A network meta-analysis of the clinical properties of various types of supraglottic airway device in children.

We conducted both conventional pairwise and Bayesian network meta-analyses to compare the clinical properties of supraglottic airway devices in children. We searched six databases for randomised clinical trials. Our primary end-points were oropharyngeal leak pressure, risk of insertion failure at first attempt, and blood staining risk. The risk of device failure, defined as the abandonment of the supraglottic airway device and replacement with a tracheal tube or another device, was also analysed. Sixty-five randomised clinical trials with 5823 participants were identified, involving 16 types of supraglottic airway device. Network meta-analysis showed that the i-gel™, Cobra perilaryngeal airway™ and Proseal laryngeal mask airway (LMA® -Proseal) showed statistically significant differences in oropharyngeal leak pressure compared with the LMA® -Classic, with mean differences (95% credible interval, CrI) of 3.6 (1.9-5.8), 4.6 (1.7-7.6) and 3.4 (2.0-4.8) cmH2 O, respectively. The i-gel was the only device that significantly reduced the risk of blood staining of the device compared with the LMA-Classic, with an odds ratio (95%CrI) of 0.46 (0.22-0.90). The risk (95%CI) of device failure with the LMA-Classic, LMA® -Unique and LMA-Proseal was 0.36% (0.14-0.92%), 0.49% (0.13-1.8%) and 0.50% (0.23-1.1%), respectively, whereas the risk (95%CI) of the i-gel and PRO-Breathe was higher, at 3.4% (2.5-4.7%) and 6.0% (2.8-12.5%), respectively. The risk, expressed as odds ratio (95%CrI), of insertion failure at first attempt, was higher in patients weighing < 10 kg at 5.1 (1.6-20.1). We conclude that the LMA-Proseal may be the best supraglottic airway device for children as it has a high oropharyngeal leak pressure and a low risk of insertion. Although the i-gel has a high oropharyngeal leak pressure and low risk of blood staining of the device, the risk of device failure should be evaluated before its routine use can be recommended.

The potential of muscle stem cells.

Skeletal muscle contains two types of stem cells: satellite cells, which function as myogenic precursors, and a population of multipotent adult stem cells. Satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. An additional stem cell population in adult muscle displays a remarkable capacity to differentiate into hematopoietic cells as well as muscle following transplantation. This article discusses the characteristics and properties of these cell populations, the relationship between them, and the potential for stem cell-based muscle therapeutics.

Reduced differentiation potential of primary MyoD-/- myogenic cells derived from adult skeletal muscle.

To gain insight into the regeneration deficit of MyoD-/- muscle, we investigated the growth and differentiation of cultured MyoD-/- myogenic cells. Primary MyoD-/- myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD-/- myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD-/- myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD-/- cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD-/- myogenic cells. Mixing of lacZ-labeled MyoD-/- cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD-/- myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell.

MyoD and myogenin act on the chicken myosin light-chain 1 gene as distinct transcriptional factors.

Expression of MyoD, myogenin, MRF4, and Myf-5 converts nonmuscle cells to muscle cells. In an attempt to analyze the roles of these factors, we have investigated their effects on transcription driven by the promoter of the chicken myosin alkaline light-chain (MLC1) gene. The activation by CMD1 or c-myogenin (chicken MyoD or myogenin, respectively) was dependent on the existence of a muscle-specific regulatory region located from positions -2096 to -1743. Its distal half, containing a pair of E boxes (CANNTG), had been previously characterized as an enhancer responsive to CMD1 but not to c-myogenin. In this study, we report the identification of another enhancer in the muscle-specific regulatory region which is preferentially responsive to c-myogenin. Deletion and mutation analyses indicated that this enhancer requires a single E box and its flanking sequences. Furthermore, analysis of chimeric proteins of CMD1 and c-myogenin indicated that regions outside the basic helix-loop-helix domain of c-myogenin are involved in the specificity of the enhancer. These results show that CMD1 and c-myogenin act on the MLC1 gene by recognizing different upstream DNA sequences and that direct or indirect interactions between the regions outside the basic helix-loop-helix domain and flanking sequences of E boxes are involved in the target sequence specificity.

NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family.

We have identified two new genes, neuroD2 and neuroD3, on the basis of their similarity to the neurogenic basic-helix-loop-helix (bHLH) gene neuroD. The predicted amino acid sequence of neuroD2 shows a high degree of homology to neuroD and MATH-2/NEX-1 in the bHLH region, whereas neuroD3 is a more distantly related family member. neuroD3 is expressed transiently during embryonic development, with the highest levels of expression between days 10 and 12. neuroD2 is initially expressed at embryonic day 11, with persistent expression in the adult nervous system. In situ and Northern (RNA) analyses demonstrate that different regions of the adult nervous system have different relative amounts of neuroD and neuroD2 RNA. Similar to neuroD, expression of neuroD2 in developing Xenopus laevis embryos results in ectopic neurogenesis, indicating that neuroD2 mediates neuronal differentiation. Transfection of vectors expressing neuroD and neuroD2 into P19 cells shows that both can activate expression through simple E-box-driven reporter constructs and can activate a reporter driven by the neuroD2 promoter region, but the GAP-43 promoter is preferentially activated by neuroD2. The noncongruent expression pattern and target gene specificity of these highly related neurogenic bHLH proteins make them candidates for conferring specific aspects of the neuronal phenotype.

High-level secretion of the extracellular domain of the human growth hormone receptor using a baculovirus system.

A chemically synthesized gene (hGHR-ED) coding for the extracellular domain (ED) of the human growth hormone (hGH) receptor (hGHR) was inserted into the genome of Autographa californica nuclear polyhedrosis virus adjacent to the polyhedrin promoter. Spodoptera frugiperda cells infected with the recombinant virus secreted a protein with hGH-binding activity into the medium. The secreted 35-kDa protein was purified to near homogeneity. The purified protein exhibited a high binding affinity (Kd = 0.2-0.3 nM) to hGH. The highest cell production capability was estimated at more than 10-20 micrograms hGHR-ED/ml of culture. The inhibition of the hGHR-ED secretion by treatment with tunicamycin suggests that glycosylation is important for secretion.

Myosin from molluscan abalone, Haliotis discus. Isolation and enzymatic properties.

Actomyosin was extracted from smooth muscle of molluscan abalone with 0.1 M PPit pH 6.4. Myosin was separated from the actomyosin by centrifugation at 100,000 X g in the presence of 5 mM ATP and 10 mM MgCl2. Myosin in the supernatant was further purified by gel filtration on a Sepharose 4B column. Paramyosin contamination of the actomyosin preparation interfered with the isolation of myosin and complete removal of actin and paramyosin from the myosin has not been accomplished. The myosin appeared to consist of a single f-chain and a single g-chain, as examined by SDS-disc electrophoresis in 8 or 13.7% acrylamide gel. The ATPase [EC 3.6.1.3] activity of this myosin in 0.5 M KCL at neutral pH and at 0 degrees was rather unstable and decreased by 10-20% per day. The effects of rho-chloromercuribenzoate and EDTA on the ATPase activity were similar to those observed with other smooth muscle myosin but the dependence upon pH or KCL concentration was different.

The enhancement of the extracellular carboxyl-terminal domain of human growth hormone receptor on growth hormone dependent responses of 3T3-F442A cells.

We have expressed the carboxyl-terminal domain (C domain) of the cytokine receptor homologous (CRH) region of human growth hormone receptor (hGHR) as a protein fused with maltose binding protein (MBP) in E. coli. Following proteolytic cleavage by restriction protease factor Xa, the C domain was purified to homogeneity as a monomeric form. The purified C domain appears to be folded properly judged by NMR spectrum and the far-UV circular dichroism (CD) spectrum. The C domain did not exhibit ligand binding activity. However, the C domain enhanced the human growth hormone (hGH) dependent differentiation of preadipose 3T3-F442A cells into adipose cells and the phosphorylation of a 34 kDa membrane protein.

Congenital midline sinus of the upper lip. Report of a case.

The occurrence of a congenital midline sinus of the upper lip is rare, only 22 cases having been previously reported. This case report describes the excision of a congenital midline sinus of the upper lip in a 2-year-old girl.

[ATPase inhibitory activities found in the soluble fraction of an ascidian (Halocynthia rotezi) muscle].

Crude extracts obtained by water extraction from the muscle of an ascidian (Halocynthia rotezi) are shown to possess an inhibitory activity on ATPase [(Na, K) ATPase, TF1-ATPase, HMM-ATPase]. Gel filtration of the extract with Sephadex G-10 separated the activity into two peaks, and the latter peak (inhibitor II) was further purified by HPLC. This inhibitor was non-competitive for ATP and associated firmly with the (Na, K) ATPase.

[Effects of prophylactic treatment of central nervous system leukemia in children. Analysis of CNS prophylactic treatment with cyclic high dose multichemotherapy, craniospinal irradiation, and high dose infusion of MTX].

Thirty-five children with previously untreated ALL or AUL who received CNS prophylactic therapy with 8 treatment regiments were analyzed. After eutering complete remission, patients received CNS-prophylaxis with one of the following regimens: Group A- cyclic high dose multichemotherapy plus intermittent intrathecal methotrexate (MTX); Group B-craniospinal irradiation plus intermittent intrathecal MTX; Group C-intermittent high dose intravenous MTX. Incidence of CNS-leukemia and bone marrow relapse was less frequent in Group B. EEG abnormalities were seen in 38.5% of Group A, 40% of Group B, and 28.6% of Group C respectively, but the abnormalities were transient. IQs of three groups were above 100, but IQs of CNS-leukemia patients, especially VIQs had a tendency to be low.

[Multiple cooperative study of UFT-adjuvant chemotherapy for malignant tumor in the jaw and oral cavities. The Oral Surgery Malignant Tumor Research Association in Kanto Kohshinetsu District].

We studied the usefulness and safety of long-term administration of uracil and tegafur (UFT) after primary therapy of the malignant tumor in jaw and oral cavity regions randomized controlled trial. 112 cases were totallized 6 institutes belonging to the Oral Surgery Malignant Tumor Research Association in Kanto Kohshinetsu District during 2 years and 10 months, beginning in September 1986. After completing the primary therapy, treatment was not performed in group A and 400 mg/day of UFT was orally administered in group B for 1 year. A variation was observed in the stages of background factors such as sex and age (more than 30 years old and less than 80 years old), while no such discrepancy was observed in other stages. No significant difference of 1-year-survival ratio and non-recurrence ratio was noted in either group, while the non-recurrence ratio was more favorable in group B than group A, and the usefulness of UFT for adjuvant chemotherapy was suggested. The incidence of side effects in group B was 42.6%, and no serious side effect was observed.

Isolation and Characterization of a New Quinoprotein Dehydrogenase, L-Sorbose/L-Sorbosone Dehydrogenase.

Gluconobacter oxydans DSM 4025 effectively oxidizes L-sorbose to 2-keto-L-gulonic acid (2 KGA), an industrial precursor of vitamin C. From this microorganism, we purified the enzyme involved in this oxidation reaction. The enzyme is a unique quinoprotein dehydrogenase catalyzing not only the conversion of L-sorbose to L-sorbosone, but also that of L-sorbosone to 2 KGA. The molecular weight of the enzyme was about 135,000, consisting of two subunits with molecular weights of 64,500 and 62,500. As its prosthetic group, non-covalently bound PQQ was found. The dye-linked spectrophotometric enzyme assay showed that the optimum enzyme activity occurred in the pH range about 7.0-9.0, and the enzyme activity was inhibited by EDTA or EGTA. The enzyme showed extremely broad substrate specificity for primary and secondary alcohols, aldehydes, aldoses, ketoses, and other sugar alcohols, but not for methanol or formaldehyde. The cytochrome c obtained from the soluble fraction of this strain was found to act as a physiological electron acceptor of the enzyme.