Ethnic differences in outcome of serum screening for Down's syndrome. Differences in median values may account for differences in false positive rates.
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Asia↗
Biomedical subjects
C Ford
Publications and source records attributed to C Ford.
Hepatitis B vaccination. All GPs in Brent and Harrow offer hepatitis B vaccination to drug users.
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Family Practice↗
Effect of replacing helical glycine residues with alanines on reversible and irreversible stability and production of Aspergillus awamori glucoamylase.
To decrease irreversible thermoinactivation of Aspergillus awamori glucoamylase, five Gly residues causing helix flexibility were replaced with Ala residues. Mutation of Gly57 did not affect thermostability. Mutation of Gly137 doubled it at pHs 3.5 and 4.5 but barely changed it at pH 5.5. The Gly139-->Ala mutation did not change thermostability at pH 3.5, improved it at pH 4.5 and worsened it at pH 5.5. The Gly 137/Gly139-->Ala/Ala mutation gave 1.5-2-fold increased thermostabilities at pHs 3.5-5.5. Mutations of Gly251 and Gly383 decreased it at all pHs. Gly137-->Ala and Gly137/Gly139-->Ala/Ala glucoamylases are the most stable yet produced by mutation. Guanidine treatment at pH 4.5 decreased the reversible stabilities of Gly137-->Ala, Gly139-->Ala and Gly137/Gly139-->Ala/Ala glucoamylases at infinite dilution while not changing those of Gly251-->Ala and Gly383-->Ala glucoamylases, which is, in general, opposite to what occurred with thermoinactivation. Mutation of Gly57 greatly improved the extracellular glucoamylase production by yeast, that of Gly137 barely affected it and those of Gly139 and of both Gly137 and Gly139 strongly impeded it. These observations suggest that alpha-helix rigidity can affect reversible and irreversible glucoamylase stability differently, that the effects of multiple mutations within one alpha-helix to improve stability are not always additive and that even single mutations can strongly affect extracellular enzyme production.
Alanine↗
Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes.
Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV.
Base Sequence↗
Vocal fold scarring: current concepts and management.
Scarring of the vocal folds can occur as the result of blunt laryngeal trauma or, more commonly, as the result of surgical, iatrogenic injury after excision or removal of vocal fold lesions. The scarring results in replacement of healthy tissue by fibrous tissue and can irrevocably alter vocal fold function and lead to a decreased or absent vocal fold mucosal wave. The assessment and treatment of persistent dysphonia in patients with vocal fold scarring presents both diagnostic and therapeutic challenges to the voice treatment team. The common causes of vocal fold scarring are described, and prevention of vocal fold injury during removal of vocal fold lesions is stressed. The anatomic and histologic basis for the subsequent alterations in voice production and contemporary modalities for clinical and objective assessment will be discussed. Treatment options will be reviewed, including nonsurgical treatment and voice therapy, collagen injection, fat augmentation, endoscopic laryngoplasty, and Silastic medialization.
Cicatrix↗
At risk nephrons and the decline in renal function in response to treatment of hypertension.
An examination of change in renal function following blood pressure lowering in more than 4,400 individuals in several clinical trials revealed that renal function declined following initiation of antihypertensive treatment in both essential hypertension and hypertensive diabetics for a period of two years before stabilizing at or near zero change. This initial decline can be related to the severity of preexisting hypertension but does not appear related to the type of antihypertensive regimen used. This phenomenon appears most readily explained by progressive obsolescence of previously damaged nephrons and not by the type of antihypertensive therapy employed. These finding raise questions about validity of interpretation of clinical trials designed to test efficacy of specific drug regimens in preserving renal function when outcome results are predominantly influenced by events during the first two years of intervention.
Antihypertensive Agents↗
Vitamin B12 levels in human milk during the first nine months of lactation.
Vitamin B12 concentration was measured by competitive binding radioassay in 48 samples of human milk from healthy mothers eating unrestricted diets. Specimens were collected 1-35 weeks after full-term delivery and were subjected to proteolytic digestion before radioassay in order to destroy binding proteins. The distribution of the results was skewed, but the distribution of the logged values was not significantly different from normal. The geometric mean vitamin B12 level remained almost unchanged during the first 12 weeks postpartum (261-297 pmol/l) and then declined to a low of 139 pmol/l at 27-35 weeks. A significant (P = 0.033) decline in vitamin B12 concentration between 6-12 weeks and 19-25 weeks postpartum was observed.
Animals↗
Private prescribing of controlled drugs.
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Drug Prescriptions↗
DNA replication. Almost licensed.
Exact duplication of all the DNA in a cell occurs during each S phase, and only once in each cell cycle. Recent results show that conserved proteins of the MCM family contribute to these precisely regulated events.
Animals↗
Cyclin B/p34cdc2 triggers phosphorylation of DNA ligase I during Xenopus laevis oocyte maturation.
Phosphorylation of DNA ligase I has been analyzed during Xenopus laevis early development. The enzyme, which is involved in DNA replication and DNA repair events, is accumulated during oogenesis to reach a maximum in the stage VI oocyte, and remains at a constant level during maturation. When maturation of the oocyte is induced (in vivo or in vitro), this leads to a post-translational modification of the protein. In stage VI oocytes, a DNA ligase I of apparent molecular mass 180 kDa is detected immunologically whereas a 190-kDa form is found in unfertilized eggs and persists until the tadpole stage. This modification is due to phosphorylation performed by a protein kinase that is turned on 3-4 h after induction of the maturation. Activation of the kinase requires protein synthesis, and appearance of phosphorylated DNA ligase coincides with activation of histone H1 kinase activity. Induction of DNA ligase I modification and maturation are induced in the absence of protein synthesis following injection of maturation promoting factor into oocytes. Immunoprecipitated oocyte DNA ligase I is phosphorylated and its molecular mass modified by purified cyclin B/p34cdc2 in vitro. DNA ligase I phosphorylation is not induced in oocyte extract where only mitogen-activated-protein kinase is induced. Phosphorylation of DNA ligase I induced by cdc2 kinase occurs at the time new DNA replication and recombination activities appear in eggs.
Animals↗
Deletion analysis of the starch-binding domain of Aspergillus glucoamylase.
The large form of glucoamylase (GAI) from Aspergillus awamori (EC 3.2.1.3) binds strongly to native granular starch, whereas a truncated form (GAII) which lacks 103 C-terminal residues, does not. This C-terminal region, conserved among fungal glucoamylases and other starch-degrading enzymes, is part of an independent starch-binding domain (SBD). To investigate the SBD boundaries and the function of conserved residues in two putative substrate-binding sites, five gluco-amylase mutants were constructed with extensive deletions in this region for expression in Saccharomyces cerevisiae. Progressive loss of both starch-binding and starch-hydrolytic activity occurred upon removal of eight and 25 C-terminal amino acid residues, or 21 and 52 residues close to the N-terminus, confirming the requirement for the entire region in formation of a functional SBD. C-terminal deletions strongly impaired SBD function, suggesting a more important role for one of the putative binding sites. A GAII phenocopy showed a nearly complete loss of starch-binding and starch-hydrolytic activity. The deletions did not affect enzyme activity on soluble starch or thermo-stability of the enzyme, confirming the independence of the catalytic domain from the SBD.
Amino Acid Sequence↗
Identification and elimination by site-directed mutagenesis of thermolabile aspartyl bonds in Aspergillus awamori glucoamylase.
Both native Aspergillus niger glucoamylase and wild-type Aspergillus awamori glucoamylase expressed in Saccharomyces cerevisiae, which have identical primary structures, undergo hydrolysis at aspartyl bonds at low pH values and elevated temperatures. In native A.niger enzyme the Asp126-Gly127 bond was preferentially cleaved at pH 3.5, while at pH 4.5 cleavage of the Asp257-Pro258 and Asp293-Gly294 bonds was dominant. In wild-type A.awamori glucoamylase, cleavage of the latter was dominant at both pH 3.5 and 4.5. Site-directed mutations Asp126-->Glu and Gly127-->Ala in wild-type enzyme decreased specific activities by approximately 60 and 30%, respectively, and increased irreversible thermoinactivation rates 3- to 4-fold at pH 4.5. Replacement of Asp257 with Glu and Asp293 with Glu or Gln decreased specific activities by approximately 20%, but greatly reduced cleavage of the Asp257-Pro258 and Asp293-Gly294 bonds. The Asp257-->Glu mutant was produced very slowly and was more thermostable than wild-type glucoamylase at pH 4.5 up to 70 degrees C. Replacement of Asp293 with either Glu or Gln significantly raised protein production and slightly increased thermostability at pH 3.5 and 4.5, but not at pH 5.5.
Aspergillus↗
Professional practice and role diversity: a team concept for patient transportation systems.
Critical care nurses providing interhospital transportation services face new challenges in structuring a professional practice model in a diverse role environment. Nurses are now finding themselves working together with a variety of health care professionals with different educational and experience levels. This article discusses the program development and shared governance development of one such interhospital transportation team. Shared governance in a unique environment such as this was achieved using a functional model (self-directed work teams) and several outcome-focused components that are described in detail. The difficulties encountered with the introduction of a governance structure are also shared as too are the resolutions. With the changing health care system and the evolving changes in critical care nursing roles, innovation is fundamental to patient care practices. Shared governance does have a place in nurse/nonnurse amalgamations.
Humans↗
Neuropsychophysiological study of children at risk for schizophrenia: a preliminary report.
OBJECTIVE: This initial report, from an ongoing study, examines whether children who have symptoms of schizophrenia spectrum disorder display neuropsychological or neuroanatomic abnormalities similar to those seen in adults with schizophrenia. METHOD: Experimental subjects were 12 children between 8 and 12 years of age who displayed symptoms of early-onset schizophrenia or schizotypal personality disorder, as assessed through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The experimental subjects were compared with 13 controls on neuropsychological test performance, magnetic resonance imaging measurements, and proton magnetic resonance spectroscopy results. RESULTS: Findings from the first phase of this project reveal significant overall group differences for several morphometric magnetic resonance imaging measurements and all neuropsychological measures. Differences between the groups were found for amygdala volume, mesial temporal volume, callosal area, and anatomic asymmetry. Magnetic resonance spectroscopy data showed a trend toward group differences. CONCLUSIONS: These findings support a neurodevelopmental model of schizophrenia which postulates that environmentally or genetically programmed events in utero disrupt the establishment of fundamental aspects of brain structure and function.
Age of Onset↗
Assessment of iron status in association with excess alcohol consumption.
Biochemical evidence of iron overload (transferrin saturation greater than 60% and/or serum ferritin concentration greater than 1000 micrograms/L) was observed in 16% of patients admitted to an alcohol withdrawal unit. No subjects in an age and sex matched control group showed such biochemical changes. Whilst changes in serum ferritin concentration closely correlated with aspartate aminotransferase activity and could be explained by alcohol induced liver damage, the increased transferrin saturation was not similarly explained. In nine patients withdrawal of alcohol resulted in a decrease in transferrin saturation and serum ferritin, the former due to a reduction in serum iron concentration. In patients with high alcohol intake biochemical measures of iron status may be misleading and a decrease in both transferrin saturation and serum ferritin concentration after withdrawal of alcohol may help to rule out the possible diagnosis of hereditary haemochromatosis.
Adolescent↗
Both cdc2 and cdk2 promote S phase initiation in Xenopus egg extracts.
Xenopus egg extracts induce S phase DNA replication in added sperm pronuclei in a highly regulated manner, similar to events in vivo. Removal of cyclin-dependant kinases (cdks) or cdk2 from these extracts using affinity matrices severely inhibits initiation of S phase. We have used p13suc1 beads to remove both cdk2 and cdc2 proteins from egg extracts and developed a method to replace either protein alone to assess their capacity to initiate DNA replication. Re-addition of either cdk2 or cdc2 proteins to depleted extracts, through translation of their respective mRNAs, restimulated replication, judged by both total synthesis and labelling index. An ATP-binding-site mutant cdk2 mRNA (cdk2.R33) failed to stimulate replication and inhibited S phase initiation in mock-depleted extracts. Both human and Xenopus cdc2 mRNAs rescued replication in this system. Human mutant mRNAs have been used to show that the stimulation induced requires cdc2 catalytic activity, though not its mitotically active form. Rescue of replication by p34cdc2 is also observed in extracts depleted of cdks with a cdk2 antibody, which still retain much of their endogenous cdc2 protein. We conclude that newly synthesised p34cdc2, but not the inherited 'old' form, can induce S phase and in this form may overlap in function with p33cdk2.
Animals↗
Multiscale renormalization group improvement of the effective potential.
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Journal Article↗
Substitution of asparagine residues in Aspergillus awamori glucoamylase by site-directed mutagenesis to eliminate N-glycosylation and inactivation by deamidation.
Aspergillus awamori glucoamylase is a secreted glycoprotein containing N-linked carbohydrate recognition sites at Asn-171, Asn-182 and Asn-395. Site-directed mutagenesis was performed at Asn-182 and Asn-395 to determine whether these residues were N-glycosylated by Saccharomyces cerevisiae, to investigate the function of any glycans linked to them, and to determine the effect of their deamidation on glucoamylase thermostability. Asn-171 and Asn-395, but not Asn-182, were N-glycosylated. Deletion of the glycan N-linked to Asn-395 did not affect specific activity, but greatly decreased enzyme secretion and thermostability. The mutant lacking the N-glycan linked to Asn-395 was synthesized very slowly, and was more associated with cell membrane components and susceptible to proteinase degradation than were wild-type or other mutant glucoamylases. Its secreted form was 30-fold less thermostable than wild-type enzyme at pH 4.5. Replacement of Asn-182 by Gln to eliminate deamidation at this site did not change glucoamylase specific activity or thermostability, while replacement by Asp decreased specific activity about 25%, but increased thermostability moderately at pH 4.5 below 70 degrees C. Both mutations of Asn-182 increased glucoamylase production.
Amino Acid Sequence↗