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At least 253 records · Page 14Linked to original sources
PubMed2004

A reanalysis of the indirect evidence for recombination in human mitochondrial DNA.

In an attempt to resolve the controversy about whether recombination occurs in human mtDNA, we have analysed three recently published data sets of complete mtDNA sequences along with 10 RFLP data sets. We have analysed the relationship between linkage disequilibrium (LD) and distance between sites under a variety of conditions using two measures of LD, r2 and /D'/. We find that there is a negative correlation between r2 and distance in the majority of data sets, but no overall trend for /D'/. Five out of six mtDNA sequence data sets show an excess of homoplasy, but this could be due to either recombination or hypervariable sites. Two additional recombination detection methods used, Geneconv and Maximum Chi-Square, showed nonsignificant results. The overall significance of these findings is hard to quantify because of nonindependence, but our results suggest a lack of evidence for recombination in human mtDNA.

DNA, Mitochondrial↗
PubMed1996

Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies.

OBJECTIVE: The significance of mild hypercholesterolaemia in subclinical hypothyroidism and whether there is beneficial reduction after thyroxine replacement, remain controversial. We aimed to describe the association between hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect of thyroid substitution therapy by an analysis of previously published intervention studies. DATA SOURCES: Intervention studies cited in the Medline database from January 1976 until January 1995, with index terms cholesterol, hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION: We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre and post-substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS: (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypothyroidism, both subclinical and clinical. (2) Precision weighted pooled estimates of the effect of thyroid substitution therapy on the plasma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS: Subclinical hypothyroidism was two to three times more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevated in patients with subclinical dysfunction of the thyroid. Thyroid substitution therapy in patients with subclinical hypothyroidism, restoring the TSH levels to normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (Cl) 0.2-0.6 mmol/l) independently of the initial plasma level. The effect of thyroid substitution therapy on HDL-cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of total cholesterol. In these patients substitution therapy decreased total cholesterol by 1.2 mmol/l (95% Cl 0.9-1.5 mmol/l) when the plasma levels were elevated up to 8 mmol/l, and by 3.4 mmol/l (95% Cl 3.0-3.7) when plasma levels were higher than 8 mmol/l. The high density lipoprotein (HDL)-cholesterol level decreased and amounted to 0.16 mmol/l (95% Cl 0.07-0.24). CONCLUSIONS: Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.

Adult↗
PubMed1999

Does sleep fragmentation impact recuperation? A review and reanalysis.

Studies have shown that next-day performance and alertness are impaired by sleep fragmentation procedures even when total sleep time (TST) is unaffected. Based on these studies it has been hypothesized that both the duration and continuity of sleep determine its recuperative value. This review of the literature suggests that when sleep fragmentation procedures increase the relative amount of stage 1 sleep, next-day performance and alertness are impaired. Other studies suggest that stage 1 sleep has little or no recuperative value. Total sleep time, however, is typically defined as the sum of time spent in sleep stages 1, 2, 3, 4, and REM. In the present paper it is shown that when stage 1 sleep is excluded from TST, a stronger relationship between TST and subsequent alertness and performance emerges--and the need to invoke 'sleep continuity' as a variable that contributes independently to recuperative sleep processes is obviated. In the same way that partial or total sleep deprivation impairs alertness and performance, it is proposed that sleep disruption also impairs alertness and performance by reducing true recuperative sleep time.

Arousal↗
PubMed1998

Socio-economic and dietary influences on leg length and trunk length in childhood: a reanalysis of the Carnegie (Boyd Orr) survey of diet and health in prewar Britain (1937-39).

Social class differences in height have been recognised for many centuries. However, few studies have examined the extent to which these differences are made up of differences in leg length or trunk length. This paper reanalyses cross-sectional information on children examined in Britain in the 1930s. We assess associations between socio-economic status and diet and the components of childhood stature. The analyses were based on the records of 2990 children aged 2 years to 14 years 9 months who were examined in the Carnegie (Boyd Orr) survey of diet and health (1937-39). z-Scores for the measures of childhood stature were calculated using polynomial regression techniques with the study population as the standard. Univariable and multivariable statistical techniques were used to assess the relationships between childhood height, leg length and trunk length, and dietary and socio-economic factors measured at the level of the household. Leg length was the component of stature most strongly associated with measures of childhood diet and socio-economic status. A greater part of the difference in stature between socio-economic groups was caused by differences in leg length rather than trunk length. In multiple regression analyses, district of residence and family food expenditure were generally the two factors most strongly related to stature. In a subsample of the surveyed children, for whom birthweight information was available, trunk length and leg length were equally strongly related to birthweight. Leg length appears to be a particularly sensitive indicator of childhood socio-economic circumstances. Although contemporary studies highlight the importance of biological factors in determining childhood height, the data analysed in this study suggest that socio-economic circumstances were also important in explaining height differentials in prewar Britain.

Adolescent↗
PubMed2004

Flowering time plasticity in Arabidopsis thaliana: a reanalysis of Westerman & Lawrence (1970).

Environmental variation in temperature can have dramatic effects on plant morphology, phenology, and fitness, and for this reason it is important to understand the evolutionary dynamics of phenotypic plasticity in response to temperature. We investigated constraints on the evolution of phenotypic plasticity in response to a temperature gradient in the model plant Arabidopsis thaliana by applying modern analytical tools to the classic data of Westerman & Lawrence (1970). We found significant evidence for two types of constraints. First, we detected numerous significant genetic correlations between plastic responses to temperature and the mean value of a trait across all environments, which differed qualitatively in pattern between the set of ecotypes and the set of mutant lines in the original sample. Secondly, we detected significant costs of flowering time plasticity in two of the three experimental environments, and a net pattern of selection against flowering time plasticity in the experiment overall. Thus, when explored with contemporary methods, the prescient work of Westerman & Lawrence (1970) provides new insights about evolutionary constraints on the evolution of plasticity.

Arabidopsis↗
PubMed1995

Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer.

BACKGROUND: Previous findings from a clinical trial (Protocol B-06) conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) indicated the worth of lumpectomy and breast irradiation for treating breast cancer. After the discovery by NSABP staff members of falsified information on patients enrolled in the study by St. Luc Hospital in Montreal, separate audits were conducted at St. Luc Hospital and other participating institutions. We report the results of both audits and update the study findings through an average of 12 years of follow-up. METHODS: Patients with either negative or positive axillary nodes and tumors 4 cm or less in diameter were randomly assigned to one of three treatments: total mastectomy, lumpectomy followed by breast irradiation, or lumpectomy without irradiation. Three cohorts of patients were analyzed. The first cohort included all 2105 randomized patients, who were analyzed according to the intention-to-treat principle. The second cohort consisted of 1851 eligible patients in the first cohort with known nodal status who agreed to be followed and who accepted their assigned therapy (among those excluded were 6 patients from St. Luc Hospital who were declared ineligible because of falsified biopsy dates). The third cohort consisted of the patients in the second cohort minus the 322 eligible patients from St. Luc Hospital (total, 1529 patients). RESULTS: Regardless of the cohort, no significant differences were found in overall survival, disease-free survival, or survival free of disease at distant sites between the patients who underwent total mastectomy and those treated by lumpectomy alone or by lumpectomy plus breast irradiation. After 12 years of follow-up, the cumulative incidence of a recurrence of tumor in the ipsilateral breast was 35 percent in the group treated with lumpectomy alone and 10 percent in the group treated with lumpectomy and breast irradiation (P < 0.001). CONCLUSIONS: Our findings continue to indicate that lumpectomy followed by breast irradiation is appropriate therapy for women with either negative or positive axillary nodes and breast tumors 4 cm or less in diameter.

Breast Neoplasms↗
PubMed2004

A demonstration and findings of a statistical approach through reanalysis of inflammatory bowel disease data.

We test the backward haplotype transmission association algorithm on genome-scan data previously studied by Rioux et al. [Rioux, J. D., et al. (2000) Am. J. Hum. Genet. 66, 1863-1870]. In their study, multipoint linkage methods were applied to affected sib-pairs with inflammatory bowel disease, and significant linkage evidence points to two susceptibility loci. After we apply our approach to these data with a global search accounting for both joint and marginal effects, very interesting results emerge, many of them intriguing. These results provide compelling support for the application of our approach to other data wherever applicable. Results from this project also make it clear that it is important to reinvestigate available family-based datasets that can be suitably reanalyzed. Given previously collected data in the literature, our approach, with its increased efficiency in using available resources, draws additional crucial information that may lead to novel and surprising results.

Genetic Linkage↗
PubMed2002

Reanalysis of ATP11B, a type IV P-type ATPase.

P-type ATPases are a venerable family of ATP-dependent ion transporters. Recently, evidence was presented that a rabbit gene in the type IV subfamily of P-type ATPases was missing a transmembrane helix (transmembrane domain 4) thought to be critical for ion transport, a deletion that would place the two major catalytic loops of the enzyme on opposite sides of the membrane. It was proposed that the resulting protein was a RING finger-binding protein that targets transcription factors to specific domains within the nucleus. From analysis of human genomic sequence data, it is shown here that the region containing transmembrane domain 4, corresponding to exon 12, is present in the human homolog of the gene, ATP11B. PCR analysis indicates that the predominant Atp11b transcripts in a rabbit cDNA library and in a mouse cDNA library also contain exon 12. The results suggest that the transcript proposed to encode the RING finger-binding protein is a minor rabbit-specific splice variant. The ATP11B gene thus may not encode a protein with a function radically different from that of other P-type ATPase transporters.

Adenosine Triphosphatases↗
PubMed2005

The Oxford Brookes basal metabolic rate database--a reanalysis.

OBJECTIVE: To produce prediction equations for basal metabolic rate (BMR) derived from weight and height covering the age range from birth to old age. DESIGN: Cross-sectional data on BMR, sex, age, weight, height, ethnicity and measurement technique from the Oxford Brookes BMR database. SETTING: Worldwide. SUBJECTS: Data for 13,910 men, women and children from 174 papers published between 1914 and 2001. RESULTS: Absolute and proportional regression models were developed for each sex, showing a steep rise in predicted BMR with age until 15 years, more pronounced in males than females, then a gradual fall through adulthood. Predicted BMR increased by 6% and 1.4%, respectively, per standard deviation increase in weight and height. Predicted BMR in Caucasians was 4% higher than in non-Caucasians, though the effect size was sensitive to the inclusion or exclusion of data from certain influential publications. The effect of measurement technique on BMR, closed-circuit versus open-circuit, was small, near 1%. CONCLUSIONS: It is possible to develop prediction equations that avoid splitting the data into arbitrary age groups. Heterogeneity between publications is greater than might be expected by chance, probably due to undocumented differences in technique.

Adolescent↗