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At least 181 records · Page 10Linked to original sources
PubMed2003

Anatomical evidence of microbial biofilms in tonsillar tissues: a possible mechanism to explain chronicity.

CONTEXT: Bacteria within biofilms are resistant to host defenses and antibiotics. The presence of bacterial biofilms within the tissue and crypts of inflamed tonsils may explain the chronicity and recurrent characteristics of some forms of tonsillitis. OBJECTIVE: To determine if microbial biofilms occur within clinically abnormal tonsils. DESIGN: In this study, we evaluated the histomorphological appearance of 19 human tonsils for evidence of biofilm formation using light and transmission electron microscopy. SUBJECTS: Human tissues were collected during surgical tonsillectomy. Fifteen specimens were removed because of a history of repeated infections, and 4 were removed because of hypertrophy and obstruction. INTERVENTIONS: No interventions were used in this study. MAIN OUTCOME MEASURE: Histological and ultrastructural evidence of bacterial biofilms within the crypts of tonsils. RESULTS: Gram-positive and gram-negative bacteria were seen within otherwise acellular deposits among crypts of 11 of 15 infected tonsils. Regions of accumulated bacteria possessed the ultrastructural appearance of typical amorphous polysaccharide biofilm matrix. Small clusters of bacterial colonies were seen in 3 of 4 tonsils removed because of hypertrophy. CONCLUSIONS: There is strong anatomical evidence for the presence of bacterial biofilms in chronically diseased tonsils. Because sessile bacteria within biofilms are resistant to host defenses and antibiotics, bacterial biofilms within tonsils may explain the chronicity and recurrent nature of some forms of tonsillitis.

Biofilms↗
PubMed1999

Explaining heterogeneity in meta-analysis: a comparison of methods.

Exploring the possible reasons for heterogeneity between studies is an important aspect of conducting a meta-analysis. This paper compares a number of methods which can be used to investigate whether a particular covariate, with a value defined for each study in the meta-analysis, explains any heterogeneity. The main example is from a meta-analysis of randomized trials of serum cholesterol reduction, in which the log-odds ratio for coronary events is related to the average extent of cholesterol reduction achieved in each trial. Different forms of weighted normal errors regression and random effects logistic regression are compared. These analyses quantify the extent to which heterogeneity is explained, as well as the effect of cholesterol reduction on the risk of coronary events. In a second example, the relationship between treatment effect estimates and their precision is examined, in order to assess the evidence for publication bias. We conclude that methods which allow for an additive component of residual heterogeneity should be used. In weighted regression, a restricted maximum likelihood estimator is appropriate, although a number of other estimators are also available. Methods which use the original form of the data explicitly, for example the binomial model for observed proportions rather than assuming normality of the log-odds ratios, are now computationally feasible. Although such methods are preferable in principle, they often give similar results in practice.

Bayes Theorem↗
PubMed1997

Large majority of single-nucleotide mutations along the dystrophin gene can be explained by more than one mechanism of mutagenesis.

The present study reports for the first time on the analysis of the possible origin of single-base mutations along the highly mutable human dystrophin gene. Seventy-two mutations were considered and analyzed for consistency with the "slipped-mispairing" and "hypermutable CpG" models of mutagenesis. Moreover, repeated and symmetric elements, which could participate in the formation of secondary structures, were searched in each stretch of sequence including a given mutant base. Unexpectedly, the frequency of CpG mutations was found less than reported for other genes, whereas the frequency of transitions was found to be much higher than expected. Base substitutions in CpG dinucleotides that could be explained by methylation-mediated deamination were all C-->T transitions. No G-->A transitions in CpG dinucleotides were found. A sequence motif, which has been shown to act as an arrest site for polymerase alpha, occurred associated with > 50% of single-base mutations. All the mutations but one can be explained by at least two mechanisms of mutagenesis. This would mean that mutation could occur with higher probability at a given position, when it might be produced independently by different mechanisms. According to the present data, direct or inverted repeats seem to play a major role in this context. Therefore, the search for repeats along the dystrophin gene might help in identifying potential sites of mutation.

Amino Acid Sequence↗
PubMed1996

Using nursing diagnoses to explain utilization in a Community Nursing Center.

The purpose of this study was to examine the usefulness of nursing diagnoses, based on the Omaha System framework, in explaining utilization of primary health care services in a Community Nursing Center (CNC). Utilization was defined as the number of client visits at the CNC. Data were obtained from a total of 331 client records where the Omaha System taxonomy was used in the documentation of nursing diagnoses with each nurse/client encounter. Hierarchic regression analysis was conducted to examine predictors of utilization. Nursing diagnoses were significant predictors of utilization at the CNC above and beyond client demographics. These findings suggest that nursing diagnoses data may be useful in explaining clients' use of CNCs.

Adolescent↗
PubMed2000

A qualitative model for the histamine H3 receptor explaining agonistic and antagonistic activity simultaneously.

A pharmacophore model for histamine H3 ligands is derived that reveals the putative interaction of both H3 agonists and antagonists with an aspartate residue of the receptor. This interaction is determined by applying the density functional theory implemented in a program package adapted for parallel computers. The model reveals a molecular determinant explaining efficacy as the conformation of the aspartic acid residue differs according to whether it is binding to agonists or antagonists. The differences in structure-activity relationships (SAR) observed for the lipophilic tails of different classes of H3 antagonists are now explained, since the model reveals two distinct lipophilic pockets available for antagonist binding.

Aspartic Acid↗
PubMed2001

Developmental mosaicism may explain spontaneous reappearance of the Axin(Fu) mutation in mice.

The Axin(Fu) mutation is caused by an IAP insertion. In a small percentage of mice, the Axin(Fu) mutation disappears and is not observed in the next generation. In these mice, [Axin(Fu)]/+, the IAP is absent and Axin(Fu) has reverted to the wild allele. Concomitantly with the loss of IAP, there is widespread reorganisation of numerous microsatellite loci across the surrounding region of chromosome. In rare cases, spontaneous reappearance of the mutation can be observed in progeny of [Axin(Fu)]/+ mice. It is revealed here that reappearance of Axin(Fu) was associated with restoration of the IAP insertion. In such mice, alleles of the surrounding microsatellite loci were identical to the alleles observed on chromosomes that carried Axin(Fu). Developmental mosaicism can potentially explain spontaneous reappearance of the Axin(Fu) mutation. Mosaicism can also explain other observations including postnatal changes at the Axin locus, unusual segregation in progeny, and the appearance of [Axin(Fu)]/+ mice that were phenotypically mutant. 2001.

Animals↗
PubMedDate not supplied

Explaining sex differences in dental caries prevalence: saliva, hormones, and "life-history" etiologies.

When dental caries rates are reported by sex, females are typically found to exhibit higher prevalence rates than males. This finding is generally true for diverse cultures with different subsistence systems and for a wide range of chronological periods. Exceptions exist, but are not common. In this paper, we present new data for sex differences in dental caries rates among the Guanches (Tenerife, Canary Islands), summarize results of meta-analyses of dental caries prevalence, and emphasize new research that stresses the critical role of female hormones and life-history events in the etiology of dental caries. Among the Guanches, corrected tooth-count caries rates for females (8.8%, 158/1,790) are approximately twice the frequency of caries among males (4.5%, 68/1,498). Higher caries prevalence among females is often explained by one of three factors: 1) earlier eruption of teeth in girls, hence longer exposure of girls' teeth to the cariogenic oral environment, 2) easier access to food supplies by women and frequent snacking during food preparation, and 3) pregnancy. Anthropologists tend to favor explanations involving behavior, including sexual division of labor and women's domestic role in food production. By contrast, the causal pathways through which pregnancy contributes to poorer oral health and higher caries rates are deemphasized or discounted. This paper presents recent research on physiological changes associated with fluctuating hormone levels during individual life histories, and the impact these changes have on the oral health of women. The biochemical composition of saliva and overall saliva flow rate are modified in several important ways by hormonal fluctuations during events such as puberty, menstruation, and pregnancy, making the oral environment significantly more cariogenic for women than for men. These results suggest that hormonal fluctuations can have a dramatic effect on the oral health of women, and constitute an important causal factor in explaining sex differences in caries rates.

Anthropology, Physical↗
PubMed1996

Segregation analysis of Alzheimer pedigrees: rare Mendelian dominant mutation(s) explain a minority of early-onset cases. French Alzheimer Collaborative Group.

Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ( < or = age 60 years) AD (EOAD) probands has been carried out, allowing for a mixture in AD inheritance among probands. The goal was to quantify the proportion of probands that could be explained by autosomal inheritance of a rare disease allele "a" at a Mendelian dominant gene (MDG). Our data provide strong evidence for a mixture of two distributions; AD transmission is fully explained by MDG inheritance in < 20% of probands. Male and female age-of-onset distributions are significantly different for "AA" but not for "aA" subjects. For "aA" subjects the estimated penetrance value was close to 1 by age 60. For "AA" subjects, it reaches, by age 90, 10% (males) and 30% (females). We show a clear cutoff in the posterior probability of being an MDG case.

Age Factors↗
PubMed2006

Scent marking in sifaka: no one function explains it all.

Various hypotheses to explain possible functions of scent-marking have been put forth and basically fall into five categories: territorial demarcation, ownership of resources, mate attraction, noncombative fighting, and self-advertisement. Verreaux's sifaka (Propithecus verreauxi verreauxi), like many prosimians, use scent-marking as one form of communication. The goal of this study was to determine the function of scent-marking in sifaka. All-occurrence of scent-marks, scent-mark context, and scent-mark style were collected on 23 sifaka in the Kirindy Forest of western Madagascar for 7 months (September 2001-March 2002). Scent-mark rates were collected using continuous focal animal sampling from November 2000-March 2002. Home range data were collected using monthly censuses and instantaneous focal sampling throughout the 17 months. Scent-marking behavior was exhibited almost exclusively by adults. Scent-mark rates were not related to the number of resident adult males, number of resident adult females, rank, or group size. The majority of scent-marks occurred in the perimeter of the home range; however, less than a quarter of the home range was used by only a single group. Sifaka did not preferentially mark food trees, mark during the mating season, or mark during intergroup encounters. The results from this study indicate that none of the five hypothesized functions best explains all scent-marking in Verreaux's sifaka. Rather, scent-marking may serve different functions for different individuals.

Animal Communication↗
PubMed1985

Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa.

Alfalfa sprouts can induce systemic lupus erythematosus (SLE) in monkeys. This property of alfalfa sprouts has been attributed to their non-protein amino acid constituent, L-canavanine. Occurrence of autoimmune hemolytic anemia and exacerbation of SLE have been linked to ingestion of alfalfa tablets containing L-canavanine. In this report we show that L-canavanine has dose-related effects in vitro on human immunoregulatory cells, which could explain its lupus-inducing potential. These effects include: 1) diminution of the mitogenic response to both phytohemagglutinin and concanavalin A but not to pokeweed mitogen, as determined in both thymidine incorporation and cell cycle studies, and 2) abrogation of concanavalin A-induced suppressor cell function, which results in increased release of both IgG and DNA binding activity into supernatants by cells from normal subjects and SLE patients. These immunoregulatory effects of L-canavanine may explain the induction or exacerbation of SLE by alfalfa.

Adult↗
PubMed2004

A mixed mechanistic-electrostatic model to explain pH dependence of glycosyl hydrolase enzyme activity.

Glycosyl hydrolases are a vast group of enzymes that share a common topology at their active site with two acidic residues that are responsible for activity. In spite of their similarity, they exhibit a wide range of pH optima that must depend on other factors. Using structural and mechanistic knowledge about glycosyl hydrolases from families 7, 10, and 16, we have formulated a new mathematical model that can include not only the ionization behavior of the catalytic residues but also as many ionizable residues as desired in the active site. In addition, the model can incorporate electrostatic influences via acid dissociation equilibrium constants and chemical relationships such as hydrogen bonds. The results of the simulations indicate a clear shift in the pH dependence of activity for the enzymes only when a close interrelation (hydrogen bond) between the catalytic and auxiliary residues in the active site is taken into account. This explains the observations from mutagenesis studies that show this type of shift and cannot be explained by a purely electrostatic interaction theory. Moreover, the presence of the kind of chemical interaction proposed could provide stabilization of the activity in the presence of environmental, structural, pH and electrostatic variations. These findings and the implications for the design of new mutagenesis strategies are discussed. The results suggest a way to modify, via site-directed mutagenesis, the acid dissociation of one of the catalytic residues in the active site independently of the other, which could have clear advantages over the purely electrostatic modifications that usually affect both residues simultaneously.

Catalysis↗
PubMed1986

The inheritance of pyloric stenosis explained by a multifactorial threshold model with sex dimorphism for liability.

The inheritance of pyloric stenosis is explained by a multifactorial threshold model with an underlying assumption that the liability for the disease is distributed in males and females showing a sex dimorphism. From the available data on familial occurrences of pyloric stenosis, it is shown, that an extra maternal effect is not required to explain the familial risk of pyloric stenosis, as opposed to the earlier literature. Explicit expressions for familial risks of a discontinuous trait exhibiting dimorphism of liability are presented, based on a model originally proposed by Rice et al [1981], which do not require the approximation of univariate normality of a conditional bivariate normal distribution.

Factor Analysis, Statistical↗
PubMed2006

Apolipoprotein E and obstructive sleep apnea: evaluating whether a candidate gene explains a linkage peak.

Evidence from both linkage analyses and association-based analyses has implicated Apoliprotein E (ApoE) as a disease susceptibility locus for obstructive sleep apnea. To further assess the putative role of ApoE in sleep apnea, we performed genotyping, association, and linkage analyses in a cohort assembled to investigate the genetic epidemiology of sleep apnea. Among a subset of the Caucasian families, ten microsatellites, spanning 20 cM, were genotyped in a region near ApoE on chromosome 19 where previous suggestive linkage had been demonstrated using a 9.1-cM genome-wide scan. Haseman-Elston regression analysis, conducted with these fine mapping markers (n=196 sibling pairs, 56 families), showed evidence for linkage to marker AFM210yg9 (p=0.00034), which was increased over that observed with the original scan. ApoE genotyping also was performed on a larger set of data (n=1,211 from 271 families, ages 3-85 years) from the cohort with available DNA. To determine whether the ApoE genotype explains the linkage peak, we included the ApoE genotype as a covariate in regression models. Inclusion of ApoE E2 allele as a covariate reduced the regression coefficient by 18%, suggesting that ApoE does not substantively explain the linkage signal. Finally, we repeated an association-based analysis in the larger sample of 1,211 individuals, and observed a higher prevalence of sleep apnea among individuals with the ApoE E2 allele. Overall, the evidence suggests that there is a disease susceptibility locus for obstructive sleep apnea in the region of ApoE, but ApoE itself is unlikely to be the causative locus.

Adolescent↗
PubMedDate not supplied

Explaining the utilisation of dental care. Experiences from the Finnish dental market.

In this paper a model based on the theory of demand for health and of supplier inducement is developed to explain the utilisation of dental care. Of special interest are the effects of money price and various forms of inducement. It is also explored how the results are affected if different model specifications and estimation techniques are applied and what is the most appropriate one, when utilisation is measured by dental expenditure. The data come from a sample of 1779 employees, whose dental expenditure is refunded from 0 to 99.75%. Other things being equal, the methodological choices make a clear difference in parameter estimates. Only a log-linear two-part model and two-part tobit with selectivity were suitable for explaining expenditure and produced quite similar results. Money price elasticity was small, but significant (-0.069). General and personal inducement appear to have a considerable effect on utilisation, but did not have any systematic connection with dentist/population ratio.

Adult↗
PubMed2004

Explaining the differences in income-related health inequalities across European countries.

This paper provides new evidence on the sources of differences in the degree of income-related inequalities in self-assessed health in 13 European Union member states. It goes beyond earlier work by measuring health using an interval regression approach to compute concentration indices and by decomposing inequality into its determining factors. New and more comparable data were used, taken from the 1996 wave of the European Community Household Panel. Significant inequalities in health (utility) favouring the higher income groups emerge in all countries, but are particularly high in Portugal and - to a lesser extent - in the UK and in Denmark. By contrast, relatively low health inequality is observed in the Netherlands and Germany, and also in Italy, Belgium, Spain Austria and Ireland. There is a positive correlation with income inequality per se but the relationship is weaker than in previous research. Health inequality is not merely a reflection of income inequality. A decomposition analysis shows that the (partial) income elasticities of the explanatory variables are generally more important than their unequal distribution by income in explaining the cross-country differences in income-related health inequality. Especially the relative health and income position of non-working Europeans like the retired and disabled explains a great deal of 'excess inequality'. We also find a substantial contribution of regional health disparities to socio-economic inequalities, primarily in the Southern European countries.

Europe↗
PubMed2002

Germline mutations in E-cadherin do not explain association of hereditary prostate cancer, gastric cancer and breast cancer.

Somatic mutations in the E-cadherin (CDH1) gene have frequently been reported in cases with diffuse gastric and lobular breast cancers. Recently, germline mutations have been identified in families with diffuse gastric cancers. In families with hereditary prostate cancer (HPC), a significant association of prostate cancer, gastric and/or breast cancer has been observed in epidemiological studies. The aim of this study was to investigate if germline mutations in CDH1 could explain the risk for cancer in HPC families with an excess of gastric and breast cancer. In total, 17 members from 13 HPC families and 3 members from 3 families with hereditary gastric cancer (HGC) were screened for germline CDH1 sequence alterations using PCR/Denaturing HPLC for initial screening of nucleotide variants followed by confirmatory direct sequencing analysis. The frequency of identified novel germline mutations were tested for in 136 cases with hereditary prostate cancer and 215 cases of sporadic prostate cancer with 422 age matched controls in an allelic discrimination assay. In total, 8 sequence variants were detected in 20 samples tested. In the HPC families, we found 2 missense mutations, A592T in exon 12 and a novel D777N in exon 15 and a mutation in intron 5, 687+92T>A. A previously known polymorphism in exon 13 and 3 sequence variations in introns and untranslated regions were also found, of which the significance is unknown. In HGC-023 with early onset diffuse gastric cancer a truncating mutation, R335X, was identified in exon 7. None of the missense mutations or 687+92T>A were found in the extended HPC material or in the sporadic prostate cancer cases with age-matched controls in the allelic discrimination assay. We found several germline mutations of unknown clinical significance in the CDH1 gene that probably do not explain the association of prostate, gastric and/or breast cancers in the HPC-families. Two missense mutations and a mutation in intron 5 were identified that do not influence the risk of hereditary or sporadic prostate cancer in general and are considered to be pedigree specific. In a family with hereditary gastric cancer of the diffuse type, we identified the first truncating germline mutation in a Scandinavian family.

Adult↗
PubMed2004

Explaining gastric cancer survival differences among European countries.

Wide geographic variability in incidence and mortality rates for gastric cancer exists throughout the world despite persistent decreases over several decades. Variability in survival from gastric cancer is also evident and countries with higher incidence rates of gastric cancer show better survival rates than countries with lower incidence. The aim of this study was to identify reasons for the association between incidence and survival and to obtain survival estimates and differences corrected for this variation, thus facilitating further interpretation by clinical factors such as stage and treatment. Relative survival rates for gastric cancer derived from the EUROCARE-2 database for 47 cancer registries in 17 European countries were analyzed with regression methods to adjust differences by age, sex, period of diagnosis, subsite of the stomach, histologic type and stage at diagnosis. Overall, nearly 60% of the variability in gastric cancer relative survival was explained by differences in these variables. Factors are related to treatment and general management of patients is expected to explain the residual variability in gastric cancer survival between European countries. There is a need to improve completeness and standardization of detailed information collected on gastric cancer patients to allow detailed comparative analyses and interpretation.

Aged↗
PubMed2005

Virus target cell conditioning model to explain some epidemiologic characteristics of childhood leukemias and lymphomas.

Frequent infections in early childhood, whole-day care and a socially unprivileged environment have been reported as protective factors for childhood leukemias and lymphomas. Conversely, a protected social environment, higher level of education and growing up in families with a low number of children are considered as risk factors. Additional risk factors involve agricultural occupation of the parents and exposure to several other occupational factors. These data led to a number of hypotheses that attempted to explain the epidemiologic observations; however, a number of questions are still open. Here we propose a new concept that could explain most of the epidemiologic characteristics. This concept is based on the assumption that persistent infections with TT virus-like agents increase the risk for specific chromosomal translocations. This risk should correlate with the viral load. Interferon induction by intermittent infections should reduce the viral load and thus decrease the risk for chromosomal modifications. Some virologic observations in support of this model are presented.

Animals↗