Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 253 records · Page 14Linked to original sources

PubMed1989

Regulation of c-fos messenger ribonucleic acid by fibroblast growth factor in cultured Sertoli cells.

The data reported here demonstrate that basic FGF and Sertoli-cell-derived FGF have rapid stimulatory effects on c-fos mRNA levels. Basic FGF appears to utilize a signal transduction pathway that is distinct from that used by FSH and serum but similar in its potency and transiency. This is consistent with other reports in the literature on FGFs mechanism of action. For example, a monoclonal antibody to phosphatidyl 4,5-biphosphate will block the effects of PDGF on thymidine incorporation into NIH 3T3 cells but has no effect on basic FGF. Our data support the emerging possibility of a novel pathway mediating FGF actions. A similar precedent has been established for serotonin-induced DNA synthesis in smooth muscle cells. The rat Sertoli cell, with both FSH and FGF rapidly inducing c-fos, is an excellent model system for addressing the mechanism of action of basic FGF, the specificity of the c-fos response and the role of FGF in the reproductive system. Stimulation of c-fos mRNA by basic FGF in the cultured Sertoli cell presents questions regarding the role of FGF and c-fos in the male reproductive system. Basic FGF has been shown to stimulate cell division and plasminogen activator activity in cultured immature porcine Sertoli cells. Plasminogen activator may play a critical role in the tissue remodeling required for spermiogenesis. Interestingly, fos has been shown to be expressed preferentially in pachytene spermatocytes in the mouse. These observations taken together with the finding that basic FGF mRNA levels in Xenopus oocytes are markedly elevated, suggests that basic FGF may be important for Sertoli cell function, spermatogonial cell proliferation and subsequent meiotic and sperm maturational events.

Animals↗

PubMed1989

Evidence for a relationship between high fibrinogen levels and decreased thrombin activity in vivo in elderly subjects.

In order to investigate whether high fibrinogen levels were associated with elevated thrombin activity, we measured fibrinogen and fibrinopeptide A in 37 elderly healthy subjects ranging from 60 to 93 years. Fibrinogen levels (519.1 +/- 127.0 mg/dl) and fibrinopeptide A (5.9, 0.9-18.1 ng/ml) were significantly higher than in younger controls. A highly significant negative linear correlation was found between fibrinogen and fibrinopeptide A in the elderly subjects (p less than 0.01). However, a polynomial regression showed that this negative relationship was present at the fibrinogen levels ranging between 420 and 700 mg/dl. Our results suggest that high fibrinogen levels in elderly subjects do not necessarily mean that their thrombin activity is concomitantly increased.

Aged↗

PubMed1989

Thrombin activity and oral anticoagulant therapy: a preliminary study.

The aim of this work was to investigate whether the thrombin activity is related to the degree of anticoagulation induced by oral anticoagulants. Moreover, we tried to detect an optimal anticoagulation range at which the lowest possible thrombin activity can be reached. We investigated 28 patients (19 women and 9 men, mean age 54 +/- 9 years). Anticoagulation had been induced by acenocoumarol for at least 1 year before the beginning of this study. The degree of anticoagulation was monitored by the thrombotest coagulation method. The therapeutic range was 5-13%. The thrombin activity was measured by means of the fibrinopeptide A radioimmunological assay. In 15, 7, and 6 of the patients, thrombotest and fibrinopeptide A were carried out twice, once, and three times, respectively. Our results show first of all a significant positive relationship between thrombotest and fibrinopeptide A (p less than 0.001). Once this result was obtained, we tried to improve our identification of the behaviour of the thrombin activity in relation to the degree of anticoagulation assessed by thrombotest. For this purpose we employed a third-degree polynomial regression analysis which showed a better fit of the data. Since the curve became steeper from about 10% thrombotest levels, we divided the FPA values on the basis of thrombotest ranges. FPA values for the 14- to 25% thrombotest range were significantly different from those in the thrombotest range of 4-10%. Moreover, FPA levels in the 11 to 13% thrombotest range were significantly different from those in the thrombotest range of 4-10%. Our results suggest that a significant decrease in thrombin activity may be achieved only with a deep anticoagulation.

Acenocoumarol↗

PubMed1989

A rat Sertoli cell factor similar to basic fibroblast growth factor increases c-fos messenger ribonucleic acid in cultured Sertoli cells.

We have shown that the cultured Sertoli cell from the immature rat contains a fibroblast growth factor (FGF)-like factor. It behaves as a cationic peptide, is a potent competence factor for BALB/c3T3 mouse embryo fibroblasts, and displays a high affinity for heparin. Both bovine basic FGF and Sertoli cell FGF-like factor rapidly increase c-fos mRNA in cultured Sertoli cells. FSH, serum, and phorbol esters individually stimulate c-fos in cultured Sertoli cells whereas platelet-derived growth factor, epidermal growth factor, and insulin-like growth factor-I have little affect. However, unlike FSH, basic FGF does not stimulate an increase in cAMP and unlike either serum or phorbol esters, basic FGF does not stimulate phosphoinositol turnover or intracellular calcium changes. When Sertoli cell protein kinase C activity is suppressed by preexposure to phorbol ester, basic FGF continues to be a potent stimulator of c-fos, indicating that the calcium/phospholipid pathway is not involved in FGF induction. Basic FGF and FSH also increase jun-B mRNA levels in cultured Sertoli cells. In response to FGF, jun-B is more transiently increased than c-fos. In contrast, in response to FSH, jun-B persists longer than c-fos. These results indicate that cultured Sertoli cells contain a FGF-like factor that increases c-fos mRNA via a mechanism not involving cAMP and the calcium/phospholipid pathways. The different responsiveness of c-fos and jun-B to FSH and basic FGF may explain differences in the ultimate actions of these two ligands.

Animals↗

PubMed1989

[Seroprevalence of antibodies against Trypanosoma cruzi in 13 departments of Uruguay].

In 1985 a study was undertaken of the prevalence of Trypanosoma cruzi antibodies in 13 departments of Uruguay where transmission of the parasite by the vector Triatoma infestans persists. A total of 5,924 serum samples were selected using a probabilistic method--3,840 from individuals over the age of 12 (sample I) and 2,084 from subjects who were 12 years old (sample II). The population was classified according to place of residence (capital city, non-capital city, suburban area, and rural area). The percentage of positive sera detected by indirect immunofluorescence in the different departments ranged from 1 to 11%, and overall seroprevalence for the area was 3.4%. Based on the results obtained, it was possible to distinguish three areas: A, with seroprevalence from 6 to 11%; B, 2 to 3.2%, and C, 1 to 1.4%. In sample II from the Departments of Paysandú, Soriano, Flores, Florida, and Durazno, no cases of Chagas' disease were detected, which suggests that there is no active transmission of T. cruzi in this age group in the area studied. The number of persons estimated to have the disease was 36,952, or 1.3% of the total population of Uruguay and 4% of the population in the area surveyed. These seroprevalence figures are similar to those recorded in the province of Entre Ríos, Argentina, and in the neighboring municipalities of Rio Grande do Sul, Brazil.

Adolescent↗

PubMed1989

[Torsade de pointes during an atropine sulfate test in a patient with congenital long QT syndrome].

After a brief revision about the long QT syndrome, we report the case of a 52 year old man admitted to hospital for a syncopal attack. His electrocardiogram was considered normal: sinus bradycardia and U waves were recorded. The echocardiogram revealed anterior mitral leaflet redundancy and possible tricuspid prolapse. During the atropine test, after a normal increment of sinus frequency, 2 runs of self-limited torsade de pointes appeared. The electrocardiogram showed lesion wave at first, and then prolonged QT. During the intracavitary study, premature ventricular stimulation caused torsade de pointes. After propranolol iv it was no more possible to induce major ventricular arrhythmias anymore. Coronarography was normal. Nadolol therapy was begun. On 6 months follow-up the patient is asymptomatic.

Arrhythmias, Cardiac↗

PubMed1989

Antenatal prevention of respiratory distress syndrome; a multicentre survey.

Obstetric and neonatal data were collected on 934 preterm deliveries in 11 Italian centres in 1980, 1985 and 1986. Therapeutic regimens for prevention of respiratory distress syndrome (RDS) were applied in 42% of the cases in 1980, 32% in 1985 and 42% in 1986. Prevention was made in most cases with corticosteroids, although their use fell progressively from 94% in 1980 to 74% in 1986. A combination of two substances was used in a percentage of cases varying from 5 to 10% in all three years. In 903 non-malformed infants, the overall incidence of RDS was not significantly different in cases in which pharmacological prevention was attempted compared with cases without prevention. The only factors significantly affecting the incidence of RDS were gestational age, birth weight and Apgar score.

Data Collection↗

PubMed1989

[Nonpsychotic involutional inhibited depressions and psycho-organic deteriorations: treatment with Viloxazine and piracetam].

Involutional depression is often the first symptom of a psycho-organic syndrome or dementia and may not present overt symptoms itself; these depressive states have been variously classified by different schools in various countries. The hypothesis of catecholamine and indolamine in the aetiopathogenic agent is oversimplistic and the theory that abnormal receptor hypersensitivity is the cause of the condition is more convincing. On the basis of this hypothesis numerous studies have been conducted into the efficacy of various antidepressants in the treatment of this hypersensitivity. Involutional depressions are more common among women and are found in about 10% of 60-65 year olds. This report claims that combined viloxazine-piracetam is the most appropriate treatment for involutional depression. This approach (200 mg oral viloxazine and 9 g oral piracetam a day) was adopted for 3 months in 33 out patients about 64 years old who were subsequently put on maintenance doses (100 mg viloxazine, 3 g piracetam a day). The various Hamilton scale parameters were assessed as were reaction times to auditory and visual simple stimuli. Result sat the start and end of treatment were then compared. About three quarters of the patients showed improvement in both depression and psycho-organic syndrome symptoms, while total remission or lasting improvement in both pathologies was obtained in about 50%.

Administration, Oral↗

PubMed1989

[Activity of the coagulation and fibrinolysis in non-insulin-dependent diabetes mellitus. In vivo study].

In vivo study of blood coagulation and fibrinolysis activities in non insulin dependent diabetes mellitus. The aim of the study was to investigate in vivo blood coagulation and fibrinolysis activities in a group of diabetic patients NIDDM with and without vascular complications. For this purpose we determined two sensitive indicators in vivo of blood coagulation and fibrinolytic activities such as fibrinopeptide A and B beta 15-42 respectively. Moreover, we computed the ratio between B beta 15-42 and fibrinopeptide A in order to investigate a possible imbalance in vivo between blood coagulation and fibrinolysis. Control groups were 15 healthy subjects and 28 non diabetic patients affected by atherosclerotic disease. Fibrinopeptide A and B beta values were significantly higher in the diabetic patients than controls but there was no difference between the former group and the atherosclerotic patients. Also, no correlation was found for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose levels. There was no difference in B beta, FPA and B beta/FPAr values for patients treated with insulin and for those treated with either hypoglycemic agents or diet. Our data indicate that in diabetic patients fibrinolysis activity is increased, but it cannot counterbalance thrombin activity which appears much more enhanced. Finally, the lack of correlation for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose suggests that blood coagulation and fibronolysis abnormalities are not related to the degree of blood glucose control.

Adult↗

PubMed1989

Experimental study on the action of diltiazem on detrusor muscle and clinical evaluation in patients with detrusor hyperactivity.

Diltiazem added to the medium before administration of the agonist, caused a concentration-dependent antagonism of potassium chloride-induced contractions in strips of rat detrusor and human detrusor. When added at the time of peak potassium chloride-induced increase in muscle tone, the drug lowered the tone gradually and concentration-dependently. Diltiazem also depressed carbachol-induced contractions. In patients with disturbances of micturition due to detrusor hyperactivity, oral diltiazem (Angizem) treatment for 10 days significantly increased bladder capacity, lowered bladder pressure and maximum detrusor pressure and raised the threshold of the second sensation of micturition. In addition, diltiazem significantly reduced frequency of diurnal and nocturnal micturition and number of episodes of incontinence. Diltiazem appears to be an effective detrusor muscle relaxant and may be useful for the treatment of disturbances of micturition due to detrusor hyperactivity.

Aged↗

PubMed1988

Adenosine potentiates forskolin-induced delay of meiotic resumption by mouse denuded oocytes: evidence for an oocyte surface site of adenosine action.

Adenosine is present in the mouse follicular fluid and has been shown to interfere with oocyte maturation in vitro. To clarify the mechanism of adenosine action on meiotic arrest, we have characterized the synergistic action of this purine with forskolin on the meiotic resumption of mouse denuded oocytes. Forskolin delays meiotic resumption by approximately 1 hour; adenosine at concentrations ranging between 30-750 microM has no significant effect. Conversely, adenosine treatment together with forskolin produces a further delay in the resumption of meiosis. This adenosine effect is dose-dependent and mimicked by adenosine analogs like N6-phenylisopropyl adenosine (PIA), 2-chloroadensoine (2-CLA), 5'-N-ethylcarboxamide (NECA). Dipyridamole, which inhibits adenosine transport, does not prevent the meiosis-arresting synergistic effect of adenosine with forskolin. Adenosine causes a 50% increase of adenosine triphosphate (ATP) content in the oocyte. However, this increase is not directly responsible for the observed delay in oocyte maturation for the following reasons: (1) the dose response of inhibition of meiotic resumption does not correlate with the doses of adenosine producing an increase in ATP; (2) dipyridamole blocks the increase in intracellular ATP, but it has no effect on the adenosine inhibition of maturation; (3) adenosine analogs inhibit oocyte maturation but do not affect intracellular ATP levels. These results suggest that the synergism of adenosine with forskolin on meiotic arrest does not require uptake of the nucleoside nor its conversion to ATP and that the adenosine effects are exerted at the level of the oocyte plasma membrane.

Adenosine↗

PubMed1988

Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment.

Plasma concentration of fibrinogen and B beta 15-42, a specific product of fibrinogen metabolism induced by plasmin, were measured in a group of patients with untreated hyperthyroidism and in controls. Significantly increased plasma levels of both parameters were observed in hyperthyroid patients. The restoration of euthyroidism either by antithyroid drug or by radioiodine caused a significant decrease of fibrinogen and B beta 15-42. These data indicate that hyperthyroidism is another clinical condition associated with increased concentration of fibrinogen and B beta 15-42.

Adult↗

PubMed1988

Adenosine receptor-dependent modulation of inhibin secretion in cultured immature rat Sertoli cells.

Inhibitory (A1) adenosine receptors that attenuate adenylate cyclase activity are present in cultured Sertoli cells. To investigate the possible effect of activating these receptors on the secretion of inhibin by the Sertoli cell, immature rat Sertoli cells were incubated for 24 h with follicle-stimulating hormone (FSH) in the absence or presence of the non-metabolizable, adenosine agonist phenyl-isopropyl-adenosine (PIA), and the accumulation of alpha-inhibin immunoreactivity was measured in the medium. Although devoid of effects when added alone, PIA inhibited the FSH-dependent secretion of alpha-inhibin in a concentration-dependent manner (ED50 = 1-1.5 nM). PIA treatment of the Sertoli cells also rendered the cells less sensitive to FSH in terms of alpha-inhibin secretion. The concentration-response curve to FSH was shifted to the right when cells were incubated in the presence of 100-1000 nM PIA. In contrast, dibutyryl cAMP stimulation of alpha-inhibin accumulation was unaffected by treatment with PIA, indicating that the site of PIA action is at the level of cAMP synthesis. These data provide experimental evidence of adenosine modulation of inhibin secretion by the Sertoli cell and suggest that adenosine may act as a local modulator within the pituitary-testicular axis.

Animals↗

PubMed1988

Structure of the rat androgen-binding protein gene.

To study hormonal regulation of rat androgen-binding protein (ABP) we have cloned and sequenced the gene. A 5.3-kbp genomic DNA fragment was found to contain the entire coding region of the gene, which consists of 8 exons. The major site of transcription initiation in the testis was localized by primer extension and is located 36 bases upstream from the site of translation initiation. The gene does not contain a "TATA box" immediately upstream from the major start site. The sequence TACCTA occurs at residue -23, which is a functional TATA-like element in the SV40 major late gene. A sequence related to the cAMP response element is at residue -126 bp. Southern blot analysis of rat genomic DNA indicated a single gene for ABP in the rat. The existence of one gene supports the idea that sex steroid-binding protein (SBP) produced by fetal rat liver is coded by the same gene. The possibility that an alternate promoter region is active in the fetal liver is discussed.

Androgen-Binding Protein↗

PubMed1988

Adenosine inhibition of the hormonal response in the Sertoli cell is reversed by pertussis toxin.

The rat Sertoli cell in culture expresses A1 inhibitory adenosine receptors. In this study, we have used pertussis toxin as a tool to characterize the mechanism of action of adenosine on these cells. Cells were preincubated for 18-24 h with pertussis toxin, and the responses to FSH and to the adenosine analog phenylisopropyladenosine (PIA) were measured by assaying cAMP accumulation. The effect of toxin on adenosine receptors was also evaluated by measuring binding of the adenosine agonist cyclohexyladenosine (CHA). The total number of specific CHA-binding sites was reduced 60-70% in membranes prepared from cells cultured for 24 h in the presence of pertussis toxin; the binding sites remaining after treatment displayed no apparent change in affinity for [3H]CHA. The effect of guanine nucleotides on CHA binding was also reduced after toxin pretreatment, but not abolished. PIA inhibited FSH-stimulated cAMP accumulation by 70-80%. Maximal inhibition was observed at a concentration of 10 nM PIA, and the ED50 of the dose-response curve was 1 nM. Pretreatment of the Sertoli cell with pertussis toxin completely blocked the PIA inhibition. The pertussis toxin effect was time and dose dependent. Reversal of the inhibition was observed after 6 h of treatment with a maximal dose of toxin (100 ng/ml). The dose of toxin producing a half-maximal effect was 10-30 ng/ml. In addition to this blockade of purine nucleotide inhibitory effects, exposure of the Sertoli cell to pertussis toxin concentrations ranging from 1-400 ng/ml consistently led to a potentiation of the FSH response measured as cAMP accumulation. In cell-free preparations (crude particulate fraction of the Sertoli cells, or sucrose gradient-purified plasma membranes), pertussis toxin catalyzed the incorporation of [32P]ADP ribose into a polypeptide with a molecular mass of 40-41 K. This peptide had electrophoretic mobility similar to that of a partially purified guanine nucleotide-binding protein (Gi). These data indicate that adenosine A1 inhibitory receptors are coupled to an inhibitory component (Gi) of adenylate cyclase. In the Sertoli cell, inhibitory and stimulatory signals interact in a bimodal regulation of adenylate cyclase and intracellular cAMP.

Adenosine↗

PubMed1988

Follicle-stimulating hormone modulation of phosphoinositide turnover in the immature rat Sertoli cell in culture.

The possibility that FSH modulates the Ca++-, phospholipid-dependent pathway was studied in cultured rat Sertoli cells. Cells were metabolically labeled with [3H]myoinositol, and accumulation of [3H]inositol phosphates [( 3H]inositol mono-, di-, and trisphosphates) was measured by extraction and fractionation on ion exchange chromatography. Fetal bovine serum increased Sertoli cell phosphoinositide (PI) turnover in a time and concentration-dependent manner (ED50 = 2-3% vol/vol). FSH by itself had no significant effect on the accumulation of inositol phosphates. On the other hand, FSH inhibited, in a concentration-dependent manner, the serum-stimulated accumulation of inositol phosphates by more than 50%. HPLC ion exchange chromatography of the inositol phosphates showed that all isomers present in serum-stimulated extracts were reduced to the same extent after treatment with FSH. The treatment of the cells with either forskolin, the beta-adrenergic agonist isoproterenol, or (Bu)2cAMP also inhibited the PI turnover stimulated by fetal bovine serum. FSH inhibition was not detected in mature Sertoli cells, in which FSH no longer stimulates cAMP accumulation. These results demonstrate that FSH, via formation of cAMP, exerts inhibitory effects on the PI turnover of the Sertoli cell. Thus, while stimulating the cAMP-dependent pathway, at the same time FSH inhibits the Ca++-, phospholipid-dependent pathway.

Animals↗

PubMed1988

The gene structure of rat androgen-binding protein: identification of potential regulatory deoxyribonucleic acid elements of a follicle-stimulating hormone-regulated protein.

A genomic clone has been characterized for androgen-binding protein (ABP), a Sertoli cell secretory protein that is regulated by androgens and FSH. A 5.3-kilobase pair Sstl DNA fragment was sequenced and found to contain the entire coding region of the gene, which is divided into 8 exons. The major transcription initiation site in the testis was localized by primer extension with two unique oligomers. In addition, a minor initiation site was identified that appears to originate from another promoter. The gene does not contain a conventional TATA box immediately upstream from the major start site; rather, the sequence TACCTA occurs at residue -24. This sequence has been described functionally as a TATA-like element in the SV40 major late gene. Other potential regulatory elements include a sequence related to the cAMP response element at residue -126 base pair. Using primary Sertoli cell cultures, it was found that (Bu)2cAMP or FSH increases ABP mRNA levels 3-5 fold, with a 2-fold increase in the level of secreted ABP. Southern blot analysis of rat genomic DNA indicated that there is a single gene for ABP in the rat. The existence of one gene supports the idea that sex hormone binding globulin produced by fetal rat liver is coded by the same gene.

Amino Acid Sequence↗

PubMed1988

Follicle-stimulating hormone induces transient expression of the protooncogene c-fos in primary Sertoli cell cultures.

The expression of the protooncogene c-fos has been associated with the transduction of cell surface stimuli into changes in nuclear function. To evaluate the possibility that this protooncogene plays a role in the gonadotropin-dependent gene regulation, the effect of FSH on the expression of c-fos was studied in primary Sertoli cell cultures. Sertoli cells were stimulated for different time intervals with FSH and c-fos mRNA levels measured by Northern RNA blot analysis. FSH treatment increased c-fos mRNA transiently with a maximal stimulation reached in 1 h. The level of c-fos mRNA returned to basal level within 4-6 h. The induction of c-fos mRNA was dependent on the concentration of FSH used with an ED50 of 3-5 ng/ml ovine FSH-16. A similar increase in c-fos expression was induced with highly purified hFSH. The c-fos mRNA was also elevated after treatment of the Sertoli cell with (Bu)2cAMP and forskolin. (Bu)2cAMP treatment led to a sustained induction of c-fos mRNA, with increased mRNA levels being maintained after 12 h. The FSH-dependent induction of c-fos mRNA was still present in cells treated for 3 h with cycloheximide, but it was greatly reduced by actinomycin D pretreatment. These data indicate that FSH induces a transient expression of c-fos in cultured Sertoli cells. This induction is probably mediated by cAMP and likely involves an increased transcription of the c-fos gene. Early expression of this gene might be an intermediate step required for gonadotropin-dependent regulation of expression of other genes.

Animals↗