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Biomedical subjects

R L Carter

Publications and source records attributed to R L Carter.

At least 19 recordsLinked to original sources
PubMed1992

Triiodothyronine (T3) decreases binding to DNA by T3-receptor homodimers but not receptor-auxiliary protein heterodimers.

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone response elements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. TR binding to TREs can be enhanced by interaction with a nuclear protein, triiodothyronine (T3) receptor auxiliary protein (TRAP). There are two major isoforms of thyroid hormone receptors, TR alpha-1 and TR beta-1, which are encoded on two separate genes. We studied the binding of TR alpha-1 and TR beta-1 to several TREs: the chick lysozyme TRE (F2), which is positively regulated by T3; rabbit beta-myosin heavy chain TRE, which is negatively regulated by T3; and an idealized inverted palindrome, TRElap. We demonstrate the formation of homodimers, TR alpha/TR beta dimers, and TR/TRAP heterodimers when receptor is bound to these DNA sequences. Surprisingly, we found that T3 decreased TR alpha-1 and TR beta-1 homodimer binding in a dose-dependent manner to these TREs as well as TR alpha/TR beta dimer binding to F2. In contrast, T3 did not affect TR/TRAP heterodimer binding to TREs suggesting that this heterodimer may be the stable complex occupying TREs in the presence of ligand.

Animals↗
PubMed1992

A random coefficient growth curve analysis of mental development in low-birth-weight infants.

In many medical studies, longitudinal data are collected on each of a sample of patients. The objectives of such studies often are: to estimate and test bivariate or multivariate relationships within each of several groups of patients from these repeated measures data; to compare these relationships among groups; and to test for the effects of baseline covariates on the relationships. This paper illustrates the use of statistical methods for growth curve analysis recently proposed by Vonesh and Carter for achieving these goals by relating a measure of preschool cognitive development to age in four race by sex groups of low-birth-weight infants. Significant declines in Bayley's Mental Development Index (MDI) with increasing age were found in all groups. Birth-weight did not significantly influence the rate of decline but did influence the overall level of performance. Even so, in the group most comparable to Bayley's normative population, predicted MDI was near the norm even for extremely low-birth-weight infants (that is, 1000 grams). Although there is some risk of mental deficit associated with prematurity, eventual developmental delays in low-birth-weight infants frequently are acquired with age. The rate of decline in MDI was significantly associated with race and mother's education. Assumptions required for the valid application of these methods are discussed and tested in the setting of this applied problem. The assumptions appeared valid in this application. We conclude with a brief discussion of available alternatives when the assumptions are violated and point to areas for future research.

Age Factors↗
PubMed1992

Peripheral nerve sheath differentiation in malignant soft tissue tumours: an ultrastructural and immunohistochemical study.

Thirteen soft tissue sarcomas with ultrastructural evidence of nerve sheath differentiation were investigated by immunohistochemistry. Three arose in a major nerve or nerve trunk and four patients had von Recklinghausen's neurofibromatosis. Ultrastructurally, 10 cases showed variable differentiation towards Schwann cells, two resembled perineurial cells and one tumour had features suggestive of both cell types. Immunostaining for S-100 protein was positive in eight Schwann cell tumours, negative in the other two Schwann cell tumours and negative in those with perineurial-like cells. No cases demonstrated epithelial membrane antigen, so that the existence of perineurial cells in malignant nerve sheath tumours remains immunohistochemically unsubstantiated; it may be that the perineurial-like cells are merely incompletely differentiated Schwann cells, with nerve sheath differentiation manifesting a continuous spectrum. Leu 7 was detected in four Schwann cell tumours, three of which were ultrastructurally well differentiated. Cytokeratin and desmin were demonstrated only in an undifferentiated pleomorphic area of one Schwann cell tumour. Electronmicroscopy can aid diagnosis by revealing nerve sheath differentiation in malignant soft tissue tumours without demonstrable S-100 protein.

Adolescent↗
PubMed1992

Measurement, analysis, and modelling of the caloric response. 1. A descriptive mathematical model of the caloric response over time.

A mathematical model for describing the caloric response over time offers many important advantages over the commercially-available qualitatively-fitted curves that are now used by the clinician for evaluating caloric results. In this report advances in the development of a nonlinear least-squares mathematical model are discussed and the roles and derivations of fitting parameters and curve-derived indices are outlined. This model provides a rigorous and objective description of the caloric response in its entirety with four continuous parameters. These fitting parameters make it possible to 1) describe individual caloric responses precisely and uniquely, 2) compare pairs of individual caloric responses or groups of caloric responses statistically, 3) extract information not previously available, 4) quantify variability within the caloric response, and 5) model physical properties of the caloric stimulus and physiological variables affecting the caloric response. Results from this model are compared with the results from our earlier models and with traditional multiparameter caloric results.

Caloric Tests↗
PubMed1992

Mixed-effects nonlinear regression for unbalanced repeated measures.

Repeated measures data, such as clinical pharmacokinetic data, growth data, and dose-response data, are often inherently nonlinear with respect to a given response function and are frequently incomplete and/or unbalanced. Nonlinear random-effects models together with a variety of estimation procedures have been proposed for the analysis of such data. This paper is concerned with a straightforward procedure for estimating and comparing the parameters of a generalized mixed-effects nonlinear regression model. The asymptotic properties of the proposed estimators are given and large-sample tests of hypothesis provided. The results are applied to in vitro data on the water transport kinetics of hemodialyzers used in the treatment of patients with chronic renal failure.

Biological Transport, Active↗
PubMed1992

Educational outcome of neonatal intensive care graduates.

Studies of developmental outcome of neonatal intensive care unit graduates have generally been limited to the first 2 to 3 years of life, with outcome determined by psychometric tests. This study followed neonatal intensive care unit graduates born 1975 through 1983 (n = 457) into the public school system and compared their educational outcomes with those of newborn nursery graduates (n = 656). Outcomes were evaluated by placement in four academic categories: regular classroom, academic problems, speech/language impairment, and major impairment. Educational outcomes for children of both groups were essentially the same. Their placement in the four academic categories were equally affected by nonmedical variables, primarily income (below/above poverty level), race, and sex. Seventy percent of poverty-level children were in one of the three problem categories, compared with 40% of children above poverty level. Neither neonatal intensive care unit treatment nor low birth weight were major predictors of educational outcome. The only clear-cut neonatal intensive care unit effect occurred among children born with sensory or physical impairments. Therefore, in order to reduce poor educational outcomes, follow-up and intervention programs should be targeted primarily to children with diagnosable handicaps and from minority, low-income families.

Child↗
PubMed1991

Crossed and uncrossed projections to cat sacrocaudal spinal cord: II. Axons from muscle spindle primary endings.

The terminal fields of primary afferent fibers from tail muscle spindle primary endings were mapped within cat sacrocaudal spinal cord (S3-Ca7), using intra-axonal recording and horseradish peroxidase staining techniques. We sought to determine the ipsilateral and contralateral projection patterns and to relate these to the fibers' muscles of origin. Fifty-three group Ia fibers were successfully stained. Segmental collaterals originated from either the ascending or descending branch within the dorsal columns. Collaterals coursed rostromedially within the dorsal columns and traversed the medial aspect of the dorsal horn. Ipsilateral terminations were similar for all fibers. Within the ventral horn, boutons were consistently observed in the medial or central portions of lamina VII. In lamina VIII, a variable number of boutons was seen on fine branches emerging from larger fibers coursing ventrally. Clusters of terminals were plentiful in the regions of motoneurons, i.e., lamina IX and the nucleus commissuralis. Terminals were found in the adjacent white matter. In addition to ipsilateral terminations, some group Ia fibers (20 of 53) had collateral branches that crossed ventrally to the central canal, terminating within the midline ventral gray commissure and/or the contralateral ventral horn. Crossed projections always originated in medial (dorsal or ventral), but not lateral, muscles of the tail. These data suggest that ipsilateral projections of group Ia fibers make connections on sacrocaudal motoneurons, on neurons mediating segmental reflex functions and on neurons conveying ascending information. It is speculated that crossed and uncrossed connections between group Ia fibers from medial muscles and bilateral dendritic trees of motoneurons subserve synchronized co-contraction of synergistic muscles located on the two sides of the body, such as with dorsal or ventral flexion of the tail. Group Ia projections from lateral muscles, that are entirely ipsilateral, would be involved with lateral movements of the tail.

Afferent Pathways↗
PubMed1991

Correlative electrophysiological and behavioral evaluation following L5 lesions in the cat: a model of spasticity.

The present work developed an animal model of hindlimb spasticity by analyzing the electrophysiological and behavioral consequences of L5 spinal cord lesions in cats. In chronically lesioned animals (1 to 6 months), the L7-S1 dorsal roots were stimulated and evoked potentials were recorded from hindlimb flexor and extensor motor nerves. Following lateral hemisection, the monosynaptic responses were 2-5 times larger (for voltage-time integral and for amplitude) on the ipsilateral side than those from the contralateral side or from control animals. Half-widths, rise-times, and latencies of the monosynaptic responses were the same on both sides. Behavioral signs of spasticity, including hypertonia and increased deep tendon reflexes, were displayed from the ipsilateral hindlimb following lateral hemisection. With lateral hemisection or with extensive dorsal quadrant lesions, hopping and proprioceptive placing reflexes were abolished; these behavioral observations impart functional significance to physiological and anatomical studies of a mid-lumbar center considered to be important for movement control. The present model represents the first demonstration of a statistically significant correlation between electrophysiological and behavioral observations of spasticity for animals with a lateral hemisection. These correlations demonstrate the utility of behavioral screening of animals for subsequent neurophysiological analyses. This facilitates the investigation of cellular events underlying spasticity and of strategies for its relief with tissue repair techniques affecting local circuitry involved in spasticity.

Animals↗
PubMed1991

Expression of members of the myf gene family in human rhabdomyosarcomas.

Northern analysis of tumour RNA has been used to examine the expression of members of the myf family of muscle determining genes (myf3, myf4, myf5 and myf6) in a series of 20 rhabdomyosarcomas. A 2.0 kb myf3 transcript was observed in 85% of tumours, a 1.8 kb myf4 transcript was detected in 70% of tumours and a 1.7 kb myf5 transcript was observed in 55% of tumours. Transcription of myf6 occurred in 28% of tumours, but there were several transcript sizes (1.2, 1.5, 2.0 and 3.5 kb) and in some individual tumours two or more transcripts were observed. Only two rhabdomyosarcomas, one classified as embryonal and one as pleomorphic, failed to exhibit transcription of members of the myf gene family. We were unable to detect transcription of myf genes in neuroblastomas, Wilms' tumours, hepatoblastomas, paediatric non-Hodgkin's lymphoma and leiomyosarcomas. When considered together these observations suggest that expression of myf genes could provide an extremely useful marker in the diagnosis of rhabdomyosarcoma.

Adolescent↗
PubMed1991

Immunohistochemical staining for ferritin in neuroblastomas.

Immunohistochemical staining for ferritin was examined in 35 neuroblastomas from 27 children and compared with serum ferritin levels. All but two of the patients presented with advanced (stages III and IV) disease, and the adrenal was the most common primary site (20/27, 74%). Immunostaining was positive in only one of 14 tumour biopsies taken at the time of diagnosis (7%), but eight of 21 neuroblastomas (38%) marked for ferritin after chemotherapy. No consistent association was established between tumour- and serum-associated ferritins in the untreated or treated groups. Ferritin staining in treated neuroblastomas was usually more marked in partly differentiated tumour cells. The increased frequency of ferritin positive neuroblastomas after chemotherapy appeared to be associated with large local accumulations of ferritin and haemosiderin within the treated tumours, and (probably) with the blood transfusions which these children received.

Antineoplastic Agents↗
PubMed1990

A longitudinal study of the cognitive function of children with renal failure.

Fifty-six children with chronic renal failure who either received a kidney transplant, were hemodialyzed or peritoneally dialyzed, or who were being medically managed were given a series of neuropsychological tests every 6 months for a total of four testing sessions. Each child was matched by age, sex, and race to healthy children who received the same sequence of tests. The performance of each treatment group was compared with their controls longitudinally, using a repeated measure analysis of variance. In general, renal subjects performed at lower levels than their controls on tasks of verbal ability, visual perception, memory and visual motor skills. Visual motor performance was the most clinically affected. When compared with controls, the renal subjects did not improve as much or actually deteriorated on some measures of memory and learning skills.

Adolescent↗
PubMed1990

Association between renal function and cognition in childhood chronic renal failure.

Forty-five children with renal failure who were either being medically managed, receiving dialysis (hemodialysis or continuous ambulatory peritoneal dialysis) therapy or who had received successful kidney transplants were longitudinally examined on multiple neuropsychological measures. A variety of medical parameters was also obtained at each time of testing. The neuropsychological variables were correlated with the medical variables using the repeated measures regression analysis method. There were associations between levels of renal function, short-term memory and list learning. Other neuropsychological variables did not in general correlate with the medical parameters consistently for all ages at the time of initial testing. Verbal performance decreased with increasing duration of renal failure in 6- to 11-year-olds and immediate recall decreased with increasing percentile rank of systolic blood pressure in 16- to 18-year-olds.

Adolescent↗
PubMed1990

Growth in children following kidney transplantation.

Growth was assessed in children following 128 separate kidney transplants using a generalized growth curve multivariate analysis. The height standard deviation score was the dependent variable. Time since transplant, prednisone dosage, and creatinine clearance were the independent variables. For the purposes of comparison patients were grouped according to sex, race, age at transplantation, initial allograft function, acute rejection episodes and the use of cyclosporin A. Patient's height standard deviation scores tended to increase negatively after transplantation. However, children who received transplants before their 7th birthday, with initial allograft function greater than 60 ml/min per 1.73 m2, exhibited "catch-up" growth. Height standard deviation scores positively improved in males but not in females, as prednisone dosage was decreased. Height standard deviation scores became more negative as renal function decreased after transplantation. Changes in renal function produced the greatest effect upon height in black children, children less than 7 years, and males.

Adolescent↗
PubMed1990

Effects of birth weight and sociodemographic variables on mental development of neonatal intensive care unit survivors.

Neonatal intensive care unit survivors (N = 494) from 10 tertiary care centers were evaluated over the first 4 to 5 years of life to determine the relative contributions of birth weight and sociodemographic factors to mental development. Six sociodemographic factors were studied: sex, race, family income, and mother's marital status, age, and educational level; the last five factors also are known to be associated with premature birth. Mental development was measured with the Bayley Scales of Infant Development (12 to 24 months) and the Stanford Binet Intelligence Test (4 to 5 years). Each factor's influence was assessed by multivariate analysis. Birth weight had limited long-term implications; at 4 to 5 years, only infants with birth weights less than 1000 gm had significantly lower scores than those in other birth weight categories. Sociodemographic variables had a greater impact on mental development, with age-dependent differences found between nonwhite and white children and between children with mothers of low, medium, and high educational levels.

Adult↗
PubMed1990

Low incidence of ras oncogene activation in human squamous cell carcinomas.

Activation of the ras gene family by point mutation at codons 12, 13 and 61 has been demonstrated in up to 20% of unselected series of human tumours. The present study was carried out to assess the incidence of ras activation in 37 squamous cell carcinomas of the head and neck, seven squamous cell carcinomas of the skin and eight squamous carcinoma cell lines. Oligonucleotide probes and the polymerase chain reaction were used on DNA extracted from achival paraffin embedded material. Mutations in codon 12 of the Harvey ras gene was found in a carcinoma of the larynx and a carcinoma of the lip, both of which had received prior irradiation. A cell line (LICR-LON-HN8) established from the same laryngeal cancer showed the same mutation. This study indicates that there is a low incidence of ras mutation in human squamous cell carcinomas and that activation of this family of genes is probably not a common factor in the development of this group of tumours.

Adult↗