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Biomedical subjects

F Pons

Publications and source records attributed to F Pons.

At least 217 records · Page 12Linked to original sources

[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon].

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.

Adult↗

Effect of endothelin-1 on blood pressure and bronchopulmonary system of the guinea pig.

The bronchopulmonary and pressor effects of endothelin-1 (ET-1), a newly described vasoconstrictor peptide produced by endothelial cells, were investigated in the guinea pig. Intravenous injection of ET-1 (1 nmol/kg) induced an increase in pulmonary inflation pressure (PIP) as well as an important and sustained increase in arterial blood pressure (BP). Pretreatment of these animals with propranolol (1 mg/kg i.v.), provoked a significant enhancement of the ET-1-induced increase in PIP, accompanied by a dramatic and significant decrease of BP. When administered by aerosol for 1 min, ET-1 (1, 5, or 10 micrograms/ml) induced a dose-dependent increase in PIP that was maximal by 4-5 min, but no significant change of BP. Pretreatment of guinea pigs with propranolol (1 mg/kg), mepyramine (1 mg/kg i.v.), nifedipine (50 mg/kg i.p.), or verapamil (0.3 mg/kg i.v.) did not inhibit the bronchopulmonary response evoked by aerosol administration of 10 micrograms/ml of ET-1. In contrast, pretreatment of the animals with indomethacin (10 mg/kg i.v.) or BN 52021 (10 mg/kg i.v.) significantly reduced the bronchopulmonary response of ET-1 given by aerosol. Injection of ET-1 (0.1, 0.3, and 1 micrograms) into isolated guinea pig lungs caused significant increases in PIP that were accompanied by the release of TxB2 but not histamine. These results demonstrate that ET-1 induces bronchopulmonary alterations in the guinea pig that appear to be dissociated from the systemic vascular effects of the peptide.

Animals↗

Anti-myosin heavy chain monoclonal antibodies reveal two IIB (fast) fiber subtypes.

Indirect immunofluorescence analysis of different rat skeletal muscles using anti-myosin heavy chain (MHC) monoclonal antibodies (MAb) revealed the presence of two immunologically distinct kinds of fibers within the IIB fibers, histochemically identified by myosin ATPase staining. Some IIB fibers (designated here as IIB1) were unreactive with one anti-fast MHC MAb, whereas they did react with another anti-fast MHC MAb; other IIB fibers (designated here as IIB2) reacted with both anti-fast MAbs. Neither of the two IIB fiber subtypes was significantly reactive with a neonatal MHC MAb. The number of each IIB fiber subtype was age-dependent, at least in the plantaris muscle. IIB1 fibers were observed only in the superficial portion of the plantaris and gastrocnemius muscle. The ratio of IIB1:IIB2 fibers was about the same throughout the extensor digitorum longus and extraocular muscles. Therefore, the two kinds of IIB fibers here observed have a different myosin heavy chain content. On the basis of their specific immunoreactivities, we suggest that IIB1 fibers contain the previously described MHCB. IIB2 fibers contain either a unique new MHC isoform or a mixture of at least two MHC, possibly composed of the MHCB and either the previously described MHCA or a new MHC isoform.

Adenosine Triphosphatases↗

Indium-111-labeled platelets in monitoring human pancreatic transplants.

We have performed 59 111In-labeled platelet scintigraphies in 12 patients with pancreas transplant, and we have compared retrospectively the 111In platelet uptake with the graft immunological situation. A diffuse uptake in the graft was seen in five of six patients with pancreatic rejection. The scans became positive before changes in biochemical tests were detected. No 111In platelet uptake was seen in five of seven normally functioning grafts. Two cases of venous thrombosis and two perigraft hematomas appeared like a focal 111In platelet accumulation. Indium-111-labeled platelet scintigraphy can be a useful method for monitoring pancreas transplants. It may be helpful in the early detection of pancreatic allograft rejection and in the differential diagnosis between this and other complications such as thrombosis or hematomas.

Adult↗

Cation binding sites on actin: a structural relationship between antigenic epitopes and cation exchange.

Divalent cations such as Mg2+ and Ca2+, which bind specifically to actin, induce conformational changes that affect its antigenic structure. The distribution of antigenic epitopes on the sequence shows that these structural modifications involve epitopes related to monomer-monomer interfaces. In the N-terminal part, the 1-7 acidic extremity is not affected, in contrast with sequence 18-28. The ability of polycations such as diamine to modify the actin structure at concentrations below 0.1 microM strengthens the hypothesis that in vivo these compounds act locally and specifically on actin polymerization.

Actins↗

Abnormal scintigraphic evolution in AA hepatic amyloidosis.

A patient with AA amyloidosis secondary to ankylosing spondylitis showed intense liver uptake of Tc-99m MDP on bone imaging. The biopsy showed hepatic amyloid deposition. A repeat bone scan with Tc-99m MDP 1 year later was negative, although the clinical signs and liver function tests of the patient had not changed. A mechanism might exist, other than the affinity of amyloid to calcium, which would explain the extraosseous uptake of pyrophosphates and diphosphonates in organs and soft tissues affected by systemic amyloidosis.

Amyloidosis↗

Uptake of technetium-99m DISIDA by bone metastasis from a hepatoma.

Uptake of Tc-99m DISIDA in a bone metastasis from a hepatoma located at the humeral head is reported. Previous literature has only shown extrahepatic uptake of hepatobiliary agents in cases of lung metastases from hepatocellular carcinoma. The use of imaging with biliary tracers can increase the diagnostic specificity when bone metastases from hepatoma are suspected.

Bone Neoplasms↗

Bone scan in systemic amyloidosis.

Thirty patients diagnosed as having systemic amyloidosis (six with primary amyloidosis and 24 with secondary amyloidosis) were given bone scans with 99Tcm-methylene diphosphonate in order to evaluate the skeletal and extra-osseous uptake and their clinical-scintigraphic correlation. Extra-osseous uptake appeared in nine instances, more frequently in primary (5/6) than in secondary (4/24) amyloidosis. Fourteen patients had clinical and echocardiographic suspicion of cardiac amyloidosis but only one showed cardiac uptake. Six patients had probable hepatic involvement but in only two cases was hepatic uptake seen. The extra-osseous uptake suggests the presence of amyloid deposits in the organs and soft tissues which take up the bone tracer. The absence of any uptake does not rule out amyloid infiltration.

Adult↗

Technetium-99m DISIDA hepatobiliary agent in diagnosis of hepatocellular carcinoma: relationship between detectability and tumor differentiation.

The present investigation was aimed to assess the usefulness of biliary agents scintigraphy in the diagnosis of hepatocellular carcinoma (HCC) and to ascertain the relationship between the uptake of these agents and the degree of HCC differentiation. Forty-four patients with this hepatic cancer were included in the study. Liver scans were performed 20 min and 3 hr after the administration of 99mTc diisopropyliminodiacetic acid (DISIDA). DISIDA scintigraphy could not be assessed in six cases. In 16 (42%) out of the remaining 38 patients, the tumor exhibited equal or greater radioactivity uptake than the surrounding liver. In six out of these 16 patients, tumor uptake was apparent in the early and delayed hepatic scans, while in the other ten subjects radioactivity uptake by the HCC could only be detected in the 3-hr delayed scans. In the remaining 22 patients, HCC appeared as a cold area. Tumor location by this technique did not differ from that observed by 99mTc-sulfur colloid scan or ultrasound. DISIDA uptake was significantly related to tumor differentiation: 70% of those well differentiated tumors exhibited DISIDA uptake, whereas it was found in only 30% of those moderately differentiated and in none of those poorly differentiated (p less than 0.05). These results show that DISIDA scintigraphy can be useful in the diagnosis of HCC. Since its sensitivity is related to the degree of tumor differentiation, it may be indicated when aspiration cytology is unable to distinguish between well differentiated HCC and reactive changes due to hepatic cirrhosis.

Carcinoma, Hepatocellular↗

Expression of myosin light chains during fetal development of human skeletal muscle.

The expression of myosin light chains (MLCs) during the development of human skeletal muscle was investigated by using two different two-dimensional electrophoretic techniques. In both electrophoretic systems the predominant light chain 1 (LC1) expressed during the whole fetal period was found to co-migrate with the adult fast LC1 (LC1F). The main LC2 expressed during the whole fetal period was found to be different from the main fast LC2 (LC2F) and slow LC2 (LC2S) usually present in adult muscle, but co-migrated with a minor component often present in adult muscle. This fetal LC2 was phosphorylatable, and the phosphorylated form co-migrated with the main component of LC2F expressed in the adult. The adult fast LC3 appeared as early as week 20 of gestation, whereas the adult slow light chains (LC1S and LC2S) appeared only during the late fetal period. A minor component of LC1, previously described in humans as an 'embryonic LC' (LCemb.) [Strohman, Micou-Eastwood, Glass & Matsuda (1983) Science 221, 955-957], was only expressed in the early fetal period and was found to co-migrate with atrial LC1 (ALC1). We discuss the expression of these specific developmental forms of MLCs co-existing with immature myosin heavy chains during fetal life.

Adult↗

Lithium as an adjuvant of iodine-131 uptake when treating patients with well-differentiated thyroid carcinoma.

Differences in the I-131 uptake by 14 metastatic lesions from well-differentiated thyroid carcinoma and 12 local remnants of normal thyroid tissue before and after an adjuvant therapy with lithium carbonate, were observed. After the adjuvant treatment and administration of an I-131 tracer dose, a considerable increase of radioiodine uptake in all metastatic lesions was found (P less than 0.001), but only a slight increase was found in 50% of the normal tissue. The response to lithium carbonate by neoplastic tissue seems to be different than that of the normal thyroid tissue, and produces a lengthening of the average I-131 biologic life that could be helpful when treating well-differentiated thyroid carcinoma.

Adenocarcinoma↗

Immunocytochemical analysis of myosin heavy chains in human fetal skeletal muscles.

Quadriceps muscle samples from human fetuses (10 weeks of gestation to term) were studied using immunocytochemical methods with monoclonal antibodies against fetal, adult-slow and adult-fast B myosin heavy chains. The monoclonal antibodies were selected for their virtually exclusive specificity for a particular isomyosin and used to investigate the expression of different myosin heavy chains during fetal development of muscle fibres. Concomitant studies of the myofibrillary ATPase pattern of muscle fibres were carried out. A fetal-specific myosin was persistently expressed during fetal life but at a continuously decreasing rate. Adult-slow myosin was observed in a small pool of muscle fibres, histochemically undifferentiated, in fetuses of 14-16 weeks of gestation. However, adult isomyosins appeared intensively only in the late fetal period, progressively replacing fetal myosin. The genes coding for adult-slow myosin are expressed earlier that those coding for adult-fast myosin. Myosin heavy chains specific for the neonatal period were not demonstrated with the antibodies used in this study. The contribution, provided by the present study, to the knowledge of the sequence of events in the expression of myosin heavy chains during normal muscle development, may allow a better understanding of eventual myosin changes which may occur in genetic muscle disorders.

Adult↗

Purification and characterization of myosins from human and rabbit skeletal muscles by using specific monoclonal antibodies.

By using immunoaffinity column chromatography slow (I) and fast (IIA, IIB) myosins were isolated from human (vastus lateralis) and rabbit (tibialis anterior, psoas and conoidal bundle) skeletal muscles. The peptide pattern revealed that slow (I) and fast (IIA, IIB) myosin heavy chains are quite distinct, as are those from pure slow (conoidal bundle) and fast (psoas) rabbit skeletal muscles. Unlike Billeter et al. (1981) the authors observed that fast human myosins were always associated with a small amount of slow myosin light chains. The fast myosins (IIA, IIB) from rabbit tibialis anterior muscle did not appear very distinct and contained only fast myosin light chains. These myosins were different from the IIB myosin from the psoas muscle. Ten per cent of the fibres revealed histochemically as fast IIA also reacted with an anti-slow myosin antibody. The classical histochemical techniques appear inadequate to demonstrate the existing differences among fibre types, but the monoclonal antibodies hold promise.

Animals↗

Myosin detection in human myometrium with a monoclonal antibody.

A monoclonal antibody was prepared from a mouse immunized with human gravid uterine myosin. This monoclonal antibody is specific for the myosin heavy chains of human smooth muscle as determined by radioimmunoassay and immunoblotting experiments. Frozen cryostat sections isolated from different uterine regions were studied by immunofluorescence in order to detect myosin distribution within cells of nongravid, gravid, and pathologic human uteri. Myosin was detectable in the cytoplasm of all uterine muscle cells. No fiber heterogeneity with regard to myosin distribution was detected among or within the different uterine regions, regardless of which physiologic or pathophysiologic situation was studied. A large increase in the cell size was observed during pregnancy. These preliminary observations suggest the value of further production of monoclonal antibodies specific for the different putative molecular variants of uterine myosin and their potential use in identifying individual cells containing different myosin variants.

Antibodies, Monoclonal↗

Characterization and distribution of myosin variants in normal and pathological human hearts.

Hybridomas were prepared from mice immunized with myosin from the enlarged left ventricle of a 53-year-old female bearing an obstructive cardiomyopathy. With several different experimental approaches using anti-myosin antibodies, at least two subpopulations of atrial and at least two subpopulations of ventricular myosin were detected, characterized and located in normal human hearts. The human atrium and human ventricle each contained small zones of myosin variation which were scattered, but probably not randomly distributed, within a large area of myocardium whose cellular distribution of myosin was constant. Recent applications of the same approach to the study of the regional variations of the different myosin forms within two pathological human hearts are discussed.

Adenosine Triphosphatases↗

Fiber types and myosin types in human atrial and ventricular myocardium. An anatomical description.

Hybridomas were prepared from mice immunized with myosin from the enlarged left ventricle of a 53-year-old female with an obstructive cardiomyopathy. The specificity of 15 monoclonal antibodies to myosin heavy chains was assessed by the reactivity of muscle extracts and of chymotryptic myosin fragments of different sizes with these antibodies, as determined by the immune replicate technique; some of the monoclonal antibodies cross-reacted only with the ventricular V3-type myosin from hypothyroid rats, whereas the other antibodies cross-reacted both with the latter and with the ventricular V1-type myosins from normal young rats. Immunological heterogeneity of the fibers from human atrial muscles and from human ventricular muscles was detected by some of the antimyosin antibodies by means of indirect immunofluorescence. Histochemical fiber heterogeneity was also detected by adenosine triphosphatase staining of the same tissues. Because of the close correspondence observed between the immunological and histochemical responses of atrial fibers, it has been postulated that at least two distinct types of myosin exist in the human atrium, each myosin form being histochemically related to either alpha- or beta-like ventricular myosin heavy chains. In contrast, there was no direct correspondence between the two experimental approaches in human ventricles, and it is postulated that at least three distinct types of myosin exist within the human ventricles, one V1-type myosin, presumably corresponding to the very rare fibers with an alkaline-stable adenosine triphosphatase activity, and two other V3-type myosins corresponding to immunologically different fibers, each having an alkaline-labile adenosine triphosphatase activity. Monoclonal antibodies that can distinguish among the different myosin variants were further used to provide the basis for an anatomical description of fiber types and myosin types within the human atrial and ventricular myocardium in the whole hearts of two young boys who died sudden violent deaths. Small zones of myosin variation were seen to be scattered, but probably not randomly distributed, within large areas of myocardium in which the cellular distribution of myosin was constant; the large areas had one myosin distribution specific for each cardiac cavity. No clear-cut conclusions can yet be made concerning the physiological role of the regional variations observed in the distribution of the different molecular forms of myosin.

Adenosine Triphosphatases↗