRNAs were stabilized. After 8 h of FSH treatment, the transcription of all five genes returned to basal rates. These data demonstrate immediate-early regulation by FSH of the expression of genes encoding components of the transcription factor, AP-1.

Animals↗
PubMed1994

Serum 2'-5'-oligoadenylate synthetase levels and clinical response to interferon-beta therapy in women with genital human papillomavirus infection.

To investigate the activity of parenterally administered interferon-beta (IFN-beta) in women with genital human papillomavirus (HPV) infection, serum 2'-5'-oligoadenylate synthetase (2'-5'OAS), an enzyme induced by IFNs, was measured before, during, and after therapy. Serum levels of 2'-5'OAS significantly increased during therapy (P = .005). The patients classified as not responding to treatment at 3 months of follow-up had baseline levels of 2'-5'OAS significantly higher than those who responded to treatment (P = .0011). Differences between the IFN-beta-treated group and untreated controls appeared at day 6 (P = .0019). 2'-5'OAS is a useful parameter in monitoring parenterally administered IFN-beta. The data suggest that women with genital HPV infection and elevated baseline levels of 2'-5'OAS are unlikely to respond to therapy with IFN-beta.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Abnormalities of blood coagulation and fibrinolysis in psoriasis.

Contrasting data have been reported about cardiovascular diseases in psoriatic patients. The aim of this study was therefore to evaluate blood coagulation and fibrinolysis in psoriatic patients. For this purpose, in a first group of 48 patients, we measured blood coagulation and fibrinolysis inhibitors [antithrombin III (AT), protein C (PC) and alpha 2-antiplasmin (AP)], the products of thrombin and plasmin activity [fibrinopeptide A (FpA) and B beta(15-42) (B beta)], plasminogen (PLG) and fibrinogen (FBG). When all patients were considered we found a significant increase in B beta and FpA levels, while PC, PLG and AP values were significantly decreased when compared to controls. FBG and AT were not different from the controls. In order to understand whether the observed abnormalities of blood coagulation and fibrinolysis were related only to psoriasis we divided all the patients into two groups: (1) patients with cardiovascular disease or other risk factors (n = 28) and (2) patients affected only by psoriasis (n = 20). Since no difference was observed between groups 1 and 2, we conclude that these findings are related to psoriasis. Subsequently we considered a different group of psoriatic patients. In these patients we measured FpA and two new thrombin activation indicators, such as prothrombin fragment 1 + 2 and thrombin-antithrombin complex (TAT). In addition we evaluated the levels of D-dimer, the product of the dissolution of cross-linking fibrin by plasmin. In this second group FpA, prothrombin fragment 1 + 2 and D-dimer were significantly higher than controls. Only TAT was not statistically different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1994

Activation of inositol phospholipid turnover and calcium signaling in rat Sertoli cells by P2-purinergic receptors: modulation of follicle-stimulating hormone responses.

To study the role of extracellular nucleotides in the regulation of Sertoli cells, the effects of ATP and its analogs on the Ca(2+)-phospholipid- and cAMP-dependent pathways were tested. Cultured Sertoli cells from immature animals were incubated with ATP or structurally related compounds, and phosphoinositide (PI) turnover or cAMP accumulation was measured. Among the several nucleotide phosphate analogs tested, adenosine 5'-O-(3-thiotriphosphate) was the agonist most potent in stimulating inositol phosphate accumulation. The effects of purine nucleotides on PI turnover were time and concentration dependent. Because nonhydrolizable ATP analogs also stimulated PI turnover, ATP metabolites or metabolic products are not responsible for the observed stimulation. The order of potency of the different ATP analogs [adenosine 5'-O-(3-thiotriphosphate) > ATP approximately equal to UTP > beta, gamma-methyleneadenosine 5'-triphosphate, 2-methylthio-ATP > adenosine] was consistent with the presence of P2U receptors (nucleotide receptors) on the surface of the Sertoli cell. Augmented PI turnover was accompanied by a transient increase in Ca2+ concentration, measured in single Sertoli cells loaded with the intracellular Ca2+ indicator fura-2. When used alone, ATP and its analogs did not have a direct effect on cAMP levels in the Sertoli cell. However, ATP or its analogs inhibited FSH-dependent cAMP accumulation by more than 70%. Purine nucleotides also efficiently blocked the effects of FSH distal to cAMP accumulation, because extracellular ATP completely reversed the changes in Sertoli cell shape induced by FSH. The nucleotide-dependent inhibition of cAMP accumulation was blocked by pertussis toxin to a different degree depending on the purine or pirimidine nucleotide used. This indicated that more than one mechanism contributes to the purine nucleotide-dependent inhibition of cAMP accumulation. These data provide evidence that purine nucleotide receptors coupled to multiple pathways are present on the Sertoli cell in culture, and that extracellular ATP has profound biological effects on the FSH responsiveness of the Sertoli cell.

Adenosine↗
PubMed1994

Renal handling of prednisolone/prednisone: effect of steroid dose and 11 beta-hydroxysteroid dehydrogenase.

UNLABELLED: The purposes of this study were: (1) to determine under steady-state conditions whether the renal clearance of prednisolone is concentration dependent, and (2) to establish whether the urinary excretion of prednisolone and its biologically inactive 11-dehydro metabolite prednisone depend upon the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). For that purpose 10 healthy volunteers were infused to steady state over a 13-h period either at a low (11 micrograms/h x kg) or a high (70 micrograms/h x kg) rate with prednisolone on two occasions, once without and once with administration of glycyrrhetinic acid, an inhibitor of 11 beta-OHSD. Prednisolone and prednisone were measured by high-pressure liquid chromatography. Mean renal clearance values of total or unbound prednisolone were several times higher during the high than the low infusion rate. The fractional renal clearance of unbound prednisolone during the high, but not during the low infusion rate exceeded 1. This indicates that in addition to unbound prednisolone, protein-bound prednisolone is excreted in urine at high plasma concentrations. Inhibition of 11 beta-OHSD increased the urinary ratios of prednisolone/prednisone in all subjects. CONCLUSIONS: (1) The renal clearance of prednisolone is concentration dependent; (2) there must be tubular secretion and/or glomerular filtration of prednisolone bound to plasma proteins; (3) the urinary excretion of prednisolone/prednisone is modulated by the activity of 11 beta-OHSD.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Synthesis and antihepatotoxic activity of silybin 11-O-phosphate.

Silybin 11-O-phosphate 3 was synthesized by selective phosphorylation of silybin with POCl3. The pharmacological activity of 3 was evaluated in the rat by using the praseodymium poisoning test. Preliminary results showed that the compound possesses antihepatotoxic activity, possibly with lower potency compared to the reference drug silybin hemisuccinate.

Alanine Transaminase↗
PubMed1993

Elevation of cAMP is required for down-regulation, but not agonist-induced desensitization, of endogenous dopamine D1 receptors in opossum kidney cells. Studies in cells that stably express a rat cAMP phosphodiesterase (rPDE3) cDNA.

D1 dopamine receptors stimulate cAMP accumulation in opossum kidney (OK) cells, but this response is attenuated by pretreatment with dopamine. Dopamine pretreatment also causes a reduction in D1 dopamine receptor number. We transfected OK cells with a rat cAMP phosphodiesterase cDNA (rPDE3) in order to determine the contribution of elevations of cAMP to those two phenomena. Wild-type (WT) OK cells were compared to three clones (C, H, and N) which demonstrated stable expression of the rPDE3 phenotype and genotype, rPDE3 RNA expression was confirmed in clones C, H, and N (but not in WT-OK cells) by reverse transcriptase-polymerase chain reaction. A functional rPDE3 phenotype was demonstrated in that dopamine-responsive cAMP accumulation was absent in clones C, H, and N in intact cells, but could be restored by preincubation with cAMP phosphodiesterase inhibitors, or by using washed membranes from those clones. All three clones had increased cAMP phosphodiesterase activity when compared to WT-OK cells (approximately 100% increase), and blunted or absent dopamine (1 microM)-induced protein kinase A activation. After pretreatment with dopamine (1 microM) for 1 h, clones C, H, and N desensitized equally well as WT-OK cells (approximately 40-50% reduction in maximal increase in cAMP). In contrast, down-regulation of D1 dopamine receptors was blunted for clone C (20% receptor loss) and absent for clones H and N, when compared to a 45% loss of receptors for WT-OK cells. These findings suggest that in OK cells pretreated with 1 microM dopamine (i) cAMP accumulation is not necessary for dopamine-induced desensitization, but (ii) is necessary for down-regulation of D1 dopamine receptors, and (iii) that the down-regulation and desensitization processes may be differentially regulated.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Metabolism of exogenous ganglioside GM1 in cultured cerebellar granule cells. The fatty acid and sphingosine moieties formed during degradation are re-used for lipid biosynthesis.

Cerebellar granule cells, differentiated in vitro, were parallelly fed with [Sph-3H]GM1 and [stearoyl-14C]GM1, under identical conditions (10(-6) M ganglioside; pulse, from 1-4 h; chase, up to 24 h after 4 h pulse) and the salvage pathways of sphingosine and stearic acid were investigated. It was observed that both sphingosine and stearic acid, liberated during the intralysosomal degradation of ganglioside, are metabolically recycled, along distinct pathways. Sphingosine is used for the biosynthesis of a number of sphingolipids, particularly ceramide, glucosyl-ceramide, gangliosides and sphingomyelin; stearic acid is utilized for the biosynthesis of sphingolipids, and to a greater extent, glycero-phospholipids, especially those endogenously richer in stearic acid (phosphatidyl-ethanolamine and phosphatidyl-choline). No evidence was provided for a salvage pathway for ceramide.

Animals↗
PubMed1993

HPV, HIV infection, and risk of cervical intraepithelial neoplasia in former intravenous drug abusers.

The relation between human immunodeficiency virus (HIV), human papilloma virus (HPV) infection, sexual habits, reproductive history, and risk of cervical intraepithelial neoplasia (CIN) has been analyzed in a cross-sectional study conducted since 1986 among female former intravenous drug abusers attending for the first time to the Colposcopic Unit of the Ospedale Luigi Sacco of Milan and women consecutively admitted to the Community for Past Drug Abusers, S. Patrignano, Rimini. A total of 434 subjects entered the study; of those 128 (30%) had a diagnosis of CIN. Compared with HIV-negative subjects, odds ratio (OR) of CIN was 8.0 (95% confidence interval (CI) 4.6-14.1) for HIV-positive ones and the frequency of CIN 2 and 3 was higher in HIV-positive than that in HIV-negative subjects (chi 2(1), trend, 6.67, P 0.01). Compared with women without current HPV infection the OR estimate was 38.0 (95% CI 20.3-71.2) in those with current diagnosis of HPV infection. Considering HIV-positive subjects only, the frequency of CIN increased with stage of HIV infection and was higher in women with lower CD4+ values. Finally, no relation emerged between CIN risk and age, indicators of sexual habits, oral contraceptive use, parity, and history of spontaneous or induced abortions.

Adult↗
PubMed1993

Sexual transmission of hepatitis C virus and HIV-1 infection in female intravenous drug users.

We examined the relationship between the presence of antibody to HCV and sexually transmitted diseases in 151 female, intravenous drug users aged 17-43 years. Anti-HCV was present in 49 of 66 HIV-1-negative women (74.2%), and 63 of 85 HIV-1-positive women (74.1%). Anti-HCV seropositivity was significantly related to sexually transmitted infections (Ureaplasma urealyticum infections excluded) in HIV-1-seronegative women, but not in HIV-1-positive women. Also, in HIV-1-negative subjects. Trichomonas vaginalis infections (and infections with M. hominis) were significantly related to anti-HCV seropositivity, and a positive relation between the number of sexual partners and the presence of anti-HCV was demonstrated. In HIV-1-positive subjects a shared use of needles and syringes was more likely, and an increased parenteral exposure to HCV may decrease the relative contribution by sexual transmission. However, in HIV-1-negative subjects, sexual transmission of HCV appears to be both a possible and important means of transmission.

Adolescent↗
PubMed1993

A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase gene is highly expressed in the limbic system of the rat brain.

Cyclic AMP and cyclic GMP serve as second messengers in a variety of neural cells, modulating their metabolic and electrical activity. The cyclic GMP-stimulated cyclic nucleotide phosphodiesterase, an enzyme whose hydrolytic activity is allosterically regulated by cyclic GMP in peripheral tissues, could play an important role in the regulation of cyclic nucleotide levels in the brain. To study the presence and distribution of cyclic GMP-stimulated phosphodiesterase in the rat brain, we cloned a portion of rat liver cyclic GMP-stimulated phosphodiesterase complementary DNA by polymerase chain reaction, using degenerate phosphodiesterase-specific oligonucleotide primers. Northern blot analysis of rat tissues reveals abundant expression of cyclic GMP-stimulated phosphodiesterase messenger RNA in the brain. Northern blot analysis of brain subregions shows especially strong expression in hippocampus and cortex, modest expression in the remainder of the forebrain and in the midbrain, and little expression in cerebellum and hindbrain. In situ hybridization studies with cyclic GMP-stimulated phosphodiesterase riboprobes confirm these northern blot results, and delineate cell groups with high levels of expression. Medial habenular nucleus is intensely labeled, as is hippocampus in the vicinity of pyramidal and granule cell bodies in areas CA1, CA2, CA3, and dentate gyrus. Other elements of the limbic system also contain cyclic GMP-stimulated phosphodiesterase messenger RNA, including olfactory and entorhinal cortices, subiculum, and amygdala. Additional cortical regions show more diffuse expression of cyclic GMP-stimulated phosphodiesterase messenger RNA, as do the basal ganglia. Cerebellum, thalamus, and hypothalamus do not show appreciable specific labeling. These studies demonstrate the presence of cyclic GMP-stimulated phosphodiesterase messenger RNA in specific regions of the rat brain, and suggest that the cyclic GMP-stimulated phosphodiesterase might modulate neuronal activity by regulating intracellular cyclic AMP levels in response to changes in intracellular cyclic GMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

ADH resistance of LLC-pk1 cells caused by overexpression of cAMP-phosphodiesterase type-IV.

The studies of animal models of nephrogenic diabetes insipidus (NDI) suggest that abnormally high activity of cAMP phosphodiesterase (cAMP-PDE), may cause unresponsiveness to the diuretic effect of AVP. We explored whether overexpression of one of the cAMP-PDE type isozymes, PDE-IV, in [8-Arg]-vasopressin (AVP) sensitive renal epithelial LLC-PK1 cells can prevent the hormone-elicited cAMP increase. LLC-PK1 cells were stably transfected with ratPDE3.1 cDNA (which encodes for rolipram-sensitive PDE-IV), inserted in plasmid pCMV5 and then were compared with sham-transfected LLC-PK1 cells and wild LLC-PK1 cells. In the stably transfected clone (LLC-PK1-S #16), the rolipram-sensitive PDE-IV activity was about five times higher than in controls, whereas activities of other types of PDEs were not different. The presence of cognate mRNA for PDE-IV was confirmed by Northern blot. Whereas in the control cells (wild LLC-PK1 cells and sham-transfected LLC-PK1 cells), the incubation with 10(-7) M AVP increased cAMP more than tenfold, the LLC-PK1-S#16 cells with overexpressed cAMP-PDE were resistant to cAMP-increasing effects of AVP and forskolin. However, in the same LLC-PK1-S#16 cells the cGMP increases in response to nitroprusside were not diminished. The AVP-dependent cAMP accumulation in LLC-PK1-S#16 cells with overexpressed PDE-IV was restored by addition of roliprams which decreased cAMP-PDE activity to the levels similar to those in wild LLC-PK1 cells and sham-transfected LLC-PK1-#A1 cells. In contrast, inhibitors of other PDE isozymes (PDE-I or PDE-III) had little or no effect. Our findings show that excessive activity of cAMP-PDE, in this case of isozyme PDE-IV, can cause resistance to AVP which is analogous to that observed in collecting ducts of mice with hereditary nephrogenic diabetes insipidus.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

[Treatment of hypertrophic cardiomyopathy with a combination of carnitine and beta blockaders. Review of the literature. Description of a clinical case and long-term follow up].

In the past decade, strategies for managing heart failure have changed. The use of beta blockers, although still in the experimental stage, has proved effective in some cases. The protective action of beta-blocking agents against chronic catecholamine stimulation may be enhanced by the combination with L-carnitine. This substance plays an important and synergistic role 1) as an important source of energy due to fatty acid oxidation, and 2) by avoiding the accumulation of lipids in the myocardium. The successful follow-up of a case of dilated cardiomyopathy is critically reviewed. Treatment with the L-carnitine-propranolol combination restored cardiac function in a 52-year-old man with dilated cardiomyopathy: a 50% reduction in mitral EPSS (E Point Septal Separation), from 20 to 10 mm was obtained with the above mentioned therapy; as well as a decrease from 60 to 57 mm in diastolic diameter. Our experience suggests promising benefits in adopting beta blockers combined with L-carnitine therapy in myocardial failure secondary to dilated cardiomyopathy.

Adrenergic beta-Antagonists↗