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PubMed2002

A review of studies on the transmission of Anaplasma phagocytophilum from sheep: implications for the force of infection in endemic cycles.

We review the findings of a longitudinal study of transmission of the intracellular tick-borne bacterium Anaplasma phagocytophilum from sheep to Ixodes ricinus ticks under natural conditions of tick attachment in the UK. In this study, sheep-to-tick transmission efficiency varied in a quadratic relationship with the number of adult ticks that were feeding on the sheep. We raise the hypothesis that this relationship may be due to conflicting effects of the density of ticks on bacterial survival and target cell (neutrophil) fluxes at the tick-host interface: in the same sheep at the same time, resistance to ticks was progressively inhibited with increasing number of feeding adult ticks, and investigation of serological responses to tick antigens suggesting loss of resistance may be associated with polarisation of host Th1 to Th2 type responses to ticks. We also raise the hypothesis that these properties, with superimposed effects on tick survival, may mean that variation in tick density is an important causal factor of observed variations in the force of A. phagocytophilum infection amongst different geographic foci.

Anaplasma phagocytophilum↗

PubMed2001

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver.

Sinusoidal endothelial cell (SEC) porosities were compared between the periportal (zone 1) and pericentral (zone 3) regions of the rat liver during regeneration following partial hepatectomy (PHx). SEC porosities and fenestration diameters were measured in control livers, as well as at 5 minutes, 24, 48, 72, 96, 120 hours, and 14 days following PHx. Bimodal maximums in both porosity and fenestration diameters were observed in both zones at 5 minutes and 5 days following PHx. SEC porosities increased significantly in both zones 1 and 3 within 5 minutes following PHx, but the increase was maintained only in zone 1 at 24 hours after resection. Following the initial rise, both zones displayed a gradual decrease to less than half their porosity values at 72 hr post-PHx. After 72 hours, porosities increased to over control levels and remained elevated until 14 days after PHx. The decrease in porosity at 72 hr post-PHx is accompanied by ultrastructural changes within the sinusoid at this time. Vascular corrosion casting and transmission electron microscopy (TEM) show sinusoid compression resulting from increased hepatic plate widths due to hepatocyte proliferation in the absence of SEC proliferation. Also at this time, we observed many SEC completely enveloped by stellate cells. The zonal variations observed for porosities throughout regeneration did not correlate with changes in laminin, collagen I and IV, or fibronectin deposition within the space of Disse. Taken together, the data reveal that SEC are dynamic regulators of porosity that respond rapidly and locally to environmental zonal stimuli during liver regeneration.

Animals↗

PubMed1997

Functional analysis of mutated purine-cytosine permease from Saccharomyces cerevisiae. A possible role of the hydrophilic segment 371-377 in the active carrier conformation.

The purine-cytosine permease (PCP) is an active transporter located in the plasma membrane of the yeast Saccharomyces cerevisiae. This protein mediates purine (adenine, guanine, and hypoxanthine) and cytosine accumulation in the cell by using an electrochemical potential difference in proton as the energy source. Various mutant strains, with altered Kt(app) (apparent Michaelis constant of transport) of uptake for one or several bases, have already been selected. Their cloning and sequencing revealed that three of them presented substitutions in the same region of the putative sequence of the PCP: this region might correspond to the hydrophilic segment 371-377 (I-A-N-N-I-P-N). Two mutants displayed single mutations, resulting in only one amino acid residue change (N377I and N374I, respectively), and the other displayed three amino acid substitutions (I371V, I375V, and N377G). Therefore, to analyze the contribution of individual amino acid changes to the phenotype of the complex mutant, single (N377G) and double (I371V,I375V) mutants were constructed by site-directed mutagenesis. The influence of single mutations in this region was studied by measuring, for adenine, hypoxanthine, and cytosine, the uptake constants on cells and equilibrium binding parameters on plasma membrane-enriched fractions. Uptake and binding constant determinations showed that all the variations observed for the Kt(app) of uptake were correlated with variations of the binding Kd(app) for the corresponding solutes. Thus, our results emphasize the role of the two asparagine residues, located at positions 374 and 377, respectively, in the binding of the bases. In addition, the sole substitution of the 377 asparagine residue by glycine is responsible for the phenotype of the triple mutant. The effect of pH on the apparent hypoxanthine binding dissociation constant showed that the effects of N377G and N377I changes were, at least partially, due to a shift of the pKa of an ionizable amino acid residue of the unliganded permease. These two amino acid residue changes induced a shift of the pKa of this group in the unliganded, deprotonated permease about two units toward acidic pH. This result suggests that the 371-377 segment might play a key role in the proper three-dimensional structure of the active purine-cytosine permease.

Alleles↗

PubMed2005

DNA-based species delineation in tropical beetles using mitochondrial and nuclear markers.

DNA barcoding has been successfully implemented in the identification of previously described species, and in the process has revealed several cryptic species. It has been noted that such methods could also greatly assist in the discovery and delineation of undescribed species in poorly studied groups, although to date the feasibility of such an approach has not been examined explicitly. Here, we investigate the possibility of using short mitochondrial and nuclear DNA sequences to delimit putative species in groups lacking an existing taxonomic framework. We focussed on poorly known tropical water beetles (Coleoptera: Dytiscidae, Hydrophilidae) from Madagascar and dung beetles (Scarabaeidae) in the genus Canthon from the Neotropics. Mitochondrial DNA sequence variation proved to be highly structured, with >95% of the observed variation existing between discrete sets of very closely related genotypes. Sequence variation in nuclear 28S rRNA among the same individuals was lower by at least an order of magnitude, but 16 different genotypes were found in water beetles and 12 genotypes in Canthon, differing from each other by a minimum of two base pairs. The distribution of these 28S rRNA genotypes in individuals exactly matched the distribution of mtDNA clusters, suggesting that mtDNA patterns were not misleading because of introgression. Moreover, in a few cases where sequence information was available in GenBank for morphologically defined species of Canthon, these matched some of the DNA-based clusters. These findings demonstrate that clusters of close relatives can be identified readily in the sequence variation obtained in field collected samples, and that these clusters are likely to correspond to either previously described or unknown species. The results suggest that DNA-assisted taxonomy will not require more than a short fragment of mtDNA to provide a largely accurate picture of species boundaries in these groups. Applied on a large scale, this DNA-based approach could greatly improve the rate of species discovery in the large assemblages of insects that remain undescribed.

Animals↗

PubMed2003

Effects of common origin and common environment on nestling plumage coloration in the great tit (Parus major).

Carotenoids cannot be synthesized by birds and thus have to be ingested with food, suggesting that carotenoid-based plumage coloration is environmentally determined. However signaling functions ascribed to plumage imply that plumage coloration is the outcome of an evolutionary process based on genetic variation. By means of a cross-fostering design we show significant effects of both a common rearing environment and the brood from which a nestling originally came from (common origin) on the plumage coloration of nestling great tits (Parus major). This demonstration of origin-related variation in carotenoid-based plumage coloration suggests that the observed variation of the trait has a partial genetic basis. Consistent with environmental determination of this trait, we also found a significant positive correlation between the color saturation of nestlings and their foster-father's plumage. There was no significant correlation between nestling plumage coloration and the food quantity provided to the nestlings by the male, the female, or both parents. This suggests that the nestling-foster father correlation arises by the carotenoid quantity ingested rather than the food quantity per se. No significant nestling-true father correlation was found, which suggests that nestling plumage coloration did not indirectly evolve due to sexual selection. Consistent with this result there was no significant correlation between the nestling's plumage color and its coloration as a breeding adult the following year, suggesting that nestling plumage color is a different trait than the first year plumage.

Animals↗

PubMed1983

Uterine histology and prostaglandin concentrations and utero-ovarian venous steroid and prostaglandin concentrations during the luteal phase of the menstrual cycle in baboons (Papio spp.) with or without an IUD.

Arachis oil was infused via the oviducts into the uterus of baboons 6-9 days after ovulation; uterine tissue was collected towards the end of the luteal phase (3-7 days after the oil infusion) for histological assessment of the occurrence of any deciduomal reaction. To exclude the possibility that a variation in the endogenous steroid concentrations was responsible for any observed variation in the incidence of the deciduomal reaction, blood samples were collected and assayed for progesterone and oestradiol-17 beta. The effect of the IUD on endometrial prostaglandin release was examined by measuring PGE and PGF concentrations in uterine tissue and utero-ovarian venous plasma. The IUD stimulated a deciduomal response in every animal, whereas the traumatization with arachis oil had no such effect; the variation in the peripheral and utero-ovarian steroid levels could not explain the variation in the incidence of the deciduomal reaction. Greater concentrations of PGF but not PGE were present in the endometria of those animals bearing an IUD and in which a deciduomal reaction had been stimulated. The corpus luteum was the major source of progesterone and of oestradiol-17 beta, although non-luteal ovarian tissue also secreted oestradiol-17 beta.

Animals↗

PubMed1991

Tender shins and steroid therapy.

To quantify previously described shin tenderness in patients receiving chronic steroid therapy, we studied 54 patients, 26 treated with steroid, by dolorimetry at 4 control, 4 "fibrositic," and 4 shin sites. To measure observer variation, assessments were done by 2 or 3 of 10 observers, one of whom examined each subject. The specific increase of tenderness at shin sites associated with steroid therapy was confirmed, with a mean (SD) threshold in the steroid group of 3.0 (1.7) kg, and in the control group 5.6 (2.4). Other effects which were not site specific were found. There was a 2.0 kg increase in control site tenderness associated with steroid therapy, and a similar general increase in tenderness in patients with lupus and in women, independent of steroid therapy, affecting control as well as fibrositic sites. Underlying mechanisms must act generally as well as being site specific.

Adult↗

PubMed1994

Gender differences in hematopoietic and lymphoproliferative disorders and other cancer risks by major occupational group among workers exposed to benzene in China.

Gender differences in risk for leukemia and other selected and combined disease categories were examined by major occupational category for 74,828 benzene-exposed workers compared to 35,805 unexposed workers from 12 cities in China. No significant differences in the relative risks for total mortality and cancer mortality were found between female and male benzene-exposed workers, although risks tended to be somewhat higher among male than among female employees. Both female and male workers in several occupational categories had notably increased risks for all hematopoietic and lymphoproliferative (HLP) malignant and nonmalignant disorders combined and for total leukemia. Variation in risk for HLP disorders by occupational category was observed in both genders, with highest risks for male and female chemical manufacturing workers, female nonproduction employees, and male printers. However, the numbers of leukemia and other HLP malignancies in each category were small. The findings suggest that both female and male benzene-exposed workers in several occupational categories experience excess leukemia and other HLP disorders with relatively minor gender differences. Although this population is one of the largest cohorts of benzene-exposed workers studied to date, evaluation of the observed variation in risk for HLP neoplasms among the occupational groups for workers of each gender is limited by the small numbers of these relatively rare malignancies.

Benzene↗

PubMed1997

Spinal anesthesia with clonidine and bupivacaine in young humans: interactions and effects on the cardiovascular system.

BACKGROUND: Clonidine, an alpha 2 agonist, is known to prolong the action of local anesthetics, and to provide a satisfactory analgesia; hypotension and bradycardia have been observed after its intrathecal administration. The aim of our study was to determine whether intrathecal administration of clonidine can reduce the dose of local anesthetic, and the effects of clonidine on the cardiovascular system, and on arousal level. METHODS: In a prospective, randomized study we evaluated 56 patients scheduled for minor surgical procedure (spermatic vein ligature) under unilateral spinal anesthesia with hyperbaric bupivacaine 1%. One half of patients received clonidine (105 micrograms) in addition to bupivacaine. Mean arterial pressure, heart rate were recorded baseline until 1 hour after surgery. Cardiac output, stroke volume, ejection fraction, systemic vascular resistance and left cardiac work were measured, by thoracic electric bioimpedance method, baseline until 1 hour after surgery. Sensory block, motor block and sedation level were measured at the beginning of anesthesia and for 6 hours after the end of surgery. RESULTS: In the clonidine treated group we did not observe variations of cardiovascular parameters; in the same group we did observe sensory block and motor block significantly prolonged, a higher sedation level and a significant postoperative analgesia. CONCLUSIONS: In summary, the addition of clonidine to hyperbaric bupivacaine seems to be particularly useful in unilateral spinal anesthesia, exerting minimal influence on haemodynamic parameters, and guaranting a satisfactory postoperative analgesia.

Adrenergic alpha-Agonists↗

PubMed2004

Context or composition: what explains variation in SCHIP disenrollment?

OBJECTIVE: To investigate (1) the relative contributions of family and contextual characteristics to observed variation in disenrollment rates from the State Children's Health Insurance Program (SCHIP), and (2) whether context explains observed family-level patterns. DATA SOURCES: We use secondary data on 24,628 families enrolled in New Jersey's SCHIP program (NJ KidCare), and county-level data from the Area Resource File, the Census, and the NJ FamilyCare provider roster. STUDY DESIGN: Information on family characteristics, SCHIP plan, and dates of enrollment and disenrollment are taken from NJ KidCare administrative records, which provided surveillance data from January 1998 through April 2000. DATA COLLECTION/ANALYSIS: We estimate a multilevel discrete-time-hazards model of SCHIP disenrollment. FINDINGS: Families enrolled in plans involving cost-sharing, blacks, and those with only one enrolled child have higher than average rates of disenrollment. Disenrollment rates for blacks are lower in counties with a high share of black physicians. These characteristics account for part of the intercounty variation in disenrollment rates; remaining intercounty variation is largely explained by physician density or population density. POLICY IMPLICATIONS: It may be worthwhile to pay special attention to black families and counties with high disenrollment rates to address the reasons for their lower retention. Addressing cultural differences between physician and client and the geographic distribution of medical providers might reduce disenrollment.

Child↗

PubMed1999

Analysis of kappa and omega repeats of the cg2 gene and chloroquine susceptibility in isolates of Plasmodium falciparum from sub-Saharan Africa.

The correlation between the structure of two short sequences from the Plasmodium falciparum cg2 gene and parasite chloroquine susceptibility was evaluated in unselected clinical isolates obtained from travellers returning mainly from Africa to France in 1995 and 1996. As determined by an isotopic semi-microtest, 74 isolates were susceptible to chloroquine (50% inhibitory concentration < 80 nM), 13 were intermediate (80 nM < 50% inhibitory concentration < 110 nM) and 53 were resistant (50% inhibitory concentration > 110 nM). Two polymerase chain reaction assays were developed, one for the kappa and one for the omega repeat domains of cg2 gene. The kappa and the omega repeat domains of 99 isolates were sequenced. A variation in the unit number of kappa and omega repeats was observed. Variations in repetitive sequences, which were not previously described, were found: three for the kappa repeat region: kappa9; kappa10 and kappa11 and three for the omega repeat region: omega8; omega9 and omega22. A polymorphism was observed inside the repeat units of kappa and omega regions. There were six possible kappa repeat units and seven possible omega repeat units. The presence of a particular pattern, containing kappa14 and omega16 repeat units, was associated with a lack of chloroquine susceptibility in 44 out of 46 cases. However, not all resistant isolates had this 'resistant' genotype. Among 43 resistant isolates, 36 (84%) had the kappa14 repeats sequence and 36 had the omega16 repeats sequence. These results lend further support to linkage between cg2 polymorphisms and chloroquine resistance without excluding the existence of other resistance component(s).

Adolescent↗

PubMed1987

[What does circulating beta 2 microglobulin signify in uremic patients on maintenance dialysis?].

The authors report a 2 years prospective study on s beta 2M variations observed in a large uremic population (237 patients, 159 M, 78 F, age: 51.1 +/- 5.9 y.o.). The study consisted in two parts. A long term follow-up of s beta 2M in patients regularly treated with various dialysis modalities; hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). s beta 2M was found elevated in the overall population (41.4 +/- 10.2 mg/l) with a 12.5% variation over time observation in stable patients, not influenced by sex, causal nephropathy, and dialysis mode in anuric patients, beta 2M was inversely correlated with residual diuresis. Residual kidney function preserved longer and in a higher proportion of PD patients was the only significant fact explaining for the difference observed in s beta 2M levels between HD (46 +/- 5) and PD (33 +/- 3) patients. Intercurrent inflammatory and tumoral states increased significantly s beta 2M level in uremic patients. The short term study showed that highly permeable membranes (AN69, polysulphone) used either in HD, HF or HDF were able to decrease s beta 2M from 50 to 60%, and to remove 150 to 200 mg per session, while on the opposite HD/cuprophane increased s beta 2M from 10 to 15%. beta 2M dialysate/plasma equilibrium ratio for peritoneal membrane after a 6 hour dwelling time was 0.20, permitting a net removal of 45 +/- 4 mg/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1977

Anatomical analysis of the developmental effects of aneuploidy in man--the 18-trisomy syndrome: I. Anomalies of the head and neck.

This paper describes the anatomical variations observed in the head and neck in eight infants with the 18-trisomy syndrome that were dissected and studied in detail. Of the usual muscles of facial expression, occipitofrontalis and the auricular and nasal muscles were hypolastic in all eight bodies and each subject showed extensive fusion of the muscles around the corner of the mouth. In each body there was a supernumerary muscle band that extended from the region near the corner of the mouth to the occipital attachment of trapezius. The otomandibular region in each body showed a variable spectrum of muscular, skeletal, arterial, and salivary gland variations bilaterally. Three of the bodies had infrahyoid muscle variations. The sum of these observations provides a more complete delineation of the variations that occur in the 18-trisomy syndrome. Tentative pathogenetic hypotheses for several of the defects are discussed, based on observations from human descriptive embryology. Poswillo's teratological model [1973] implicating hemorrhaging as a causal mechanism in human first and second branchial arch malformations is suggested as a possible mechanism to explain the bilateral otomandibular defects.

Chromosomes, Human, 16-18↗

PubMed2001

Complex signatures of natural selection at the Duffy blood group locus.

The Duffy blood group locus (FY) has long been considered a likely target of natural selection, because of the extreme pattern of geographic differentiation of its three major alleles (FY*B, FY*A, and FY*O). In the present study, we resequenced the FY region in samples of Hausa from Cameroon (fixed for FY*O), Han Chinese (fixed for FY*A), Italians, and Pakistanis. Our goals were to characterize the signature of directional selection on FY*O in sub-Saharan Africa and to understand the extent to which natural selection has also played a role in the extreme geographic differentiation of the other derived allele at this locus, FY*A. The data from the FY region are compared with the patterns of variation observed at 10 unlinked, putatively neutral loci from the same populations, as well as with theoretical expectations from the neutral-equilibrium model. The FY region in the Hausa shows evidence of directional selection in two independent properties of the data (i.e., level of sequence variation and frequency spectrum), observations that are consistent with the FY*O mutation being the target. The Italian and Chinese FY data show patterns of variation that are very unusual, particularly with regard to frequency spectrum and linkage disequilibrium, but do not fit the predictions of any simple model of selection. These patterns may represent a more complex and previously unrecognized signature of positive selection.

Alleles↗

PubMed2001

Variability in target volume delineation on CT scans of the breast.

PURPOSE: To determine the intra- and interobserver variation in delineation of the target volume of breast tumors on computed tomography (CT) scans in order to perform conformal radiotherapy. MATERIALS AND METHODS: The clinical target volume (CTV) of the breast was delineated in CT slices by four radiation oncologists on our clinically used delineation system. The palpable glandular breast tissue was marked with a lead wire on 6 patients before CT scanning, whereas 4 patients were scanned without a lead wire. The CTV was drawn by each observer on three separate occasions. Planning target volumes (PTVs) were constructed by expanding the CTV by 7 mm in each direction, except toward the skin. The deviation in the PTV extent from the average extent was quantified in each orthogonal direction for each patient to find a possible directional dependence in the observer variations. In addition, the standard deviation of the intra- and interobserver variation in the PTV volume was quantified. For each patient, the common volumes delineated by all observers and the smallest volume encompassing all PTVs were also calculated. RESULTS: The patient-averaged deviations in PTV extent were larger in the posterior (42 mm), cranial (28 mm), and medial (24 mm) directions than in the anterior (6 mm), caudal (15 mm), and lateral (8 mm) directions. The mean intraobserver variation in volume percentage (5.5%, 1 SD) was much smaller than the interobserver variation (17.5%, 1 SD). The average ratio between the common and encompassing volume for the four observers separately was 0.82, 0.74, 0.82, and 0.80. A much lower combined average ratio of 0.43 was found because of the large interobserver variations. For the observer who placed the lead wire, the intraobserver variation in volume was decreased by a factor of 4 on scans made with a lead wire in comparison to scans made without a lead wire. For the other observers, no improvement was seen. Based on these results, an improved delineation protocol was designed. CONCLUSIONS: Intra- and especially interobserver variation in the delineation of breast target volume on CT scans can be rather large. A detailed delineation protocol making use of CT scans with lead wires placed on the skin around the palpable breast by the delineating observer reduces the intraobserver variation. To reduce the interobserver variation, better imaging techniques and pathology studies relating glandular breast tissue to imaging may be needed to provide more information on the extent of the clinical target volume.

Breast Neoplasms↗

PubMed1993

Observer reliability in assessing villitis of unknown aetiology.

AIMS: To evaluate observer variation in diagnosis of villitis of unknown aetiology. METHODS: Fifty haematoxylin and eosin stained sections were circulated to three pathologists who were asked to assess if villitis was present. These slides, with an additional 20, were recirculated and reassessed by the same pathologists. RESULTS: Intra-observer agreement was 84.7% (range 74--92%) and interobserver agreement was 81%. A conjoint review by the three pathologists revealed that sources of differences included the overlooking of isolated single or small numbers of affected villi, the difficulty in assessing stromal cellularity close to infarcted parenchyma, and apparent stromal hypercellularity in immature villi. CONCLUSIONS: Experienced pathologists can show a significant interobserver variation in assessing villitis of unknown aetiology. Future studies on villitis of unknown aetiology should address the problem of observer reproducibility of diagnosis.

Chorionic Villi↗

PubMed2004

Study of microporosity of active carbon spheres using inverse gas chromatographic and static adsorption techniques.

Active carbon spheres (ACSs) with different porous structures prepared in the laboratory were characterized by static adsorption studies and inverse gas chromatographic (IGC) technique. Surface properties such as BET surface area, micropore volume and pore size in different regions of porosity were determined using different theoretical approaches. Thermodynamic parameters such as isosteric heat of adsorption, free energy of adsorption and dispersive component of the surface energy were determined using IGC technique from corrected retention volume of normal alkanes and corresponding branched alkanes. Thermodynamic parameters were used to assess the molecular sieving property of ACSs. It is observed that thermodynamic properties strongly depend on microporous character of ACSs. The variations observed in pore size determined by both of the techniques that is by static adsorption measurements and IGC may be attributed to the variation in analysis temperature, i.e. liquid N2 temperature for adsorption studies and elevated temperature for IGC technique.

Adsorption↗

PubMed1995

Heterozygosity and fitness: no association in Scots pine.

The association of six quantitative traits related to fitness with heterozygosity at 12 allozyme loci has been examined in three populations of Scots pine, Pinus sylvestris. Because of several characteristics of this organism and of this extensive data set, it appeared that this study would show a positive association between heterozygosity and these traits if indeed heterozygotes had higher values for these quantitative traits. Using several different statistical techniques including analysis of variance, regression with the scaling recommended from the adaptive distance model, and multiple regression, no evidence of an association was found. For example, only between 7 and 8% of the regression tests were significant at the 5% level and half of these showed a positive association and half showed a negative association. Further, the multiple regression analysis explained on average only 5.8% of the variation observed in the six different traits and only 1.5% of this variation was explained by a positive association. Power analysis was carried out (for the first time on these type of data), both for the single locus heterozygous advantage and the association of individual multiple locus heterozygosity and the quantitative traits. For diameter and height, two traits often used in similar studies, the average power to detect a single locus heterozygous advantage of 0.10 was 0.737 and the average power to detect a mean heterozygote advantage of 0.05 per locus for multiple loci was 0.797. As a result of this study and an examination of the published results from other studies, it appears that what positive associations have been observed are probably not, in large part, due to the presence of intrinsic heterozygote advantage.

Genes, Plant↗