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PubMed1998

Death certification by doctors in non-metropolitan Victoria.

OBJECTIVE: To examine the completeness and accuracy of death certification by general practitioners, specialists and resident medical officers (RMOs) in non-metropolitan Victoria. DESIGN: An examination of the death certificates written by a representative sample of community and hospital doctors and comparison with the clinical history. SETTING: The Ballarat statistical district. RESULTS: Eighteen percent of the death certificates at initial assessment, were unsatisfactory (the percentage for those written by RMOs were significantly higher). After review of the clinical record, 27% of certificates were found to inaccurately represent the cause of death, (again the percentage for RMOs was higher) Eighteen percent of certificates required a change of code. CONCLUSION: Monitoring the health of the public relies in part on information gained from death certificates. It is thus of concern that such a high percentage of death certificates are inaccurate to the extent that they are incorrectly coded. Consideration should be given to new educational initiatives and to the promotion of the existing toll free telephone advice service to doctors.

Death Certificates↗

PubMed1998

[Trends in average life expectancy in the Saxony Free State--results of a cause of death-specific table analysis].

We conducted a specific table analysis on mortality causes that was mainly oriented on the lines of the chapters of ICD-9 to explore the average life expectancy for the population in Saxony particularly since 1988. The drop in average life expectancy of males observed since 1990 can be fully explained only for those around 18 years of age by "accidents" as the cause of death. Between 30 and 55 years of age there were additional losses of average life expectancy via the mortality causes "diseases of the digestive tract", "neoplasms" and "psychiatric diseases". The significance of neoplasms and of psychiatric diseases is receeding in respect of the average life expectancy. In 1991 there was an increase in the incidence of suicide in the age bracket around 51 years in males. Seen on an overall scale across all age brackets the development of the suicide rate has increased average life expectancy. Significant average life expectancy increase developed in the range of death causes due to embryonic or congenital damage as well as cardiovascular diseases, diseases of the respiratory system and infectious diseases. As far as the female population is concerned, only accidents and diseases of the digestive tract had a negative effect on average life expectancy in 1990 and 1991 whereas the negative effect exercised by the mortality cause "neoplasms" is systematically flattening out. There are excessive gains in life expectancy in respect of cardiovascular diseases, clearly in the range of embryonal and congenital diseases and remarkably in respect of suicide. How many of these specific differentiations of causes of death are due to changes in coding, has not yet been assessed. Leaving aside the unnatural causes of death these figures point to a marked influence of improved medical care on average life expectancy.

Adolescent↗

PubMed1983

Colour coding in the cerebral cortex: the responses of wavelength-selective and colour-coded cells in monkey visual cortex to changes in wavelength composition.

The reaction of wavelength-selective (WL), wavelength-opponent (WLO) and colour-coded (CO) cells in monkey visual cortex to changes in the wavelength composition of the light reflected from the area in their receptive fields was studied, using multicoloured displays. Wavelength-selective and wavelength-opponent cells were found to be very sensitive to changes in the wavelength composition of the light reflected from the areas in their receptive fields, irrespective of their perceived natural and void colours. Changes in the wavelength composition of the light reflected from surrounding areas did not affect their responses. They were also sensitive to the order in which lights of various wavelengths illuminated the areas in their receptive fields. Colour-coded cells were not affected by changes in the wavelength composition nor were they sensitive to the sequence with which the area in their receptive fields was illuminated by lights of different wavelengths. However, they required that the display, with the area of their preferred colour in their receptive fields, be trichromatically illuminated. This and other evidence suggested that such cells were sensitive not only to the illumination of the area in their receptive fields, but of surrounding areas as well. This evidence reinforces further the distinction between wavelength-selective and colour-coded cells and leads to the conclusion that one function of the wavelength-selective cells must be to register the changes in wavelength composition which occur throughout the day.

Animals↗

PubMed1990

Structural studies of the lysozyme coded by the pneumococcal phage Cp-1. Conformational changes induced by choline.

The CPL-1 lysozyme coded by the pneumococcal phage Cp-1 has been overproduced in Escherichia coli under the control of a modified lipoprotein lactose promoter. This result has provided the conditions to analyse the CPL-1 secondary structure by circular dichroism (CD). The CD spectra recorded in the far-ultraviolet region showed, at neutral pH, two minima at 210 nm and 230 nm and a shoulder at 217 nm, whereas two bands at 260 nm and 295 nm were observed in the near-ultraviolet region. It has been estimated, by using the CDPROT program, that the protein is composed of 19% alpha-helix, 32% beta-sheet, 28% beta-turn and 21% random coil. Minor changes in the CD spectra were detected either when the pH was varied over 6-10 or when the ionic strength was increased to 1 M NaCl. Choline, a well known modulator of the enzyme activity that is present in the pneumococcal cell wall, induced remarkable changes in the intensities of the bands at 210, 230 and 295 nm, with the appearance of an unusual positive band at 225 nm. The conformational change was reversible and correlated with the competitive inhibitory effect of choline on the lysozyme activity, supporting, by a new and direct experimental approach, the basic role of choline in the recognition of the cell wall substrate. The analyses of the secondary structure prediction and the CD data reported here are compatible with the two-domain structure of CPL-1 reinforce our hypothesis that the C-terminal region is directly involved in the binding of the enzyme to the pneumococcal teichoic and lipoteichoic acids.

Amino Acid Sequence↗

PubMed1996

[Study on the principles of base change in 4-fold degenerate sites of protein coding genes].

The relationship of transition and transversion of base change in 4-fold degenerate sites of coding genes of 6 proteins, which showed 70% homology in wmposition investigated. Taking into account of the effects of base composition on base substitution, it was found that the transition-transversion bias was evident but not as pronounced as in mitochondrial DNA. Comparison of different kinds of transition or transversion indicated that they happened with rather equal vate, with 0.65-0.73 for different kinds of transversion and 0.99 for A-G transition assuming that T-C transition was 1. The causes for transition-transversion bias is discussed and it is proposed that mutagens may play a role in it.

Animals↗

PubMed2003

Flattening the glucocorticoid rhythm causes changes in hippocampal expression of messenger RNAs coding structural and functional proteins: implications for aging and depression.

Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calcium-calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

Aging↗

PubMed1994

Mutations in the helper component protease gene of zucchini yellow mosaic virus affect its ability to mediate aphid transmissibility.

The nucleotide sequence of the helper component protease (HC-Pro) genes of three zucchini yellow mosaic virus (ZYMV) strains has been compared with that of a helper-deficient strain of ZYMV-HC. The comparisons revealed three unique deduced amino acid differences. Two of these mutations were located in regions which are conserved in other potyviruses. The role of these mutations in aphid transmissibility was examined by exchanging DNA fragments of part of the deficient HC-Pro gene with the respective section within the gene of the infectious full-length clone of the aphid-transmissible ZYMV. The first exchange included two of the three mutations, the first coding for a change from Asp to Gly (in a non-conserved region) and the second coding for a change from Arg to Ile [within the Phe-Arg-Asp-Lys (FRNK) conserved box]. This exchange resulted in a reduced transmission (20.6% for the mutated virus compared with 57.4% in the normal ZYMV when acquired from plants and 37.2% compared with 83.1%, respectively, when acquired from membranes). The second exchange incorporated a single mutation [conferring a change from Thr to Ala within the Pro-Thr-Lys (PTK) conserved box]. This single mutation resulted in almost total loss of HC activity in aphid transmission both from plants and from membranes. The Lys residue in the conserved Lys-Ile-Thr-Cys (KITC) box, which is related to loss of HC activity in potato virus Y, tobacco vein mottling virus and in the Michigan strain of ZYMV, is unchanged in the helper-deficient ZYMV. It is therefore proposed that more than one site in HC-Pro may be functionally related to aphid transmissibility. The possible reasons for the role of these mutations in helper activity in aphid transmission of ZYMV are discussed.

Amino Acid Sequence↗

PubMed2005

A novel strategy using MASCOT Distiller for analysis of cleavable isotope-coded affinity tag data to quantify protein changes in plasma.

A novel strategy consisting of cleavable Isotope-Coded Affinity Tag (cICAT) combined with MASCOT Distiller was evaluated as a tool for the quantification of proteins in "abnormal" patient plasma, prepared by pooling samples from patients with acute stroke. Quantification of all light and heavy cICAT-labelled peptide ion pairs was obtained using MASCOT Distiller combined with a proprietary software. Peptides displaying differences were selected for identification by MS. These preliminary results show the promise of our approach to identify potential biomarkers.

Algorithms↗

PubMed1993

Health care reform: managed competition and beyond.

Since the election, the health care reform debate has focused on three broad features: implementation of managed competition, changes in the tax treatment of health insurance, and the imposition of budget caps or targets. The basic element of managed competition is the creation of sponsors who act as collective purchasing agents for large groups of individuals. One of the potentially most politically difficult issues in implementing any health care reform proposal is likely to be defining the minimum standard benefit package. It will determine the costs society bears, the income of providers, the health of many individuals, and the attributes of a workable health care reform package. Managed competition is intended to foster competition among health plans on the basis of cost and quality. The measures of quality actually employed in the health care system will determine in large part the incentives faced by insurers, providers, and consumers. The problem of adverse selection is potentially the most important issue in reforming the health insurance market. If individuals can opt not to purchase health benefits, poorer risks will be more likely to purchase health insurance than good risks, and at minimum the price of these benefits will be higher than would otherwise be the case. Managed competition requires that individuals share at least some of the financial consequences of their choices among health plans. As a result, most managed competition proposals change the tax code by limiting the exclusion of employer contributions to health insurance from worker's taxable income. Changing the health insurance market, mandating employer health benefits, and changing the tax code may have significant effects on the health care delivery system, but they are unlikely to reduce health care cost inflation in the near term. One of the proposals for restraining the growth in health care costs is the imposition of a budget on the amount spent on health care services. The combination of the constraints placed on federal governmental action by the budget and the significant political problems involved in reaching a consensus on the important elements of health care reform may limit the ability of the federal government to implement national health care reform in the near term. As a result, individual states may be encouraged by the federal government to continue to experiment with their own health reform programs.

Budgets↗

PubMed2005

Functional characterization of novel allelic variants of CYP2C9 recently discovered in southeast Asians.

CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher Km and a >90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians.

Alleles↗

PubMed1990

The genetic code in mitochondria and chloroplasts.

The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences.

Animal Population Groups↗

PubMedDate not supplied

Molecular characterization of three mutations in katG affecting the activity of hydroperoxidase I of Escherichia coli.

Hydroperoxidase I (HPI) of Escherichia coli is a bifunctional enzyme exhibiting both catalase and peroxidase activities. Mutants lacking appreciable HPI have been generated using nitrosoguanidine and the gene encoding HPI, katG, has been cloned from three of these mutants using either classical probing methods or polymerase chain reaction amplification. The mutant genes were sequenced and the changes from wild-type sequence identified. Two mutants contained G to A changes in the coding strand, resulting in glycine to aspartate changes at residues 119 (katG15) and 314 (katG16) in the deduced amino acid sequence of the protein. A third mutant contained a C to T change resulting in a leucine to phenylalanine change at residue 139 (katG14). The Phe139-, Asp119-, and Asp314-containing mutants exhibited 13, less than 1, and 18%, respectively, of the wild-type catalase specific activity and 43, 4, and 45% of the wild-type peroxidase specific activity. All mutant enzymes bound less protoheme IX than the wild-type enzyme. The sensitivities of the mutant enzymes to the inhibitors hydroxylamine, azide, and cyanide and the activators imidazole and Tris were similar to those of the wild-type enzyme. The mutant enzymes were more sensitive to high temperature and to beta-mercaptoethanol than the wild-type enzyme. The pH profiles of the mutant catalases were unchanged from the wild-type enzyme.

Base Sequence↗

PubMedDate not supplied

[Ethics in nursing].

Synopsis about the evolution of moral principles adopted by brazilian nursing since 1923 to nowadays. It indicates a metaphysical, abstract and spiritual tendencies in the codes of 1958 and 1975, and a change in the code of 1993, which searches to observe valuables of historic form and based on material conditions of existence.

Brazil↗

PubMed1983

Levels of translatable mRNA coding for rat liver glucokinase.

Changes in the level of translatable mRNA coding for glucokinase under different physiological conditions were determined using a reticulocyte lysate translation system and immunoprecipitation. Poly(A+) RNA isolated from livers of rats fed a high carbohydrate diet displayed a 10-fold increase in glucokinase template activity when compared to starved rats. Livers from streptozotocin-induced diabetic rats had only 9% of the glucokinase template activity displayed by controls. Administration of insulin to diabetic rats produced an increase in the level of mRNA coding for glucokinase within 20 min and reached a maximum 13-fold increase 1 h following insulin treatment. Under all experimental conditions examined, changes in the level of glucokinase mRNA were accompanied by similar changes in direction and magnitude of enzyme activity and the relative rate of synthesis of the enzyme in vivo. In addition, the developmental appearance of glucokinase activity at the 16th day following birth was accompanied by a corresponding increase in the amount of glucokinase mRNA. Thus, it appears that dietary, hormonal, and developmental changes in the activity of glucokinase arise as the result of changes in the amount of functional mRNA coding for the enzyme.

Animals↗

PubMed2004

Human-specific amino acid changes found in 103 protein-coding genes.

We humans have many characteristics that are different from those of the great apes. These human-specific characters must have arisen through mutations accumulated in the genome of our direct ancestor after the divergence of the last common ancestor with chimpanzee. Gene trees of human and great apes are necessary for extracting these human-specific genetic changes. We conducted a systematic analysis of 103 protein-coding genes for human, chimpanzee, gorilla, and orangutan. Nucleotide sequences for 18 genes were newly determined for this study, and those for the remaining genes were retrieved from the DDBJ/EMBL/GenBank database. The total number of amino acid changes in the human lineage was 147 for 26,199 codons (0.56%). The total number of amino acid changes in the human genome was, thus, estimated to be about 80,000. We applied the acceleration index test and Fisher's synonymous/nonsynonymous exact test for each gene tree to detect any human-specific enhancement of amino acid changes compared with ape branches. Six and two genes were shown to have significantly higher nonsynonymous changes at the human lineage from the acceleration index and exact tests, respectively. We also compared the distribution of the differences of the nonsynonymous substitutions on the human lineage and those on the great ape lineage. Two genes were more conserved in the ape lineage, whereas one gene was more conserved in the human lineage. These results suggest that a small proportion of protein-coding genes started to evolve differently in the human lineage after it diverged from the ape lineage.

Animals↗

PubMed2000

Adverse drug errors in anesthesia, and the impact of coloured syringe labels.

PURPOSE: To describe the frequency and pattern of drug errors in clinical anesthesia, and to evaluate whether a change to colour coded syringe labels, along with education, could reduce the problem of drug errors. METHODS: We prospectively recorded anesthesia-related information from all anesthetic cases for 36 mo, totally 55,426 procedures. Intraoperative problems, including drug errors, were recorded. After eighteen months we changed to colour coded syringe labels, and the effect of this change and education on drug errors was assessed. Errors were divided into four groups: syringe swap, ampoule swap, other 'wrong drug' errors, and wrong dose errors. The problems were graded into four levels, according to severity. RESULTS: A drug error was recorded in 63 cases (0.11%). There were 28 syringe swaps, and muscle relaxants were erroneously given in 15. There were nine ampoule swaps. There were eight 'other wrong drug' cases, and 18 cases where a wrong dose of the correct drug was given. Three of the drug errors were classified as serious, and 27 were of moderate severity. We found no differences between the two periods except for decreased number of ampoule swaps (P = 0.04). CONCLUSION: Drug errors are uncommon, and represent a small part of anesthesia problems but still have the potential for serious morbidity. Syringe swaps occurred most often between syringes of equal size, and were not eliminated by colour coding of labels. As muscle relaxant drugs are most commonly involved, and can cause lasting morbidity, special preventive measures should be taken for this group of drugs.

Adult↗

PubMed2003

Mutations in mitochondrial aldehyde dehydrogenase (ALDH2) change cofactor affinity and segregate with voluntary alcohol consumption in rats.

Genetic factors influence alcohol consumption and alcoholism. A number of groups have bred alcohol drinker and non drinker rat strains, but genetic determinants remain unknown. The University of Chile rat lines UChA (low drinkers) and UChB (high drinkers) display differences in the relative K(m) for NAD+ of mitochondrial aldehyde dehydrogenase (ALDH2) but no V(max) differences. The relative K(m) differences may be due to mitochondrial changes or to genetic differences coding for ALDH2. We investigated whether there are differences in the coding regions of ALDH2 cDNA in these lines and whether the Aldh2 genotype predicts the phenotype of alcohol consumption and the K(m) of ALDH2 for NAD+. Liver cDNA was prepared, and the Aldh2 transcript was amplified, cloned and sequenced. Genotyping was conducted by DNA amplification and restriction enzyme digestion. When compared to Aldh21 of Sprague-Dawley, 94% of the UChA (low drinker) rats (n = 61), presented a mutation that changes Gln67 to Arg in the mature enzyme (allele referred to as Aldh22). In UChB (high drinker) rats (n = 69), 58% presented the Aldh21 allele, while 42% presented the Gln67Arg change plus a second mutation that changed Glu479 to Lys (allele Aldh23). The Aldh22 allele was absent in high drinker rats. Rats of different Aldh2 genotypes displayed marked phenotypic differences in both ethanol consumption (g/kg/day; means +/- SE): (Aldh21/Aldh21) = 5.7 +/- 0.2, (Aldh22/Aldh22) = 0.9 +/- 0.2 and (Aldh23/Aldh23) = 4.6 +/- 0.2; and K(m)s for NAD+ of 43 +/- 3 microm, 132 +/- 13 microm and 41 +/- 2 microm, respectively (Aldh22 versus Aldh21 or Aldh23; P < 0.0001 for both phenotypes). Overall, the data show that alleles of Aldh2 strongly segregate with the phenotype of ethanol consumption and the relative K(m) for NAD+ of ALDH2. Bases mutated suggest that non drinker Aldh22 is ancestral with regard to the coding changes in either Aldh21 or Aldh23, variants which would allow ethanol consumption and may provide an evolutionary advantage by promoting calorie intake from fermented products along with carbohydrates.

Aldehyde Dehydrogenase↗

PubMed1990

Partial nucleotide sequence of South American yellow fever virus strain 1899/81: structural proteins and NS1.

We have partially cloned and sequenced the genome of a Peruvian yellow fever virus isolate (1899/81) and compared the nucleotide and deduced amino acid sequences of this strain with the previously published sequence of the West African yellow fever virus strain Asibi. In the 3594 base region sequenced, which contains the structural genes (C, M, E), all but the 72 3'-terminal nucleotides of the NS1 gene and 108 nucleotides of the 5' non-coding region, 515 nucleotide substitutions were detected. Nucleotide divergence was lowest in the 5' non-coding region, 2.8%, compared with an average rate of 14.7% in the coding regions. Over 91% of the 512 nucleotide changes in the coding region were silent; 44 amino acid substitutions resulted. The capsid protein was the least conserved, whereas the M protein was the most highly conserved (6.7% and 1.3% divergence, respectively). The envelope protein had 18 amino acid changes (3.7% divergence), one of which created an additional site for potential glycosylation of the 1899/81 virus. NS1 protein divergence (3.9%) was similar to that seen in the E protein. Of the 44 amino acid substitutions found, 34 (77%) were conservative. The highest number of nonconservative differences occurred in the envelope glycoprotein. These changes may significantly affect the antigenic and biological functions of the viruses.

Amino Acid Sequence↗