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Retrospective analysis of the accuracy of conversion equations and multiple-trait, across-country evaluations of Holstein bulls used internationally.

In 1995, the multiple-trait across country genetic evaluation procedure replaced regression-based conversion equations as the preferred method for international genetic comparisons of dairy bulls. In the present study, February 1999 estimated breeding values of 632 foreign Holstein bulls that were used in Canada, Germany, Italy, The Netherlands, Sweden, and the US were compared with January 1995 predictions from home country data only. January 1995 predicted breeding values for each importing country were calculated using three methods: the multiple-trait, across-country evaluation procedure; conversion equations based on the multiple-trait, across-country evaluations; and conversion equations based on the Wilmink method. Mean correlations between 1999 estimated breeding values in the importing countries and 1995 predictions from international data were from 0.76 to 0.81 for all methods. The multiple-trait, across-country evaluation procedure is expected to lead to selection of different bulls, because bulls were allowed to be ranked differently in each country, but no significant increase in accuracy of selection was observed. The lack of improvement in accuracy of prediction was most likely due to limitations in data structure. International genetic comparisons are largely driven by data from a relatively small number of evaluated bulls with exported semen. Data from siblings and more distant relatives provide only weak, indirect genetic links between countries, and inclusion of such data seems to provide a minimal improvement in accuracy. Limitations in data structure might be alleviated by methods that define environments by climate or management factors rather than country borders.

Animals↗

Identification of a functional determinant of differentiation-dependent expression in the involucrin gene.

Involucrin is an integral component of the cornified envelope which is a characteristic feature of the differentiated keratinocyte. Involucrin expression is tightly linked to the onset of differentiation and first expressed in the immediate suprabasal layers of the epidermis. We have identified a transcriptional response element within the distal 5'-flanking region of the involucrin gene which contributes to differentiation-dependent expression. Deletion of this site impairs differentiation-dependent promoter activity in transient transfection analysis, and conversely, this region imparts differentiation-dependent expression to a heterologous promoter. The identified site bears sequence similarity to several AP2-like response elements identified in keratinocyte-specific genes and binds a protein complex (keratinocyte differentiation factor, KDF-1) which is distinct from AP2 by several criteria. The migration of KDF-1 is distinct from AP2 in electrophoretic mobility shift assays, KDF-1 is antigenically unrelated to AP2 since AP2 specific antibodies do not supershift the KDF-1-DNA complex and KDF-1 is poorly competed by oligonucleotides representing consensus AP2 recognition sequences. In addition, the KDF-1 complex is not detected in nuclear extracts derived from human dermal fibroblasts or an enriched population of basal keratinocytes. These findings provide insights to the underlying basis of differentiation-dependent expression of a keratinocyte specific gene.

Binding Sites↗

Assessing dentin color changes from nightguard vital bleaching.

BACKGROUND: At-home bleaching with 10 percent carbamide peroxide in a custom-fitted tray has been reported to change the color of dentin. The purpose of this study was to validate the color change of dentin and to determine whether the color change was uniform or occurred from the outside (the dentinoenamel junction) to the inside (the pulpal wall). METHODS: The authors sectioned 10 extracted human teeth incisogingivally through the midfacial long axis, and sealed their cut surface against glass microscope slides. Identifying marks were placed on the glass over the tooth sections to serve as a color control and in the dentinal areas closest to the dentinoenamel junction and the pulpal wall. Teeth were bleached for 10 days with 10 percent carbamide peroxide. Photographs were taken from the glass-covered side of the teeth, digitized and converted to gray-scale levels (consisting of 256 shades of gray ranging from black to white). Marked areas were measured with a National Institutes of Health Image software program and analyzed statistically for changes in lightness between the control marks and the inner and outer dentinal marks over time. RESULTS: Paired t-tests and analysis of variance indicated a significant increase in lightness (P = .01) for the inner and outer dentinal areas during bleaching compared with the control areas. No significant differences were found in the rate of change for the inner and outer dentinal areas (P = .89). CONCLUSIONS: The increase in lightness confirms that a significant color change occurred in the dentin during bleaching with 10 percent carbamide peroxide. This change occurred throughout the dentin at a uniform rate, rather than from the outside inward. CLINICAL IMPLICATIONS: The results of this study show that at-home bleaching with 10 percent carbamide peroxide can change the color of dentin, which is important to treat intrinsic stains from tetracycline treatment, trauma and aging or inherited discolorations. The bleaching material easily penetrates the tooth to change the dentin color at the same rate throughout, indicating that the type of stain may be the important factor in determining bleaching success.

Absorptiometry, Photon↗

Elevated pulmonary artery systolic storage volume associated with improved ventilation-to-perfusion ratios in acute respiratory failure.

The possibility that an elevated pulmonary artery systolic storage volume (PASSV) correlates with improved overall ratios of ventilation-to-perfusion and hence benefits gas exchange in acute respiratory failure was examined. We examined this by assessing the correlation between PASSV and both the physiologic dead space to tidal volume ratio (VD/VT) and intrapulmonary shunt fraction (Qsp/Qt). The VD/VT and Qsp/Qt were used as an index of distribution of ventilation-to-perfusion as well as efficiency of pulmonary gas exchange. Twenty-eight patients suffering from acute respiratory failure were included. All required mechanical ventilation. PASSV was calculated from the pulmonary artery (PA) compliance and mean PA systolic distending pressure. Pulmonary arteriolar pressures were computed by Fourier analysis. PA compliance was derived from the PA time constant and the PA resistance. Storage volume fraction of stroke volume index (PASSV/SVI) was used to compare individual variations. There were inverse linear relationships between PASSV/SVI and VD/VT (r = 0.693, p less than 0.0001), and between PASSV/SVI and Qsp/Qt (r = 0.427, p = 0.012). Also, a direct correlation was found between VD/VT and PA time constant (r = 0.503, p = 0.002). The patients were divided into two groups based on PASSV/SVI to evaluate the effect of other hemodynamic data on PASSV. Comparison of the two groups revealed that VD/VT and Qsp/Qt were lower (p less than 0.0001, and p = 0.018, respectively), PA time constant was higher (p less than 0.001), and right ventricular stroke-work index was higher (p = 0.005) in the group with a high PASSV/SVI. There were no differences in other hemodynamic data between the two groups. These data suggest that an elevated PASSV may indeed benefit gas exchange in acute respiratory failure.

Acute Disease↗

Is there a place for shelf acetabuloplasty in the management of adult acetabular dysplasia? A survivorship study.

We followed up 76 consecutive hips with symptomatic acetabular dysplasia treated by acetabular shelf augmentation for a mean period of 11 years. Survival analysis using conversion to hip replacement as an end-point was 86% at five years and 46% at ten years. Forty-four hips with slight or no narrowing of the joint space pre-operatively had a survival of 97% at five and 75% at ten years. This was significantly higher (p = 0.0007) than that of the 32 hips with moderate or severe narrowing of the joint-space, which was 76% at five and 22% at ten years. There was no significant relationship between survival and age (p = 0.37) or the pre- and post-operative centre-edge (p = 0.39) and acetabular angles (p = 0.85). Shelf acetabuloplasty is a reliable, safe procedure offering medium-term symptomatic relief for adults with acetabular dysplasia. The best results were achieved in patients with mild and moderate dysplasia of the hip with little arthritis.

Acetabulum↗

Cusum analysis of trends in operative selection and conversion rates for laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) requires a high degree of technical ability, spatial resolution and dexterity. Assessing trainees and competent operators is an important aspect of quality assurance in patient care. Most institutions quote mean conversion rate as a method of comparing operators' performance. The purpose of the present study was to use the technique of cumulative sum (cusum) analysis to determine whether a learning curve phenomenon exists in operators performing LC. METHODS: Data were obtained retrospectively by reviewing the operative records of all patients undergoing elective and acute cholecystectomy for a 30-month period coinciding with the commencement of LC at North Shore Hospital. Patients' age and gender, date and type of operative procedure, duration of operation, and name of operator were recorded. Mean and cusum-transformed data were derived for all operations as well as for four individual operators' performances. RESULTS: Over the study period a total of 614 cholecystectomies was performed, with 85% attempted laparoscopically. A total of 9.8% required conversion to the open technique. Time trend analysis with the cusum technique for all surgeons revealed an inverse relationship between selection rate and conversion rate. Analysis of four individual surgeons revealed three different time trend profiles. CONCLUSION: There was a direct inverse relationship between conversion rate and selection rate, in that careful selection is associated with a low conversion rate. Comparison of individual surgeons' performance showed wide variation, with only one surgeon exhibiting the phenomenon of a learning curve. Contrary to other reports, we found that performance on LC was not always related to operative experience. This highlights the need for a more objective method to analyse operator competence than operator experience alone.

Adolescent↗

Calibration error in dark adaptometer.

We noted that the adjustable fixation device present on some models of the Goldmann-Weekers dark adaptometer has a calibration error that results in a consistent and predictable overestimation of retinal eccentricity. The error occurs because the eye being tested is not in the geometric center of the projection sphere. The true retinal locus may be computed by trigonometric analysis. A conversion table is available for reference.

Calibration↗

Retinoids and their receptors in skeletal development.

The embryonic vertebrate limb serves as an excellent experimental model system in which to study mechanisms that regulate morphogenesis of the skeleton. The appendicular skeleton arises through the process of endochondral ossification, whereby a cartilage template is initially formed and subsequently replaced by bone. One molecule that has a dramatic effect on these processes is the vitamin-A metabolite, retinoic acid (RA). RA functions through a class of nuclear hormone receptors, the retinoic acid receptors (RARs) and retinoid-X-receptors (RXRs), to regulate gene transcription. Experimental evidence from RA teratogenesis suggests that the presence of ligand-activated RARs and/or inappropriate expression of RARs inhibits chondrogenesis. Conversely, genetic analysis has shown that the absence of the receptors can lead to deficiencies in cartilage formation while also promoting chondrogenesis at ectopic sites. Taken together, these studies suggest that the RARs play a fundamental role in the early stages of skeletal development, specifically those involved in the formation of prechondrogenic condensations and their subsequent differentiation into chondroblasts.

Animals↗

The effect of bleomycin on mitochondrial DNA.

Covalently closed circular mitochondrial DNA (mt-DNA) from mouse fibroblasts (L-cells) forms a separate band from nicked circular or linear DNA molecules in ethidium bromide-cesium chloride byoyant density gradient analysis. The conversion of covalently closed circular mt-DNA to nicked circular or linear DNA may serve as a sensitive method of detecting DNA strand breaks induced by bleomycin (BLM). At a very high concentration BLM induces the conversion of closed circular mt-DNA to nicked circular or linear DNA, however even after 24 h of exposure to BLM at a high concentration a considerable amount of closed circular mt-DNA molecules remains intact.

Animals↗

Coevolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication.

The recent availability of genomic sequence information for the class I region of the MHC has provided an opportunity to examine the genomic organization of HLA class I (HLAcI) and PERB11/MIC genes with a view to explaining their evolution from the perspective of extended genomic duplications rather than by simple gene duplications and/or gene conversion events. Analysis of genomic sequence from two regions of the MHC (the alpha- and beta-blocks) revealed that at least 6 PERB11 and 14 HLAcI genes, pseudogenes, and gene fragments are contained within extended duplicated segments. Each segment was searched for the presence of shared (paralogous) retroelements by RepeatMasker in order to use them as markers of evolution, genetic rearrangements, and evidence of segmental duplications. Shared Alu elements and other retroelements allowed the duplicated segments to be classified into five distinct groups (A to E) that could be further distilled down to an ancient preduplication segment containing a HLA and PERB11 gene, an endogenous retrovirus (HERV-16), and distinctive retroelements. The breakpoints within and between the different HLAcI segments were found mainly within the PERB11 and HLA genes, HERV-16, and other retroelements, suggesting that the latter have played a major role in duplication and indel events leading to the present organization of PERB11 and HLAcI genes. On the basis of the features contained within the segments, a coevolutionary model premised on tandem duplication of single and multipartite genomic segments is proposed. The model is used to explain the origins and genomic organization of retroelements, HERV-16, DNA transposons, PERB11, and HLAcI genes as distinct segmental combinations within the alpha- and beta-blocks of the human MHC.

Alu Elements↗

Reproducibility of the signal-averaged electrocardiogram.

Variation in measurements made from signal-averaged electrocardiograms was examined. Averaging 200 beats in 18 normal subjects, pairs of high-frequency QRS and low-amplitude signal durations correlated at immediate, short-term, and long-term intervals. The percent high-frequency (60 Hz to 120 Hz) voltages in the late potential region had modest correlations. However, 95% confidence intervals of differences in paired measurements were as much as 7% for high-frequency QRS, 20% for a low-amplitude signal, and 53% for percent high-frequency, similar at all time intervals. With electrocardiograms averaged to 0.3 microV noise, high-frequency QRS and low-amplitude signals prolonged, but variation was similar to that of 200 beat pairs. In contrast, low noise reduced percent high-frequency and lessened variation to 29%. Therefore variation in signal-averaged electrocardiographic measurements was considerable (high-frequency voltage greater than durations). Noise did not appreciably influence variation in durations but was critical to consistent voltage measurements in the frequency domain.

Adult↗

Effects of urea and molybdate on the chick oviduct progesterone receptor.

The chick oviduct cytosol progesterone receptor, when complexed with ligand, can be exposed to urea concentrations as high as 3 M (at 0 degrees C) without loss of steroid binding capacity. The ligand dissociation rate is increased greater than or equal to 10 fold under these conditions. The "native" 8 S form of the receptor is progressively converted to a 4 S species by urea (greater than 2 M) as seen in ultracentrifugation analysis. This conversion is inhibited by Na2MoO4 (5-50 mM) suggesting that molybdate stabilizes the 8 S molecule by direct interaction. At urea concentrations above 2 M, the ligand-free receptor looses progressively its binding capacity. The "transformed", 4 S receptor was less stable than the 8 S species, and could not be protected by molybdate.

Animals↗

A temperature conversion nomogram for glycosylated hemoglobin analysis.

Analysis of glycosylated hemoglobins by commercial mini-column methods was shown to vary linearly with the ambient temperature. However, the slopes of the temperature dependence lines for diabetic and healthy individuals was different. A method for temperature correction and a nomogram is proposed.

Chromatography↗

Effects of stimulus frequency on the blink reflex during rest and a task.

Blink reflexes were studied in 84 healthy subjects, applying 4 different stimulation frequencies. The experiments were subdivided into 3 periods: rest, binary choice task and final rest period. Independent of the applied stimulation frequency, an increment of R1 during the task was found, and it was concluded that R1 amplitude reflects the state of arousal of the subject. Within each of the 3 periods, R1 amplitudes decreased independently of the applied frequency, while R2 amplitudes decreased dependent on the applied frequency, i.e. at lower frequencies a smaller decrement in time could be observed. It was concluded that R2 habituated at frequencies lower than those so far reported.

Analog-Digital Conversion↗

Degradation of 2-phosphoglycerate by cytotoxin B of Clostridium difficile.

Cytotoxin B of C. difficile was highly purified by selective ammonium sulfate precipitation, Biogel A5m chromatography, phenyl boronate hydrophobic interaction chromatography and ultracentrifugation. The final cytotoxic product had a specific activity of 7.8 X 10(8) units/mg protein and showed a single protein band with an estimated molecular weight of 163,000 when subjected to SDS-PAGE. Immunoelectrophoresis of the final product showed a single precipitin arc. The addition of cytotoxin B to imidazole-HCl buffer (pH 7.4) containing MgSO4, KCl and the substrate 2-phosphoglycerate resulted in the formation of phosphoenolpyruvate as demonstrated by spectrophotometric analysis. Phosphoglycerate conversion was absent when the cytotoxin was heat-inactivated of reacted with specific antitoxin prior to assay.

Adrenal Glands↗

Neuropeptide Y in the intermediate lobe of the frog pituitary acts as an alpha-MSH-release inhibiting factor.

The presence of neuropeptide tyrosine (NPY) in the intermediate lobe of the frog pituitary was demonstrated using indirect immunofluorescence, the immunogold technique and a specific radioimmunoassay combined with high pressure liquid chromatography (HPLC). A high density of NPY-containing fibers, was found among the parenchymal cells of the intermediate lobe. These fibers originated from the ventral infundibular nucleus, travelled via the median eminence to the pars intermedia. At the electron microscopic level, NPY-like material was found exclusively in nerve fibers where the product of the immunoreaction was associated to dense-core vesicles. High concentrations of NPY-like peptide were found in neurointermediate lobe extracts. After Sephadex G-50 gel filtration the major peak of immunoreactive material appeared to co-elute with synthetic porcine NPY. Conversely, HPLC analysis revealed that the NPY-like peptide of the frog pituitary had a retention time shorter than the porcine NPY. The localization of NPY-like material in the pars intermedia suggested a possible role of NPY in the regulation of melanotropic cell secretion. In fact, graded concentrations of synthetic NPY induced a dose-dependent inhibition of alpha-melanotropin (alpha-MSH) release in vitro. The lack of effect of a dopaminergic antagonist on NPY-induced alpha-MSH release inhibition demonstrated that the local dopaminergic system could not account for the NPY action. These results indicate that NPY located in the hypothalamo-hypophyseal system of the frog may act as a melanotropin-release inhibiting factor.

Animals↗

Multiple sclerosis and the HLA-D region: linkage and association studies.

Inheritance patterns of multiple sclerosis (MS) in multiplex families suggest a complex aetiology involving environmental and genetically determined components. The association between the HLA class II DR15, DQ6, Dw2 haplotype and MS has been well documented in patients with ancestral origins in Northern Europe. Conversely, linkage analysis of this region in multiplex families, derived from a population base, has generated negative results. Thus, given the Dw2 specificity association, evidence implicating this locus in disease susceptibility appears contradictory. We have collected and determined the HLA-DR and -DQ haplotypes of 115 sibling pairs with multiple sclerosis, and confirm a significant association with the Dw2-associated haplotype, both in index cases and their affected siblings compared with controls. However, using a sibling pair linkage analysis that restricts haplotype sharing probabilities to defined genetic models, we have not observed linkage of this region to susceptibility in MS. We discuss the basis for association and linkage and conclude that the DR15, DQ6, Dw2 haplotype does represent a susceptibility locus but its contribution to the pathogenesis is small; although it may interact epistatically with other susceptibility genes, this haplotype is not necessary for disease expression.

Adult↗