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Biomedical subjects

C Johnston

Publications and source records attributed to C Johnston.

At least 55 records · Page 3Linked to original sources

Multiple endocrine neoplasia type 1Burin from Mauritius: a novel MEN1 mutation.

We describe a kindred from Mauritius with an incomplete variant of multiple endocrine neoplasia type 1 (MEN 1Burin). In this family the syndrome is related to a novel MEN 1 gene mutation (deletion of A) at nucleotide 1021 of codon 304 resulting in frame shift and downstream protein truncation at codon 320. Compared to mainstream MEN 1, MEN 1Burin is characterized by a high prevalence of prolactin-secreting pituitary adenomas, late-onset of hyperparathyroidism and rare pancreatic involvement. The family described represents the fifth in the literature with the MEN 1 Burin phenotype; 2 out of the other 4 were related to R460X, Y312X respectively and no mutation within the coding sequence of MEN 1 was found in the other 2. Thus, similar to the classic syndrome, MEN 1Burin phenotype shows poor correlation to MEN 1 genotype.

Adenoma↗

Families of children with attention-deficit/hyperactivity disorder: review and recommendations for future research.

This review integrates and critically evaluates what is known about family characteristics associated with childhood Attention-Deficit/Hyperactivity Disorder (ADHD). Evidence suggests that the presence of ADHD in children is associated to varying degrees with disturbances in family and marital functioning, disrupted parent-child relationships, specific patterns of parental cognitions about child behavior and reduced parenting self-efficacy, and increased levels of parenting stress and parental psychopathology, particularly when ADHD is comorbid with conduct problems. However, the review reveals that little is known about the developmental mechanisms that underlie these associations, or the pathways through which child and family characteristics transact to exert their influences over time. In addition, the influence of factors such as gender, culture, and ADHD subtype on the association between ADHD and family factors remains largely unknown. We conclude with recommendations regarding the necessity for research that will inform a developmental psychopathology perspective of ADHD.

Attention Deficit Disorder with Hyperactivity↗

Effects of medication, behavioral, and combined treatments on parents' and children's attributions for the behavior of children with attention-deficit hyperactivity disorder.

Seventy-four mothers and 41 fathers and their 6 to 13 year old sons with attention-deficit hyperactivity disorder (ADHD) watched videos of child ADHD symptoms, compliance, and noncompliance. Participants were told either that the child was receiving medication, behavioral treatment, a combination of the two, or was not receiving treatment and were asked to rate the cause of the behavior. Parents attributed less control but greater stability to positive child behaviors when the child was receiving medication. However, for negative behaviors, medication increased attributions of control but diminished stability. With behavior management. compliance was seen as more external and stable and noncompliance as more controllable but less stable. For all treatments, boys reported increased control over ADHD symptoms and noncompliance. The implications of these treatment-related attributions for parenting and children's self-perceptions are discussed.

Adolescent↗

Professional perceptions of the benefits of orthodontic treatment.

The aim of this study was to assess general dental practitioners' and orthodontists' perceptions of the benefits of orthodontic treatment. A specially designed questionnaire was sent to a random sample of 150 general dental practitioners (GDPs) and all orthodontists in Northern Ireland (excluding hospital practitioners) with a postgraduate qualification (n = 29). There was a 93 per cent response rate by the general dental practitioners and all but one specialist practitioner returned the questionnaire. The questionnaire comprised 14 visual analogue scales (VAS) whereby participants were asked to rate the importance of various possible dental health and psychosocial benefits of orthodontic treatment. In addition to the VAS, the influence of dentist variables such as number of years since qualification, orthodontic cases completed, referral rates and attendance at postgraduate lectures were examined. When ratings on the 14 dental health and psychosocial scales were examined overall, GDPs rated an improvement in self-esteem while orthodontists considered an improvement in physical attractiveness as the most important benefit of orthodontic treatment. Even though psychosocial variables received the highest ratings, examination of the mean ratings (and 95 per cent confidence intervals) revealed that some dental health factors were also rated highly by both groups. While the results do indicate an encouraging awareness of the psychosocial benefits of orthodontic treatment, they also suggest that both GDPs and orthodontists have an unrealistic expectation of the dental health gain likely to result from orthodontic treatment.

Dentists↗

Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence.

The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xist gene structure both between different vole species and relative to mouse and human Xist/XIST. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution.

3' Untranslated Regions↗

Forelimb tendon loading during jump landings and the influence of fence height.

Lameness in athletic horses is often caused by forelimb tendon injuries, especially in the interosseus tendon (TI) and superficial digital flexor tendon (SDF), but also in the accessory ligament (AL) of the deep digital flexor tendon (DDF). In an attempt to explain the aetiology of these injuries, the present study investigated the loading of the tendons during landing after a jump. In jumping horses, the highest forces can be expected in the trailing limb during landing. Therefore, landing kinematics and ground reaction forces of the trailing forelimb were measured from 6 horses jumping single fences with low to medium heights of 0.80, 1.00 and 1.20 m. The tendon forces were calculated using inverse dynamics and an in vitro model of the lower forelimb. Calculated peak forces in the TI, SDF and DDF + AL during landing were 15.8, 13.9 and 11.7 kN respectively. The relative loading of the tendons (landing forces compared with failure forces determined in a separate study) increased from DDF to TI to SDF and was very high in SDF. This explains the low injury incidence of the DDF and the high injury incidence of the SDF. Fence height substantially influenced SDF forces, whereas it hardly influenced TI forces and did not influence AL strain. Reduction of fence height might therefore limit the risks for SDF injuries, but not for TI and AL injuries.

Animals↗

In vivo transmission of impact shock waves in the distal forelimb of the horse.

There is a high prevalence of lameness among Standardbred trotters, most commonly caused by noninfectious joint diseases, mainly related to training and competition. In this context, impact-related shock waves transmitted through the skeleton and joints have been proposed to be one important factor in the development of osteoarthritis. The aim of the present study was to investigate the characteristic pattern of the events immediately following first contact, with a focus on the in vivo transmission of impact shock waves in the distal forelimb. Two horses were trotted by hand over a force plate. Recordings of 3-D kinematics of the distal forelimb were carried out by use of a 240 Hz video system. Tri-axial accelerometer data were collected from a bone-mounted accelerometer on the midlateral side of the third metacarpal bone (McIII) and from another accelerometer attached to the lateral side of the hoof. Force plate and accelerometer data were sampled at 4.8 kHz using a 16-bit A/D-converter, synchronised with the kinematic data. The results indicate that the time lapse of the horizontal retardation of the hoof is an important factor in the attenuation of the impact. A shorter period of hoof braking showed higher amplitudes in the longitudinal retardation of McIII and a more rapid oscillation. This makes all parameters that affect the horizontal hoof braking potentially important to the orthopaedic health of the horse.

Animals↗

In vivo and in vitro heel expansion in relation to shoeing and frog pressure.

The objective of this study was to validate a simple method to measure the mediolateral expansion of the heels and to apply this method in an in vivo experiment. It was also the aim to quantify the mediolateral expansion in different areas of the heel using an in vitro model. In the in vitro study, 5 right and 5 left distal forelimb specimens from 5 Standardbreds were mounted vertically in a custom-made compressive test machine. The heel expansion was measured using optical kinematic analysis and a potentiometer system. Specimens were tested unshod, with frog pressure and with the weightbearing rim raised. In the in vivo study, a potentiometer system was fitted to the left forelimb of 5 Standardbred trotters. Measurements were performed with the horses at hand, in walk and in trot. They were tested unshod, shod with a standard 8 mm iron shoe and finally with a shoe combined with an inflatable hoof-cushion. The results showed a good correlation between the 2 measurement systems (r = 0.98). This study describes the effect of different frog pressures on heel movement. Increased pressure on the frog and the sole increased heel expansion, but some heel expansion still occurred when the frog and sole were unsupported. The study supports, therefore, both the depression and the pressure theory. The significance of these results is the manipulation of heel movement as affected by farrier techniques and its possible relationship to health of the hoof. Further studies are needed to apply this knowledge correctly to farrier practice.

Animals↗

Three-dimensional kinematics of the equine spine during canter.

Most research on equine kinematics has previously been performed in the walking and/or trotting animal. This is also true for the few studies on the kinematics of the equine back. These studies have, for the major part, focused on the flexion-extension movement in the sagittal plane. However, vertebrae can rotate in 3 dimensions. This study was designed to determine all 3 rotations in various segments of the vertebral column of a cantering horse. Five Dutch Warmblood horses were measured during treadmill canter (7.3 m/s). Steinmann pins were inserted into the dorsal spinous processes of 8 thoracic (T), lumbar (L) and sacral (S) vertebrae and into both tubera coxae. A set of 4 markers was rigidly attached to each pin. The marker data were used to calculate a rotation matrix that was subsequently decomposed into 3 orthogonal rotations (flexion/extension [FE]; lateral bending [LB] and axial rotation [AR]). For the 3 rotations the variability between the horses was low for FE, slightly larger for AR and largest for LB. The maximal range of motion (mean +/- s.d.) for FE, LB and AR was 15.8 +/- 1.3 degrees, 5.2 +/- 0.7 degrees and 7.8 +/- 1.2 degrees, respectively. With respect to relative angles, the largest FE motion was found between L5 and S3 with values for the range of motion up to 8.6 degrees. Simultaneous rotation of successive vertebrae was observed particularly during the single support and suspension phases in the stride cycle, which increases spinal stability. For all rotations, a close correlation was observed between the timing of the vertebral rotations and the pro- and retraction of the limbs.

Animals↗

Identification of genes involved in the host response to neurovirulent alphavirus infection.

Single-amino-acid mutations in Sindbis virus proteins can convert clinically silent encephalitis into uniformly lethal disease. However, little is known about the host gene response during avirulent and virulent central nervous system (CNS) infections. To identify candidate host genes that modulate alphavirus neurovirulence, we utilized GeneChip Expression analysis to compare CNS gene expression in mice infected with two strains of Sindbis virus that differ by one amino acid in the E2 envelope glycoprotein. Infection with Sindbis virus, dsTE12H (E2-55 HIS), resulted in 100% mortality in 10-day-old mice, whereas no disease was observed in mice infected with dsTE12Q (E2-55 GLN). dsTE12H, compared with dsTE12Q, replicated to higher titers in mouse brain and induced more CNS apoptosis. Infection with the neurovirulent dsTE12H strain was associated with both a greater number of host genes with increased expression and greater changes in levels of host gene expression than was infection with the nonvirulent dsTE12Q strain. In particular, dsTE12H infection resulted in greater increases in the levels of mRNAs encoding chemokines, proteins involved in antigen presentation and protein degradation, complement proteins, interferon-regulated proteins, and mitochondrial proteins. At least some of these increases may be beneficial for the host, as evidenced by the demonstration that enforced expression of the antiapoptotic mitochondrial protein peripheral benzodiazepine receptor (PBR) protects neonatal mice against lethal Sindbis virus infection. Thus, our findings identify specific host genes that may play a role in the host protective or pathologic response to neurovirulent Sindbis virus infection.

Alphavirus Infections↗

Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies.

BACKGROUND: In epidemiological studies, within-person variability in plasma total homocysteine (tHcy) measurements may dilute the association of 'usual' levels of tHcy with risk of cardiovascular disease, referred to as 'regression dilution'. The aim of this report was to estimate the magnitude of regression dilution after varying intervals of follow-up. METHODS: Regression dilution ratios (RDR) for tHcy were calculated using replicate tHcy measurements obtained after 3, 6 and 8 years from the Rotterdam, Hordaland and Framingham studies, respectively, and after 3, 6, 9 and 12 years from the United Kingdom Prospective Study of type 2 Diabetes Mellitus (UKPDS). RESULTS: The RDR for tHcy decreased with increasing interval in the three population-based studies and in the UKPDS. Moreover, the rate of decline of the RDR in the population-based studies was similar to that obtained in the UKPDS. Using linear regression analysis for the population-based studies, these results suggest an RDR of 0.83 at 2 years, 0.71 at 6 years and 0.53 at 12 years. CONCLUSIONS: These results have important implications for the interpretation of prospective studies of tHcy and cardiovascular disease. Failure to correct for increasing regression dilution using lower RDRs for longer follow-up may underestimate the relative risks of cardiovascular disease associated with tHcy by about one-fifth after 2 years and one-half after 10 years.

Aged↗

Commercialism in classrooms.

Opinions expressed in commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees. Commentaries are not peer-reviewed.

Advertising↗

Basic three-dimensional kinematics of the vertebral column of horses trotting on a treadmill.

OBJECTIVE: To determine movements of the vertebral column of horses during normal locomotion. ANIMALS: 5 young Dutch Warmblood horses that did not have signs of back problems or lameness. PROCEDURE: Kinematics of 8 vertebrae (T6, T10, T13, T17, L1, L3, L5, and S3) and both tuber coxae were determined, using bone-fixated markers. Measurements were recorded when the horses were trotting on a treadmill at a constant speed of 4.0 m/s. RESULTS: Flexion-extension and axial rotation were characterized by a double sinusoidal pattern of motion during 1 stride cycle, whereas lateral bending was characterized by 1 peak and 1 trough. Ranges of motion for all vertebrae were: flexion-extension, 2.8 degrees to 4.9 degrees; lateral bending, 1.9 degrees to 3.6 degrees; axial rotation, 4.6 to 5.8 degrees, except for T10 and T13, where the amount of axial rotation decreased to 3.1 degrees and 3.3 degrees, respectively. CONCLUSION AND CLINICAL RELEVANCE: During locomotion, 3 types of rotations are evident in the thoracolumbar vertebrae. Regional differences are observed in the shape and timing of the rotations. These differences are related to actions of the limbs. The method described here for direct measurement of vertebral column motion provides insights into the complex movements of the thoracolumbar portion of the vertebral column in trotting horses. Information on normal kinematics is a prerequisite for a better understanding of abnormal function of the vertebral column in horses.

Animals↗

Joint moments in the distal forelimbs of jumping horses during landing.

Tendon injuries are an important problem in athletic horses and are probably caused by excessive loading of the tendons during demanding activities. As a first step towards understanding these injuries, the tendon loading was quantified during jump landings. Kinematics and ground reaction forces were collected from the leading and trailing forelimbs of 6 experienced jumping horses. Joint moments were calculated using inverse dynamic analysis. It was found that the variation of movement and loading patterns was small, both within and between horses. The peak flexor joint moments in the coffin and fetlock joints were larger in the trailing limb (-0.62 and -2.44 Nm/kg bwt, respectively) than in the leading limb (-0.44 and -1.93 Nm/kg bwt, respectively) and exceeded literature values for trot by 82 and 45%. Additionally, there was an extensor coffin joint moment in the first half of the stance phase of the leading limb (peak value 0.26+/-0.18 Nm/kg bwt). From these results, it was concluded that the loading of the flexor tendons during landing was higher in the trailing than in the leading limb and that there was an unexpected loading of the extensor tendon in the leading limb.

Animals↗

Renormalized expression for the turbulent energy dissipation rate.

Conditional elimination of degrees of freedom is shown to lead to an exact expression for the rate of turbulent energy dissipation in terms of a renormalized viscosity and a correction. The correction is neglected on the basis of a previous hypothesis [W. D. McComb and C. Johnston, J. Phys. A 33, L15 (2000)] that there is a range of parameters for which a quasistochastic estimate is a good approximation to the exact conditional average. This hypothesis was tested by a perturbative calculation to second order in the local Reynolds number, and the Kolmogorov prefactor (taken as a measure of the renormalized dissipation rate) was found to reach a fixed point which was insensitive to initial values of the kinematic viscosity and to values of the spatial rescaling factor h in the range 0.4< or =h< or =0.8.

Journal Article↗

Structure and promoter activity of the mouse CDC25A gene.

CDC25A is a member of a group of highly related, dual-specificity phosphatases that promote cell cycle phase transitions by regulating the activity of cyclin-dependent kinases. Here we report the cloning and genomic sequence of 21,067 nucleotides encompassing the mouse CDC25A gene. The coding sequence is expressed from 17,904 bp of genomic DNA comprising 15 exons. We also mapped the transcription initiation site to a consensus initiator element proximal to an SP1 site. Approximately 1 kb of sequence upstream of the transcription initiation site confers promoter activity and cell type specificity to a reporter gene construct. Surprisingly, transcription from this promoter was repressed by over-expression of catalytically active but not catalytically inactive CDC25A protein. We also show, using NIH 3T3 cells, that murine CDC25A mRNA levels fluctuate only modestly over the cell cycle. Our findings provide insights into the regulation of CDC25A expression and have facilitated construction of gene knock-out vectors.

3T3 Cells↗