Search PubMed⌕ Search

Biomedical subjects

G Lyons

Publications and source records attributed to G Lyons.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Results of repeated pulmonary resection in new homolateral neoplastic localization after conservative resection].

From 1978 through 1992, 93 patients with a previous lobectomy for bronchogenic cancer were referred for homolateral cancer recurrence. Forty-six patients were contraindicated for carcinologic reasons (30 stage IIIb and 16 stage IV). Forty-seven patients (50.5%) were resectable, but 17 did not undergo surgery for associated medical problems (n = 11) or refusal (n = 6). The remaining 30 patients form the population of the present study: 29 males and 1 female; mean age of 61 years (range 47-72). The previous cancer was stage I in 26 and stage II in 4. The mean interval between the 2 cancer diagnoses was 30 months (range 6-97). Three patients underwent an exploratory thoracotomy (10%): 2 had mediastinal involvement and 1 had pleural metastases. Twenty-two (73%) underwent a completion pneumonectomy, and 5 had miscellaneous conservative resections. There were 4 operative deaths (13%): one intraoperative bleeding, 1 postoperative bleeding, 1 pulmonary embolism, 1 pneumonia. Four patients had nonfatal surgical complications: 2 clottings (reexploration), 1 empyema (lavage) and 1 bronchopleural fistula (thoracoplasty). Resected patients were staged as follows: 13 stage I, 4 stage II, 10 stage III. Survival following resection including operative mortality at 3 an 5 years was estimated as 52.5% and 44% for the whole series (72% for stage I). We conclude that repeat surgery conveys an increased risk, but may achieve valuable long-term results.

Aged↗
PubMed1993

In vitro chamber specification during embryonic stem cell cardiogenesis. Expression of the ventricular myosin light chain-2 gene is independent of heart tube formation.

The molecular cues that control patterning of the heart tube during early cardiogenesis are largely unknown. The present study has explored the embryonic stem (ES) cell differentiation system to determine if this in vitro model could be useful in studying the process of regional specification of cardiac muscle cells at the earliest possible stages. As assessed by polymerase chain reaction, ribonuclease protection, in situ hybridization, and immunohistochemical analyses, ES cell differentiation into embryoid bodies is characterized by the transcriptional and translational activation of the ventricular regulatory (phosphorylatable) myosin light chain gene, demonstrating that ventricular specification occurs during ES cell cardiogenesis. The finding of a ventricular-specific marker in an in vitro system in the absence of an intact heart tube provides evidence for cardiac regional specification independent of positional cues or physiologic stimuli. The temporal expression of the myogenic regulatory factors, myogenin and MyoD, suggests activation of the skeletal muscle program following cardiac myogenesis in vitro, indicating temporal fidelity to the progression of in vivo myogenesis. These data establish the mouse embryonic stem cell system as a model for cardiac chamber specification and suggest a promising approach in the study of regional specification in genetically engineered cardiac muscle cells.

Animals↗
PubMed1993

Modulation of contractile protein gene expression in fetal murine crural muscles: emergence of muscle diversity.

The modulation of contractile protein gene expression in mouse crural muscles (i.e., muscles located in the region between the knee and ankle) during the fetal period (defined as 15 days gestation to birth), resulting in diversity among and within these muscles, has been evaluated with in situ hybridization and correlated with morphogenetic events in the extensor digitorum longus and soleus muscles. During the fetal period extensive secondary myotube formation occurs in the crural muscles, and the myotubes become innervated (Ontell and Kozeka [1984a,b] Am. J. Anat. 171:133-148, 149-161; Ontell et al. [1988a,b] Am. J. Anat. 181:267-278, 181:278-288). At 15 days gestation, hybridization with 35S-labeled antisense cRNA probes demonstrates the accumulation of transcripts for alpha-cardiac and alpha-skeletal actin; MLC 1A, MLC 1F, and MLC 3F; and MHC emb, MHC pn, and MHC beta/slow. At 16 days gestation, accumulation of MHC emb transcripts is reduced (as compared with earlier developmental stages); intensity of signal following hybridization with the probe for alpha-skeletal actin is, for the first time, equal to that for the cardiac isoform; and MLC 1V mRNA accumulation is discernible. At this stage, variation in transcript accumulation for some mRNAs among and within crural muscles becomes evident. Two factors may play a role in the selective distribution of these transcripts: 1) the stage of muscle maturation; and 2) the future myofiber type. At 16 days gestation anterior crural muscles (which mature approximately 2 days before posterior crural muscles; Ontell and Kozeka [1984a,b], ibid., Ontell et al. [1988a,b], ibid.) exhibit a greater accumulation of transcripts for alpha-skeletal actin and for MLC 3F than is found in posterior crural muscles. In muscles that in the neonate are composed, in large part, of slow myofibers, MHC beta/slow and MLC 1V mRNAs accumulate in greater amounts, whereas MHC pn transcripts are less abundant in the soleus muscle than in other crural muscles. By 19 days gestation regionalization of transcript accumulation is more pronounced. The soleus muscle, a predominantly slow twitch muscle in the newborn mouse (Wirtz et al. [1983] J. Anat. 137:109-126) exhibits strong signal after hybridization with probes specific for MHC beta/slow and MLC 1V. While the level of transcript accumulation for the development isoforms, MHC emb, MLC 1A, and alpha-cardiac actin, is greatly reduced in most crural muscles at 19 days gestation, these transcripts persist in the soleus muscle at levels equal ot or exceeding their amount in limb muscles of 13 day gestation mouse embryos.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Contractile protein gene expression in primary myotubes of embryonic mouse hindlimb muscles.

The time course of contractile protein [actin, myosin heavy chain (MHC) and myosin light chain (MLC)] gene expression in the hindlimb muscles of the embryonic mouse (< 15 days gestation) has been correlated with the expression of genes for the myogenic regulatory factors, myogenin and MyoD, and with morphogenetic events. At 14 days gestation, secondary myotubes are not yet present in crural muscles (M. Ontell and K. Kozeka (1984) Am. J. Anat. 171, 133-148; M. Ontell, D. Bourke and D. Hughes (1988) Am. J. Anat. 181, 267-278); therefore, all transcripts for contractile proteins found in these muscles must be produced in primary myotubes. In situ hybridization, with 35S-labeled antisense cRNAs, demonstrates the versatility of primary myotubes in that transcripts for (1) alpha-cardiac and alpha-skeletal actin, (2) MHCembryonic, MHCperinatal and MHC beta/slow, and (3) MLC1A, MLC1F and MLC3F are detectable at 14 days gestation. While the general patterns of early activation of the cardiac genes and early activation of the genes for the developmental isoforms are preserved in both myotomal and limb muscles (D. Sassoon, I. Garner and M. Buckingham (1988) Development 104, 155-164 and G. E. Lyons, M. Ontell, R. Cox, D. Sassoon and M. Buckingham (1990) J. Cell Biol. 111, 1465-1476 for myotomal muscle), there are a number of differences in contractile protein gene expression. For example, in the myotome, when myosin light chain genes are initially transcribed, hybridization signal with probe for MLC1A mRNA is greater than that with probe for MLC1F transcripts, whereas the relative intensity of signal with these same probes is reversed in the hindlimb. The order in which myosin heavy chain genes are activated is also different, with MHCembryonic and MHCperinatal preceding the appearance of MHC beta/slow transcripts in limb muscles, while MHCembryonic and MHC beta/slow appear simultaneously in the myotomes prior to MHCperinatal. In the myotome, an intense hybridization signal for alpha-cardiac and a weak signal for alpha-skeletal actin transcripts are detectable prior to myosin mRNAs, whereas in the limb alpha-cardiac actin transcripts accumulate with myosin transcripts before alpha-skeletal actin mRNA is detectable. These differences indicate that there is no single coordinate pattern of expression of contractile protein genes during initial formation of the muscles of the mouse.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1993

[Induction phenomena during vertebrate limb development and homeo box gene expression].

In tetrapod vertebrates, limbs are formed as a result of inductive interactions between ectoderm and mesoderm. The mesoderm from the limb field induces the formation, in the ectoderm, of a pseudo-stratified epithelium, the apical ectodermal ridge, which in turn is required for limb mesoderm outgrowth and patterning. Homeobox genes from the msh family are expressed in the apical region of limb bud mesoderm. Using the potential of chick experimental embryology, we have demonstrated that these genes respond to ecto-mesodermal induction at this site and may be implicated in the response of the mesoderm to the ectodermal inductive activity. This property appears to be more general for the sites in the embryo which grow and are patterned as a result of interactions between ectoderm and subjacent mesoderm, since many of them are places for the expression of the msh-related genes (e.g. fronto-nasal and maxillary processes, tooth germ, genital tubercle). These genes might be implicated in patterning events at these sites through the activation of other genes directly involved in the definition of positional information, such as Hox genes.

Amino Acid Sequence↗
PubMed1992

MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites.

The accumulation of two myogenic regulatory proteins, MyoD and myogenin, was investigated by double-immunocytochemistry and correlated with myosin heavy chain expression in different classes of myoblasts in culture and during early myogenesis in vivo. During in vitro differentiation of fetal myoblasts, MyoD-positive cells were detected first, followed by the appearance of cells positive for both MyoD and myogenin and finally by the appearance of differentiated myocytes and myotubes expressing myosin heavy chain (MHC). A similar pattern of expression was observed in cultures of embryonic and satellite cells. In contrast, most myogenic cells isolated from newly formed somites, expressed MHC in the absence of detectable levels of myogenin or MyoD. In vivo, the appearance of both myogenin and MyoD proteins was only detected at 10.5 d postcoitum (d.p.c.), when terminally differentiated muscle cells could already be identified in the myotome. Parasagittal sections of the caudal myotomes of 10.5-d-old embryos showed that expression of contractile proteins preceded the expression of myogenin or MyoD and, when coexpressed, MHC and myogenin did not co-localize within all the cells of the myotome. In the limb bud, however, many myogenin (or MyoD) positive/MHC negative cells could be observed in the proximal region at day 11. During further embryonic development the expression of these proteins remained constant in all the muscle anlagens examined, decreasing to a low level during the late fetal period. Western and Northern analysis confirmed that the myogenin protein could only be detected after 10.5 d.p.c. while the corresponding message was clearly present at 9.5 d.p.c., strongly suggesting a posttranscriptional regulation of myogenin during this stage of embryonic development. These data show that the first myogenic cells which appear in the mouse myotome, and can be cultured from it, accumulate muscle structural proteins in their cytoplasm without expressing detectable levels of myogenin protein (although the message is clearly accumulated). Neither MyoD message or protein are detectable in these cells, which may represent a distinct myogenic population whose role in development remains to be established.

Animals↗
PubMed1992

Combined epidural/spinal anaesthesia for caesarean section. Through the needle or in separate spaces?

An evaluation of a 30 gauge spinal needle in a combined epidural/spinal anaesthetic technique for Caesarean section revealed a 25% failure rate of the spinal element. In this unit, no more than 4% of spinal anaesthetics might be expected to fail. One of the reasons for the higher failure rate was that, when using the Tuohy needle as an introducer, the dura was not identified. This prompted us to compare the 'through-the-Tuohy' or needle within needle approach for combined epidural/spinal anaesthesia, with a technique that involved siting the epidural and spinal sequentially in separate spaces. One hundred women requiring elective Caesarean section under spinal anaesthesia were randomised into single or double space groups. The technique failed in 16% of through-the-needle cases, and in 4% of sequential sitings. Combined spinal/epidural anaesthesia for Caesarean section is more successful if each procedure is performed using separate spaces.

Adult↗
PubMed1992

Diclofenac for analgesia after caesarean section.

The analgesic efficacy of a single intramuscular dose of 75 mg diclofenac given after elective Caesarean section was studied in 50 women in a double-blind randomised manner using a patient-controlled analgesia system. The mean 18 h papavaretum consumption of the placebo group was significantly greater (91.4 mg compared to 61.4 mg). Subjective experience of pain and observed sedation were significantly greater in the control group up to 6 h after operation.

Adult↗
PubMed1992

Apical ridge dependent and independent mesodermal domains of GHox-7 and GHox-8 expression in chick limb buds.

The homeobox-containing genes GHox-7 and GHox-8 have been proposed to play fundamental roles in limb development. The expression of GHox-8, by the apical ridge cells, and GHox-7, in the subridge mesoderm, suggests the involvement of these two genes in limb outgrowth and proximo-distal pattern formation. A straightforward way to test this is to remove the apical ridge. Here we report the relationship between the mesodermal expression of GHox-7 and GHox-8 and the apical ectodermal ridge in the chick limb bud. The data from ridge removal experiments indicate that there are at least two domains of GHox-7 expression in the apical limb bud mesoderm. The posterior subridge GHox-7 domain in the progress zone requires the influence of the apical ridge for continued expression, while the anterior GHox-7 domain continues expression after ridge removal. Posterior subridge mesoderm is exquisitely sensitive to the loss of the ridge in that GHox-7 expression by these cells is reduced in only two hours and undetectable by three hours after ridge removal. It would appear that one of the ways progress zone cells respond to the apical ridge signal is by expressing GHox-7. The loss of ridge influence whether by growth at the apex or by ridge removal is followed by an unusually rapid decline in detectable GHox-7 transcripts. Maintenance of GHox-8 expression by the anterior mesoderm appears to be independent of the presence of the apical ridge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Expression of muscle genes in the mouse embryo.

Using isogene specific probes and in situ hybridization on sections, we have examined the expression of structural and regulatory genes in the mouse embryo during the formation of cardiac and skeletal muscle. The temporal and spatial information thus obtained about the onset of expression of muscle genes provides insight into the regulation of myogenesis in vivo. Actin and myosin sequences present in different compartments of the adult heart are initially all co-expressed in the cardiac tube (between 7-8 days). The process of spatial restriction to atrial or ventricular compartments of the heart takes place asynchronously later. In contrast, the onset of expression of actin and myosin genes in the first skeletal muscle, the myotome, which corresponds to the central compartment of the somite, as well as their subsequent down-regulation in different skeletal muscle masses, takes place very asynchronously. One might predict that factor(s) responsible for the transcriptional activation of these genes are present in sufficient quantity in the cardiac tube, whereas in skeletal muscle individual genes are responding to variable levels of factor(s). In fact the four myogenic regulatory sequences present in the mouse - MyoD1, myogenin, myf-5 and myf-6 - do show distinct patterns of expression during the development of skeletal muscle. None of these sequences have been detected in the heart. In the myotome there is no general correlation between the appearance of a particular myogenic sequence and the activation of a particular structural gene. A striking example of this is provided by the muscle isoform of creatine phosphokinase. We would propose that each muscle structural gene has a different threshold of activation, depending on the quantity and nature of the myogenic factor present. We have also examined the onset of expression of the X-linked dystrophin gene known to be expressed in adult heart and skeletal muscle. In the myotome dystrophin transcripts are first detected at the time when myosin heavy chains first accumulate and muscular contraction is initiated. In contrast in the cardiac tube dystrophin transcripts are not detected initially, at a time (from 8 days) when the heart contracts. This observation can be correlated with the pathology of the disease which points to a more essential role of dystrophin in skeletal muscle. No muscle structural gene examined is expressed in the somite prior to myotome formation. If the myogenic regulatory sequences are implicated in muscle cell determination then they should be expressed in the dermomyotome of the immature somite which gives rise to muscle precursor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1992

Carbonic anhydrase 3 (CA3), a mesodermal marker.

Carbonic anhydrase 3 (CA3) is an abundant muscle protein characteristic of adult type 1, slow-twitch, fibres. The protein plays an important role in facilitated CO2 diffusion and diverse processes involving H+ and HCO-3 transport. Nucleotide sequence comparisons have identified putative promoter and enhancer regions in the 5' flanking sequences of the CA3 gene. Functional assays show that 2.8kb of 5' flanking sequence efficiently promotes transcription of a reporter gene in a muscle specific manner. Removal of sequences 5' to -722bp leads to a major loss of activity and this result implies that the proximal promoter region which includes a GArG box and four potential MyoD1 binding sites is not adequate for maximal transcription. The longest CA3 promoter construct is also active in 10T1/2 cells, which are precursor mesodermal cells and do not normally express CA3. In situ hybridization to mRNA in developing mouse embryos reveals a pattern of expression in myotomes and pre-muscles masses of the limb buds which is consistent with the regulation of CA3 by myogenic determination factors. These studies also showed that CA3 expression is not confined to cells of the muscle lineage since it is expressed in primitive mesoderm prior to the onset of myogenesis. Later in embryogenesis CA3 defines a subset of mesodermal cell types which includes not only skeletal muscle but also notochord and adipocytes.

Animals↗
PubMed1991

The apical ectodermal ridge regulates Hox-7 and Hox-8 gene expression in developing chick limb buds.

We show that expression of the two related chicken homeo box genes, Hox-7 and Hox-8, which is widespread in the lateral mesoderm at early stages, becomes restricted to the mesoderm underlying the apical ectodermal ridge as limbs develop. Expression in the limb bud mesoderm is not maintained in the limbless mutant, which does not form an apical ridge. The mutant can be rescued by grafting normal ectoderm to the limb field. This leads to expression of the two homeo box genes in the mesoderm under the induced ridge. Phenocopies of eudiplopodia, which form an ectopic ridge on the limb bud, express the two genes under both ridges. When a quail ridge is grafted over nonexpressing mesoderm, a new site of expression is induced. Therefore, Hox-7 and Hox-8 depend on a functional ridge for their continued expression in the limb bud and can be induced by it.

Amino Acid Sequence↗
PubMed1991

Awareness during caesarean section.

Between 1982 and 1989 over 3000 patients were questioned about recall and dreaming after general anaesthesia for Caesarean section. Some 28 (0.9%) patients were able to recall something of their operation and 189 (6.1%) reported dreams. There was uniform adherence to a rigid anaesthetic protocol up to and including 1985, but a much publicized incident reported from the courtroom stimulated a relaxation of this regimen. Consequently the incidence of awareness decreased from 1.3% to 0.4%, and the incidence of dreaming was also reduced. Recollections of surgery were confined to manipulations, noises and voices. None of our patients complained of pain at the time of interview, although one since has. The inadequacies of the initial protocol and an approach to informed consent are discussed.

Adult↗
PubMed1991

Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo.

We have analysed by in situ hybridization the expression of myf-5, the murine homologue of the human myogenic regulatory sequence myf5, during embryogenesis in the mouse. myf-5 sequences were first detected in the earliest somites (from about 8 days p.c.) in the dermomyotome, before formation of the dermatome, myotome and sclerotome. The dermomyotome is classically considered to give rise to the precursor muscle cells of body and limb skeletal muscle. myf-5-positive cells were also detected early in the visceral arches and limb buds. In this case, as in somites, myf-5 expression precedes that of the two related myogenic regulatory sequences, myogenin and MyoD1, and indeed any other skeletal muscle marker examined to date. myf-5 is not detected at any stage in developing cardiac muscle. From 11.5 days p.c., the level of myf-5 transcripts begins to decrease to become undetectable (by in situ hybridization) from 14 days p.c. Both the appearance and disappearance of myf-5 follow the anteroposterior gradient of somite formation and maturation in the embryo. The time and place of myf-5 expression are consistent with a role in the early events of myogenic differentiation, possibly during determination of the myogenic lineage.

Animals↗