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Biomedical subjects

F Tomé

Publications and source records attributed to F Tomé.

17 recordsLinked to original sources
PubMed2000

Open analogues of arcyriaflavin A. Synthesis through Diels-Alder reaction between maleimides and 1-aryl-3-tert-butyldimethylsiloxy-1, 3-butadienes.

The preparation of a range of open analogues of arcyriaflavin A is described. The synthetic approach is based on the use of perhydroisoindole-1,3,5-triones as key intermediates, which were obtained via Diels-Alder methodology using 1-aryl-3-siloxy-1, 3-butadienes as starting materials. Fischer indolization and aromatization processes afforded different methoxy-substituted arylpyrrolocarbazoles. The stereochemistry and conformation of the Diels-Alder products and the regiochemistry of the indolization reactions are supported by NMR and molecular modeling studies.

Antineoplastic Agents↗
PubMed1999

Synthesis and inotropic activity of hydroindene derivatives.

A synthetic approach to hydroindenic inotropic agents has been developed, starting from enantiopure Hajos-Parrish (1). Hajos-Wiechert (2), and related diketones. Their transformation into C-1 formyl derivatives and other subsequent synthetic targets is described. The results of the thermodynamic equilibration between both epimers of each formyl derivative are analysed. The inotropic activities of selected compounds on right and left atrial preparations are also evaluated and discussed.

Animals↗
PubMed1998

Hydroindenic-guanylhydrazones. Synthesis and evaluation as inotropic agents.

The synthesis and inotropic activity of two families of hydroindenic compounds are described. Among them, a bis-guanylhydrazone derivative has demonstrated to produce an interesting positive inotropic effect on guinea pig atria, displaying at higher dosis a similar effect to that elicited by digoxin.

Animals↗
PubMed1998

A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy.

Desmin-related myopathies (DRM) are inherited neuromuscular disorders characterized by adult onset and delayed accumulation of aggregates of desmin, a protein belonging to the type III intermediate filament family, in the sarcoplasma of skeletal and cardiac muscles. In this paper, we have mapped the locus for DRM in a large French pedigree to a 26-cM interval in chromosome 11q21-23. This region contains the alphaB-crystallin gene (CRYAB), a candidate gene encoding a 20-kD protein that is abundant in lens and is also present in a number of non-ocular tissues, including cardiac and skeletal muscle. AlphaB-crystallin is a member of the small heat shock protein (shsp) family and possesses molecular chaperone activity. We identified an R120G missense mutation in CRYAB that co-segregates with the disease phenotype in this family. Muscle cell lines transfected with the mutant CRYAB cDNA showed intracellular aggregates that contain both desmin and alphaB-crystallin as observed in muscle fibers from DRM patients. These results are the first to identify a defect in a molecular chaperone as a cause for an inherited human muscle disorder.

Animals↗
PubMed1997

Muscle-eye-brain disease: a neuropathological study.

A combination of congenital central nervous, ocular and muscular abnormalities is characteristic of muscle-eye-brain disease (MEB), of Fukuyama congenital muscular dystrophy (FCMD), and of Walker-Warburg syndrome (WWS). The nosological relationship of these inherited malformative disorders is still unestablished, although the genetic locus for FCMD has been excluded in MEB. We present the first postmortem neuropathological study of MEB based on 2 male patients. Apart from sharply limited occipital agyric areas, their brains showed coarse gyri with an abnormally nodular surface ("cobblestone cortex"). Both the cerebral and cerebellar cortices showed a total disorganization without horizontal lamination. The haphazardly oriented cortical neurons formed irregular clusters or islands, separated by gliovascular strands extending from the pia. The ocular abnormalities included a pronounced glial preretinal membrane. Although MEB shares the cobblestone cortex-type malformation with FCMD and WWS, the cerebral and ocular manifestations are less severe than in WWS. Furthermore, a consistently weak staining for laminin alpha2 chain (merosin) was found in muscle biopsy specimens from 4 MEB patients, while normal immunoreactivity was observed for the laminin beta2 chain, reported to be severely deficient in WWS. These findings support nosological independence of MEB.

Adult↗
PubMed1996

Partial laminin alpha2 chain restoration in alpha2 chain-deficient dy/dy mouse by primary muscle cell culture transplantation.

Laminin-2 is a component of skeletal and cardiac basal lamina expressed in normal mouse and human. Laminin alpha2 chain (LAMA2), however, is absent from muscles of some congenital muscular dystrophy patients and the dystrophia muscularis (dy/dy) mouse model. LAMA2 restoration was investigated following cell transplantation in vivo in dy/dy mouse. Allogeneic primary muscle cell cultures expressing the beta-galactosidase transgene under control of a muscular promoter, or histocompatible primary muscle cell cultures, were transplanted into dy/dy mouse muscles. FK506 immunosuppression was used in noncompatible models. All transplanted animals expressed LAMA2 in these immunologically-controlled models, and the degrees of LAMA2 restoration were shown to depend on the age of the animal at transplantation, on muscle pretreatment, and on duration time after transplantation in some cases. LAMA2 did not always colocalize with new or hybrid muscle fibers formed by the fusion of donor myoblasts. LAMA2 deposition around muscle fibers was often segmental and seemed to radiate from the center to the periphery of the injection site. Allogeneic conditionally immortalized pure myogenic cells expressing the beta-galactosidase transgene were characterized in vitro and in vivo. When injected into FK506-immunosuppressed dy/dy mice, these cells formed new or hybrid muscle fibers but essentially did not express LAMA2 in vivo. These data show that partial LAMA2 restoration is achieved in LAMA2-deficient dy/dy mouse by primary muscle cell culture transplantation. However, not all myoblasts, or myoblasts alone, or the muscle fibers they form are capable of LAMA2 secretion and deposition in vivo.

Age Factors↗
PubMed1995

Heterolignanolides: antitumor activity of furyl-, thienyl-, and pyridyl analogs of lignanolides.

A new class of heteroaromatic analogs of lignans, called heterolignanolides, have been tested against several tumor cell lines. These compounds carry diverse heterocyclic rings, instead of the trimethoxyphenyl ring found in the natural lignans yatein and podorhizol. They have moderate antineoplastic activity (P-388, A-549, HT-29) compared with that of yatein. None of the tested compounds has discernible antiviral (HSV-1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activity.

Animals↗
PubMed1993

Prion protein is abnormally accumulated in inclusion-body myositis.

In muscle biopsies of 8 sporadic inclusion-body myositis (S-IBM) and 4 hereditary inclusion-body myopathy (H-IBM) patients, vacuolated muscle fibers contained within their vacuoles strongly immunoreactive inclusions with 2 polyclonal and 1 monoclonal antibodies against prion protein (PrP). By light-microscopy, PrP deposits co-localized with beta-amyloid protein (A beta) and ubiquitin (Ub). By immuno-electronmicroscopy, both PrP and A beta were present on amorphous material and on 6-10 nm amyloid-like fibrils; and PrP and Ub co-localized on cytoplasmic twisted tubulofilaments (TTFs) and on amorphous material. Our study provides the first demonstration of abnormally accumulated PrP in pathological tissue other than brain, and it suggests that PrP may play a role in the pathogenesis of IBM.

Adult↗
PubMed1993

Prion protein is strongly immunolocalized at the postsynaptic domain of human normal neuromuscular junctions.

Using three well-characterized polyclonal and monoclonal antibodies against prion protein (PrP), we demonstrated a strong concentration of PrP at human neuromuscular junctions (NMJs). Applying double and triple fluorescence-labeling, we found that PrP immunoreactivity exactly co-localized with alpha-bungarotoxin (alpha-BT) identified acetylcholine receptors, as well as with the high junctional concentrations of beta-amyloid precursor protein, beta-amyloid protein, desmin, ubiquitin and dystrophin. Therefore, PrP was considered to be located on the postsynaptic muscle membrane. At all NMJs identified by bound alpha-BT, strong PrP immunoreactivity was obtained with all PrP antibodies. This appears to be the first demonstration of PrP concentrated at human NMJs.

Antibodies, Monoclonal↗
PubMed1992

Are cysteine-rich and COOH-terminal domains of dystrophin critical for sarcolemmal localization?

It has been hypothesized that the tight localization of dystrophin at the muscle membrane is carried out by its cysteine-rich and/or carboxyl domains. We report the results of biochemical and immunocytochemical investigations of dystrophin in muscle from a 1-yr-old patient with a large deletion that removes the distal part of the dystrophin gene, thus spanning the exons coding for the cysteine-rich and the carboxy-terminal domains, and extends beyond the glycerol kinase and congenital adrenal hypoplasia genes. Immunological analysis of muscle dystrophin shows that the deletion results in the production of a truncated, but stable, polypeptide correctly localized at the sarcolemma. These data indicate that neither the cysteine-rich domain, nor the carboxyl domain, are necessary for the appearance of normal dystrophin sarcolemmal localization.

Cysteine↗
PubMed1989

[Familial myopathy with "cytoplasmic body" (or "spheroid") type inclusions, disclosed by respiratory insufficiency].

Three patients, 72, 45 and 18 years old belonging to 3 successive generations presented with respiratory insufficiency. The clinical onset was at about 40 years of age in the two older patients and at 18 years in the youngest one. Serum enzymes of muscle origin were within normal range as well as leucocyte maltase activity. The muscle biopsy in all three patients showed numerous cytoplasmic (spheroid) bodies within type I muscle fibers. Familial cytoplasmic body myopathy with familial incidence has rarely been reported and still more rarely has been revealed by respiratory insufficiency in adult life.

Adolescent↗
PubMed1983

Control points in Neurospora crassa nuclear division cycle: different effects of the inhibition of protein accumulation.

The correlation between protein synthesis and the nuclear division cycle in Neurospora crassa hyphae was studied by inhibiting protein accumulation by two different experimental procedures: (1) starvation for lysine in a lysine-requiring mutant (lys-1); and (2) addition of cycloheximide. Lysine starvation in a lys-1 strain of N. crassa quickly blocked the nuclear division cycle and nuclei accumulated in G1 phase, as judged by their DNA content. After re-addition of lysine to starved cultures, a discontinuous pattern of uridine incorporation into DNA can be seen, showing that the nuclei were well synchronized. On the other hand, treatment with cycloheximide caused the arrest of a large proportion of the nuclei, also, in the G2 phase of the cell cycle. These results indicate that inhibition of protein synthesis may have multiple effects on the cell cycle in N. crassa and that, while moderate inhibition specifically blocks nuclei at a regulatory point in late G1, strong or complete inhibition demonstrates requirement for protein synthesis at other points in the cycle that are not necessarily regulatory points.

Cell Division↗
PubMedDate not supplied

[Multiple disc herniation after chiropractic manipulation].

We present a case of multiple cervical spine disc herniation in a previously healthy patient following chiropractic manipulation. The aim of this paper is to review the medical literature about the complications following spinal manipulation to emphasize the potential risks of this widely extended therapeutic procedure, performed in many cases by non-qualified personnel without medical training.

Adult↗