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Biomedical subjects

F Pons

Publications and source records attributed to F Pons.

At least 181 records · Page 10Linked to original sources
PubMed1993

Myosin expression in semitendinosus muscle during fetal development of cattle: immunocytochemical and electrophoretic analyses.

The pattern of expression of different types of myosin and the development of different muscle cell populations were studied in the semitendinosus muscle of cattle from 39 d of gestation to 30 d of post-natal life. Monoclonal antibodies specific to different myosin heavy chains were used. Two cell generations were identified during myogenesis. They appeared successively and were characterized by different patterns of expression of myosins. The first population, which was present from the first stage studied (39 d of gestation), gave rise to type I fibers, which, in the mature animal, express only slow myosin. A second generation became differentiated at about 120 d of fetal life and then developed into type II fibers (IIa, IIb or IIc). The beginning of differentiation was characterized in all the cell populations by the expression of specific types of embryonic or fetal myosins. A comparison of these results with findings from previous works shows a marked similarity between species in the pattern of myogenesis but great differences in the length of the different stages of development. In this respect, myogenesis in cattle closely resembles that in man.

Animals↗
PubMed1993

Mdx transgenic mouse: restoration of recombinant dystrophin to the dystrophic muscle.

We report the restoration of the 430-kD dystrophin in mdx, the mouse model of Duchenne muscular dystrophy, by expression of a single-copy recombinant dystrophin transgene. Muscle-specific expression was achieved using a creatine kinase promoter influenced by two enhancers. Immunostaining with anti-Xp21-coded dystrophin monoclonal antibodies showed that the recombinant dystrophin was localized to the muscle fiber membrane. However, there was variability in the level of dystrophin expression in various animals with aging, between fast and slow muscles, and within different regions of the same muscle. Curiously, recombinant dystrophin was relatively absent in the diaphragm muscle of these mdx transgenic animals. Our studies indicate that there is a direct correlation between the level of muscle fibers expressing recombinant dystrophin and the level of muscle fibers with peripheral nuclei, indicating an improvement in muscle pathology. These studies indicate that the regional expression of recombinant dystrophin in dystrophic muscle leads to regional restoration of normal muscle morphology.

Animals↗
PubMed1993

Detection and quantitative analysis of joint activity inflammation with 99Tcm-polyclonal human immunoglobulin G.

99Tcm-polyclonal human immunoglobulin G (HIG) scintigraphy was used to detect active joint inflammation and to obtain ratios of joint uptake in noninvolved and inflammatory joints. Imaging was performed at 4 and 24 h in 16 patients with rheumatoid arthritis (RA) and 16 with degenerative joint disease (control group). All joints (total of 1344) were scored for pain, swelling and visual analysis of uptake in both scans. Joint to background (J:B) ratios were also calculated. Clinical and visual scores correlated in both scans (r = 0.7, P < 0.01). In RA patients, 246 joints were clinically involved. Visual analysis of scans detected 213 (87%) of them at 4 h and 196 (80%) at 24 h. Joints with no pain or swelling showed significantly higher J:B ratios than the control group and lower ratios than joints clinically involved. In the control group, statistically significant differences in J:B ratios between the various joints were found, so it was necessary to establish a normal range for every joint. J:B ratios were significantly higher at 4 h than at 24 h in both groups of patients. 99Tcm-HIG scintigraphy allows detection and measurement of joint inflammation. Scans performed at 4 h are preferable to scans at 24 h. Quantitative analysis can measure more objectively the degree of activity and could be useful in the management of these patients.

Aged↗
PubMed1993

Radioimmunoscintigraphy of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody (CYT-103) has been performed in 24 patients with five primary lesions and 10 suspicious of recurrence (in one of these patients two RIS were made). Histopathological confirmation of the disease and surgical liver examination were carried out in all primary tumours and in 12 possible recurrences. In the remaining eight patients a final diagnosis was established according to the clinical course and other diagnostic procedures. Planar and tomographic scans were obtained at 48 and 72 h postinjection in all patients. All primary tumours were detected by RIS. In the group with recurrences confirmed pathologically the results were nine true positive, two true negative and one false positive in a patient affected only with liver disease. The nine true positive studies corresponded to four positive by computed tomography (CT), four negative by CT and one nonconclusive by CT. Surgical liver examination results were 15 true negative and two false negative. No correlation was found between serum levels of carcinoembryonic antigen or TAG-72 and the detection of the lesions. In 10 patients human anti-mouse antibody (HAMA) levels were studied. In conclusion, RIS with an anti-TAG-72 monoclonal antibody is a useful technique for the study and localization of colorectal tumours, mainly in cases of recurrence, being also indicated in patients with normal TAG-72 serum levels.

Aged↗
PubMed1993

Role of platelet-activating factor (PAF) in platelet accumulation in rabbit skin: effect of the novel long-acting PAF antagonist, UK-74,505.

1. The contribution of platelet-activating factor (PAF) to platelet deposition and oedema formation induced by exogenous soluble mediators, zymosan particles and associated with a reversed passive Arthus (RPA) reaction in rabbit skin was investigated by use of a novel long-acting PAF receptor antagonist, UK-74,505. 2. Oedema formation and platelet accumulation were simultaneously measured by i.v. injection of [125I]-albumin and 111In-labelled rabbit platelets. UK-74,505 was either administered i.v. or used to pretreat radiolabelled platelets in vitro before their injection into recipient animals. Platelets pretreated with UK-74,505 were also labelled with the fluorescent calcium indicator, Fura-2, to assess their ex vivo reactivity to PAF at the end of the in vivo experiment. 3. UK-74,505 (0.5 mg kg-1), administered i.v., inhibited PAF-induced oedema formation, but did not affect oedema induced by zymosan particles, bradykinin (BK), histamine, formyl-methionyl-leucylphenylalanine (FMLP), zymosan-activated plasma (ZAP, as a source of C5a des Arg), leukotriene B4 (LTB4) or interleukin-8 (IL-8). 4. UK-74,505, administered i.v. also suppressed the small platelet accumulation induced by exogenous PAF, but had no effect on accumulation induced by IL-8 or ZAP. Although oedema induced by zymosan was not affected by i.v. UK-74,505, zymosan-induced platelet accumulation was significantly attenuated by the antagonist. 5. The RPA reaction in rabbit skin was associated with marked oedema formation and platelet accumulation which were both inhibited by i.v. UK-74,505. 6. In vitro, UK-74,505 inhibited aggregation and the increase in intracellular calcium concentration induced by PAF in rabbit washed platelets in a concentration-dependent manner (IC50 = 1.6 x 10-8 M and 1.1 x 10-8 M, respectively). Platelets pretreated with 10-6 M UK-74,505, and maintained at 37 degrees C,were unresponsive to PAF, whilst responding normally to thrombin, for up to 4 h.7. In a second series of in vivo experiments, platelets were labelled with 111In and loaded with Fura-2.The platelets were then pretreated with 10-6 M UK-74,505, washed, and injected into recipient rabbits.These platelets, prepared from blood samples taken at the end of the in vivo experiments, exhibited an 80% reduction in their response to PAF as measured ex vivo with Fura-2. However, in contrast to the effects of i.v. UK-74,505, platelets pretreated with the antagonist did accumulate effectively in the RPA reaction, a significant reduction only being observed in responses at the lowest antibody dose. In addition, pretreatment of platelets had no effect on the small platelet accumulation induced by PAF.8. These results suggest that PAF is an important mediator of oedema formation and platelet accumulation in the RPA reaction in rabbit skin. However, they question the role of PAF receptors on platelets in this model. The results also indicate that PAF may be involved in platelet accumulation induced by zymosan in rabbit skin.

Animals↗
PubMed1993

Clinical evolution of sacral stress fractures: influence of additional pelvic fractures.

OBJECTIVES: To evaluate the clinical evolution of sacral stress fractures in relation to the scintigraphic pattern and the presence of additional pelvic fractures. METHODS: This was a retrospective study of 14 patients with sacral fractures. RESULTS: Six patients had additional pelvic fractures. Four bone scintigraphic patterns were found. The resolution of symptoms was longer in patients with associated pelvic fractures (30 weeks v three weeks). No relation was found between the bone scintigraphic pattern and the time of evolution. CONCLUSION: Associated pelvic fractures delay the resolution of symptoms in patients with sacral fractures, regardless of scintigraphic pattern.

Aged↗
PubMed1992

Involvement of a phosphoramidon-sensitive endopeptidase in the processing of big endothelin-1 in the guinea-pig.

In anaesthetized and ventilated guinea-pigs, i.v. injection of 1 nmol/kg big endothelin-1 (big ET-1) did not evoke significant changes in pulmonary inflation pressure (PIP) and mean arterial blood pressure (MBP), whereas injection of the same dose of endothelin-1 (ET-1) induced marked and rapid bronchoconstrictor and pressor responses. Administered at the dose of 10 nmol/kg, big ET-1 provoked significant increases in PIP and MBP, which developed slowly and were long-lasting as compared to those evoked by ET-1. When big ET-1 was incubated for 45 min at 37 degrees C with alpha-chymotrypsin (2 mU/nmol) or pepsin (1 microgram/nmol) and then injected into guinea-pigs at the dose of 1 nmol/kg, marked bronchoconstrictor and pressor responses were observed, with kinetics similar to those noted after administration of the same dose of ET-1. The magnitude of the alpha-chymotrypsin- or pepsin-treated big ET-1 responses was similar to that induced by ET-1, incubated or not with the enzymes. Injected i.v. at the dose of 5 mg/kg, 5 min before the challenge, phosphoramidon almost totally inhibited the bronchoconstrictor and pressor responses induced by 10 nmol/kg big ET-1, whereas thiorphan (5 mg/kg) partially reduced the increase in PIP and exerted a minimal effect on the changes in MBP. Administered at the dose of 20 mg/kg per os, 1 h before i.v. administration of 10 nmol/kg big ET-1, enalapril maleate and captopril did not significantly alter the bronchoconstriction and the hypertensive response evoked by the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

The effect of hormone replacement therapy on postmenopausal bone loss.

Eighty-four postmenopausal women who were randomly allocated to one of four groups, completed a 1 year follow-up. The first group (n = 20) received 0.625 mg/day conjugated estrogens cyclically (CE; 25 days/month). The second (n = 23) received 0.625 mg/day of CE continuously, and the third (n = 17) received 50 micrograms/day of transdermal 17 beta-estradiol cyclically (24 days/month). All these groups also received 2.5 mg of medroxiprogesterone acetate sequentially for the last 12 days of hormone replacement therapy, while the fourth group (n = 24) constituted a treatment-free control group. Dual photon absorptiometry was carried out before therapy and was repeated after 1 year. Serum calcium, phosphate and osteocalcine levels, and the urinary calcium/creatinine and hydroxyproline/creatinine ratios, were measured prior to treatment and 6 and 12 months thereafter. All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous CE treatment group (4.4%, P less than 0.05) and in transdermal group (7.1%, P less than 0.01). Concomitant biochemical effects at 6 and 12 months, reduction in urine calcium and hydroxyproline, reduction in blood calcium, phosphate and osteocalcine, were compatible with the observed effects on bone mineral.

Bone Density↗
PubMed1992

Proteolytic susceptibility of the central domain in chicken gizzard and skeletal muscle dystrophins.

We investigated proteolytic susceptibility of the central domain in dystrophin molecules from chicken smooth and skeletal muscles. Dystrophin-enriched preparations from both muscles were made as described in Pons et al. (Proc. Natl. Acad. Sci. USA (1990) 87, 7851-7855). These preparations contained other protein components in addition to dystrophin. Three enzymes (Staphylococcus aureus proteinase, chymotrypsin and trypsin) having different proteolytic specificities were used. Time-courses of proteinase degradation were examined by the Western immunoblot technique using a specific polyclonal serum directed against a fragment (residues 1173-1728) of the dystrophin central domain. We observed accumulation of some major proteinase-resistant fragments, in the 110-160 kDa range originating from that central region of the molecule. Cleavage patterns of the smooth and skeletal muscle preparations were quite similar, but molecular weights of the breakdown products differed slightly. Interpretation of the results was based on two predictive structural models of the dystrophin central domain (Koenig and Kunkel (1990) J. Biol. Chem. 265, 4560-4566 and Cross et al. (1990) FEBS Lett. 262, 87-90). Skip residues at the end of repeat 13 (around the 1740th residue of the dystrophin amino acid sequence), as hypothesized in the Cross model, constitute probably the most sensitive site within the dystrophin central domain for any exogenous (or even endogenous) proteinase. Variations observed between dystrophins from skeletal and smooth muscles also suggest that the structures of both dystrophins differ slightly even within the dystrophin central domain. This precise identification of proteinase-resistant dystrophin fragments of variable lengths is a first step towards further physicochemical studies on the very large and rare dystrophin molecule.

Animals↗
PubMed1992

Diagnostic value of technetium-99m-MIBI as a myocardial perfusion imaging agent: comparison of long and short intervals between rest and stress injections.

To assess the diagnostic value of technetium-99m-MIBI (99mTc-MIBI) as a myocardial perfusion imaging agent, and if rest and exercise scans could be performed on the same day, 21 patients with coronary artery disease were studied. Qualitative planar 201-thallium (201Tl) scans, coronary angiography, or both were also performed (median between studies 11 days). In 10 patients an injection of 740 mBq of 99mTc-MIBI at stress was followed by a second injection of 740 mBq at rest 24 h later (long interal) (LI). In 11 patients injection of 370 mBq at rest was followed 3 h later by an injection of 740 mBq at stress (short interval) (SI). Exercise scans were performed to similar maximal work load (LI = 6.6 +/- 1.8 METs; SI = 6.3 +/- 1.7 METs; 201Tl = 6.8 +/- 1.2 METs; p = NS) and double product (LI = 19551 +/- 7370; SI = 19900 +/- 6797; 201Tl = 19965 +/- 5282; p = NS). Overall, 99mTc-MIBI and 201Tl agreed in 92% of the patients tested and in 165 of 180 (92%) left ventricular segments in both 99mTc-MIBI protocols using short and long intervals between injections. In 15 patients with significant stenosis, 99mTc-MIBI correctly identified 13 patients (sensitivity of 87%). Thus, 99mTc-MIBI is a useful imaging agent with similar diagnostic value as 201Tl. In spite of its lack of myocardial redistribution, 99mTc-MIBI rest and exercise scans performed on the same day seem to have a similar concordance rate with 201Tl as when performed on separate days.

Adult↗
PubMed1992

Probing myosin light chain 1 structure with monoclonal antibodies.

Five monoclonal antibodies that react with different regions of myosin light chain 1 from human ventricular myocardial muscle were used to obtain information on interactions between the light chain 1 and heavy chains and generally on the tertiary structure of the light chain 1 within the myosin head. We performed Western blot assays of the five antibodies with myosins from different cardiac and skeletal muscles, with different proteolytic fragments of bovine ventricular myosin light chain 1 (LC1) and to different recombinant fragments of human ventricular LC1 and rat fast skeletal light chain LC1/LC3. The five antibodies were mapped in three different regions of the light chain 1: two antibodies mapped within the first eight amino-terminal residues, two between residues 71 and 74, and one between residues 129 and 134. The apparent dissociation constants of the last three antibodies, determined by antibody-antigen equilibria in solution, were lower than when isolated light chains were used as antigens. It is probable that the corresponding amino acids involved in the antibody epitopes were either involved in interactions between the light and heavy myosin subunits, or somehow hindered by the myosin heavy chain bulk. In contrast, the apparent dissociation constants measured for both other antibodies were higher when myosin, rather than isolated light chains, was used as antigen. Thus LC1 fixation to heavy chains within the myosin molecule induced conformation changes at the amino-terminal end of the light chain 1. No difference in the accessibility of this mobile LC1 segment was detected in the presence of actin. Finally, observed differences in epitope accessibility on the light chain LC1 in myosin, as compared with chymotryptic subfragment 1 (SF1), indicated conformational differences between native myosin and extensively studied SF1 molecules.

Amino Acid Sequence↗
PubMed1992

Properties of chicken cardiac dystrophin.

We investigated the presence of dystrophin by immunoblot and immunofluorescence analyses, negative staining, rotatory shadowing and immunogold electron microscopy in chicken cardiac muscle. Saponin was found to be better than Triton X-100 for providing a new 'dystrophin-enriched' solution for use in biochemical studies of the molecule. By Western blot analysis, only a 400-kDa band was revealed with polyclonal antibodies directed against a central region (residues 1178-1723) of the dystrophin molecule and no cross-reactions with other proteins or degraded products were observed. Specific cleavage of the dystrophin molecule showed that the central rod-shaped domain corresponded to a resistant 'core'. This structure might rigidify the protein. By immunofluorescence, dystrophin was localized at the periphery of cardiac ventricular cells. The molecule was examined by electron microscopy and found to have variable lengths (140-160 nm for the monomeric from and about 260 +/- 10 nm or more for oligomeric forms). These oligomeric structures are considered to be associated molecules which are only partially overlapped lengthwise. The precise distribution of dystrophin within the cardiac muscle was determined by visualisation of gold particles in immuno-electron microscopy. Gold particles were found on the sarcolemma with no evidence of any association with cytoplasmic structures. The present data provide further details on the cardiac dystrophin molecule and suggest that its capacity of self-association may elasticize the dystrophin dimer.

Animals↗
PubMed1992

[Electromyographic, histoenzymologic and immunocytochemical aspects of affected muscles in HIV infection. Observations of five cases].

In 5 acquired-immunodeficiency syndrome (AIDS) cases without peripheral neuropathy, we observed myogen clinical signs (diffuse amyotrophy of lower limbs or cramps) or an isolated increase in seric enzyme (LDH, CK). EMG abnormalities were observed in all cases: spontaneous activities (fibrillations and positive sharp waves) in 5 cases, myogenic signs in 2 case. Muscular biopsies were normal in 3 cases and showed myopathic changes in 1 case and polymyositis in another case. Antidystrophin and antilaminin antibodies reactions were altered in 1 case. The spontaneous activities together with these modifications could be in favour of a lesion at the membrane level.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Expression of various NCAM isoforms in human embryonic muscles: correlation with myosin heavy chain phenotypes.

Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol-anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol-anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development.

Aging↗
PubMed1992

Radioimmunoscintigraphy of colorectal carcinoma with a 99Tcm-labelled anti-CEA monoclonal antibody (BW 431/26).

Radioimmunoscintigraphy (RIS) with BW 431/26 monoclonal antibody (MoAb) labelled with 99Tcm (962 MBq) has been performed in 64 patients with colorectal carcinoma, one of them with two independent tumours. The group consisted of 46 primary lesions, 15 pelvic recurrences and four suspected recurrences which were shown to be liver metastases. Imaging of liver was obtained in all patients, but surgical liver examination was performed in only 56 of them. Planar scans were obtained at 4 and 24 h postinjection. Tomographic images were also performed in five patients. The final diagnosis was confirmed in all patients by their clinical course and by findings at surgery and pathology. A comparative study between the RIS results and the final diagnosis gave a global sensitivity in primary tumours and pelvic recurrences of 59.7% with an accuracy of 59.0%. When rectal tumours were excluded, the results were 81.1 and 84.9%, respectively. In liver metastases the sensitivity was 50%, with an accuracy of 85.7% and a specificity of 100%. No correlation has been found between CEA serum levels and lesion detection. In conclusion, RIS is a useful technique for the study and localization of colorectal tumours, being also indicated in patients with normal carcinoembryonic antigen (CEA) serum levels and clinical suspicion of illness.

Aged↗
PubMed1992

Reduced spinal and femoral bone mass and deranged bone mineral metabolism in chronic alcoholics.

Prevalence and factors which may influence the development of osteoporosis have been assessed in 32 chronic alcoholic males by measuring the bone mineral density (BMD) of the lumbar spine and femoral neck by dual photon absorptiometry. Serum bone Gla-protein, as an index of bone formation, 25-hydroxyvitamin D, testosterone and cortisol levels were also measured. Eleven patients (34%) had osteoporosis. In seven the lumbar BMD was below the fracture threshold. Lumbar and femoral neck age-matched BMD were below mean normal values in 20 and in 23 patients, respectively. Moreover, the age-matched BMD was significantly lower in the femoral neck (91.7 +/- 14.4%) than in the lumbar spine (100.1 +/- 17.1%) (P < 0.001). Duration of alcoholism was significantly higher in patients with age-matched BMD below 100% than in those with age-matched BMD above 100%. Bone GLA-protein and 25- hydroxyvitamin D were below normal levels in 67% and 56% of patients, respectively. Serum testosterone was normal in all but two patients, and cortisol was within normal values in all patients tested. In addition a direct correlation was found between the days of abstinence before the study and serum levels of bone GLA-protein (r = 0.64, P < 0.001). In conclusion, chronic alcoholics frequently have bone loss of the lumbar spine and femoral neck related with the duration of alcohol intake. The correlation between bone-GLA protein levels and the days of abstinence suggests that alcohol directly depresses bone formation. Likewise, the low levels of vitamin D also support that this deficiency may contribute to the development of osteopenia in chronic alcoholism.

Adult↗