Mandibular phenotype of p20C/EBPbeta transgenic mice: Reduced alveolar bone mass and site-specific dentin dysplasia.

CCAAT enhancer binding proteins (C/EBP) comprise a family of basic-leucine zipper transcription factors that regulate cellular differentiation and function. To determine the role of C/EBP transcription factors in osteoblasts and odontoblasts, we generated a transgenic (TG) mouse model with Co1a1 (pOBCol3.6) promoter-targeted expression of a FLAG-tagged dominant negative C/EBP isoform, p20C/EBPbeta (previously LIP). Two of the four transgenic lines presented with abnormalities in the developing incisors, including breakage, overgrowth, and malocclusion. Histological examination revealed that the amount of alveolar bone was reduced in TG compared to wild-type (WT) mice. By microcomputed tomography (microCT), the bone volume fraction of the mandible was reduced at the level of the first and third molars, demonstrating a severe mandibular osteopenia. The lingual dentin morphology of TG incisors differed dramatically from WT. Labial dentin (enamel side) showed normal thickness and tubular dentin structure, whereas the lingual dentin was thinner (25-30% of WT at the alveolar crest) with an amorphous globular structure characteristic of dentin dysplasia. FLAG immunostaining was seen in both lingual and labial odontoblasts, indicating that the site-specific defect was not due to a lack of labial transgene expression. Northern blot analysis demonstrated reduced osteocalcin expression in TG mandibles, while bone sialoprotein was increased, consistent with prior results in calvariae and long bones. Dental sialophosphoprotein, a marker of the odontoblast lineage whose absence causes dentin dysplasia, was modestly reduced in TG mice by Northern blot and in situ hybridization analysis. By fluorescence microscopy, pOBCol2.3-GFP, a marker of the odontoblast lineage, was expressed in both labial and lingual odontoblasts, although GFP-marked lingual odontoblasts were more flattened than WT cells. Moreover, GFP-positive processes in the lingual dentin tubules were truncated and less organized than those in WT dentin. MicroCT analysis showed reduced tissue density in the lingual dentin. These data suggest that C/EBP transcription factors may be involved in the regulation of odontoblast polarization and dentin matrix production.

Involvement of CCAAT enhancer binding protein transcription factors in the regulation of prostaglandin G/H synthase 2 expression by interleukin-1 in osteoblastic MC3T3-E1 cells.

Interleukin-1 (IL-1) stimulates prostaglandin production in bone by a rapid and transient activation of prostaglandin G/H synthase 2 (PGHS-2) gene expression. In osteoblastic MC3T3-E1 cells, IL-1 caused a transient increase in PGHS-2 messenger RNA (mRNA), which peaked at 2 h. IL-1 caused a 2- to 4-fold activation of a 371-base pair (bp) murine PGHS-2 promoter/luciferase construct in stable transfectants. This response mapped to a proximal promoter element(s) located between -150 and -40 bp. This region contains a putative CCAAT enhancer binding protein (C/EBP) site (centered at -135 bp), which shows enhanced binding of C/EBPbeta and C/EBPdelta by mobility shift analysis after IL-1 treatment. A transient cotransfection approach was used to examine the effects of C/EBPbeta and C/EBPdelta overexpression. IL-1 caused a maximal 3- to 7-fold stimulation of PGHS-2 promoter activity after 2.5 h. Overexpression of murine C/EBPbeta and C/EBPdelta caused a dose-dependent increase in basal and IL-1-stimulated luciferase activity. C/EBPdelta caused a greater enhancement of basal and IL-1-stimulated promoter activity than C/EBPbeta, suggesting that C/EBPdelta is a stronger transactivator. Overexpression of p20C/EBPbeta, a dominant negative inhibitor of C/EBP function, blocked the stimulation of PGHS-2 promoter activity by IL-1 and blocked the ability of overexpressed C/EBPbeta and C/EBPdelta to increase basal and IL-1-stimulated promoter activity. Mutagenesis of the C/EBP site reduced, but did not abolish, the stimulation of PGHS-2 promoter activity by IL-1 and blunted the effect of overexpressed C/EBPdelta on basal and IL-1-stimulated promoter activity. These results suggest an essential role for C/EBPbeta and C/EBPdelta in the induction of PGHS-2 gene expression by IL-1 in osteoblastic cells.

Interleukin-1 represses COLIA1 promoter activity in calvarial bones of transgenic ColCAT mice in vitro and in vivo.

Interleukin-1 (IL-1) inhibits collagen synthesis in osteoblastic cell lines and primary osteoblast-like cells. However, promoter elements regulating type I collagen A1 (COLIA1) expression in vivo and in organ culture may differ from those regulating expression in cell culture. We have examined the effects of IL-1 on reporter gene activity in neonatal transgenic mouse calvariae bearing COLIA1 promoter-chloramphenicol acetyltransferase (ColCAT) fusion genes. The parent construct, ColCAT 3.6, contains 3.5 kb of 5' flanking sequence and 115 bp of 5' untranslated region fused to the CAT reporter. In 48-h calvarial organ cultures, IL-1 repressed ColCAT 3.6 promoter activity and collagen synthesis in a dose-related manner, with a maximal inhibition of 40-65%. This repression was retained in 5' deletion constructs truncated to-1719 bp. The inhibition of transgene mRNA was blocked by cycloheximide, indicating a requirement for new protein synthesis. Pretreatment with indomethacin diminished the inhibitory effect of IL-1 on CAT activity and collagen synthesis, suggesting partial mediation by prostaglandins. Local in vivo injection of IL-1 (500 ng) decreased calvarial transgene mRNA after 8 h, an effect that was partially blocked by indomethacin. ColCAT transgenic mice represent a useful model for in vitro and in vivo assessment of COLIA promoter regulation by cytokines and other factors.

Cross-modal compatibility effects with visual-spatial and auditory-verbal stimulus and response sets.

Within the visual-spatial and auditory-verbal modalities, reaction times to a stimulus have been shown to be faster if salient features of the stimulus and response sets correspond than if they do not. Accounts that attribute such stimulus-response compatibility effects to general translation processes predict that similar effects should occur for cross-modal stimulus and response sets. To test this prediction, three experiments were conducted examining four-choice reactions with (1) visual spatial-location stimuli assigned to speech responses, (2) speech stimuli assigned to keypress responses, and (3) symbolic visual stimuli assigned to speech responses. In all the experiments, responses were faster when correspondence between salient features of the stimulus and response sets was maintained, demonstrating that similar principles of translation operate both within and across modalities.

Home blood pressure monitoring: a survey of potential users.

Fifty respondents were surveyed using a recently developed questionnaire designed to evaluate the educational needs of the users of self-monitoring blood pressure apparatus. The categories evaluated included each subject's background and family health history, general knowledge about blood pressure, lifestyle factors affecting blood pressure, and factors affecting the measurement of blood pressure, as well as questions about owning a home monitor and recalibration and maintenance factors. The results indicate considerable disparity between the subjects' levels of knowledge about lifestyle factors affecting blood pressure and the subjects' knowledge of factors essential to accurate self-monitoring of blood pressure. The implications of and need for the design of educational training protocols are discussed.

Anthropometry of the elderly: status and recommendations.

Available anthropometric information on the elderly in the United States is discussed. Demographic data as well as information on performance capabilities and limitations (such as strength, endurance, and mobility) are needed for ergonomic design of tools, utensils, equipment, and vehicles to improve the working and living environment for the elderly. Recommendations are made for collection of more information.

Effect of sleep and sleep deprivation on ventilatory response to bronchoconstriction.

To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36-h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold.

Age differences in cardiovascular and cognitive performance under noise conditions.

Ambient white noise (80 dB), compared with quiet (52-dB) testing conditions, improved the performance of elderly and younger subjects on simple addition. Reliable age-related interactions were found on health measures of systolic and diastolic blood pressure, as well as heart rate. Heightened sensory conditions reduced the physiological measures of arousal in the younger group, whereas significant cardiovascular reactivity was found among the older group. The results are suggestive of the potential for increased cardiovascular risk as a function of sensory stimulation in the elderly despite improvements on cognitive tasks. Additional research is needed to evaluate the multidimensional effects of extended sensory stimulation on the elderly.

Extracranial and digital vascular events: an analysis of methods in BVP amplitude and biofeedback research.

The purpose of the present study was to assess and compare the effects of within and between-session exposure to environmental context on left temporal artery pulse amplitude, right temporal artery pulse amplitude, and left digital pulse amplitude. Subjects were individually tested for 20 min daily over a period of eight consecutive days. A significant interaction was found for Position X Interval. These results show that exposure to the experimental context occurs with diametrically opposite effects on temporalis and digital pulse amplitude within session. Moreover, these results would support the hypothesis that controversial findings within the headache and biofeedback literature may be partially attributable to methodological differences where, for example, different authors use different transducer locations and/or evaluate pulse amplitude at different points within or among sessions. Indeed, research on the effects or lack thereof of therapeutic manipulations may have little or nothing to do with the intervention or experimental manipulations themselves. These effects may be masked or augmented by subject and methodological confounds during baseline and testing conditions.

Effect of sleep on nocturnal bronchoconstriction and ventilatory patterns in asthmatics.

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.

Pupillometric assessment of arousal to sexual stimuli: novelty effects or preference?

The pupillary response of male and female subjects to various sexual stimuli was examined. Change in pupil size was compared using light and dark control slides and nude male and female, heterosexual, and homosexual stimulus slides. Attempts were made to control for the many confounds inherent in pupillometric research. Pupil size was measured using video-recording techniques that magnified pupils to an easily measured size. Greater pupil change was found when the stimulus slide was preceded by a relatively lighter control slide. In addition, pupil change was related to familiarity with the stimulus slide and the relative pupil response changed as subjects gained experience with the stimulus material. Explanations and implications for further research are discussed.

Human factors and design evaluation of digital blood pressure/pulse meters.

This study provides a comparison of self-measurement blood pressure devices, with respect to the standards published by the American National Standards Institute/Association for the Advancement of Medical Instrumentation and statements from the American Heart Association and the National High Blood Pressure Education Program. The results show a wide disparity among the recommendations of select committees, on issues of education and compliance and on design features of this instrumentation. Procedural problems in determining compliance in this study highlight the need for improved objectivity in statements in national standards and for improved awareness of those statements by manufacturers.

Estimates of ventilation from inductance plethysmography in sleeping asthmatic patients.

To assess the accuracy of the respiratory inductance plethysmograph (RIP) for monitoring ventilation during sleep-associated bronchoconstriction, five adult patients with nocturnal worsening of their asthma were monitored overnight in the sleep laboratory. Three of the five patients demonstrated episodic paradoxic respiratory motion of the lower rib cage undetected by the RIP. Such paradoxic motion was consistently associated with overestimation of volumetric data by RIP compared to pneumotachygraphic measurements. With onset of lower rib cage paradox, the mean error of RIP-derived VT measurements increased from 9.1 +/- 1.7 to 27.9 +/- 3.8 percent (p less than .001). Flow measurements derived from RIP were also inaccurate in the presence of lower rib cage paradox, with the mean error of the measurement increasing from 9.0 +/- 2.5 to 33.5 +/- 5.3 percent (p less than .001). We conclude that RIP is an unreliable technique for quantitatively monitoring ventilation in sleeping asthmatic patients.

Home health-care: accuracy, calibration, exhaust, and failure rate comparisons of digital blood pressure monitors.

This study provides a detailed comparison of 22 digital, blood pressure monitors intended for home use. Blood pressure and pulse-rate readings from each electronic monitor were compared with concurrent measures obtained using the mercury column and auscultation. Correlation coefficients and linear regressions were performed to evaluate accuracy. Separate analyses of variance were used to determine significant calibration errors for each model. The results showed considerable disparity among available home monitors under controlled testing conditions. Variables associated with accuracy and home use by the layperson are discussed.