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PubMedDate not supplied

[Deeper understanding of fetal acid-base equilibrium].

PROBLEM: Actual pH-measurements, which are used worldwide for quality control in obstetrics, give no information about the extent of metabolic and respiratory pathways involved in the synthesis of H(+)-ions. Therefore we looked for a new method to quantify the de novo-synthesis of H(+)-ions due to both pathways and to correlate them with the clinical condition of the newborn. METHODS: Using pH-, pCO2 (mmHg)- (and pO2 (mmHg)) measurements in umbilical blood (artery (UA), vein (UV)) of 8882 newborns, which were delivered vaginally in vertex position without cord-entanglements and without major malformations, the pHqu40 (metabolic pathway) and the pHnm (non-metabolic pathway) were computed. Thus both components of fetal acidosis could be determined together with actual pH in one unity i.e. H(+)-ion-concentration (nmol/l). By introduction of a reference-point, which denotes the mean actual pH- (7.373) and the mean pCO2- (36.4 mmHg) value in umbilical venous blood of 599 Apgar 10-babies it is possible to compute the mean de novo-synthesis of H(+)-ions in different clinical neonatal conditions (Apgar-score 1 min). RESULTS: In the case of slightly depressed neonates (Apgar 7-10) the respiratory acidosis dominates the metabolic one. In moderately asphyxiated newborns (Apgar 4-6) both components are equally involved. In severe fetal asphyxia (Apgar 0-3) both components can probably be determined by extrapolation: the metabolic component seems to be dominant. The computed mean actual pH-value in babies scoring Apgar 0 amounts to approximately 7.100 +/- 0.075. CONCLUSIONS: The diagnostic range of Apgar-scoring and pH-measurements is not congruent: newborns with actual pH-values in UA-blood between 6,7 and approximately 7,1 do show Apgar-scores (1 min) of 0 or 1 without a possibility to further differentiate the degree of asphyxia by clinical criteria. This means, that actual pH-measurements are of high clinical importance in severely asphyxiated newborns. They should not be abandoned. The intercorrelation of some variables of the fetal acid-base-balance is demonstrated in 738 newborns sharing Apgar-scores of 8 after one minute. The diagnostic potential of acid-base-variables in UV-blood as a mirror of placental function is outlined.

Acid-Base Equilibrium↗

PubMed1996

Molecular and evolutionary analyses of a variable series of genes in Borrelia burgdorferi that are related to ospE and ospF, constitute a gene family, and share a common upstream homology box.

In this study we report on the molecular characterization of a series of genes that constitute a gene family related to ospE and ospF. Some members of this family appear to represent recombined or variant forms of ospE and ospF. Variant ospE and ospF genes were found in several Borrelia burgdorferi isolates, demonstrating that their occurrence is not a phenomenon relevant to only a single isolate. Hybridization analyses revealed that the upstream sequence originally identified 5' of the full-length ospEF operon exists in multiple copies ranging in number from two to six depending on the isolate. This repeated sequence, which we refer to as the upstream homology box (UHB), carries a putative promoter element. In some isolates, UHB elements were found to flank copies of ospE and ospF that exist independently of each other. We refer to this group of UHB-flanked genes collectively as the UHB gene family. The evolutionary relationships among UHB gene family members were assessed through DNA sequence analysis and gene tree construction. These analyses suggest that some UHB-flanked genes might actually represent divergent forms of other previously described genes. Analysis of the restriction fragment length polymorphism patterns of the UHB-flanked genes among B. burgdorferi isolates demonstrated that these patterns are highly variable among isolates, suggesting that these genes are not phylogenetically conserved. The variable restriction fragment length polymorphism patterns could indicate recombinational activity in these sequences. The presence of numerous copies of the UHB elements and the high degree of homology among UHB-flanked genes could provide the necessary elements to allow for homologous recombination, leading to the generation of recombination variants of UHB gene family members.

Amino Acid Sequence↗

PubMed2005

The contribution of genetic and environmental factors to quantitative variability of erythrocyte membrane proteins in primary hypotension.

Our previous studies have shown that, compared with healthy individuals, patients with primary arterial hypotension (PAH) have significant quantitative changes in erythrocyte membrane proteins. The purpose of the present study was to evaluate the contribution made by genetic and environmental factors to quantitative variation of erythrocyte membrane proteins in PAH. We studied 109 hypotensive patients, 124 normotensive subjects, 222 of their first-degree relatives and 24 twin pairs by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. The decomposition of total phenotypic variance of erythrocyte membrane proteins to genetic and environmental components was performed on the basis of correlations among first-degree relatives by the least squares method. The genetic dominance and shared environmental factors were found to influence the variability of cytoskeletal membrane proteins whose contents were changed in PAH. Furthermore, variations in alpha-spectrin, actin and anion exchanger in hypotensives were substantially influenced by major gene and maternal effects. Ankyrin 2.1 and actin content was under the control of common underlying genes. Variations in membrane-associated glutathione-S-transferase and tropomyosin were predominantly affected by polygenes. These findings suggest that the putative major genes with pleiotropic effects appear to be involved in the control of quantitative disorders of erythrocyte membrane proteins in primary hypotension.

Actins↗

PubMed1988

Diverse organization of immunoglobulin VH gene loci in a primitive vertebrate.

The immunoglobulin (Ig) heavy chain variable (VH) gene family of Heterodontus francisci (horned shark), a phylogenetically distant vertebrate, is unique in that VH, diversity (DH), joining (JH) and constant region (CH) gene segments are linked closely, in multiple individual clusters. The V regions of 12 genomic (liver and gonad) DNA clones have been sequenced completely and three organization patterns are evident: (i) VH-D1-D2-JH-CH with unique 12/22 and 12/12 spacers in the respective D recombination signal sequences (RSSs); VH and JH segments have 23 nucleotide (nt) spacers, (ii) VHDH-JH-CH, an unusual germline configuration with joined VH and DH segments and (iii) VHDHJH-CH, with all segmental elements being joined. The latter two configurations do not appear to be pseudogenes. Another VH-D1-D2-JH-CH gene possesses a D1 segment that is flanked by RSSs with 12 nt spacers and a D2 segment with 22/12 spacers. Based on the comparison of spleen, VH+ cDNA sequences to a germline consensus, it is evident that both DH segments as well as junctional and N-type diversity account for Ig variability. In this early vertebrate, the Ig genes share unique properties with higher vertebrate T-cell receptor as well as with Ig and may reflect the structure of a common ancestral antigen binding receptor gene.

Amino Acid Sequence↗

PubMed2004

Neuronal control of turtle hindlimb motor rhythms.

The turtle, Trachemys scripta elegans, uses its hindlimb during the rhythmic motor behaviors of walking, swimming, and scratching. For some tasks, one or more motor strategies or forms may be produced, e.g., forward swimming or backpaddling. This review discusses experiments that reveal characteristics of the spinal neuronal networks producing these motor behaviors. Limb-movement studies show shared properties such as rhythmic alternation between hip flexion and hip extension, as well as variable properties such as the timing of knee extension in the cycle of hip movements. Motor-pattern studies show shared properties such as rhythmic alternation between hip flexor and hip extensor motor activities, as well as variable properties such as modifiable timing of knee extensor motor activity in the cycle of hip motor activity. Motor patterns also display variations such as the hip-extensor deletion of rostral scratching. Neuronal-network studies reveal mechanisms responsible for movement and motor-pattern properties. Some interneurons in the spinal cord have shared activities, e.g., each unit is active during more than one behavior, and have distinct characteristics, e.g., each unit is most excited during a specific behavior. Interneuronal recordings during variations support the concept of modular organization of central pattern generators in the spinal cord.

Animals↗

PubMed2003

Competitive spillovers across non-profit and for-profit nursing homes.

The importance of non-profit institutions in the health care sector has generated a vast empirical literature examining quality differences between non-profit and for-profit nursing homes. Recent theoretical work has emphasized that much of this empirical literature is flawed in that previous studies rely solely on dummy variables to capture the effects of ownership rather than accounting for the share of non-profit nursing homes in the market. This analysis considers whether competitive spillovers from non-profits lead to higher quality in for-profit nursing homes. Using instrumental variables to account for the potential endogeneity of non-profit market share, this study finds that an increase in non-profit market share improves for-profit and overall nursing home quality. These findings are consistent with the hypothesis that non-profits serve as a quality signal for uninformed nursing home consumers.

Aged↗

PubMed1999

Heritability of recurrent exertional rhabdomyolysis in Thoroughbred racehorses.

OBJECTIVE: To determine the likely mode of inheritance and identify probable foundation horses for recurrent exertional rhabdomyolysis (RER) in Thoroughbred (TB) racehorses. ANIMALS: 4 families of TB racehorses with a high prevalence of RER, consisting of 3 to 53 horses/family, were used to determine mode of inheritance. Sixty-two TB horses with RER and 34 control TB racehorses without RER were used to identify probable foundation horses for the RER trait. PROCEDURE: RER was diagnosed by a veterinarian and verified by detecting high serum creatine kinase activity. Pedigrees dating from 1930 for all horses were entered into a database. Pedigrees of horses in 4 families were visually inspected for a pattern of inheritance and used for calculation of foundation horse contributions and inbreeding coefficients. The Markov chain Monte Carlo technique was used to analyze pedigrees of the 62 affected and 34 control horses for the conditional probability of foundation genotypes. A dominant mode of inheritance with variable expression model was used. RESULTS: Pedigree analysis supported an autosomal dominant mode of inheritance with variable expression. All affected horses from the 4 families shared a common ancestor. This ancestor and 5 other stallions had a conditional probability of 1.00 for being affected. All 6 stallions shared a common male ancestor within 3 to 5 generations. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of this study, the RER trait has been in TB racehorses for more than 70 years and may be inherited as an autosomal dominant trait with variable expression.

Alleles↗

PubMed2005

Measurement of CYP2D6 and CYP3A4 activity in vivo with dextromethorphan: sources of variability and predictors of adverse effects in 419 healthy subjects.

OBJECTIVE: Dextromethorphan (DEM) shares part of the adverse event profile of opioids and is widely used as a probe drug for CYP2D6 phenotyping and for the assessment of CYP2D6 activity. It has also been used to assess CYP3A4 activity. This study examined the influence of anthropometric variables, oral contraceptives, smoking habits, mu-opioid receptor and MDR1 genetic polymorphisms and components of the DEM ratios on the variability of CYP2D6 and CYP3A4 metabolic ratios and on the occurrence of adverse events following DEM administration. METHODS: This was a retrospective analysis of a database in 419 healthy subjects. CYP2D6 and CYP3A4 metabolic ratios were measured as the log of the ratios of the amount of DEM to the amount of dextrorphan (DOR) and of the amount of DEM to the amount of 3-methoxy-morphinan (MET) excreted in urine during a 12-h time period, respectively, following the oral administration of 80 mg of dextromethorphan hydrobromide. Logistic regression was performed to examine the factors associated with changes in metabolic ratios and with the occurrence of adverse events. RESULTS: The CYP2D6 metabolic ratio allowed identification of extensive and poor metabolizers of DEM. The CYP2D6 and CYP3A4 metabolic ratios were not strictly independent one from each other. Based on multivariate analysis, the CYP2D6 metabolic ratio was a stronger independent predictor of adverse events (p<0.0001) than the CYP2D6 phenotype (p=0.05). Anthropometric variables, oral contraceptives, smoking habits, mu-opioid receptor and MDR1 genetic polymorphisms did not significantly contribute to changes in metabolic ratios or to the occurrence of adverse events. CONCLUSIONS: Dextromethorphan can be used for CYP2D6 phenotyping, but the CYP2D6 and CYP3A4 metabolic ratios are not strictly independent one from each other. The CYP2D6 metabolic ratio predicts adverse events to DEM as does CYP2D6 phenotype, and extensive metabolizer subjects are not protected against adverse events.

Adult↗

PubMed1990

Assessing family sharing of diabetes responsibilities.

This study examined sharing of diabetes responsibilities between mothers and their diabetic children and the relationship between patterns of mother-child sharing of responsibility for diabetes tasks and demographic variables, adherence, and metabolic functioning in children with insulin-dependent diabetes mellitus (IDDM). A factor analysis of the Diabetes Family Responsibility Questionnaire (DFRQ), a 17-item questionnaire developed for the present study, resulted in a meaningful three-factor solution. Factors included responsibilities related to regimen tasks, General Health Maintenance, and Social Presentation of Diabetes. Analysis indicated that the DFRQ had adequate internal consistency and concurrent validity. One hundred and twenty-one children with IDDM, 6-21 years of age, and their mothers completed the DFRQ. Glycosylated hemoglobin (HbA1c) was used to index the child's level of metabolic control. Results of multiple regression analyses indicated that the child's age, disease duration, and sex are significant predictors of mother and child patterns of sharing diabetes responsibilities. Disagreements between mothers and children in perceptions of who is assuming responsibility and adherence level were significant predictors of HbA1c. Results indicated that children assume increasing responsibility with increasing age. Clinicians should not assume that mothers and children communicate about the sharing of diabetes responsibilities in the family or about changes in expectations of who is responsible as children develop. To foster better control and adherence in diabetic children, members of the health care team can help to identify diabetes tasks for which no one in the family takes responsibility.

Adolescent↗

PubMed2006

The influence of economic development level, household wealth and maternal education on child health in the developing world.

This study estimates the relative importance to child health (indicated by weight and height for age) of economic development level [gross domestic product (GDP) converted to international dollars using purchasing power parity (PPP) rates: GDP-PPP], household wealth and maternal education and examines the modifying influence of national contexts on these estimates. It uses information collected from mothers aged 15-49-years participating in Demographic Health Surveys (DHS) conducted in 42 developing countries. In multilevel regression models, the three study variables exhibited strong independent associations with child health: GDP-PPP accounted for the largest amount of unique variation, followed by maternal education and household wealth. There was also substantial overlap (shared variance) between maternal education and the other two study variables. The regressions of child health on household wealth and maternal education exhibited substantial cross-national variation in both strength and form of association. Although higher education levels were associated with disproportionately greater returns to child health, the pattern for household wealth was erratic: in many countries there were diminishing returns to child health at higher levels of household wealth. We conclude that there are inextricable links among different strategies for improving child health and that policy planners, associating benefits with these strategies, must take into account the strong moderating impact of national context.

Adolescent↗

PubMed2006

Bayesian variable selection for gene expression modeling with regulatory motif binding sites in neuroinflammatory events.

Multiple transcription factors (TFs) coordinately control transcriptional regulation of genes in eukaryotes. Although numerous computational methods focus on the identification of individual TF-binding sites (TFBSs), very few consider the interdependence among these sites. In this article, we studied the relationship between TFBSs and microarray gene expression levels using both family-wise and memberspecific motifs, under various combination of regression models with Bayesian variable selection, as well as motif scoring and sharing conditions, in order to account for the coordination complexity of transcription regulation. We proposed a three-step approach to model the relationship. In the first step, we preprocessed microarray data and used p-values and expression ratios to preselect upregulated and downregulated genes. The second step aimed to identify and score individual TFBSs within DNA sequence of each gene. A method based on the degree of similarity and the number of TFBSs was employed to calculate the score of each TFBS in each gene sequence. In the last step, linear regression and probit regression were used to build a predictive model of gene expression outcomes using these TFBSs as predictors. Given a certain number of predictors to be used, a full search of all possible predictor sets is usually combinatorially prohibitive. Therefore, this article considered the Bayesian variable selection for prediction using either of the regression models. The Bayesian variable selection has been applied in the context of gene selection, missing value estimation, and regulatory motif identification. In our modeling, the regressor was approximated as a linear combination of the TFBSs and a Gibbs sampler was employed to find the strongest TFBSs. We applied these regression models with the Bayesian variable selection on spinal cord injury gene expression data set. These TFs demonstrated intricate regulatory roles either as a family or as individual members in neuroinflammatory events. Our analysis can be applied to create plausible hypotheses for combinatorial regulation by TFBSs and avoiding false-positive candidates in the modeling process at the same time. Such a systematic approach provides the possibility to dissect transcription regulation, from a more comprehensive perspective, through which phenotypical events at cellular and tissue levels are moved forward by molecular events at gene transcription and translation levels.

Amino Acid Motifs↗

PubMed1996

Development of a common variable immunodeficiency in IgA-deficient patients.

IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) are two primary immunodeficiencies that share clinical features. Occasionally, both diseases have been diagnosed in the same family, which suggests the existence of some common pathogenic mechanism, but progression from IgA-D to CVID has rarely been documented. We report three cases of CVID diagnosed 1 to 12 years after IgA-D was detected. Two of these patients presented autoimmune diseases followed by a progressive decline in IgG levels. They are currently on intravenous immunoglobulin therapy with complete remission of their autoimmune and infectious symptoms.

Adult↗

PubMed2001

Characterization of cryptic flagellin genes in Shigella boydii and Shigella dysenteriae.

Flagellin (fliC) genes of 12 Shigella boydii and five Shigella dysenteriae strains were characterized. Though these strains are nonmotile, the cryptic fliCSB gene, cloned from S. boydii strain C3, is functional for expression of flagellin. It consists of 1,704 bp, and encodes 568 amino acid residues (57,918 Da). The fliCSD gene from S. dysenteriae strain 16 consists of 1,650 bp encoding 549 amino acid residues (57,591 Da) and contains an IS1 element inserted in its 3' end. The two genes are composed of the 5'-constant, central variable and 3'-constant sequences, like other known fliC genes. The two genes share high homology in nucleotide and amino acid sequences with each other and also with the Escherichia coli fliCE gene, indicating that both genes are closely related to the fliCE gene. Comparison of the central variable sequences of six different fliC genes showed that the fliCSB and fliCSD genes share low homology in amino acid sequence with the other fliC genes, suggesting that they encode antigenic determinants intrinsic to respective subgroups. However, Southern blotting using as probes the central variable sequences of several fliC genes showed that four of 12 S. boydii strains have a fliC gene similar to that of Shigella flexneri, and that among five fliC genes from S. dysenteriae strains, one is similar to that of S. flexneri, two are similar to that of S. boydii, and only one is unique to S. dysenteriae. Some of these variant alleles were verified by immunoblotting with flagellins produced from cloned fliC genes. The presence of variant fliC alleles in S. boydii and S. dysenteriae indicates that subdivision into subgroups does not reflect the ancestral flagella H antigenic relationships. These data will be useful in considering the evolutionary divergence of the Shigella spp..

Alleles↗

PubMed2001

Immunogenetic analysis of variable regions encoding AB1 and gamma-type AB2 antibodies from the NeuGc-containing ganglioside family.

The variable regions from P3, a murine monoclonal antibody (MAb) against NeuGc-containing gangliosides, and two anti-idiotype MAbs directed to P3 MAb were cloned and sequenced. Comparisons with previously reported sequences showed that P3 is a germline antibody encoded by genes from the V(H)Q52 and V(kappa)19 families. Analysis of nucleotides at the heavy chain CDR3 (H-CDR3) showed the presence of an extensive 3' N region that contains almost 50% of the nucleotides of this CDR. In addition, amino acid sequence analysis of the H-CDRs of this MAb revealed the presence of three arginines, two of which are present in the H-CDR3, that could be involved in the interaction of P3 MAb with its electronegative epitope on gangliosides. Anti-idiotype 1E10, which seems to define a "regulatory" idiotope on P3 MAb (it induces Id+ Ab3), represents a germline Ab2 that belongs to the V(H)J558 and V(kappa)10 gene families. By contrary, the anti-idiotype 3B11 is an extensively mutated antibody that belongs to the V(H)3660 and V(kappa)4/5 gene families, defining a "private" idiotope on P3 MAb. Even when different V genes contribute to the variable regions of 1E10 and 3B11 MAbs, they share an acidic motif E/D-D-Y/D-Y-D in H-CDR3, suggesting that both Ab2s recognize paratope positive residues on the Ab1. Therefore, complementary electrostatic interactions involving H-CDR3 from both Ab1 and Ab2, might provide a clue to understand the molecular basis for the generation of gamma-type anti-idiotype antibodies to V regions recognizing glycolylated ganglioside antigens.

Amino Acid Sequence↗

PubMed1999

Tryptophan at position 181 of the D2 protein of photosystem II confers quenching of variable fluorescence of chlorophyll: implications for the mechanism of energy-dependent quenching.

The lumenal CD loop region of the D2 protein of photosystem II contains residues that interact with a reaction center chlorophyll and the redox-active Tyr(D). Using combinatorial mutagenesis, photoautotrophic mutants of Synechocystis sp. PCC 6803 have been generated with multiple amino acid changes in this region. The CD loop mutations were transferred into a photosystem I-less Synechocystis strain to facilitate characterization of photosystem II properties in the mutants. Most of the combinatorial photosystem I-less mutants obtained had a high yield of variable fluorescence, F(V). However, in three mutants, which shared a replacement of Phe181 by Trp, the F(V) yield was dramatically reduced although a high rate of oxygen evolution was maintained. A site-directed F181W D2 mutant shared similar properties. Picosecond time-resolved fluorescence measurements revealed that in the combinatorial F181W mutants the fluorescence lifetimes in closed and open photosystem II centers were essentially identical and were similar to the fluorescence lifetime in open centers of the control strain. These results are explained by quenching of variable fluorescence in the mutants by charge separation between Trp181 and excited reaction center chlorophyll. This reaction competes efficiently with fluorescence and nonradiative decay in closed photosystem II centers, where the lifetime of the excitation in the chlorophyll antenna is long. Thermodynamic considerations favor the formation of oxidized tryptophan and reduced chlorophyll in the quenching reaction, presumably followed by charge recombination. A possible role of tryptophan-chlorophyll charge separation in the mechanism of energy-dependent quenching of excitations in photosynthesis is discussed.

Amino Acid Sequence↗

PubMed2000

Life expectancy as an indicator of environmental health.

Whether or not life expectancy at birth is related to the quality of life as expressed by global economical, environmental and nutritional measures is the primarily studied question in this article. Two models, set of independent variables and multivariate analysis was performed. An attempt to estimate the role of studied variables in overall life expectancy was done, too. A descriptive, ecological study design was used. The population of 156 countries have been taken into account, using data from published databases [7, 9]. Access to safe drinking water, per capita gross domestic product, literacy, calories available as percentage of needs and per capita public health expenditures were taken as exposure, and compared with life expectancy at birth. A linear regression model was used to estimate the role of different exposures on life expectancy at birth. A correlation matrix for all variables and life expectancy at birth is presented in the article. Literacy and access to safe drinking water are statistically significant variables (p < 0.001) also after fitting a linear regression model. The correlation coefficient for the linear model was 0.8823 (R2 = 0.7784). Shares of years of life from overall life expectancy attributed to studied variables were 28.06, 9.42, 2.04 and 1.93% for literacy, access to safe drinking water, GDP and calories available as percentage of needs, respectively.

Educational Status↗

PubMed2003

Combinatorics and quantum nonlocality.

We use techniques for lower bounds on communication to derive necessary conditions (in terms of detector efficiency or amount of superluminal communication) for being able to reproduce the quantum correlations occurring in Einstein-Podolsky-Rosen-type experiments with classical local hidden-variable theories. As an application, we consider n parties sharing a Greenberger-Horne-Zeilinger-type state and show that the amount of superluminal classical communication required to reproduce the correlations is at least n(log((2)n-3) bits and the maximum detector efficiency eta(*) for which the resulting correlations can still be reproduced by a local hidden-variable theory is upper bounded by eta(*)</=8/n and thus decreases with n.

Journal Article↗

PubMedDate not supplied

Load sharing and graft forces in anterior cruciate ligament reconstructions with the Ligament Augmentation Device.

Buckle transducers were used to directly measure load sharing and overall force in three segment (semitendinosus, gracilis, Ligament Augmentation Device) and two segment (patellar tendon, LAD) composite ACL grafts during the application of anteriorly directed loads to a series of five fresh knee specimens with a pneumatic load apparatus. The total graft forces generated in the two segment and three segment composite reconstructions during this immediate postoperative state were highly variable when compared to the normal ACL in each specimen, and were irreproducible among the five specimens. Load sharing among the graft components occurred and was also variable in both reconstructions, with this variation being greater in the three segment graft. The LAD carried an average of 45% of the total graft force in the three segment graft and 28% in the two segment graft. Further work is required to clarify the source of the variability in the total graft force and load sharing observed in this study.

Biomechanical Phenomena↗