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PubMed1976

Variability of the diagnosis of stroke by clinical judgement and by a scoring method.

Existing criteria for the diagnosis of acute cerebrovascular disease (stroke) have not been satisfactory in epidemiological studies. Variability of the diagnosis of stroke, which had not been studied before, was investigated in a WHO collaborative study. Intra-observer and inter-observer variation of the diagnosis of stroke was studied by means of 45 case reports drawn at random from among those included in the study. Diagnosis of stroke and of the type of stroke was made by clinical judgement and by a scoring method. The clinical diagnosis of stroke was more consistent and more comparable than the diagnosis of the type of stroke. Inter-observer agreement in clinical diagnosis was improved by using the score method.

Cerebrovascular Disorders↗

PubMed1987

Plasma catecholamine and metabolic changes during cooling and rewarming in dogs.

A slow and progressive fall in colonic temperature occurred in dogs immersed in cold water (8-16 degrees C) when heat production reached a maximum value (CVO2 max). When moderate hypothermic dogs were placed in air (21 degrees C), they continued to shiver and progressively recovered a normal core temperature. Plasma epinephrine (E) and norepinephrine (NE) concentrations, metabolic rate (VO2), arterial and venous blood gas, pH, saturation and oxygen content values were compared, for the same colonic temperature, during cooling and during rewarming. Plasma lactic acid, glucose and free fatty acid (FFA) concentrations, were also measured under both conditions. 1) VO2 was lower during rewarming than during cooling. 2) Plasma NE decreased from maximal value observed during cooling but was still significantly higher than precooling control. During rewarming as well as during cooling a correlation was found between plasma NE and mixed venous oxygen saturation and between plasma NE and mixed venous oxygen content. 3) As NE, plasma E was lower during rewarming than during cooling but was still significantly higher than precooling control. During cooling an acidosis was observed and plasma E was significantly correlated with venous and arterial pH. 4) During rewarming: arterial acidosis disappeared, plasma lactate and glucose concentrations were lower and FFA were higher than during cooling. These results suggest that for the same degree of moderate hypothermia there was less involvement of the sympathoadrenal system during rewarming than during cooling. The simultaneous decrease in metabolic rate and the variations observed in blood pH and in plasma substrate concentrations suggest a relationship between the level of plasma catecholamine concentrations and metabolic adjustments associated with rewarming from hypothermia.

Animals↗

PubMed1997

Oral health status among secondary school students in Harare, Zimbabwe.

In 1993 a demonstration oral care programme to evaluate the ART procedure for dental caries under field conditions began among secondary school students in Greater Harare. The programme was preceded by an oral epidemiological survey. Of the 569 students examined, with a mean age of 13.9 years, 58.7 per cent were caries free. The mean DMFS and DMFT scores were 1.4 and 1.1, respectively. Very few missing and filled teeth were observed. Excluding those with pulp involvement, small dentinal lesions which could not be penetrated with an excavator at the time of examination, constituted 49 per cent of the mean DMFS score. 84 per cent of dentinal lesions needing treatment were judged to be treatable using the ART procedure. Using the index of Green and Vermillion (1964), the mean plaque score was 5.6 with substantial variation observed between the schools. Calculus was observed among 89.5 per cent of the students examined. 18 per cent of them had a central diastema in the maxilla. Crowding or spacing in the upper and lower anterior region of the jaws was observed in 67.5 per cent and 60.5 per cent of the students, respectively. 15.8 per cent were dissatisfied with the position of their teeth whilst 15 per cent indicated that they would like to undergo corrective treatment. It was concluded that these secondary students lack preventive and curative oral care and that the vast majority of the dentinal lesions observed could be treated using the ART procedure.

Adolescent↗

PubMed2004

Stable isotope ratios as a tool in microbial forensics--Part 2. Isotopic variation among different growth media as a tool for sourcing origins of bacterial cells or spores.

Since the anthrax attacks of 2001 the need for methods to trace the origins of microbial agents has become urgent. The stable isotope ratios of bacteria record information from both the nutrients and the water used to make their culture media and could potentially be used to provide information about their growth environment. We present a survey of carbon (C), nitrogen (N), and hydrogen (H) stable isotope ratios in 516 samples of bacteriological culture media. The observed variation was consistent with expected isotopic variation in the plant and animal products upon which the media are based. The variation is sufficient to translate into substantial isotope variation in cultures grown on different batches of media, and thus to allow investigators to determine whether seized media could have been used to produce seized bioweapons agents.

Agar↗

PubMedDate not supplied

[Variations in ATP synthetase activity of rat liver mitochondria during aging and under the effect of thyroxine].

Experiments with 1-, 3-, 12- and 24-month male rats show a decrease in the rate of ATP synthesis by the liver mitochondria with oxidation of succinate and alpha-glycerophosphate. Administration of thyroxin to animals for 2 and 9 days evokes a more pronounced increase of ATP-synthetase activity in 12- and 24-month rats and an essential decrease of the age differences of the activity. It is suggested that the character of observed variations is caused by age changes in the system of the hormonal metabolism control.

ATP Synthetase Complexes↗

PubMed2005

Inferring the effects of demography and selection on Drosophila melanogaster populations from a chromosome-wide scan of DNA variation.

Identifying regions of the Drosophila melanogaster genome that have been recent targets of positive Darwinian selection will provide evidence for adaptations that have helped this species to colonize temperate habitats. We have begun a search for such genomic regions by analyzing multiple loci (about 250) dispersed across the X chromosome in a putatively ancestral population from East Africa and a derived European population. For both populations we found evidence for past changes in population size. We estimated that a major bottleneck associated with the colonization of Europe occurred about 3,500-16,000 years ago. We also found that while this bottleneck can account for most of the reduction in variation observed in the European sample, there is a deficit of polymorphism in some genomic regions that cannot be explained by demography alone.

Africa↗

PubMed1984

An anatomical study of human otocephaly.

This study describes the gross anatomic variations observed in a 32-week male fetus diagnosed as having otocephaly. Special attention was given to the muscular, peripheral nervous, and vascular systems of the entire body. External features included approximation of the ears on the front of the neck, underdevelopment of the lower jaw, and a small oral cavity. The mandible, maxillae, and zygomatic bones were smaller than normal and appeared shifted in a ventrocaudal direction. The middle ear ossicles were fused and abnormally positioned. The tongue was positioned abnormally and malformed. The muscles of mastication were fused in the midline and formed the floor of the oral cavity. The variations were similar to the spectrum of abnormalities reported in two cases in the literature. Because of this finding, it is possible that the causative events leading to these deviations were similar in the three cases. Possible mechanisms are considered which could lead to the observed malformations seen in these cases. There were also several muscle and nerve anomalies outside of the head region.

Abnormalities, Multiple↗

PubMed2005

Molecular evidence for an activator-inhibitor mechanism in development of embryonic feather branching.

The developmental basis of morphological complexity remains a central question in developmental and evolutionary biology. Feathers provide a unique system to analyze the development of complex morphological novelties. Here, we describe the interactions between Sonic hedgehog (Shh) and bone morphogenetic protein 2 (Bmp2) signaling during feather barb ridge morphogenesis. We demonstrate that activator-inhibitor models of Shh and Bmp2 signaling in the tubular feather epithelium are sufficient to explain the initial formation of a meristic pattern of barb ridges and the observed variation in barb morphogenesis in chick natal down feathers. Empirical tests support the assumptions of the model that, within the feather ectoderm, Shh (activator) up-regulates its own transcription and that of Bmp2 (inhibitor), whereas Bmp2 signaling down-regulates Shh expression. More complex models incorporating a second activator and dorsal/ventral polarized modification of activator signaling can produce all of the barb morphogenesis patterns observed during the growth of more complex branched pennaceous feathers: new barb ridge formation, helical growth, and barb ridge fusion. An integrated model of feather morphogenesis and evolution suggests that plumulaceous feather structure evolved by the establishment of activator-inhibitor interactions between Shh and Bmp2 signaling in the basal epithelium of the feather germ. Subsequently, pennaceous feather structure evolved through the integration of barb ridge morphogenesis with a second, local inhibitor and a dorsal/ventral signal gradient within the feather. The model is congruent with paleontological evidence that plumulaceous feathers are primitive to pennaceous feathers.

Animals↗

PubMed1997

The geographic distribution of human Y chromosome variation.

We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or "YAP" element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five "YAP haplotypes" in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 "combination haplotypes". All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions.

Gene Frequency↗

PubMed2000

Solvent accessibility and purifying selection within proteins of Escherichia coli and Salmonella enterica.

The neutral theory of molecular evolution predicts that variation within species is inversely related to the strength of purifying selection, but the strength of purifying selection itself must be related to physical constraints imposed by protein folding and function. In this paper, we analyzed five enzymes for which polymorphic sequence variation within Escherichia coli and/or Salmonella enterica was available, along with a protein structure. Single and multivariate logistic regression models are presented that evaluate amino acid size, physicochemical properties, solvent accessibility, and secondary structure as predictors of polymorphism. A model that contains a positive coefficient of association between polymorphism and solvent accessibility and separate intercepts for each secondary-structure element is sufficient to explain the observed variation in polymorphism between sites. The model predicts an increase in the probability of amino acid polymorphism with increasing solvent accessibility for each protein regardless of physicochemical properties, secondary-structure element, or size of the amino acid. This result, when compared with the distribution of synonymous polymorphism, which shows no association with solvent accessibility, suggests a strong decrease in purifying selection with increasing solvent accessibility.

Aldose-Ketose Isomerases↗

PubMed2006

Linkage disequilibria and haplotype structure of four SNPs of the interleukin 1 gene cluster in seven Asian Indian populations.

Variation at four single nucleotide polymorphism (SNP) sites of the interleukin 1 (IL1) gene cluster was investigated among 280 unrelated individuals, representing 7 caste groups from the state of Karnataka, India, and one European American community of Boston, Massachusetts. Allele and haplotype frequencies, strength of linkage disequilibrium, and signatures of recombination varied considerably among populations. Variable community sizes and traditions of consanguinity may account for the observed variation.

Cardiovascular Diseases↗

PubMed2002

[Melatonin and its role in human reproduction].

Melatonin may be a key factor in regulation of seasonal variation in gonadal activity. The circadian disturbances related to reproduction are probably subsequent to the seasonal change. Moreover, melatonin might also be considered essential to both spermatogenesis and folliculogenesis. Exposure to bright light, suppressing the concentration of melatonin in circulation, is hypothesized to be useful in treatment of both male and female infertility in couples with abnormal melatonin metabolism. In women, seasonal variation observed in the concentrations of gonadotropins and gonadal steroids is associated with melatonin synthesis. This hormone may exert an inhibitory effect on the GnRH pulse generator to decrease gonadotropin secretion. Consequently, it has been implicated in the control of the pubertal onset and timing of ovulation. The number of irregular menstrual cycles with anovulation in creases in winter compared to summer. In addition, there is circadian variation in the time of ovulation, occurring usually in the morning during summer and in the evening during winter. Hormonal interactions and phases of the cycle are important variables contributing to the fluctuations in melatonin levels during the menstrual cycle.

Adult↗

PubMed1997

Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis. Evidence of a new susceptibility locus in Caucasian and Chinese patients.

CONTEXT: Susceptibility to multiple sclerosis (MS) involves a genetically complex autoimmune component. However, except for genes in the HLA system, specific susceptibility loci are unknown or unconfirmed. OBJECTIVE: To investigate several loci spanning 3 candidate regions for a role in multiple sclerosis (MS) susceptibility in 2 ethnic groups using both single-locus and haplotype analyses. The 3 regions include HLA on chromosome 6p21.3, APOE on chromosome 19ql 3.2, and MBP(myelin basic protein) on chromosome 18q23. DESIGN: Case-control association testing. SUBJECTS: A total of 120 Caucasian patients with MS and 107 unrelated control individuals from California, and 32 patients and 32 unrelated control individuals from Beijing, China. All patients with MS were diagnosed as having clinically definite disease according to published criteria. MAIN OUTCOME MEASURES: Chi2 Testing of loci and individual alleles and haplotypes. Haplotype frequencies were estimated with standard maximum likelihood methods. RESULTS: The HLA effect is due to the class II DR2 haplotype, DRB1*1501-DQA1*0102-DRB1*0602; contributions to MS susceptibility from additional DRB1-DQB1 alleles or other HLA region loci were not observed. Variation within the MBP locus on chromosome 18q23 showed no effect in MS. The distribution of haplotypes from 5 loci within the chromosome 19q13.2 region, including D19S178, D19S574, APOE, APOC2, and D19S219, differed between patient and control samples. D19S574 showed a significant effect (P=.015) in Caucasian patients with MS due to the increased frequency of a single allele (P=.002). The APOE variation, prominent in other neurological diseases, showed no influence on MS susceptibility, despite its location within the chromosome 19q13.2 region. Interaction effects between DR2 and chromosome 19q13.2 or MBP in MS susceptibility were not apparent. CONCLUSIONS: The significant chromosome 19q13.2 single-locus and multilocus haplotype associations with MS in Caucasian and Chinese patient samples indicate an effect from a nearby disease susceptibility locus. These initial observations are an encouraging step toward the description of non-HLA genetic susceptibility to MS.

Alleles↗

PubMed1993

Observation on the short and long term response to anti-lipemic drugs in southern Thailand.

Patients with dyslipidemia were evaluated with regard to the 5 drugs regimen: simvastatin (average dose, 11.8 mg/day), gemfibrozil (dose 963 mg/day), bezafibrate (433 mg/day), fenofibrate (211 mg/day) and acipimox (667 mg/day). The responses to the drug were divided into different time periods and the magnitude of responses were presented either as average changes in per cent from baseline or as proportion of patients (also in %) whose levels changed by a predetermined percentage. These predetermined percentage took into account the variation observed among patients who had more than 3 measurements during baseline. These levels for significant changes were 16 per cent for total cholesterol (TC), 25-30 per cent for high- and low-density lipoprotein (HDL and LDL), and 44 per cent for triglyceride (TG). Our subjects responded to the drugs within the range reported by other investigators except for acipimox which produced no alteration. Sixty to 100 per cent of patients reduced their TC by 16 per cent with an average change in TC of around -16 per cent to -24 per cent. Simvastatin and fenofibrate appeared most effective in altering TC. The HDL increased 10 per cent to 29 per cent depending on the drug but in terms of proportion that responded by an increment greater than 25 per cent, this was seen in only 23 per cent to 45 per cent of the patients. Long term follow-up which was possible only on 42 patients showed 11 who lessened their response and 6 whose response became more marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2006

Estimating sex-specific processes in human populations: Are XY-homologous markers an effective tool?

Homologous markers on the sex-specific regions of the X- and Y-chromosomes are differentially inherited through males and females, and have similar molecular characteristics. They may therefore be useful as a complement to the comparison of mtDNA and Y-chromosomal haplotypes for estimating sex-specific processes shaping human population structure. To test this idea, we analyzed XY-homologous microsatellite diversity in 33 human populations from Africa, Asia and Europe. Interpopulation comparisons suggest that the generally discordant pattern of genetic variation observed for X- and Y-linked markers could be an outcome of sex-specific migration processes (m(females)/m(males) approximately 3) or sex-specific demographic processes (N(females)/N(males) approximately 11) or a combination of both. However, intrapopulation diversity estimated by the X/Y ratio Watterson estimator (theta(H(Y))/theta(H(X))) suggests that the scenarios required to explain the global genetic variation of XY-homologous markers are many and complex, and that the sex-specific processes (effective population size and migration rate) shaping human population structures are likely to be specific to each population under study. XY-homologous markers provide an insight into the genuine complexity of sex-specific processes, and their further exploitation in human population studies seems worthwhile.

Africa↗

PubMed1991

In vivo genomic variability of human T-cell leukemia virus type I depends more upon geography than upon pathologies.

To investigate the geography- and disease-associated genomic variation of human T-cell leukemia virus type I (HTLV-I), we studied ex vivo DNA from peripheral blood lymphocytes from nine patients by polymerase chain reaction and direct DNA sequencing. For each viral strain, 1,917 bp was sequenced, including parts of the long terminal repeat, the env gene, and the px II, px III, and px IV coding frames of the px region. The number of genomic variations observed in the U3 region of the long terminal repeat was higher than that seen in the env and px genes. Very few mutations were present in the px II and px III genes. In contrast, the px IV open reading frame exhibited numerous single point mutations. While no specific mutation could be linked to any pathology (adult T-cell leukemia/lymphoma or tropical spastic paraparesis/HTLV-I-associated myelopathy), variations among HTLV-I isolates from different geographic areas (Ivory Coast, Caribbean, and Japan) existed. The Ivory Coast HTLV-I appeared to represent a group by itself.

Base Sequence↗

PubMed2003

Molar intercuspal dimensions: genetic input to phenotypic variation.

Molecular studies indicate that epigenetic events are important in determining how the internal enamel epithelium folds during odontogenesis. Since this process of folding leads to the subsequent arrangement of cusps on molar teeth, we hypothesized that intercuspal distances of human molar teeth would display greater phenotypic variation but lower heritabilities than overall crown diameters. Intercuspal distances and maximum crown diameters were recorded from digitized images of dental casts in 100 monozygotic and 74 dizygotic twin pairs. Intercuspal distances displayed less sexual dimorphism in mean values but greater relative variability and fluctuating asymmetry than overall crown measures. Correlations between intercuspal distances and overall crown measures were low. Models incorporating only environmental effects accounted for observed variation in several intercuspal measures. For those intercuspal variables displaying significant additive genetic variance, estimates of heritability ranged from 43 to 79%, whereas those for overall crown size were higher generally, ranging from 60 to 82%. Our finding of high phenotypic variation in intercuspal distances with only moderate genetic contribution is consistent with substantial epigenetic influence on the progressive folding of the internal enamel epithelium, following formation of the primary and secondary enamel knots.

Adolescent↗

PubMed2001

Third-molar removal patterns in an insured population.

BACKGROUND: The authors examined third-molar removal patterns in an insured population to see how these patterns compare with recommendations in the literature. METHODS: The source of treatment data was insurance claims for services rendered from July 1991 through December 1999; it included approximately 100 million dental procedures provided to about 7.4 million patients from all 50 states. The insured were public and private employees or retirees and their dependents. RESULTS: The authors found that third molars were the most commonly extracted permanent teeth, and they most often were removed from adolescents. Friday was the day of the week on which most extractions occurred, and the favored month was August, followed by July, December and June. Another important pattern revealed by the authors' analysis was that there was substantial variation among dental practices in whether patients had third molars removed and in the timing of the removal. They found that adolescent patients in some dental practices rarely were referred for third-molar removal, while in other practices, most or all had third molars removed. CONCLUSIONS: Third-molar removal patterns suggest that many third molars are not removed in response to acute pathology, and the observed variation in the likelihood and timing of these extractions reflects the lack of consensus on this topic in the dental literature. CLINICAL IMPLICATIONS: The apparent lack of consensus on third-molar removal should be resolved for the profession to maintain the confidence of the public that the recommended care is based on sound evidence.

Adolescent↗