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PubMedDate not supplied

Cuneiform and cuboid wedge osteotomies for correction of residual metatarsus adductus: a surgical review.

Metatarsus adductus is a deformity in which the metatarsals are deviated in the transverse plane when compared with the longitudinal axis of the lesser tarsus. A brief review of the deformity is presented including the causes, radiographic analysis, conservative treatment, and a surgical approach. A series of cases of metatarsus adductus is presented in which a proximal surgical approach consisted of cuneiform and cuboid wedge osteotomies with staple fixation. The described procedure has advantages over the traditional metatarsal wedge osteotomies by providing large cancellous bone-to-bone interfaces for excellent healing potential, easier fixation, sagittal plane stability, and avoidance of the physis at the base of the first metatarsal.

Adolescent↗
PubMed2001

Mouse beta-mannosidase: cDNA cloning, expression, and chromosomal localization.

Beta-mannosidase is an exoglycosidase involved in the degradation of N-linked oligosaccharides moieties of glycoproteins. Lack of beta-mannosidase activity leads to the lysosomal disorder beta-mannosidosis (MIM 248510). We have isolated and sequenced the gene encoding the mouse beta-mannosidase. Comparison of the deduced amino acid sequence of mouse, human, bovine, and goat beta-mannosidase showed 64%, identity, reflecting a high degree of evolutionary conservation. Analysis of a multiple tissue northern blotting revealed a major transcript of about 3.7 kb in all tissues examined. The northern analysis also demonstrates that there is differential tissue mRNA expression. The mouse beta-mannosidase gene (Bmn) was mapped to the distal end of Chromosome (Chr) 3, in a region that is homologous with a segment of human Chr 4 containing the orthologous human gene.

Animals↗
PubMed2003

The oxygenase component of phenol hydroxylase from Acinetobacter radioresistens S13.

Phenol hydroxylase (PH) from Acinetobacter radioresistens S13 represents an example of multicomponent aromatic ring monooxygenase made up of three moieties: a reductase (PHR), an oxygenase (PHO) and a regulative component (PHI). The function of the oxygenase component (PHO), here characterized for the first time, is to bind molecular oxygen and catalyse the mono-hydroxylation of substrates (phenol, and with less efficiency, chloro- and methyl-phenol and naphthol). PHO was purified from extracts of A. radioresistens S13 cells and shown to be a dimer of 206 kDa. Each monomer is composed by three subunits: alpha (54 kDa), beta (38 kDa) and gamma (11 kDa). The gene encoding PHO alpha (named mopN) was cloned and sequenced and the corresponding amino acid sequence matched with that of functionally related oxygenases. By structural alignment with the catalytic subunits of methane monooxygenase (MMO) and alkene monooxygenase, we propose that PHO alpha contains the enzyme active site, harbouring a dinuclear iron centre Fe-O-Fe, as also suggested by spectral analysis. Conserved hydrophobic amino acids known to define the substrate recognition pocket, are also present in the alpha-subunit. The prevalence of alpha-helices (99.6%) as studied by CD confirmed the hypothized structural homologies between PHO and MMO. Three parameters (optimum ionic strength, temperature and pH) that affect kinetics of the overall phenol hydroxylase reaction were further analyzed with a fixed optimal PHR/PHI/PHO ratio of 2/1/1. The highest level of activity was evaluated between 0.075 and 0.1 m of ionic strength, the temperature dependence showed a maximum of activity at 24 degrees C and finally the pH for optimal activity was determined to be 7.5.

Acinetobacter↗
PubMed1999

Orthotopic ileal neobladder in male patients: functional outcomes of 66 cases.

BACKGROUND: Orthotopic urinary diversion has become the preferred form of bladder reconstruction after cystectomy. We report on our experience with 66 male patients undergoing this procedure from November 1990 to February 1998. METHODS: A neobladder was constructed using an ileal segment with a Hautmann type bladder. Complications were assessed and subdivided into early and late types. Voiding function was evaluated in terms of voiding pattern and continence. Median follow up was 19.5 (range 3.5-87.7) months. RESULTS: There was one (1.5%) perioperative death. The most frequent pouch-related and unrelated early complications were persistent urine leak (7.6%) and prolonged ileus (16.7%), respectively, the majority of cases of which were managed conservatively. Analysis of late complications revealed 6.2% ureteroileal stenosis and 1.5% urethrointestinal stenosis rates, but no case of bladder stone formation. Of the 61 patients in whom voiding function was evaluable, 95.1% achieved excellent daytime continence, while only 67.2% had night-time continence. With regard to posture at voiding, 23 (37.7%) voided in a sitting position. Three of the patients (4.9%) were unable to void and required regular intermittent catheterization. CONCLUSIONS: An orthotopic neobladder can be constructed with acceptable morbidity and excellent functional results. We believe that orthotopic urinary diversion offers an attractive alternative to a bladder substitute when cystectomy is required.

Adult↗
PubMed1996

Colocalization of cell division proteins FtsZ and FtsA to cytoskeletal structures in living Escherichia coli cells by using green fluorescent protein.

In the current model for bacterial cell division, FtsZ protein forms a ring that marks the division plane, creating a cytoskeletal framework for the subsequent action of other proteins such as FtsA. This putative protein complex ultimately generates the division septum. Herein we report that FtsZ and FtsA proteins tagged with green fluorescent protein (GEP) colocalize to division-site ring-like structures in living bacterial cells in a visible space between the segregated nucleoids. Cells with higher levels of FtsZ-GFP or with FtsA-GFP plus excess wild-type FtsZ were inhibited for cell division and often exhibited bright fluorescent spiral tubules that spanned the length of the filamentous cells. This suggests that FtsZ may switch from a septation-competent localized ring to an unlocalized spiral under some conditions and that FtsA can bind to FtsZ in both conformations. FtsZ-GFP also formed nonproductive but localized aggregates at a higher concentration that could represent FtsZ nucleation sites. The general domain structure of FtsZ-GFP resembles that of tubulin, since the C terminus of FtsZ is not required for polymerization but may regulate polymerization state. The N-terminal portion of Rhizobium FtsZ polymerized in Escherichia coli and appeared to copolymerize with E. coli FtsZ, suggesting a degree of interspecies functional conservation. Analysis of several deletions of FtsA-GFP suggests that multiple segments of FtsA are important for its localization to the FtsZ ring.

Adenosine Triphosphate↗
PubMed1996

Lipase activation by nonionic detergents. The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex.

The crystal structure of the ternary porcine lipase-colipase-tetra ethylene glycol monooctyl ether (TGME) complex has been determined at 2.8 A resolution. The crystals belong to the cubic space group F23 with a = 289.1 A and display a strong pseudo-symmetry corresponding to a P23 lattice. Unexpectedly, the crystalline two-domain lipase is found in its open configuration. This indicates that in the presence of colipase, pure micelles of the nonionic detergent TGME are able to activate the enzyme; a process that includes the movement of an N-terminal domain loop (the flap). The effects of TGME and colipase have been confirmed by chemical modification of the active site serine residue using diisopropyl p-nitrophenylphosphate (E600). In addition, the presence of a TGME molecule tightly bound to the active site pocket shows that TGME acts as a substrate analog, thus possibly explaining the inhibitory effect of this nonionic detergent on emulsified substrate hydrolysis at submicellar concentrations. A comparison of the lipase-colipase interactions between our porcine complex and the human-porcine complex (van Tilbeurgh, H., Egloff, M.-P., Martinez, C., Rugani, N., Verger, R., and Cambillau, C.(1993) Nature 362, 814-820) indicates that except for one salt bridge interaction, they are conserved. Analysis of the superimposed complexes shows a 5.4 degrees rotation on the relative position of the N-terminal domains excepting the flap that moves in a concerted fashion with the C-terminal domain. This flexibility may be important for the binding of the complex to the water-lipid interface.

Animals↗
PubMed2004

Crystal structure of human eIF3k, the first structure of eIF3 subunits.

eIF3k, the smallest subunit of eukaryotic initiation factor 3 (eIF3), interacts with several other subunits of eIF3 and the 40 S ribosomal subunit. eIF3k is conserved among high eukaryotes, including mammals, insects, and plants, and it is ubiquitously expressed in human tissues. Interestingly, eIF3k does not exist in some species of yeast. Thus, eIF3k may play a unique regulatory role in higher organisms. Here we report the crystal structure of human eIF3k, the first high-resolution structure of an eIF3 component. This novel structure contains two distinct domains, a HEAT (named for Huntington, elongation factor 3, A subunit of protein phosphatase 2A, target of rapamycin) repeat-like HAM (HEAT analogous motif) domain and a winged-helix-like WH domain. Through structural comparison and sequence conservation analysis, we show that eIF3k has three putative protein-binding surfaces and has potential RNA binding activity. The structure provides key information for understanding the structure and function of the eIF3 complex.

Amino Acid Motifs↗
PubMed2006

Genetic variation and the mitogen-activated protein kinase (MAPK) signaling pathway.

Non-synonymous single nucleotide polymorphisms (nsSNPs) are known to alter protein function, contributing to disease susceptibility. This report explores the nature of nsSNPs in the gene products of the highly conserved mitogen-activated protein kinase (MAPK) signaling pathways already implicated in cancer development. MAPK signaling pathways regulate cellular processes such as proliferation, differentiation, apoptosis, and survival mediated through interconnected signaling cascades. Using the dbSNP database, we have identified 25 nsSNPs in 17 out of 98 MAPK genes studied. Computational algorithms were used to predict whether the amino acid substitutions were evolutionarily tolerated, or affected putative functional units such as phosphorylation sites, protein motifs and domains. This study predicts that 36% of nsSNPs are likely to have functional consequences, based on evolutionary conservation analysis, and 36% based on phosphorylation prediction analysis. All such nsSNPs represent potentially functional and disease-causing/modifying alleles. More interestingly, the epistatic relationships discussed in this report represent potential synergistic/ antagonistic/additive effects of nsSNP combinations found within the same protein, or within members of the same protein complex and cascades. This strategy can effectively determine which nsSNPs potentially alter protein function, and can be utilized to study the genetic architecture and disease association of other biological protein complexes and networks.

Algorithms↗
PubMed2006

Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response.

MOTIVATION: Human Nbs1 and its homolog Xrs2 in Saccharomyces cerevisiae are part of the conserved MRN complex (MRX in yeast) which plays a crucial role in maintaining genomic stability. NBS1 corresponds to the gene mutated in the Nijmegen breakage syndrome (NBS) known as a radiation hyper-sensitive disease. Despite the conservation and the importance of the MRN complex, the high sequence divergence between Nbs1 and Xrs2 precluded the identification of common domains downstream of the N-terminal Fork-Head Associated (FHA) domain. RESULTS: Using HMM-HMM profile comparisons and structure modelling, we assessed the existence of a tandem BRCT in both Nbs1 and Xrs2 after the FHA. The structure-based conservation analysis of the tandem BRCT in Nbs1 supports its function as a phosphoserine binding domain. Remarkably, the 5 bp deletion observed in 95% of NBS patients cleaves the tandem at the linker region while preserving the structural integrity of each BRCT domain in the resulting truncated gene products.

Amino Acid Sequence↗
PubMed1994

Structure and expression of rat and mouse mRNAs for Zn-alpha 2-glycoprotein.

Rat and mouse cDNAs for Zn-alpha 2-glycoprotein (Zn alpha 2gp) were isolated from liver libraries (lambda gt11) and compared with the human one. The lengths of cDNA inserts analyzed were 1,233 and 1,273 nucleotides for rat and mouse, respectively. The deduced amino acid sequences suggested that rat and mouse Zn alpha 2gp proteins consist of 279 and 290 amino acid residues in the mature form, respectively. They have 59.4% (rat) and 58.6% (mouse) identities in amino acid sequence with the human counterpart, and between rat and mouse the identity is 88.5%. Among the three domains, domain B is best conserved; the identities are 74.7, 73.6, and 95.6% between human and rat, human and mouse, and rat and mouse, respectively. Four cysteine and eight tryptophan residues are all conserved, and two of the three asparagine residues that carry a glycan in the human protein are conserved. Analysis of rat tissues by Northern blot suggested that its mRNA is expressed in liver, and, to a much lesser extent in submandibular gland, lung, kidney, and stomach. A more detailed study by in situ hybridization demonstrated that some epithelial cells of renal tubules and the isthmus and the neck zone cells of gastric fundic glands express Zn alpha 2gp mRNA.

Animals↗
PubMed1993

Sodium- and chloride-dependent transporters in brain, kidney, and gut: lessons from complementary DNA cloning and structure-function studies.

The family of Na(+)- and Cl(-)-dependent, 12 transmembrane domain transporter proteins now includes transporters for neurotransmitter molecules in the brain and for substances important in extraneuronal tissues, including adrenal, kidney, and gut. Transported substrates include monoamine and amino acid neurotransmitters and nonperturbing osmolytes. A common protein topology is predicted and features intracellular N- and C-termini possessing phosphorylation sites and at least one large extramembranous loop with N-linked glycosylation. Using the rat dopamine transporter as a template, molecular modeling of putative transmembrane domains coupled with amino acid sequence conservation analysis indicates amino acid residues potentially involved in substrate and/or ion recognition. Targeting such residues with site-directed mutagenesis will help clarify substrate and ion binding sites and should facilitate rational design of therapeutics to combat depression, locomotor disorders, and substance abuse.

Amino Acid Sequence↗
PubMed2006

Observation of turbulent-driven shear flow in a cylindrical laboratory plasma device.

An azimuthally symmetric radially sheared plasma fluid flow is observed to spontaneously form in a cylindrical magnetized helicon plasma device with no external sources of momentum input. A turbulent momentum conservation analysis shows that this shear flow is sustained by the Reynolds stress generated by collisional drift turbulence in the device. The results provide direct experimental support for the basic theoretical picture of drift-wave-shear-flow interactions.

Journal Article↗
PubMed1997

Ab initio structure determination and refinement of a scorpion protein toxin.

The structure of toxin II from the scorpion Androctonus australis Hector has been determined ab initio by direct methods using SnB at 0.96 A resolution. For the purpose of this structure redetermination, undertaken as a test of the minimal function and the SnB program, the identity and sequence of the protein was withheld from part of the research team. A single solution obtained from 1 619 random atom trials was clearly revealed by the bimodal distribution of the final value of the minimal function associated with each individual trial. Five peptide fragments were identified from a conservative analysis of the initial E-map, and following several refinement cycles with X-PLOR, a model was built of the complete structure. At the end of the X-PLOR refinement, the sequence was compared with the published sequence and 57 of the 64 residues had been correctly identified. Two errors in sequence resulted from side chains with similar size while the rest of the errors were a result of severe disorder or high thermal motion in the side chains. Given the amino-acid sequence, it is estimated that the initial E-map could have produced a model containing 99% of all main-chain and 81% of side-chain atoms. The structure refinement was completed with PROFFT, including the contributions of protein H atoms, and converged at a residual of 0.158 for 30 609 data with F >or= 2sigma(F) in the resolution range 8.0-0.964 A. The final model consisted of 518 non-H protein atoms (36 disordered), 407 H atoms, and 129 water molecules (43 with occupancies less than unity). This total of 647 non-H atoms represents the largest light-atom structure solved to date.

Journal Article↗
PubMed2004

The effectiveness of personally tailored computer-generated advice letters for smoking cessation.

AIM: To assess the effectiveness of a new computer-generated tailored advice programme designed to be used by smokers and recent quitters having problems staying stopped. DESIGN: Randomized trial comparing a series of questionnaire assessments leading to tailored computer-generated advice letters mailed at strategically relevant times, to a no extra treatment control sent standardized printed self-help materials. SETTING: Victoria, Australia. PARTICIPANTS: A total of 1058 smokers or recent quitters recruited from callers to the Quitline. MEASUREMENTS: Smoking status and sustained abstinence at 12-month follow-up, plus extent of participation in the intervention. FINDINGS: Using a conservative analysis (missing data coded as a treatment failure), 6-month sustained abstinence was reported by significantly more participants in the computer-generated tailored advice (20%) than the standard printed materials condition (12%) at 12-month follow-up OR 1.82 (1.31-2.55)). Group differences in point prevalence abstinence (28% intervention, 25% control) were not significant. Among participants in the tailored advice condition, 6-month sustained abstinence was associated with the number of advice letters received. CONCLUSION: The provision of a series of tailored, computer-generated advice letters resulted in greater rates of sustained cessation than for controls. A dose-response relationship was found, with increased compliance with the intervention associated with improved cessation outcomes. The programme appears to have much of its effect by preventing relapse.

Adult↗
PubMed1990

Comparison of the cancer risk of methylene chloride predicted from animal bioassay data with the epidemiologic evidence.

Methylene chloride has been shown to be a lung and liver carcinogen in the mouse; yet, the current epidemiologic data show no adverse health effects associated with chronic exposure to this compound. Hearne et al. have compared the results of a large mortality study on occupational exposure to methylene chloride to the human risk predictions based on the rodent bioassay to point out the inconsistency between the animal toxicologic and human epidemiologic data. The maximum number of lung and liver cancers predicted due to methylene chloride exposure based on the rodent bioassay data was 24 compared to 14 deaths from these cancers actually observed in the Hearne et al. epidemiology study. We assess the minimum risk detectable by the human study in order to calculate the upperbound potency of methylene chloride and compare it to the potency derived from the bioassay data. Results from the epidemiology study imply an upperbound potency of 1.5 x 10(-2) per ppm, compared to 1.4 x 10(-2) per ppm calculated using the most conservative analysis of the animal data. We conclude that the negative epidemiology study of Hearne et al. is not sufficiently powerful to show that the risk is inconsistent with the human risk estimated by modeling the rodent bioassay data. Specifically, the doses to which the workers were exposed, the population studied, and the latency period were not adequate to determine that the risks are outside the bounds of the risk estimates predicted by low-dose modeling of the animal data.

Air Pollutants, Occupational↗
PubMed1991

Xylose (glucose) isomerase gene from the thermophile Thermus thermophilus: cloning, sequencing, and comparison with other thermostable xylose isomerases.

The xylose isomerase gene from the thermophile Thermus thermophilus was cloned by using a fragment of the Streptomyces griseofuscus gene as a probe. The complete nucleotide sequence of the gene was determined. T. thermophilus is the most thermophilic organism from which a xylose isomerase gene has been cloned and characterized. The gene codes for a polypeptide of 387 amino acids with a molecular weight of 44,000. The Thermus xylose isomerase is considerably more thermostable than other described xylose isomerases. Production of the enzyme in Escherichia coli, by using the tac promoter, increases the xylose isomerase yield 45-fold compared with production in T. thermophilus. Moreover, the enzyme from E. coli can be purified 20-fold by simply heating the cell extract at 85 degrees C for 10 min. The characteristics of the enzyme made in E. coli are the same as those of enzyme made in T. thermophilus. Comparison of the Thermus xylose isomerase amino acid sequence with xylose isomerase sequences from other organisms showed that amino acids involved in substrate binding and isomerization are well conserved. Analysis of amino acid substitutions that distinguish the Thermus xylose isomerase from other thermostable xylose isomerases suggests that the further increase in thermostability in T. thermophilus is due to substitution of amino acids which react during irreversible inactivation and results also from increased hydrophobicity.

Aldose-Ketose Isomerases↗
PubMed2005

Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.

OBJECTIVES: To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision. DESIGN: Randomised controlled trial. SETTING: Dunedin and Auckland, New Zealand. PARTICIPANTS: 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up. INTERVENTIONS: Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96). MAIN OUTCOME MEASURES: Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme. RESULTS: Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented. CONCLUSION: The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.

Accidental Falls↗
PubMed2005

Modelling the cost implications of using carboxymethylcellulose dressing compared with gauze in the management of surgical wounds healing by secondary intention in the US and UK.

OBJECTIVE: To estimate the costs of using carboxymethyl cellulose dressing (CMCD; Aquacel* Hydrofiber) compared to gauze in managing surgical wounds healing by secondary intention in the US and UK. STUDY DESIGN: This was a modelling study performed from the perspective of payers (i.e. the hospital and community sector in the US and the National Health Service (NHS) in the UK). METHODS: Clinical outcomes attributable to managing surgical wounds healing by secondary intention with gauze were obtained from the published literature in the English language. There were no published studies on wounds healing by secondary intention with CMCD. Hence, the analysis conservatively assumed that wound healing rates associated with gauze would be the same for CMCD. These data were combined with resource utilisation estimates derived from a panel of clinicians enabling us to perform decision modelling. The models were used to determine the expected direct healthcare costs eight weeks after the surgical wounds were dressed by CMCD or gauze and left to heal by secondary intention in the US and UK. RESULTS: All wounds are expected to heal within eight weeks, irrespective of dressing. Managing abscesses and other surgical wounds with CMCD instead of gauze in the US is expected to reduce costs by 4% in both wound types (i.e. $247 and $507 respectively) per patient over eight weeks. In the UK, managing abscesses and other surgical wounds with CMCD instead of gauze is expected to reduce costs by 30% (574 pounds) and 12% (581 pounds) respectively per patient over eight weeks. The lower cost of managing CMCD-treated patients is due to decreased nursing costs associated with a lower frequency of CMCD changes compared to gauze dressing changes. CONCLUSION: Dressing surgical wounds healing by secondary intention with CMCD instead of gauze is expected to lead to a reduction in healthcare costs in both the US and UK. Hence, the purchase price of a dressing is not indicative of the cost effectiveness of a given method of surgical wound care.

Bandages, Hydrocolloid↗