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Biomedical subjects

M C Carter

Publications and source records attributed to M C Carter.

At least 19 recordsLinked to original sources

Transforming growth factor beta 1 (TGF beta 1) reduces cellular levels of p34cdc2, and this effect is abrogated by adenovirus independently of the E1A-associated pRB binding activity.

We have used E1A probes to study the roles of the p34cdc2 kinase and the retinoblastoma tumor susceptibility gene product (pRB) in transforming growth factor beta 1 (TGF beta 1)-mediated growth suppression in mink lung epithelial (Mv1Lu) cells. In agreement with previous reports, we see a decline in p34cdc2 kinase activity and a loss of pRB phosphorylation after TGF beta 1 treatment. We report here that TGF beta 1 induces not only a change in p34cdc2 kinase activity but a strong repression of p34cdc2 synthesis. Loss of p34cdc2 kinase activity is not seen until the steady-state level of p34cdc2 declines, suggesting that the intra-cellular signals induced by TGF beta 1 affect p34cdc2 at the level of expression, rather than by altering the posttranslational modifications of p34cdc2 that regulate its kinase activity. Infection with adenovirus expressing either wild-type E1A or a mutant E1A (pm928) defective for pRB binding alleviated TGF beta 1-mediated suppression of DNA synthesis, indicating that E1A does not need to bind pRB physically to keep cell growth-suppressing functions from being activated by TGF beta 1. The E1A.928 mutant virus is able to maintain p34cdc2 expression and kinase activity, as well as pRB phosphorylation in the presence of TGF beta 1, which may account for its ability to maintain cell cycle activity without directly sequestering pRB. Overall our results suggest that TGF beta 1 acts by signaling changes at the level of control of G1 gene expression, not at the level of posttranslational modification of p34cdc2 or its substrates.

Adenoviridae

The survivors of childhood solid tumors.

With the improvement in cancer therapy in recent years, the number of cancer survivors is rapidly increasing. Potential late medical and psychosocial sequelae of cancer therapy are reviewed. A practical guide for the primary health care giver is provided.

Central Nervous System

Simian virus 40 large-T antigen expresses a biological activity complementary to the p300-associated transforming function of the adenovirus E1A gene products.

In this report we present evidence that simian virus 40 T antigen encodes a biological activity that is functionally equivalent to the transforming activity lost by deletion of the E1A p300-binding region. T-antigen constructs from which the pRb-binding region has been deleted are virtually unable to induce foci of transformed cells in a ras cooperation assay in primary baby rat kidney cells. Nevertheless, such a construct can cooperate with an E1A N-terminal deletion mutant, itself devoid of transforming activity, to induce foci in this assay. The heterologous trans-cooperating activity observed between E1A and T-antigen deletion products is as efficient as trans cooperation between mutants expressing individual E1A domains. The cooperating function can be impaired by a deletion near the N terminus of T antigen. Such a deletion impairs neither the p53-binding function nor the activity of the pRb-binding region.

Adenovirus Early Proteins

Assessment of cardiotocographs.

In recent years advances in medical electronic equipment for monitoring, diagnosis and treatment of patients have led to a large increase in the number and variety of instrumentation available to the medical profession. There is a considerable amount of duplication of equipment and in the absence of readily available information buyers are unlikely to make informed decisions about the ideal instrument for their particular circumstances. One method of increasing the users' awareness is a comparative, independent assessment of equipment, with the results disseminated to the interested parties. This paper describes the essential qualities of cardiotocographs: how they are assessed as part of the UK Department of Health's evaluation programme and the measures to inform users of the latest evaluation information.

Cardiotocography

Effects of hyperoxia in the presence of acute lung injury.

We employed a multiple-dose, oleic acid (OA) model to evaluate the susceptibility to oxygen toxicity of rabbits with acute lung injury (ALI). The rabbits were partitioned into four groups: ALI group (n = 8) received OA (0.04 ml/kg iv) and again at two consecutive 24-h intervals and breathed room air (RA); hyperoxic O2/ALI group (n = 8) underwent similar OA injection protocol and breathed an FIO2 greater than or equal to 0.96; oxygen group (n = 8) received identical injection protocol with normal saline (NS) and breathed an FIO2 greater than or equal to 0.96; and control (CTR) group (n = 5) received isovolume NS injections and breathed RA. Arterial blood pH and gas tensions were measured before and 24, 48, and 60 h after ALI. Surviving animals were killed at 72 h and body weight (BW) was determined at autopsy; then the lungs were removed and weighed (LW). The mortality for animals exposed to hyperoxia was significantly (p less than or equal to .02) greater than those breathing RA, regardless of the presence or absence of ALI. Blood pH was lower (p less than or equal to .05) in all animals but the CTR group. However, acidemia was significantly greater in both hyperoxic groups compared to animals in the CTR and ALI/RA. Inflation and deflation lung-thorax compliances were lower (p less than or equal to .05) and percent lung weight of terminal body weight (LW/BW) was higher (p less than or equal to .05) after hyperoxia with or without ALI compared to CTR animals regardless of FIO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The Parental Stressor Scale: Pediatric Intensive Care Unit.

This article details the development of an instrument designed to assess the impact of certain environmental stressors in the pediatric intensive care unit (ICU) on parents of hospitalized children. A theoretical framework based on stress theory and developed by the authors provided the framework for this project. This 62-item scale assessing seven dimensions of the PICU environment was developed in three stages. The first phase in the development of the instrument established the sampling domain of the items, supported content validity, conceptualized the dimensions, developed the scaling, and helped support stability over time. In the second phase of the project, the instrument was administered to 165 parents of children recently discharged from four midwestern ICUs to further evaluate reliability and validity. Results of factor analysis, internal consistency reliability, and construct validity analyses were used to revise the instrument. In the third phase of the project, the revised instrument was administered to 510 parents while their children were in one of five pediatric ICUs. Factor analysis provided seven orthogonal, invariant factors. An alpha coefficient of .95 was obtained for the total instrument; subscale coefficients ranged from .72 to .99 providing support for internal consistency and construct validity.

Child, Preschool

The pediatric intensive care unit environment as a source of stress for parents.

Parents of children hospitalized in one of five midwestern pediatric intensive care units (ICU) were interviewed about the stress experienced from aspects of the ICU environment. Subjects were 324 mothers and 186 fathers of 350 children. Data were collected using the Parental Stressor Scale: Pediatric ICU which assesses seven dimensions of the environment: Child's Behavior and Emotions, Child's Appearance, Sights and Sounds, Procedures, Staff Communication, Anomie, and Parental Role Alteration. The dimensions Child's Behavior and Emotions and Parental Role Alteration were found to be the most stressful aspects of the experience. The items from the dimension Child's Behavior and Emotions that were most stressful were seeing my child in pain, seeing the child frightened and sad, and the inability of the child to communicate with the parent. The items from the Parental Role Alteration dimension with the highest stress scores were: feeling unable to protect my child and not knowing how to best help my child. Findings suggest that alterations in the parent-child relationship are more stressful than aspects of the physical environment. In particular, feeling helpless in the parenting role is a great source of stress for parents.

Adaptation, Psychological

Testing a theoretical model: correlates of parental stress responses in the pediatric intensive care unit.

This study was designed to evaluate a theoretical framework, based on stress theory, which identifies potential sources of stress in parents of children hospitalized in an intensive care unit (ICU). The framework suggests that personal, situational, and ICU environmental stress stimuli interactively impact on the overall parental stress response. Multiple regression techniques were used to evaluate the interaction of personal family factors, situational stimuli, and ICU environmental stressors and to assess their impact upon the overall parental stress response. Data were collected from 510 parents of children hospitalized in one of five midwestern ICUs. Instruments used were the Parental Stressor Scale: Pediatric ICU (Carter & Miles, 1984), the State-Trait Anxiety Scale (Spielberger, Gorsuch, & Luschene, 1970), the Review of Life Experiences Scale (Hurst, Jenkins, & Rose, 1978), and a personal-experiential questionnaire. Results indicate that a number of personal and situational variables were predictive of higher stress. In addition two aspects of the ICU environment contributed the most variance to the overall stress of parents: alterations in the parental role and the child's behavioral and emotional responses. In evaluating the full framework, one personal variable (Trait Anxiety); two situational variables (perception of severity and type of admission); and three ICU environmental dimensions, (parental role alteration, the child's behavior and emotional response, and the child's appearance) significantly predicted stress (State Anxiety). The findings support the theoretical framework underlying this study as a useful model for studying and evaluating parental stress during a child's admission to an ICU. Results also suggest that additional personal family and situational factors, such as uncertainty, may need to be added to the model to more fully predict parental stress responses.

Adolescent

Analysis of electromyographic signals in human jaw closing muscles at various isometric force levels.

The effect of sustained isometric contraction on surface electromyograph (EMG) and force signals derived from these muscles was examined. Premolar-molar region force was measured with a small unilaterally positioned force transducer. Subjects produced and sustained 25, 50, 75 and 100 per cent isometric force levels, and measurements were made at the beginning and end of these efforts. There was no significant change in the resulting EMG/force ratio at any of the force levels. The EMG signal did exhibit a significant shift in its frequency both as the force level increased and during the sustained effort. Neuromuscular fatigue, when defined as a change in the EMG/force ratio, was not demonstrated even though there was a consistent change in the frequency of the EMG signal.

Adult

Fetal monitoring.

This paper introduces fetal monitoring by describing the medical problems of the fetus in utero. The various methods currently used to monitor the fetus are reviewed with their respective advantages and shortcomings. New methods of surveillance of the fetus are highlighted as well as the mother's reaction to the technology.

Acid-Base Equilibrium

Simultaneous control of two rhythmical behaviors. I. Locomotion with paw-shake response in normal cat.

We investigated the ability of normal cats, trained to maintain a constant position while walking on a treadmill, to combine the paw-shake response with quadrupedal locomotion. Hindlimb paw-shake responses were elicited during walking after the right hindpaw was wrapped with tape. To assess intralimb and interlimb coordination of the combined behaviors, electromyographic (EMG) recordings from forelimb extensor muscles and from selected flexor and extensor muscles at the three major hindlimb joints were correlated with joint motion by using high-speed, cinefilm analysis. When paw shaking was combined with walking, the response occurred during the swing phase of the taped hindlimb. To accommodate the paw-shake response, swing duration of the shaking hindlimb and of the homolateral forelimb increased and was followed by a brief recovery step. Concurrently, to compensate for the response, stance durations of the contralateral forelimb and hindlimb increased. The magnitude of these adjustments in interlimb coordination was influenced by the number of paw-shake cycles, which ranged from one to four oscillations. Transitions between the muscle synergies for the paw-shake response and swing were smooth in the shaking limb. Early in the swing phase, when the flexor muscles were still active (F phase), the paw shake was initiated by an early onset of knee extensor activity, which preceded extensor activity at the hip and ankle. This action provided a transition from the general reciprocal synergy between flexor and extensor muscles of locomotion to the mixed synergy that is typical of the paw shake (30). Following the last paw-shake cycle, an extensor synergy initiated the E-1 phase of swing, and the resultant joint motion was in-phase extension of the hip, knee, and ankle to lower the paw for stance. Average cycle period and burst duration for muscles participating in the paw-shake response were similar to those reported for normal cats assuming a standing posture (28, 30). The average number of paw-shake cycles, however, decreased from eight to three when the response occurred during walking, suggesting that the response was truncated to provide for continued locomotion. Further, hip motion was variable when the paw shake was combined with swing, and sometimes the hip failed to oscillate and its trajectory was similar to that of an unperturbed swing phase. When hip joint oscillations occurred during the paw-shake response, they were in-phase with ankle motions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Simultaneous control of two rhythmical behaviors. II. Hindlimb walking with paw-shake response in spinal cat.

The simultaneous control of the hindlimb paw-shake response and hindlimb walking at slow treadmill speeds (0.2-0.4 m/s) was examined in adult cats spinalized at the T12 level, 3-6 mo earlier. Paw shaking was elicited by either 1) application of adhesive tape or 2) water to the right hindpaw. To assess intralimb and interlimb coordination of the combined behaviors, activity from selected flexor and extensor muscles at the hip, knee, and ankle was recorded, and the kinematics of these joints were determined from high-speed cinefilm. When paw shaking was combined with hindlimb walking, the response in the stimulated limb was initiated during swing (F phase) of the step cycle. The onset of knee extensor activity provided the transition from the flexor synergy of swing to the mixed synergy of paw shake. At the end of the paw shake, an extensor synergy initiated the E-1 phase of swing, and the resultant joint motion was in-phase extension at the hip, knee, and ankle to lower the paw for contact with the treadmill belt. During the rapid (81 ms) paw-shake cycles, knee extensor and ankle flexor muscles exhibited single, coactive bursts that were reciprocal with coactive hip and ankle extensor bursts. This mixed synergy was reflected in the limb coordination, as knee flexion coincided with ankle extension and knee flexion coincided with ankle extension. Phasing of hip motions was variable, reflecting the role of the proximal in stabilization during paw shake (16). Although the number of paw-shake cycles combined during swing varied greatly from 2 to 14, average cycle periods, burst durations, and intralimb synergies were similar to those previously reported for spinal cats tested under conditions in which the trunk was suspended and hindlimbs were pendent (23, 27). For step cycles during which a long paw-shake response of 8-14 cycles occurred, swing duration of the shaking limb increased by 1 s, and during this prolonged interval, the contralateral hindlimb completed two support steps. Stance duration of the support steps was also prolonged. This adjustment maximized the duration of paw-contact and minimized any period of nonsupport by the contralateral hindlimb during paw shake. Completion of the paw-shake response was followed by either an alternating, or a nonalternating, gait pattern on the recovery steps. One spinal cat combined locomotion with short two-cycle paw-shake responses, and because the shortened response was limited primarily to the time ordinarily devoted to swing, interlimb adjustments were slight.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Advances in electronic fetal monitors--real or imaginary.

Changes in the technologies used in the latest generation of electronic fetal monitors has resulted generally in an improvement in the quality of the FHR data produced. However, in a number of instruments the use of inappropriate printers and signal processing has led to a degradation in the FHR trace. This may result in difficulties in interpretation of the data thereby putting the compromised fetus at risk. This paper discusses the factors which affect the interpretation of the data, such as signal detection and rejection of noise, errors due to the signal processing and rate determination, and the effect of the chart recorder on the presentation of the data. Finally information is given about the UK Departments of Health evaluation programme for electronic fetal monitors (cardiotocographs).

Electrocardiography

Instability of succinyl ester linkages in O2'-monosuccinyl cyclic AMP-protein conjugates at neutral pH.

Chromatographic and immunological evidence is presented regarding the hydrolysis of the ester linkage of O2'-monosuccinyl cyclic AMP in neutral solutions. Such hydrolysis occurs whether the nucleotide derivative is present in free form in solution or conjugated through its succinyl carboxyl group via an amide bond to proteins. The latter process apparently occurs when succinyl cyclic AMP is conjugated to human serum albumin for use as an immunogen in the production of anti-cyclic AMP antibodies and when the derivative is coupled to the enzyme glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49). The enzyme conjugate has been used in developing a homogeneous enzyme immunoassay for cyclic AMP. Inhibition of the catalytic activity of enzyme-cyclic AMP conjugates by anti-cyclic AMP antibody decreases with time, apparently due to the loss of cyclic AMP from enzyme-cyclic AMP conjugates stored in neutral solutions. In addition, the ability of free cyclic AMP to completely reverse the inhibition process decreases with time because of the presence of antibodies in the anti-cyclic AMP sera that apparently inhibit enzyme activity because of their binding specificity for the residual succinate-protein determinant sites of the enzyme conjugates. Lyophilization of the conjugates immediately after preparation helps to overcome the problem; however, in vivo hydrolysis of immunogens prepared with the succinyl cyclic AMP derivative may always occur. The consequence of this hydrolysis reaction and the subsequent formation of anti-succinyl-protein antibodies will be discussed with regard to existing RIAs for cyclic AMP and a new homogeneous enzyme immunoassay for the nucleotide.

Antibody Specificity

Electromyographic study of human jaw-closing muscle endurance, fatigue and recovery at various isometric force levels.

The effect of a sustained isometric clenching, at various force levels or maximum voluntary bite-force levels, was evaluated on normal jaw-function subjects. Surface electromyographic (EMG) recordings of the masseter and temporalis were taken and bite force was measured using an intra-oral force transducer placed unilaterally in the 2nd premolar-1st molar region. Subjects sustained isometric force at the 25, 50, 75 and 100 per cent force level. Maximal bite force and EMG contraction levels were measured before, during and after these sustained isometric tasks. Subjects showed no change in their brief maximal contraction or force levels during or after various fatigue-inducing isometric tasks. The findings suggested a lack of contractile failure in the jaw-closing muscles. Pain intolerance rather than neuromuscular fatigue is the limiting factor of a sustained submaximal or even maximal clenching effort.

Adult