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Biomedical subjects

B T Smith

Publications and source records attributed to B T Smith.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cyclic AMP-dependent protein kinase does not regulate CTP:phosphocholine cytidylyltransferase activity in maturing type II cells.

CTP:phosphocholine cytidylyltransferase catalyses a rate regulatory step in the de novo synthesis of surfactant phosphatidylcholine in alveolar type II cells. To investigate if cytidylyltransferase can be regulated by cAMP-dependent protein kinase, we first studied the ontogeny of cAMP-dependent protein kinase activity in type II cells of fetal rat lung. Total cAMP-dependent protein kinase activity, measured in the presence of 10 microM cAMP, as well as endogenous activity, measured without cAMP, increased with advancing gestation. Phosphocholine cytidylyltransferase activity showed a similar developmental profile. This temporal relationship between cAMP-dependent protein kinase and cytidylyltransferase supports a potential role for cAMP-dependent protein kinase in regulating cytidylyltransferase phosphorylation. Cytidylyltransferase purified from adult rat lung was, indeed, phosphorylated in vitro by cAMP-dependent protein kinase. Despite the phosphorylation, however, no change in cytidylyltransferase activity was noted. Pre-incubation of fetal type II cell cytosol with ATP and Mg2+ did not affect cytidylyltransferase activity. Addition of either cAMP, dibutyryl-cAMP or the catalytic subunit of cAMP-dependent protein kinase to the pre-incubation medium did also not alter cytidylyltransferase activity. Furthermore, neither cAMP-dependent protein kinase inhibitor peptide, nor H8, a cyclic nucleo-dependent protein kinase inhibitor, affected cytidylyltransferase activity in fetal type II cell cytosol. Treatment of intact fetal type II cells with either cAMP, dibutyryl-cAMP or 8-[4-chlorophenylthio]cAMP activated cAMP-dependent protein kinase activity but did not alter cytidylyltransferase activity. We conclude that the increase in cytidylyltransferase activity in fetal type II cells at late gestation is not regulated by the developmental activation of cAMP-dependent protein kinase.

Animals↗
PubMed1994

Functional neuromuscular stimulation: outcomes in young people with tetraplegia.

Percutaneous intramuscular functional neuromuscular stimulation (FNS) systems were fitted to the forearms of five adolescents with tetraplegia in an effort to provide active grasp and release. Two assessments designed at Case Western Reserve University to evaluate functional outcomes of FNS in adults were employed. The common object test (COT) was used to assess hand function during five activities of daily living (ADLs): eating, drinking, writing, brushing teeth and applying toothpaste. A usage survey provided information on the frequency of FNS use in environments outside of the laboratory. In addition, interviews were employed using open-ended questions to gain a deeper understanding of the perceptions of FNS in the adolescents' own environments. Based on the COT results, each adolescent was able to perform ADLs with and without FNS. However, FNS allowed unilateral function so that the extremity without FNS was freed to assist in balance or participate in bilateral tasks. Also, FNS reduced the need for multiple devices, providing users with the potential to perform activities in a variety of environments without transporting adaptive equipment. Those who reported using FNS most often obtained hard-bound school books, held pens during classroom and homework assignments, engaged in leisure activities and performed hygiene tasks. FNS was also used as a means to communicate and socialize through hand gestures. Well-known factors that influence the independence of people with tetraplegia also appeared to affect FNS use.

Activities of Daily Living↗
PubMed1994

Reliability of percutaneous intramuscular electrodes for upper extremity functional neuromuscular stimulation in adolescents with C5 tetraplegia.

Chronically indwelling percutaneous intramuscular electrodes were implanted in the upper extremity muscles of five adolescents with C5 or C5-6 tetraplegia in an effort to provide lateral and palmar prehension using the neuroprosthetic system designed by Case Western Reserve University. The responses from 177 electrodes were evaluated at 3-month intervals and included measurements of electrical impedance and an assessment of recruitment properties. Electrode failures were categorized as breakage, an altered stimulated response or adverse sensation during stimulation. Survival probabilities were generated for all electrodes, each muscle group, the volar and dorsal exit sites, intrinsic and extrinsic muscles, and according to the subjects' time postinjury. The overall probability of an electrode surviving to 6 months was 0.75 and the 1 year survival probability was 0.56. Among muscle groups, the finger extensor and thumb adductor electrodes had the highest proportion of failures and the poorest survival likelihoods within the first year after implant. According to the Breslow test, significantly smaller survival chances were predicted for electrodes exiting dorsally and for the newly-injured adolescents (< 1 year postinjury). The cumulative survival likelihoods of this study are smaller than those reported in adult applications using the same electrode design. Factors that may account for the disparate results are discussed.

Adolescent↗
PubMed1993

Regulation of phosphatidylcholine synthesis in fetal type II cells by CTP:phosphocholine cytidylyltransferase.

Phosphatidylcholine synthesis increases in fetal rat type II cells during late gestation, as demonstrated by an increased incorporation of radiolabeled palmitate, glycerol, acetate, and choline into phosphatidylcholine. However, the percentage of phosphatidylcholine present in the saturated form remains essentially constant. The developmental profile of the enzymes of the CDP-choline pathway suggests that CTP:choline-phosphate cytidylyltransferase catalyses a rate regulatory step in de novo phosphatidylcholine synthesis by fetal type II cells. When cytidylyltransferase activity is assayed in different subcellular fractions, the greatest increase, as a function of development, is found in microsomes. This developmental increase is accompanied by a shift in subcellular distribution of cytidylyltransferase activity from cytosol to microsomes in fetal type II cells during late gestation. This shift is evident even when cytidylyltransferase activity is assayed in the presence of 0.5 mM phosphatidylcholine/oleic acid (1/1 molar ratio) vesicles. We speculate that either a subcellular translocation of CTP:phosphocholine cytidylyltransferase from cytosol to microsomes or an increase in cytidylyltransferase gene expression are responsible for the developmental increase of de novo phosphatidylcholine synthesis by fetal type II cells.

Animals↗
PubMed1992

The application of a modified neuroprosthetic hand system in a child with a C7 spinal cord injury. Case report.

A neuroprosthetic hand system developed at Case Western Reserve University has been modified for use by an 8 year old child with an incomplete C7 spinal cord injury. This system has been adapted to accommodate voluntary thumb and finger extension, and provides stimulated finger flexion and thumb position for lateral and palmar prehension. Three months were required to develop grasp with sufficient strength and coordination for functional use. This period consisted of: implantation and immobilization of percutaneous intramuscular electrodes; stimulated exercise of the muscles of the hand and forearm; programming grasp patterns; and system training. Functional assessments show that the neuroprosthetic hand system allows the subject to perform unilateral and bilateral tasks that were otherwise impossible or were previously performed bimanually. The ability to perform activities of daily living with one hand frees the contralateral upper extremity to be used either for balance which increases the work area, or to stabilize an object allowing manipulation with the instrumented hand. Telephone interviews suggest that the hand system is used on a consistent basis at home and school. This single subject application indicates that a stimulation system designed for adults with C5-6 spinal cord injuries can enhance hand function and facilitate independence in a child with a low level cervical lesion.

Activities of Daily Living↗
PubMed1992

Bipolar latissimus dorsi transposition and functional neuromuscular stimulation to restore elbow flexion in an individual with C4 quadriplegia and C5 denervation.

A bipolar latissimus dorsi transposition was performed on a 17-year-old male patient with a C4 spinal cord injury and complete peripheral denervation at C5. Electrical stimulation of the paralyzed but excitable latissimus dorsi provided elbow flexion that could not be achieved with the paralyzed and denervated elbow flexors. The muscle was attached from the coracoid to the ulna allowing the elbow to be flexed with the forearm and wrist maintained in the neutral position. Following a 6-week immobilization period, the transposed muscle was exercised daily with intramuscular stimulation to increase both strength and endurance. By the fourth month after surgery, the subject could control elbow flexion proportionally with contralateral shoulder elevation using a shoulder position transducer. Functionally, the subject was able to use the neuroprosthetic system to bring his hand to his mouth and feed himself with the aid of a universal cuff and a support to stabilize the shoulder.

Adolescent↗
PubMed1992

Optimal controller for intraaortic balloon pumping.

An optimal control algorithm was adapted to identify and track the optimal deflation time of the intraaortic balloon pump (IABP). Routines for handling physiologically imposed constraints were added to the algorithm which was implemented in a computer-controlled system. The system was designed to provide real time optimization for the clinical setting. The controller continuously maximizes a performance index while observing the constraints. The index is composed of clinically available hemodynamic variables which indicate changes in myocardial energy balance. Proper values for the algorithm parameters were determined and the system was tested in animal experiments. The results indicate that controlling deflation time relative to the R wave, which precedes the next ejection phase, reduces the time required for optimization when the heart rate varies.

Algorithms↗
PubMed1992

Cocaine hepatotoxicity during protein undernutrition of retrovirally infected mice.

Effects of cocaine administration on lipid peroxidation and liver damage in immunocompromised mice fed different levels of dietary proteins were investigated. Indices of lipid peroxidation and serum aminotransferases as evidence of free radical attack and liver damage were compared in mice fed a low protein (4%) or regular protein diet (20% protein) for 3 weeks and then infected with murine leukemia virus and given daily intraperitoneal injections of increasing progressive doses of 5-45 mg.kg-1.day-1 of cocaine for 11 weeks. Cocaine administration significantly increased hepatic triglycerides, serum aminotransaminases, conjugated dienes, lipid fluorescence, and malondialdehyde levels. These changes were exacerbated by retroviral infection and also by protein undernutrition. Retroviral infection additively increased indices of cocaine-induced lipid peroxidation and hepatic damage. Significant increases in indices of lipid peroxidation and greater liver injury were also detected in similarly treated mice that received the low protein diet compared with well-nourished mice. These results show that immunocompromised mice fed low levels of dietary protein form significantly increased immunogenic lipid peroxidation adducts during cocaine treatment.

Animals↗
PubMed1992

Developing a publicity plan for library research: the Rochester Study.

The hospital librarians in Rochester, New York and a research team developed and administered a questionnaire to measure the impact of information provided by the librarian on physicians' clinical decision making. While the research was underway, the librarians also developed a publicity plan. The goal of the plan was to create awareness of the study results in the local client population, as well as in the health care community at large. The plan served to describe and put in priority order the types of media that the librarians would use to publicize the study to target groups. This article includes examples of a nationwide and an institution-specific publicity plan. those developing publicity plans for future library research may want to allocate adequate funds to hire a media consultant to increase their prospects for national exposure.

Decision Making↗
PubMed1991

Spatial and temporal differences in fibroblast behavior in fetal rat lung.

Fibroblast-epithelial interactions were investigated in cells from late-gestation fetal rat lung. Fibroblasts from the pseudoglandular stage of lung development stimulated epithelial cell proliferation, whereas fibroblasts from the saccular stage promoted epithelial cell differentiation. The developmental switch from proliferation to differentiation seemed to be controlled by both cell types. Fibroblast-derived epithelial cell growth-promoting activity, evident in cells from the pseudoglandular period, decreased during development and almost disappeared in cells from the saccular stage. Interestingly, the response of epithelial cells to this growth-promoting activity declined with advancing gestational age as epithelial cells became more responsive to fibroblast-derived differentiation factor(s). Production of differentiation factor(s) by fibroblasts increased during the canalicular stage of lung development. Platelet-derived growth factor (PDGF) and low concentrations of transforming growth factor-beta (TGF-beta) stimulated epithelial cell proliferation. PDGF did not affect differentiation, whereas TGF-beta was inhibitory. Dependent on their proximity to the epithelium, two subpopulations of fibroblasts that differed in their ability to promote epithelial cell proliferation or differentiation were isolated. Fibroblasts in close proximity to the epithelium mainly produced differentiation factors, whereas more distant fibroblasts primarily stimulated proliferation.

Animals↗
PubMed1989

Necrotizing enterocolitis and volvulus in the premature neonate.

Premature infants presenting to the neonatal intensive care unit at the Hospital for Sick Children with a surgical abdomen over a 5-year period were studied retrospectively to determine the factors leading to the diagnosis of malrotation with volvulus and necrotizing enterocolitis (NEC). Fifteen preterm infants (less than 37 weeks) were diagnosed as having volvulus, and 54 had surgically treated NEC. Those with NEC were more likely to be systematically ill with grossly bloody stools, abdominal tenderness, and thrombocytopenia (P less than .005). Bilious vomiting and bilious gastric residuals were the only hallmarks of volvulus (P less than .005). Although the radiographic findings of thickened bowel walls and intramural air were significantly related to NEC, the accuracy and interobserver reliability in diagnosing these features was variable as was the ability to distinguish NEC from volvulus or normal on plain abdominal radiographs. Volvulus is an important cause of surgical abdomen in the preterm infant and can be misdiagnosed as NEC. An unusual course or the presence of bilious vomiting in any patient thought to have NEC should alert the clinician to the possibility of this diagnosis.

Birth Weight↗
PubMed1989

Fibroblast-pneumonocyte factor.

Fibroblast-pneumonocyte factor (FPF) is an organ-specific differentiation factor produced, under glucocorticoid regulation, by the fetal lung fibroblast, which in turn enhances the differentiation of the alveolar type II cell with respect to surfactant production. In this article we review the appearance of the type II cell phenotype during fetal life and the action of FPF to time full acquisition of this phenotype. Evidence supporting a physiological role for this factor is reviewed as are details of its production by the fetal lung fibroblast and action on the type II cell. Finally we summarize possible future clinical advantages of using such a material to regulate lung maturation compared with currently used maternal glucocorticoid therapy. These include a more rapid effect and bypassing the inhibition of glucocorticoid action seen in male fetuses and in infants of diabetic mothers.

Animals↗
PubMed1988

Histochemical and immunocytochemical identification of alveolar type II epithelial cells isolated from fetal rat lung.

Primary cultures of epithelial cells isolated from organotypic cultures of fetal (Days 18 through 22) rat lung have been characterized by histochemical and immunocytochemical parameters. Immunocytologic analysis with monoclonal antibodies to cytokeratins and with those to adult type II cells (JBR-1) demonstrated that the cell cultures were composed almost entirely of epithelial type II cells. Additional evidence that the cultures had the type II phenotype was obtained by Maclura pomifera lectin binding studies and by positive immunocytochemical demonstration of surfactant apoproteins. Comparison of cell cultures established from fetal lung at the early canalicular and saccular stages of rat lung development revealed that early fetal type II cells (Day 19) contained much glycogen and few lamellar bodies. The reverse was observed in type II cells isolated from fetal lungs at 21 days of gestation. Immunohistochemically determined surfactant apoproteins showed a similar developmental pattern to lamellar bodies. The cell cultures exhibited alkaline phosphatase activity, but this did not increase with development. Administration of dexamethasone to pregnant rats at 19 days gestation resulted in a significant loss of glycogen from fetal type II cells isolated 24 h later. This decrease in glycogen content was accompanied by an increase in the number of cells containing lamellar bodies. These findings indicate that freshly isolated fetal type II cells retain the morphologic features of the type II cells in vivo and provide a good system for the study of biochemical events occurring in these cells during specific stages of lung development.

Animals↗
PubMed1987

Characteristics of lung pericytes in culture including their growth inhibition by endothelial substrate.

Pericytes and endothelial cells from the same sample of adult rat lung have been separately established in culture by use of selective growth media. The endothelial cells are positive and the pericytes negative for angiotensin-converting enzyme activity and tissue plasminogen activator. Morphologically in culture, the pericytes are similar to pericytes from bovine retina and other sites and show positive immunofluorescence to both human platelet (non-muscle) myosin and smooth muscle myosin. In this respect they resemble smooth muscle cells grown from the rat main pulmonary artery, but lack the myofilaments and dense bodies characteristic of muscle cells. Lung endothelial cells and fibroblasts are positive only for platelet myosin. Pericytes in culture demonstrate an unusual growth response to endothelial substrate, obtained by removing confluent endothelial monolayers with nonionic detergent or alkali. When plated onto this material at low density, pericyte growth is inhibited. By contrast, the substrate stimulates the growth of endothelial cells and has no effect on smooth muscle cells. Initial attachment of endothelial cells and pericytes to the substrate is similar.

Animals↗
PubMed1987

Temporal linkage of glycogen and saturated phosphatidylcholine in fetal lung type II cells.

The developmental profiles of glycogen and surfactant-associated saturated phosphatidylcholine were investigated in type II cells isolated from fetal rat lung. Incorporation of radiolabeled glucose into glycogen and type II cell unlabeled glycogen content decreased as a function of gestational age. Conversely, an increase was noted in radioactive choline incorporation into saturated phosphatidylcholine and in the content of unlabeled saturated phosphatidylcholine as a function of gestational age. Type II cells from days 19 and 21 of gestation were also studied by electron microscopy. Temporal relationships similar to those noted biochemically were observed by morphometric analysis. A decrease in glycogen content and an increase in lamellar bodies (the storage organelles for the pulmonary surfactant) were noted as gestation progressed. These studies biochemically and morphologically demonstrate a temporal relationship between glycogen degradation and saturated phosphatidylcholine synthesis in type II cells isolated from fetal rat lung. These findings provide further support for the use of such type II cell preparations for studies of development at the cellular level.

Animals↗