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At least 1,189 records · Page 66Linked to original sources
PubMed1985

Elevated rate of DNA synthesis and its correlation to cAMP-phosphodiesterase activity during induction of polydactyly in mouse embryos heterozygous for Hemimelia-extra toe (Hmx).

The induction of polydactyly in mouse embryos heterozygous for Hemimelia-extra toe (Hmx) is associated with aberrant outgrowth of the developing autopod on day 12 of gestation. We have quantitated the rate of DNA synthesis and the activity of cAMP-phosphodiesterase (PDE) that is characteristic of the prospective polydactylous region. Mid-stage 18 hind-limb buds were labeled with [3H]dThd either in situ using whole embryo culture, or as isolated preaxial autopod fragments cultured on a membrane substratum. The mean specific activities of incorporation were compared for normal (+/+) and mutant (Hmx/+) genotypes. A significant (P less than or equal to 0.01) 19% increase, peculiar to the prospective polydactylous region, was measured after 4 hours in embryo culture. The same increment was detected after 4 hours in organ culture, but was amplified linearly to 55% when incubation was extended to 20 hours. During this period, continuous exposure to 1.0 mM IBMX (3-isobutyl-1-methyl xanthine), an inhibitor of cAMP-PDE activity, "slowed down" the rate of DNA synthesis to untreated +/+ proportions. When cAMP-PDE activity was assayed in uncultured autopods, a significant (P less than or equal to 0.01) 18% increase was detected within the prospective polydactylous region specifically on stage 18 of gestation. This is the developmental phase during which polydactylous outgrowth is induced in situ. Thus, uncontrolled cAMP-PDE activity may, in part, provoke the enhanced rate of cell proliferation.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Dorsoventral patterning of the telencephalon is disrupted in the mouse mutant extra-toes(J).

Little is known about the mechanisms that control the development of regional identity in the mammalian telencephalon. The Gli family of transcription factor genes is involved in the regulation of pattern at many sites in the embryo and is expressed in the embryonic mouse telencephalon. We have analyzed telencephalic patterning in the extra-toes (J) (Xt(J)) mouse mutant, which carries a deletion in the Gli family member Gli3. We report that dorsoventral patterning of the telencephalon is dramatically disrupted in the Xt(J) mutant. Specific dorsal telencephalic cell types and gene expression patterns are lost in homozygous Xt(J) mutants, and features of ventral telencephalic identity develop ectopically in the dorsal telencephalon. This partial ventralization of the dorsal telencephalon does not appear to be induced by an expansion of Sonic hedgehog expression in the telencephalon, but may be due to a loss of Bmp and Wnt gene expression in a putative dorsal telencephalic signaling center, the cortical hem. Our findings suggest that in dorsal telencephalon Gli3 is needed to repress ventral telencephalic identity.

Animals↗
PubMed2002

The Fused toes (Ft) mouse mutation causes anteroposterior and dorsoventral polydactyly.

Mouse mutants have been proven to be a valuable system to analyze the molecular network governing vertebrate limb development. In the present study, we report on the molecular and morphological consequences of the Fused toes (Ft) mutation on limb morphogenesis in homozygous embryos. We show that Ft affects all three axes as the mutant limbs display severe distal truncations of skeletal elements as well as an anteroposterior and an unusual form of dorsoventral polydactyly. Ectopic activation of the Shh signalling cascade in the distal-most mesoderm together with malformations of the AER likely account for these alterations. Moreover, we provide evidence that a deregulated control of programmed cell death triggered by Bmp-4 and Dkk-1 significantly contributes to the complex limb phenotype. In addition, our analysis reveals a specific requirement of the genes deleted by the Ft mutation in hindlimb morphogenesis.

Animals↗
PubMed2000

A novel candidate gene for mouse and human preaxial polydactyly with altered expression in limbs of Hemimelic extra-toes mutant mice.

Polydactyly is a common malformation of vertebrate limbs. In humans a major locus for nonsyndromic pre-axial polydactyly (PPD) has been mapped previously to 7q36. The mouse Hemimelic extra-toes (Hx) mutation maps to a homologous chromosome segment and has been proposed to affect a homologous gene. To understand the molecular changes underlying PPD, we used a positional cloning approach to identify the gene or genes disrupted by the Hx mutation and a closely linked limb mutation, Hammertoe (Hm). High resolution genetic mapping identified a small candidate interval for the mouse mutations located 1.2 cM distal to the Shh locus. The nonrecombinant interval was completely cloned in bacterial artificial chromosomes and searched for genes using a combination of exon trapping, sample sequencing, and mapping of known genes. Two novel genes, Lmbr1 and Lmbr2, are entirely within the candidate interval we defined genetically. The open reading frame of both genes is intact in mutant mice, but the expression of the Lmbr1 gene is dramatically altered in developing limbs of Hx mutant mice. The correspondence between the spatial and temporal changes in Lmbr1 expression and the embryonic onset of the Hx mutant phenotype suggests that the mouse Hx mutation may be a regulatory allele of Lmbr1. The human ortholog of Lmbr1 maps within the recently described interval for human PPD, strengthening the possibility that both mouse and human limb abnormalities are due to defects in the same highly conserved gene.

Amino Acid Sequence↗
PubMed1987

Effects of standing cycling and the use of toe stirrups on maximal oxygen uptake.

Twenty-eight subjects (6 normal men, 14 distance runners, and 8 rowers) were tested for maximal oxygen uptake (VO2max) and associated physiological measures during bicycle ergometer exercise with toe stirrups while standing (BEts) and during treadmill exercise (TM). Correlation between BEts VO2max and TM VO2max was high (r = 0.901, p less than 0.05). No significant difference existed between the two VO2max values (60.3 +/- 8.9 vs. 60.5 +/- 9.7 ml.kg-1.min-1; n = 28). No differences were found even when three different subgroups were separately compared. It is concluded that the higher VO2max elicited during BEts as compared with normal sitting cycling may be attributed to the increased muscle blood flow and/or involvement of a larger muscle mass, the latter being partly evidenced by the observation of greater electromyographic activity during BEts.

Adult↗
PubMed2002

The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster.

As a result of transgenic insertional mutagenesis, heterozygous Fused toes (Ft) mice display a syndactyly of forelimbs and a thymic hyperplasia. Homozygous Ft/Ft embryos die in midgestation, exhibiting a deformation of craniofacial structures, a syndactyly and a polydactyly of fore- and hindlimbs, a disorganization of the ventral spinal cord, and defects in left-right axis formation. Here we report on our structural analyses of the Ft mutation. We established a physical as well as a gene map of the Ft locus, showing that the transgene integration resulted in a deletion of 1.6 Mb of genomic sequences on mouse Chromosome 8. Owing to this deletion, six genes, including the entire IroquoisB (IrxB) gene cluster, are directly affected by the Ft mutation.

Animals↗
PubMed1999

Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation.

The Fused toes (Ft) mouse mutation was created by insertional mutagenesis, resulting in the deletion of several hundred kb of genomic sequences of mouse Chromosome (Chr) 8. Mice heterozygous for the Ft mutation are characterized by partial syndactyly of forelimbs and massive thymic hyperplasia indicating that programmed cell death is affected. Homozygous Ft/Ft embryos die at midgestation and show severe malformations of craniofacial structures. Furthermore, establishment of left-right asymmetry is random. Here we report on the positional cloning of a novel gene by exon trap analysis of a genomic clone encoding wild-type sequences corresponding to parts of the deletion in Ft mutants. RT-PCR experiments demonstrated that the newly identified gene, Fatso (Fto), is expressed throughout embryonic development. Wide expression was also found in tissues of adult mice. We show that expression of Fto is completely absent in mouse embryonic fibroblasts homozygous for the Ft mutation. In addition, we isolated the full-length cDNA which encodes a putative 58-kDa protein showing no similarities to known proteins or protein motifs. The expression data of Fto define it as a candidate gene involved in processes such as programmed cell death, craniofacial development, and establishment of left-right asymmetry.

Amino Acid Sequence↗
PubMed1999

From head to toe: conservation of molecular signals regulating limb and craniofacial morphogenesis.

Recent evidence indicates that many molecules involved in generating and patterning the limbs also play a role during craniofacial morphogenesis. On the surface, this is an unexpected finding given that these regions of the body have separate evolutionary origins, are composed of different embryonic tissues, and are quite dissimilar in their anatomy. Results from several experiments involving Sonic hedgehog and retinoic acid point to a remarkable conservation of the signaling pathways mediated by these morphogens across multiple organ systems. Moreover, mutants such as the extra-toes and doublefoot mouse, and the talpid chicken also provide insights on common developmental processes that underlie the formation of the limbs and face. The identification of highly conserved aspects of morphogenesis is important for understanding fundamental mechanisms of development, as well as for revealing the common denominator of countless birth defects and providing new strategies for their prevention and cure.

Animals↗
PubMed2005

Utility of grommets for implant arthroplasty of the great toe in a patient with rheumatoid arthritis: a case report.

We report a case of rheumatoid arthritis treated by bilateral flexible hinge toe implant arthroplasty, using grommets only on one side, which resulted in bilateral fractures requiring removal of the implants 6.5 years after the surgery. Both implants were completely fractured at the bottom of the distal stems. Macroscopically, synovitis was present around both fractured stems, although the severity of synovitis and fragmentation of the fractured implant was relatively mild on the right side in which grommets were used. The shape of the body of the fractured implant was relatively preserved on the right side in which grommets were used. There was no damage or fracture of the grommets. The grommet might have acted to prevent pressures and scratches that would cause synovitis and deformity of the body of the implant, but might not completely prevent fractures of implants.

Journal Article↗
PubMed1988

Different effects of norepinephrine and serotonin on the electrical toe stimulation-induced reflexes in the rat spinal cord.

1. Electrical toe stimulation was shown to elicit reflex potentials in the ipsilateral common peroneal nerve in the rat. 2. This reflex consisted of the spinal reflex and the spino-bulbo-spinal reflex (SBS reflex). 3. Administration of norepinephrine into the subarachnoid space enhanced the spinal reflex but depressed the SBS reflex. On the other hand, serotonin enhanced both reflexes. 4. These different effects of norepinephrine and serotonin suggest different control of nociceptive reactions by these biogenic amines.

Animals↗
PubMed1984

Joseph Babinski: the phenomenon of the toes.

Joseph Babinski first described the plantar cutaneous reflex that bears his name in two papers in 1896 and 1898. He linked the sign, which he termed "the phenomenon of the toes," to disturbances of the pyramidal tract. In the nearly 90 years that have elapsed since the original description, little significant elaboration has been made upon Babinski's initial works. Although the reflex is best known in conjunction with organic disease involving structural injury to the corticospinal tract, it may be present in a number of toxic and metabolic disturbances. These are diverse, and no satisfactory explanation exists to explain the presence of the reflex in such clinical entities. In some instances the reflex reverts to normal following improvement of the underlying condition.

France↗
PubMed1990

Mapping of the two mouse engrailed-like genes: close linkage of En-1 to dominant hemimelia (Dh) on chromosome 1 and of En-2 to hemimelic extra-toes (Hx) on chromosome 5.

The mouse genome contains two genes, En-1 and En-2, with sequence similarity to the engrailed gene of Drosophila. Using conventional linkage crosses, we have shown that En-1 maps approximately 0.28 cM distal to the dominant hemimelia (Dh) gene on chromosome 1 and that En-2 maps approximately 1.1 cM proximal to the hemimelic extra-toes (Hx) gene on chromosome 5. We have also shown by Northern blot analysis that En-1 transcripts in Dh homozygotes and En-2 transcripts in Hx homozygotes are of normal size and abundance. These data, in conjunction with previously published studies of the patterns of En-1 and En-2 expression in developing mouse embryos, suggest that Dh and Hx are very unlikely to be mutant alleles of En-1 or En-2, respectively. Instead, we suggest that En-1-Dh and En-2-Hx represent paralogous linkage groups that evolved following duplication of a common ancestral chromosome segment.

Animals↗
PubMed2006

Evidence for transmitter operated electrical synapses (TOES) in ampullary electroreceptor organs.

Afferent fibres of ampullary electroreceptor organs in electrosensitive fish fire spontaneously, that is, they fire without external stimulus. In the past it has been postulated that the spontaneous activity originates from a sustained level of neurotransmitter release delivered by the electroreceptor cells. The spontaneous activity can be modulated by electrical stimuli. Blocking of the chemical synapse, however, reduces the susceptibility to electrical stimuli to 2% or less, but the spontaneous activity to 60% only. By evaluating existing experimental evidence it is concluded that spontaneous firing of afferents is based on two processes. (1) A membrane bound oscillator, which does not depend on transmitter release, is almost free of frequency fluctuations, and is described by Hodgkin/Huxley-equations (HH-equations). (2) Release of neurotransmitter, which increases the firing level, adds frequency noise, and raises the susceptibility of the afferent to electrical stimuli. There is evidence that neurotransmitter release acts as a gating process, which makes the generator area of the afferents directly accessible to electrical stimuli from the outside. Apparently, the activated synapse behaves as a transmitter operated electrical synapse (TOES).

Animals↗
PubMed2005

The great toe proximal phalanx osteotomy: the final step of the bunionectomy.

As the final step of correction of hallux valgus deformity, the great toe proximal phalanx osteotomy is useful. It is popular in France and throughout Europe. Our purpose is to distinguish and to describe different locations and three types of osteotomies according to the required final correction of the hallux valgus.

Combined Modality Therapy↗
PubMed2003

Toe out angle: a functional index for the evaluation of sciatic nerve recovery in the rat model.

In experimental peripheral nerve studies, the rat sciatic nerve model is widely used to examine functional outcome following nerve injury and repair. A variety of evaluation methods exist in the literature, but an adequate selection continues to be a critical point for the researcher. Rats with sciatic nerve injury typically ambulate with an external rotation of the foot. A new functional assessment instrument, the toe out angle (TOA) is quantified using computerized gait analysis. We compared Sciatic Functional Index (SFI) with TOA parameter after peripheral nerve transection and entubulation repair. We found a good correlation between SFI and TOA measurements in terms of predicting functional recovery. Moreover, the TOA provides information on the biomechanical consequences of the external rotation of the foot in the stance phase of walking.

Animals↗
PubMed1997

Irreducible Lisfranc's injury: the 'toe up' sign.

A new physical sign (the 'toe up' sign) is described in relation to an irreducible Lisfranc injury, the cause being the interposed lateral slip of the tibialis anterior tendon. Surgical exploration is advocated.

Accidents, Occupational↗