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Identification of novel genetic loci for bone size and mechanosensitivity in an ENU mutant exhibiting decreased bone size.

UNLABELLED: Using a dominant ENU mutagenesis screen in C57BL/6J (B6) mice to reveal gene function, we identified a mutant, 917M, with a reduced bone size phenotype, which is expressed only in males. We show that mutation results in osteoblasts with reduced proliferation, increased apoptosis, and an impaired response to in vitro mechanical load. The mutation is mapped to a novel locus (LOD score of 7.9 at 10.5 cM) on chromosome 4. INTRODUCTION: Using a dominant ENU mutagenesis screen in C57BL/6J (B6) mice to reveal gene function, we identified a mutant, 917M, with a reduced bone size phenotype, which is expressed only in males. In this report, we show the chromosomal location of this mutation using linkage analysis and cellular characterization of the mutant phenotype. MATERIALS AND METHODS: The mutant mouse was bred to wildtype B6 to produce progeny for characterization of the bone size phenotype. Periosteal osteoblasts isolated from the tibia and femur of mutant and wildtype mice were studied for proliferation, differentiation, and apoptosis potential. To determine the chromosomal location of the mutation, a low-resolution linkage map was established by completing a genome-wide scan in B6C3H F2 male mice generated from intercross breeding of mutant mice. RESULTS AND CONCLUSIONS: Mutant progeny (16 weeks old) displayed a total body bone area that was 10-13% lower and a periosteal circumference that was 5-8% lower at the femur and tibia midshaft compared with wildtype B6 mice. Periosteal osteoblasts from mutant mice showed 17-27% reduced cell proliferation and 23% increased apoptosis compared with wildtype controls. In addition, osteoblasts from mutant mice showed an impaired response to shear stress-induced proliferation rate, an in vitro model for mechanical loading. Interval mapping in B6C3H F2 males (n = 69) indicated two major loci affecting bone size on chromosome 1 at 45 cM (LOD 4.9) and chromosome 4 at 10.5 cM (LOD 7.9, genome-wide p < 0.01). Interval mapping using body weight as covariate revealed only one significant interval at chromosome 4 (LOD 6.8). Alleles of the chromosome 4 interval inherited from the B6 mutant strain contributed to a significantly lower bone size than those inherited from C3H. A pairwise interaction analysis showed evidence for a significant interaction between loci on chromosome 1 with the chromosome 4 quantitative trait loci. The 917M locus on chromosome 4 seems to be novel because it does not correspond with those loci previously associated with bone size on chromosome 4 in B6 and C3H/HeJ mice or other crosses.

Alkylating Agents↗

The effect of check size on VEPs in healthy humans: a parabolic relationship between check size and N145 wave.

The effect of check size on pattern reversal VEPs was examined in healthy adult volunteers. The subjects were exposed to full-field binocular stimulation. Five checkerboard patterns with check sizes 13', 25', 50', 75' and 100' were used as the visual stimuli. The patterns reversed at a rate of 1 reversal/sec. Well-defined pattern reversal VEPs were obtained for all check sizes in all subjects. As the check size increased a transition from a triphasic to an almost monophasic wave form was observed. N75 and P100 amplitudes, together with N75 latency, revealed linear relationships with check size; the N145 amplitude displayed a parabolic relationship with check size. No significant relationships were found for P100 and N145 latencies. It is concluded that the N75 wave originated mainly from the activity of the foveola, whereas the more eccentric regions contribute more to the formation of P100, and the interaction of both regions elicited the N145 wave.

Adult↗

Does size matter? Positive predictive value of MRI-detected breast lesions as a function of lesion size.

OBJECTIVE: The purpose of this study was to determine the impact of lesion size on the positive predictive value (PPV) of biopsy in MRI-detected breast lesions. MATERIALS AND METHODS: A retrospective review was performed of 666 consecutive nonpalpable, mammographically occult lesions that had MRI-guided localization. MRI examinations were performed using a 1.5-T magnet. Lesions were measured by the interpreting radiologist before biopsy. Malignancy rate versus lesion size was determined. RESULTS: The median MRI lesion size was 1 cm (range, 0.3-7.0 cm). Malignancy was present in 149/666 (22%) lesions, of which 80 (54%) were ductal carcinoma in situ (DCIS), 66 (44%) were invasive cancer, and three (2%) were lymphoma. The frequency of malignancy increased significantly (p = 0.0005) with lesion size, with malignancy found in one (3%) of 37 lesions less than 5 mm, 44 (17%) of 254 lesions 5-9 mm, 37 (25%) of 151 lesions 10-14 mm, 21 (28%) of 74 lesions 15-19 mm, and 46 (31%) of 150 lesions 20 mm or larger. Lesions less than 5 mm accounted for 37 (6%) of 666 lesions that had a biopsy and one (< 1%) of 149 cancers (one DCIS). Among lesions less than 10 mm, the likelihood of malignancy was highest in postmenopausal women (22% malignant) and in the extent of disease setting (22% malignant), and lowest in premenopausal women (10% malignant) and in the high-risk screening setting (10% malignant). CONCLUSION: The PPV of biopsy for lesions identified at breast MRI using a 1.5-T magnet significantly increased with increasing lesion size. Biopsy is rarely necessary for lesions smaller than 5 mm because of their low (3%) likelihood of cancer. Further work is needed to develop an algorithm that uses size in addition to other patient and lesion factors to guide biopsy recommendations for MRI-detected breast lesions.

Adult↗

Accuracy of estimations of body-frame size as a function of sex and actual frame size.

Body-frame size is an important factor in determining an optimal body weight for a given height. Previous studies have indicated that many individuals incorrectly estimate their body-frame size, and, as a result, incorrectly assess their ideal weight. The present study investigated the accuracy of estimation of body-frame size as a function of sex and actual frame size. The subjects were 66 men and 52 women participating in a community adult fitness program. Data indicated that medium-framed individuals were the most accurate in their estimations of body-frame size. Also, women were twice as likely to be accurate as were men. These results are interpreted to mean that most people assume they are medium-framed and that there is a sex difference in the way body-frame size is estimated.

Adult↗

Comparison of bite size, biting rate and grazing time of beef heifers from herds distinguished by mature size and rate of maturity.

Sixteen-month-old heifers from herds having known genetic growth patterns were compared for differences in grazing behavior in a 3-yr study. Treatments were heifers from four size-maturity groups defined by the mature size and maturing rate of cow herds in which they originated. Average growth curve parameters indicating mature BW and rate of maturing in these cow herds were 387 kg and .19%/d for treatment Group I; 413 kg and .18%/d for Group II; 468 kg and .15%/d for Group III; and 589 kg and .16%/d for treatment Group IV. Data were from three heifers per treatment group grazing Midland bermudagrass during June and July observation periods. With the exception of the Group II vs Group III comparison, bite size increased with current or mature BW. Biting rate values were similar for all treatment groups but lower than those previously reported on other grass swards. Grazing time increased (P less than .01) in treatment groups defined by larger mature BW. Differences in grazing time for Group IV vs the other treatments and Group I vs Group II and Group III were observed repeatedly; the Group II vs Group III comparison was significant in one period during each of the 3 yr. Diurnal variations in grazing patterns among the treatments were observed. Period of observation affected (P less than .001) bite size and grazing time. These effects were not associated with month but could best be explained by differences in forage height and total mass. Forage availability had a direct influence on bite size, and a compensating effect of longer grazing time with smaller bite size was demonstrated as a regulator of intake. Differences in ingestive behavior were associated with genetic growth patterns in cattle.

Aging↗

Full-size digital storage phosphor chest radiography: effect of 4K versus 2K matrix size on observer performance in detection of subtle interstitial abnormalities.

PURPOSE: To compare observer performance in the detection of subtle interstitial abnormalities on 3,520 x 3,520 (4K) matrix and 1,760 x 1,760 (2K) matrix full-size digital storage phosphor (DSP) chest radiographs. MATERIALS AND METHODS: Thirty-five 4K DSP chest radiographs with subtle interstitial abnormalities (n=27) or normal lungs (n=8) were processed with a half-band low-pass filter to produce 2K DSP radiographs. Although the actual matrix size of the 2K DSP radiographs remained 4K, the effective matrix size was reduced to 2K. Four chest radiologists independently evaluated full-sized hard-copy of the 4K and 2K DSP radiographs, and scored the presence of interstitial abnormalities for both right and left lungs on a five-point confidence scale. With findings on high-resolution computed tomography as the reference standard, observer performance was evaluated using multireader-multicase receiver operating characteristic (ROC) analysis. RESULTS: The average area under the ROC curve (Az) values for 4K and 2K DSP radiographs were 0.791+/-0.055 and 0.804+/-0.050, respectively. Both individual and averaged Az values showed no statistically significant differences (p>0.05) between 4K and 2K DSP radiographs. CONCLUSION: Observer performance in the detection of subtle interstitial abnormalities on 4K full-size DSP chest radiographs was equivalent to that on 2K full-size DSP chest radiographs.

Humans↗

An investigation to relate the overall size of the maxillary arch and the area of palatal mucosa in cleft lip and palate cases at birth to the overall size of the upper dental arch at five years of age.

The area of palatal mucosa and the size of the maxillary arches were measured in a group of 30 newborn infants with unilateral clefts of the lip and palate. The overall size of the maxillary arch together with the arch width and arch height were also measured when the children had reached 5 years of age. For comparison purposes, a group of 30 newborn normal children and 30 normal 5-year-old children were similarly measured. The cleft children were found to have a mean deficiency of palatal mucosa of 16.41% at birth, although the overall size of their maxillary arches was 17.08% greater than normal. In the cleft cases there was no significant correlation between the area of palatal mucosa at birth and the overall size of the arch at 5 years of age. A significant correlation did exist between the overall size of the arch at birth and the overall size when the child was 5 years old. The significance of this and other findings is discussed.

Aging↗

Of creatures large and small: size anxiety, psychic size, shame, and the analytic situation.

The authors investigates what he terms "size anxiety" and "psychic size." Psychic size is composed of experiences of smallness and largeness with respect to parental figures, fantasies of being large or small, and the meanings of such experiences and fantasies in specific two-person situations. Size anxiety includes the anxiety about being a particular size with respect to a significant other (real or fantasized). Drawing on Gulliver's Travels and on Ferenczi's paper on Gulliver fantasies, the author discusses how experiences of psychic size, rivalry, and shame provide important analytic material. Dreams and clinical vignettes illustrate the thesis.

Anxiety↗

[Heart size and left ventricular function in coronary artery disease: I. Heart size, exercise tolerance, cardiac output and filling pressures (author's transl)].

The possible relationship between the cardiac volume, as determined radiologically in the supine position in 119 patients with angiographically proven coronary artery disease, and the results of ergometry and balloon catheterization was investigated. There was no relationship between the heart size on the one side and the maximum exercise tolerance and the maximum cardiac output on the other, except for the fact, that these parameters tended to decrease with increasing heart size. This was especially true in patients with angina. The maximum cardiac output of patients with angina was always below the value of patients without angina but comparable heart size. Reduced cardiac output under exercise (exertional cardiac insufficiency) was present in 50% of patients with enlarged hearts but already in 22% of patients with heart volumes in the lower range of normal. The diastolic pulmonary artery pressure, determined under exercise, was the only parameter with a significant relationship to the heart size: The larger the heart size, the higher the diastolic pulmonary artery pressure. On the other hand: the diastolic pulmonary artery pressure at rest was abnormal with significant frequency only, when the heart was enlarged. Our data suggest, that the hemodynamics are determined by 2 factors: Myocardial scarring secondary to infarction and coronary insufficiency (ischemia). Of these two factors only the former influences cardiac size. Therefore, determination of the heart volume helps evaluating the respective role of these two factors in individual cases.

Adult↗

Size of family of orientation and family size preference: a replication.

"Past studies have found a modest, positive association between size of family of orientation and preferred family size and fertility behavior in the family of procreation. While there is some consistency in the findings, contradictions are also noted. The present study replicates earlier studies dealing with preferred family size, and seeks to resolve some of the contradictions by utilizing multiple classification analysis to determine the simultaneous impact of parental family size, religion, happiness, life style stability, and birth order on family size preference." The data, collected in 1981-1982, concern 379 U.S. college students.

Americas↗

Capillary zone electrophoresis of sub-microm-sized particles in electrolyte solutions of various ionic strengths: size-dependent electrophoretic migration and separation efficiency.

To gain insight into the mechanisms of size-dependent separation of microparticles in capillary zone electrophoresis (CZE), sulfated polystyrene latex microspheres of 139, 189, 268, and 381 nm radius were subjected to CZE in Tris-borate buffers of various ionic strengths ranging from 0.0003 to 0.005, at electric field strengths of 100-500 V cm(-1). Size-dependent electrophoretic migration of polystyrene particles in CZE was shown to be an explicit function of kappaR, where kappa(-1) and rare the thickness of electric double layer (which can be derived from the ionic strength of the buffer) and particle radius, respectively. Particle mobility depends on kappaR in a manner consistent with that expected from the Overbeek-Booth electrokinetic theory, though a charged hairy layer on the surface of polystyrene latex particles complicates the quantitative prediction and optimization of size-dependent separation of such particles in CZE. However, the Overbeek-Booth theory remains a useful general guide for size-dependent separation of microparticles in CZE. In accordance with it, it could be shown that, for a given pair of polystyrene particles of different sizes, there exists an ionic strength which provides the optimal separation selectivity. Peak spreading was promoted by both an increasing electric field strength and a decreasing ionic strength. When the capillary is efficiently thermostated, the electrophoretic heterogeneity of polystyrene microspheres appears to be the major contributor to peak spreading. Yet, at both elevated electric field strengths (500 V/cm) and the highest ionic strength used (0.005), thermal effects in a capillary appear to contribute significantly to peak spreading or can even dominate it.

Electrolytes↗

Testicle size of orang-utans in relation to body size.

Few data are available for assessing the relative testicle size of orang-utans, Pongo pygmaeus, so measures were obtained for 31 individuals of varying age. It was shown that the volume of the testicles, calculated from in situ measures of testicle length and breadth, closely approximates testicle weight when multiplied by the specific gravity of solid tissue. Growth curves for body weight and data published for wild specimens were evaluated to obtain the weight most characteristic of male Pongo, and the ratio of testicle weight to body weight was calculated. The mean ratio for individuals with fully adult stature is 0.034, similar to but smaller than that of humans at about 0.050, and larger than the ratios reported for 5 gorillas at 0.013. The testicles mature faster than the body, however, so the mean ratio for young adult orang-utans is about 0.056 and resembles the ratio for humans more closely than the full adults. The differences between the ratios for a monogamous gibbon species, orang-utans, and humans is accounted for when testicle size relative to the weight of the female is considered. This is consistent with a sperm dilution effect produced by variation in the size of the female reproductive tract. The small relative testicle size of the gorilla is anomalous and requires verification as does the application of female size to scale the testicles.

Animals↗

Changes of islet size and islet size distribution resulting from protein-malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean (Fa/Fa) and obese (fa/fa) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Bodyweight gain, food intake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75%) and obese (-54%) rats fed low protein compared with that in controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (< or = 100 microns2) and a decrease in the population of large islets (> 20,000 microns2). In lean and obese rats fed low protein, beta-cell weight was significantly lower, beta cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancrease in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.

Animals↗

Sizing it up: cellular MRI using micron-sized iron oxide particles.

There is rapidly increasing interest in the use of MRI to track cell migration in intact animals. Currently, cell labeling is usually accomplished by endocytosis of nanometer-sized, dextran-coated iron oxide particles. The limitations of using nanometer-sized particles, however, are that millions of particles are required to achieve sufficient contrast, the label can be diluted beyond observability by cell division, and the label is biodegradable. These problems make it difficult to label cells other than macrophages in vivo, and to conduct long-term engraftment studies. It was recently demonstrated that micron-sized iron oxide particles (MPIOs) can be taken up by a number of cell types. In this study we examined the MRI properties of single MPIOs with sizes of 0.96, 1.63, 2.79, 4.50, and 5.80 microm. Furthermore, the capacity of cells to endocytose these MPIOs was investigated, and the MRI properties of the labeled cells at 7.0 and 11.7 Tesla were measured as a function of image resolution and echo time (TE). Cells labeled with MPIOs generally contained iron levels of approximately 100 pg, which is approximately threefold higher than those obtained with the best strategies to label cells using nanometer-sized particles. On occasion, some cells had levels as high as approximately 400 pg. We demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)-based imaging methods. These measurements indicate that MPIOs should be useful for improving cell tracking by MRI.

Animals↗

Separation and size distribution of red blood cells of diverse size, shape, and origin by flow/hyperlayer field-flow fractionation.

Red blood cells (RBCs) from human, equine, canine, feline, and bovine whole blood samples have been separated and characterized by high-speed flow/hyperlayer field-flow fractionation (Fl/HyFFF). The elution-based separation of RBCs by this method is based mainly on the size and shape of the cell particles. The typical separation time for RBCs is less than 3 min. Size distributions can be derived from the fractograms of cell samples using a calibration plot based on retention data for uniform polystyrene beads. The method is shown to be effective both to separate and to characterize cell populations, including those with cells of abnormal shape and size. In order to investigate differences in cell morphology, shape and size changes induced by 500,000 Da Dextran were monitored. The changes in the Fl/HyFFF elution profiles indicate that the RBCs decrease in size but become partially aggregated in the presence of the dextran. These changes were found to depend on polymer concentration and specific blood samples. Some of the results from Fl/HyFFF were compared with those from the Coulter counter and from microscopy.

Animals↗

Phenotypic plasticity of body size in a temperate population of Drosophila melanogaster: when the temperature-size rule does not apply.

A natural population of Drosophila melanogaster in southern France was sampled in three different years and 10 isofemale lines were investigated from each sample. Two size-related traits, wing and thorax length, were measured and the wing/thorax ratio was also calculated. Phenotypic plasticity was analysed after development at seven different constant temperatures, ranging from 12 degrees C to 31 degrees C. The three year samples exhibited similar reaction norms, suggesting a stable genetic architecture in the natural population. The whole sample (30 lines) was used to determine precisely the shape of each reaction norm, using a derivative analysis. The practical conclusion was that polynomial adjustments could be used in all cases, but with different degrees: linear for the wing/thorax ratio, quadratic for thorax length, and cubic for wing length. Both wing and thorax length exhibited concave reaction norms, with a maximum within the viable thermal range. The temperatures of the maxima were, however, quite different, around 15 degrees C for the wing and 19.5 degrees C for the thorax. Assuming that thorax length is a better estimate of body size, it is not possible to state that increasing the temperature results in monotonically decreasing size (the temperature-size rule), although this is often seen to be the case for genetic variations in latitudinal clines. The variability of the traits was investigated at two levels-within and between lines-and expressed as a coefficient of variation. The within-line (environmental) variability revealed a regular, quadratic convex reaction norm for the three traits, with a minimum around 21 degrees C. This temperature of minimum variability may be considered as a physiological optimum, while extreme temperatures are stressful. The between-line (genetic) variability could also be adjusted to quadratic polynomials, but the curvature parameters were not significant. Our results show that the mean values of the traits and their variance are both plastic, but react in different ways along a temperature gradient. Extreme low or high temperatures decrease the size but increase the variability. These effects may be considered as a functional response to environmental stress.

Analysis of Variance↗

Polyribosome size analysis. Measurement of number-average polyribosome sizes.

The analysis of translational efficiencies of specific mRNAs requires a determination of the polyribosome size. The appropriate value to use in such calculations is the number-average size. A method is described for accurately measuring the number-average size of total and of specific protein synthesizing polyribosomes using isokinetic sucrose density gradients and 125I-labeled antibodies. By this method, we demonstrated that albumin synthesizing polyribosomes from a serum albumin secreting mouse hepatoma cell line exist over a broad range from trimers to 20-mers (mean 6-10). The specificity of antibody interaction with polyribosomes was demonstrated using cells not synthesizing mouse serum albumin, and by demonstrating that 125I-anti ovalbumin does not bind to mouse hepatoma polyribosomes. Treatment of the mouse hepatoma cells with 1 MUM cycloheximide shifted practically all of the monomers into polyribosomes resulting in an increase in the number-average size of the albumin synthesizing polyribosomes. Cycloheximide treatment, however, did not eliminate the size heterogeneity in the albumin synthesizing polyribosomes.

Albumins↗

New aspects of the effect of size and size distribution on the setting parameters and mechanical properties of acrylic bone cements.

The effect of the size and the size distribution of poly(methyl methacrylate) (PMMA) beads on the classical kinetic parameters, peak temperature and setting time, for acrylic bone cement formulations prepared with PMMA particles in the range 10-60 microns of average diameter and a relatively wide size distribution is analysed. In addition, the combined effects of the concentration of the free radical initiator benzoyl peroxide and the activator N, N-dimethyl-4-toluidine for the different particle sizes are studied and compared with those commercially available formulations like CMW or Rostal. The results obtained indicated that the use of PMMA particles with average diameter of 50-60 microns, and a relatively wide size distribution (10-140 microns diameter), significantly changes the curing parameters (peak temperature and setting time) of the cement formulations in comparison with the classical behaviour of the commercial systems of CMW and Rostal, without any noticeable loss in the mechanical properties, such as tensile strength, elastic moduli, and compressive strength and plastic strain.

Benzoyl Peroxide↗