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Biomedical subjects

M Franco

Publications and source records attributed to M Franco.

At least 127 records · Page 7Linked to original sources
PubMed1996

A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic murine tumours.

Resistance of tumour-bearing mice to a second tumour challenge, that is concomitant resistance, was evaluated in euthymic and nude mice using nine tumours with widely different degrees of immunogenicity. Two temporally separate peaks of concomitant resistance were detected during tumour development. The first one was exhibited only by small immunogenic tumours; it was tumour specific and mediated by classical immunological T-cell-dependent mechanisms. The second peak was shared by both immunogenic and non-immunogenic large tumours; it was non-specific, thymus independent and correlated with the activity of a serum factor (neither antibody nor complement) that inhibited the in vitro proliferation of tumour cells. This factor was eluted from a Sephadex G-15 column at fractions corresponding to a molecular weight of approximately 1000 Da and it was recovered from a high-performance liquid chromatography column in one peak presenting maximum absorption at 215 and 266 nm. The data presented in this paper suggest for the first time, to our knowledge, that in spite of the differences between immunogenic and non-immunogenic tumours, a common serum-mediated mechanism seems to underlie the concomitant resistance induced by both types of tumours at late stages of tumour development.

Adenocarcinoma↗
PubMed1996

Synthesis and anticonvulsant activity of some 1,2,3,3a-tetrahydropyrrolo[2,1-b]-benzothiazol-, -thiazol- or -oxazol-1-ones in rodents.

To identify more potent anticonvulsant agents and to gain insights into the structural properties determining the potency of a new class of anticonvulsants, some 3a-substituted tetrahydropyrrolo[2,1-b]benzothiazol-1-ones (1a-d) and the thiazole and oxazole analogues (2a-c and 3a-c, respectively) have been synthesized and tested for anticonvulsant activity against isoniazid-induced seizures in rodents. The most active compound, 2a, with a median effective dose (ED50, i.p.) of 24.3 mg kg-1 and 15.9 mg kg-1 in mice and in rats, respectively, was more extensively investigated and found to strengthen the effects of diazepam. No clear correlation was observed between the anticonvulsant activity and molecular lipophilicity descriptors of compounds 1-3. Structural similarity between the antiepileptic drug phenobarbital and compounds 1-3 was evidenced by molecular modelling studies and used to derive preliminary structure-activity relationships. The results demonstrate that 2a is an attractive candidate as an anticonvulsant agent worthy of further study and may help the design of other anticonvulsant drugs.

Animals↗
PubMed1996

Participation of adenosine in the renal hemodynamic abnormalities of hypothyroidism.

To investigate the participation of adenosine (ADO) in the abnormalities of renal function associated with hypothyroidism, glomerular hemodynamics were evaluated in normal (Nl) and 2-wk thyroidectomized (Htx) rats. Studies were performed before and during intravenous infusion of the ADO blocker 1,3-dipropyl-8-p-sulfophenyl xanthine (PSPX, 20 mM, 1.2 ml/h), intra-aortic ADO (100 nmol.kg-1.min-1), or vehicle. In addition, single-nephron glomerular filtration rate (SNGFR) was measured during the infusion of different intrarenal ADO doses (1, 10, and 35 nmol.kg-1.min-1); plasma and renal content of ADO were measured by high-performance liquid chromatography in additional groups. Decreased SNGFR, glomerular blood flow (QA), and ultrafiltration coefficient (Kf) were found in Htx rats. PSPX did not modify glomerular hemodynamics in Nl rats; in contrast, in Htx rats, the antagonist increased SNGFR, QA, and Kf, with a fall in afferent (RA) and efferent (RE) resistances. ADO infusion in Nl rats produced renal vasoconstriction characterized by a fall in SNGFR, QA, and Kf, with an increased RA and RE. Paradoxically, in Htx rats, ADO increased SNGFR, QA, and Kf, decreasing RA and RE. However, when ADO was infused through the renal artery, it induced a 20% reduction of SNGFR at 1 nmol.kg-1.min-1 that rose to control values at 10 nmol.kg-1.min-1 and increased to 38.3% to 35.kg-1.min-1. Renal ADO content was markedly low in Htx rats (4.37 +/- 0.79 and 115.46 +/- 14.9 nmol/g wet wt for Htx and Nl rats, respectively). Renal vasodilation induced by PSPX in Htx rats suggests predominant activation of A1 receptors in this condition. The vasodilatory response to exogenous ADO suggests additional activation of A2 receptors.

Adenosine↗
PubMed1996

[Long-term clinical course of acute myocarditis. Prospective study of a series of 99 patients (1987-1995)].

BACKGROUND: The natural history of acute myocarditis is not well known. The aim of our study was to assess the spontaneous outcome of patients with this disease and its possible relation with progression to chronic dilated cardiomyopathy. METHODS: With this aim, we have carried out a prospective study of 99 patients consecutively diagnosed with acute myocarditis in our hospital from 1987 to April 1995, with a mean follow-up of 34 +/- 25 months. Acute myocarditis was diagnosed by clinical, echocardiographic and isotopic (detection of myocite damage) data, in absence of any other cardiac lesion. RESULTS: Mean age was 26 +/- 17 years; 70% of the patients were male. Initial symptoms were dyspnea in 58% of the patients, chest pain in 33% and arrhythmias in 9%. Severe heart failure was present in 62% of the patients, ventricular arrhythmias in 16% and supraventricular arrhythmias in 16%. Cardiothoracic index was 0.50 +/- 0.07. Left ventricular ejection fraction was 0.40 +/- 0.18, although in 44% of the patients it was lower than 0.30. Immunosuppressive therapy was not used in any case. Outcome was favorable in 70% of the patients, who had a normal ejection fraction, while 13% died or needed heart transplantation during follow-up and 17% progressed to stable chronic dilated cardiomyopathy. Final ejection fraction was 0.53 +/- 0.17, significantly higher than the initial, 0.40 +/- 0.18 (p < 0.05); this improvement in ejection fraction was mainly observed during the first month after diagnosis (0.49 +/- 0.18). The proportion of patients with an ejection fraction of less than 0.30 decreased from 44% to 21% at the end of follow-up. CONCLUSIONS: Spontaneous outcome of acute myocarditis is good in the majority of patients, although an unfavourable evolution was observed in almost 30% of the patients (death, need of heart transplantation or chronic dilated cardiomyopathy). Improvement in ventricular function mainly occurs at short-term, during the first month of evolution in our study.

Acute Disease↗
PubMed1996

[Spinal cord protection in surgery of the thoracic, descending, and thoraco-abdominal aorta. Comparison of methods].

The authors compare the strategus needed for the elimination of paraplegia and for protection of abdominal organs after replacement of descending thoracic or thoraco-abdominal aorta. They analyse single technique considering the advantages and the controindications; furthermore they compare these properties and those of possible variants in the light of the presentation; type of disease and general conditions of the patient. These considerations are in agreement with later literature as well as the attitude of the surgeon.

Aortic Aneurysm↗
PubMed1996

The role of apoptosis in the inhibition of a secondary tumor by concomitant resistance in a mouse model of metastases.

Resistance of tumor-bearing mice to a second tumor challenge, that is, concomitant resistance, was studied using the LB tumor model. In a secondary LB tumor implant inhibited by concomitant resistance an increase in the percentage or apoptotic cells and alterations in cell cycle distribution were observed. Similar alterations were observed in LB tumor cells incubated with serum from tumor-bearing mice. The data presented in this paper suggest that apoptosis is one of the mechanisms involved in tumor dormancy due to concomitant resistance.

Animals↗
PubMed1996

[Role of connective tissue in the tumor-host relationship].

In the embryo, both differentiation and temporospatial organization are regulated by the mesoderm. Some of these functions are expressed by the connective tissue during wound or organ repair and regeneration. The normal development of the latter depends on the epithelium-mesenchyme interrelationship and the formation of an adequate amount of stroma and a certain type of collagen or proteoglycans. Our hypothesis proposes that cancer is a regenerative process which has failed as a consequence of alterations in the connective tissue. The object of this paper was to investigate whether the connective tissue and the amorphous fundamental substance (SFA) are capable of regulating the proliferation and death of normal and tumor cells and to duplicate the mechanisms involved. The results obtained in vivo, ex-vivo and in vitro experiments indicate that following: 1) SFA exerts a direct and selective cytotoxic effect on tumor cells; 2) SFA reduces the proliferative capacity of normal and tumor cells; 3) both the cytotoxic and antiproliferative effects of SFA are independent of cellular and humoral immune responses but are dependent on the chemical integrity of its component since its denaturalization reduces its antitumoral activity; 4) the tumor cells modulate the regulatory effects of SFA through endocellular enzymes liberated by cell death induced by the cytotoxic action of SFA itself. These results suggest that in the absence of the inhibitory effect of SFA, the tumor cells which remain viable con now proliferate actively due to enzyme stimulation. In conclusion, the regulatory function of the connective tissue on the proliferation and viability of tumor cells would depend on the molecular constitution of SFA.

Animals↗
PubMed1996

[Concomitant antitumor resistance].

Concomitant resistance of tumor-bearing mice against a second tumor challenge was evaluated in euthymic and athymic mice using 17 tumors with different degrees of immunogenicity. Two temporarily separated peaks of concomitant resistance were detected during tumor development: the first peak was only observed associated with small immunogenic tumors (< 500 m3., it was tumor-specific and mediated by T cell-dependent immunological mechanisms. The second peak was exhibited by large tumors (> 2000 mm3) independently of their immunogenicity; it was non-tumor specific, thymus-independent and correlated with a serum-activity (neither antibodies nor complement) which inhibited the in vitro proliferation of tumor cells. Out of 17 tumors studied, 15 tumors exhibited a moderate or strong concomitant resistance. The remaining two, which exhibited a weak or undetectable concomitant resistance and correlatively, a low or absent serum-inhibitory activity were the only tumors which included lung metastases. This fact suggested a correlation between concomitant resistance, absence of metastases and the existence of an inhibitory factor(s) in the serum. This inhibitory factor was partially characterized: it was resistant to boiling (5-10' at 100 degrees C) and to variations of pH; its molecular weight was estimated between 850 and 1200 D; it was recovered in only one fraction from HPLC (high power liquid chromatography) columns presenting maximum absorption at 215 and 266 nm; amino acid analysis and magnetic nuclear resonance studies suggested the presence of a molecule of thyrosine and one or two molecules of carbohydrates in its structure.

Animals↗
PubMed1995

A soluble protein negatively regulates phospholipase D activity. Partial purification and characterization.

Phosphatidylcholine-specific phospholipase D (PLD) is an important signalling phospholipase in mammalian cells. Recently, PLD activity has been shown to be positively regulated by the GTP-binding protein ARF (ADP-ribosylating factor). In the present work, we document the presence of a factor negatively regulating PLD activity in bovine brain cytosol. The inhibitory factor is characterized as a large protein or a complex of proteins with a molecular mass higher than 300 kDa. Using permeabilized and pre-permeabilized HL-60 cells depleted of their cytosol, we demonstrate that the inhibitor acts on GTP[S]-stimulated PLD activity. This effect is immediate, persistent and dose dependent for GTP[S]-stimulated PLD. Different possibilities for a mechanism of action of the inhibitory factor on the regulation of GTP binding of ARF were investigated. This inhibitory factor is not the guanine-dissociating inhibitor (GDI) for the small G-binding proteins Rho (Rho-GDI), reported to be a PLD inhibitor, since specific antibodies against this protein did not recognize a protein in the peak containing the inhibitory factor for PLD activity. Furthermore, the inhibitory factor does not prevent the binding of GTP[S] to ARF in the presence of HL-60 membranes. This excludes its possible role as an inhibitor of an ARF/guanine exchange factor. The inhibitory factor not only inhibits a pathway of PLD through GTP[S] activation in particular of the small GTP-binding protein, ARF, but it also inhibits PLD activated via either protein kinase C (PKC) or tyrosine kinase activation. The inhibitory factor also decreases PLC activity and this effect seems to be secondary to the inhibition of PLD activity. We discuss a mechanism of action of the inhibitor on PLD and the importance of this enzyme activity for membrane traffic.

Animals↗
PubMed1995

The small G-protein ARF1GDP binds to the Gt beta gamma subunit of transducin, but not to Gt alpha GDP-Gt beta gamma.

AlF4- activates heterotrimeric G-proteins G alpha subunits but not small GDP/GTP-binding proteins like ARF1. On retinal membranes containing holotransducin (Gt alpha GDP-Gt beta gamma) and incubated with ARFGDP, AlF4- induced Gt alpha GDP-AlF4 release and ARFGDP binding, probably to the remaining membrane-attached Gt beta gamma. On phospholipid vesicles reconstituted with Gt beta gamma, ARFGDP bound in proportion to Gt beta gamma, and was released upon subsequent Gt alpha GDP addition. Thus ARFGDP competes with Gt alpha GDP for binding to Gt beta gamma, probably through a conserved motif in the 'alpha 2 helix' of Gt alpha and ARF. This motif is found in the C-terminal helix of PH domains that bind to G beta gamma.

ADP-Ribosylation Factor 1↗
PubMed1995

Modulation of the release of adenosine by glucose and chemical hypoxia in cultured renal cells (MDCK line).

The effect of changes in the external concentrations of glucose on the release of adenosine of cultured renal cells (MDCK line) was studied. Adenosine release was markedly increased by the addition of glucose (5.5 mM) to monolayers of MDCK cells deprived of glucose for 24 hours. Addition of glucose to either the apical or basolateral side of the monolayer elicited a marked release of adenosine at the contralateral compartment. Removal of sodium in the external media blunted the response to glucose. Methylglucose that is transported into the cell but not metabolized also markedly increased adenosine release. Deoxyglucose that induces chemical hypoxia stimulated the release of adenosine. These results suggest that variations in extracellular glucose might be a physiological modulator of the cell regulation of adenosine.

Adenosine↗
PubMed1995

Comparison of rest-redistribution thallium-201 imaging and reinjection after stress-redistribution for the assessment of myocardial viability in patients with left ventricular dysfunction secondary to coronary artery disease.

Thallium (Tl)-201 reinjection after stress-redistribution (RI) imaging has been proven to accurately identify ischemic and viable myocardium. Quantitative Tl-201 analysis after stress has also shown viable myocardium in most mild to moderate (51% to 85% of normal uptake) irreversible Tl-201 defects. However, if the main clinical question is whether a region is viable, and not whether there is inducible ischemia, a resting protocol may be more appropriate. The aim of this study was to determine whether rest-redistribution (RD) quantitative Tl-201 single-photon emission tomographic imaging provides the same information on viable myocardium as Tl-201 RI. Thus, 15 patients (mean age 58 +/- 9 years) with chronic coronary artery disease and left ventricular dysfunction (ejection fraction 35 +/- 8%) were studied by both RI and RD Tl-201 single-photon emission tomography. Regional Tl-201 uptake was assessed quantitatively using a 16-segment model. When Tl-201 images were classified as normal/reversible (viable) or irreversible (nonviable), RI showed viable myocardium in 145 of 240 myocardial regions (60%), whereas RD showed it in 103 of 240 myocardial regions (43%). The 2 imaging protocols provided concordant information in 176 of 240 myocardial regions (73%). Among the 64 (27%) discordant regions, 53 (22%) were viable by RI and nonviable by RD, whereas 11 (5%) were viable by RD and nonviable by RI (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Myristoylation of ADP-ribosylation factor 1 facilitates nucleotide exchange at physiological Mg2+ levels.

Recombinant N-myristoylated bovine ADP-ribosylation factor 1 (myr-rARF1) has been expressed in bacteria and purified to near homogeneity with a high (85%) myristoylation efficiency. Myr-rARF1 and nonmyristoylated rARF1 have been compared with respect to their kinetics of guanine nucleotide exchange and their interactions with phospholipids. Myristoylation is shown to allow the release of bound GDP at physiological (mM) concentrations of Mg2+. GDP dissociation is slow in the absence of phospholipids but is accelerated 2-fold in the presence of phospholipid vesicles. On the contrary, myristoylation decreases 10-fold the rate of dissociation of GTP or guanosine 5'-O-(thiotriphosphate) (GTP gamma S) in the presence of phospholipids. As a result, myr-ARF1 can be spontaneously activated by GTP or GTP gamma S (t1/2 approximately 30 min at 37 degrees C) at 1 mM Mg2+, in the sole presence of phospholipid membranes without the need for a nucleotide exchange factor. In contrast to the nonacylated protein, the GDP-bound form of myr-ARF1 interacts with phospholipids, as demonstrated by its cosedimentation with phospholipid vesicles and its comigration with phospholipid/cholate micelles on gel filtration. The interaction is, however, weaker than for the GTP-bound form, suggesting that only the myristate in myr-ARF1GDP interacts with phospholipids, whereas both the myristate and the amino-terminal hydrophobic residues in myr-ARF1GTP bind to phospholipids.

ADP-Ribosylation Factor 1↗
PubMed1995

Effect of macrophage blockade on the resistance of inbred mice to Paracoccidioides brasiliensis infection.

The effect of macrophage blockade on the natural resistance and on the adaptative immune response of susceptible (B10.D2/oSn) and resistant (A/Sn) mice to Paracoccidioides brasiliensis infection was investigated. B10.D2/oSn and A/Sn mice previously injected with colloidal carbon were infected ip with yeast cells to determine the 50% lethal dose, and to evaluate the anatomy and histopathology, macrophage activation, antibody production and DTH reactions. Macrophage blockade rendered both resistant and susceptible mice considerably more susceptible to infection, as evidenced by increased mortality and many disseminated lesions. P. brasiliensis infection and/or carbon treatment increased the ability of macrophages from resistant mice to spread up to 25 days after treatment. In susceptible mice the enhanced spreading capacity induced by carbon treatment was impaired at all assayed periods except at 1 week after infection. Macrophage blockade enhanced DTH reactions in resistant mice, but did not alter these reactions in susceptible mice, which remained anergic. To the contrary, macrophage blockade enhanced specific antibody production by susceptible mice, but did not affect the low levels produced by resistant mice. The effect of macrophage blockade confirms the natural tendency of resistant animals to mount DTH reactions in the course of the disease and the preferential antibody response developed by susceptible mice after P. brasiliensis infection. On the whole, macrophage functions appear to play a fundamental role in the natural and acquired resistance mechanisms to P. brasiliensis infection.

Animals↗
PubMed1995

A vasoactive serum component and reactivity of isolated rat aorta after chronic alcohol administration.

Norepinephrine-induced contractility and relaxation to acetylcholine of isolated aortas taken from normal and chronic alcoholic rats were measured. Similar experiments were performed adding serum from normal (NS) or alcoholic rats (AS), with or without norepinephrine and acetylcholine. Responses of normal and alcoholic aortas to agonists were comparable. NS and AS induced contractions on normal aorta, but the responses of alcoholic aortas were lower; contractions induced by AS on both aortas were larger than those induced by NS. AS decreased verapamil-induced relaxation more than NS. A pressor circulating factor might be responsible.

Acetylcholine↗
PubMed1995

Direct detection of proviral gag segment of human immunodeficiency virus in peripheral blood lymphocytes by colorimetric PCR assay as a clinical laboratory tool applied to different at-risk populations.

We used a colorimetric polymerase chain reaction (PCR)-based assay in kit form to detect directly human immunodeficiency virus type 1 (HIV-1) proviral gag sequences in peripheral blood cells from 68 healthy blood donors, 51 subjects at risk for HIV infection, 122 patients with HIV-1 infection, 11 patients with indeterminate Western blot (immunoblot) results, 4 blood donors HIV-1 positive by enzyme immunoassay, and 13 children born to HIV-1-seropositive mothers. The results obtained in the blood donors and HIV-1-infected patients demonstrated the high degree of diagnostic specificity and sensitivity of the PCR method. HIV-1 infection was excluded in 10 of the 11 patients with indeterminate Western blot results and in all four enzyme immunoassay-positive blood donors. A diagnosis of HIV infection was ruled out by negative PCR results in 5 of 13 children from seropositive mothers, which excluded vertical transmission of the infection in these cases; these children were younger than 3 months and had positive serological results. Two at-risk patients with negative serological results had positive PCR results. All results were confirmed by conventional PCR. In conclusion, colorimetric PCR, which is commercially available in kit form, is an easy and reliable technique that can be used to detect proviral HIV-1 genomes in blood cells, and despite the limitations owing to HIV genome variability, it is useful in the clinical setting for the diagnosis of HIV infection in selected categories of patients.

Blotting, Western↗
PubMed1995

[Acute myocarditis with severe cardiac dysfunction in the pediatric population. The evolution and differential characteristics with respect to adult myocarditis].

AIMS: The aim of our study was to assess the spontaneous outcome of acute myocarditis associated with severe cardiac dysfunction in children, as well as to compare these features with those occurring in adult patients. METHODS: Fifty patients consecutively diagnosed of acute myocarditis during the last 7 years in our hospital were studied; 15 patients were children younger than 14 years, and 35 were adults. Immunosuppressive therapy was not used in any patient. RESULTS: Mean age was 2 +/- 3 years in children, ranging from 2 months to 12 years. One patient required temporary pacing for a third-degree atrioventricular block, while the remaining 14 children had severe congestive heart failure, with a left ventricular ejection fraction of 30 +/- 12% (16 to 44%). After a mean follow-up of 21 +/- 26 months, only 3 children died, at 1, 4 and 10 months after the initial diagnosis. Death was sudden in all 3 patients. Left ventricular ejection fraction rose to 45 +/- 14% at 1 month after diagnosis, and to 58 +/- 15% at the end of follow-up. Unfavorable evolution (death or evolution to chronic dilated cardiomyopathy, with a left ventricular ejection fraction < 45%) occurred in 6 children (40%) at 1 month after diagnosis and in only 4 (25%) at the end of follow-up. The 9 children with 1-month favorable outcome were alive and had an ejection fraction > 45% at long-term, while only 2 of the 6 children with 1-month unfavorable outcome were alive and had an ejection fraction > 45% at long-term. Only the 3 children who died had an ejection fraction < 30% at 1-month. Favorable outcome was more frequent in children that in adult patients with acute myocarditis (75% versus 46%). CONCLUSIONS: The outcome of acute myocarditis with severe cardiac dysfunction was favorable in a majority of pediatric patients; this favorable evolution was less frequent in adults. Patients in whom left ventricular ejection fraction did not increase at short-term had a higher risk of death, and they should probably be considered for heart transplantation.

Acute Disease↗