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Biomedical subjects

B T Smith

Publications and source records attributed to B T Smith.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1987

Characterization of proteoglycans synthesized by fetal rat lung type II pneumonocytes in vitro and the effects of cortisol.

The synthesis of proteoglycans by primary cultures of 19-day gestation fetal rat lung Type II pneumonocytes was studied. The cells were grown in the presence of [3H]-glucosamine and/or [35S]-Na2SO4 and the radioactive label incorporated into proteoglycans was analyzed. Proteoglycans of high molecular weight (approximately 200 Kd) were isolated by gel permeation chromatography and contained both [3H] and [35S]. The glycosaminoglycan composition of the proteoglycans was determined by electrophoresis and autoradiography. The medium contained 65-80% of the labeled proteoglycans and was enriched for hyaluronate, with lesser amounts of the sulfated glycosaminoglycans (dermatan sulfate greater than heparan sulfate greater than chondroitin sulfate). The cell layers retained 20-35% of the labeled proteoglycans and was enriched for heparan sulfate, with lesser amounts of chondroitan sulfate greater than dermatan sulfate greater than hyaluronate. The synthesis of proteoglycans was time-dependent and was stimulated by increasing concentrations of fetal bovine serum. Cortisol inhibited proteoglycan synthesis, apparently by decreasing the availability of proteoglycan core-protein.

Animals↗
PubMed1987

Surfactant sufficiency for immature infants--prenatal induction vs. postnatal treatment.

The prenatal and postnatal therapeutic management of surfactant insufficiency are reviewed. Prenatal maternal glucocorticoid therapy promotes lung maturation and enhances lung surfactant levels in the neonate, but a minimum of 24 hr treatment is required and the therapy is of limited effectiveness even under optimal conditions. Relatively few women in premature labour are good candidates for glucocorticoid therapy. Research into combinations of glucocorticoids with hormones (e.g. thyroid), and adrenergic agents in progress. The authors are studying the effects of fibroblast-pneumonocyte factor (FPF) on the fetal lung surfactant system. Postnatal therapy with insufflated natural and artificial surfactants has been studied in several centres with varying degrees of success. Currently, the risk:benefit ratios favour attempts to reduce the risks of respiratory distress syndrome (RDS) by both prenatal surfactant induction and postnatal replacement therapy. Greater understanding of the underlying mechanisms should permit the establishment of more satisfactory treatment.

Female↗
PubMed1986

The cellular mechanism of glucocorticoid acceleration of fetal lung maturation. Fibroblast-pneumonocyte factor stimulates choline-phosphate cytidylyltransferase activity.

The cellular mechanism by which glucocorticoids stimulate phosphatidylcholine biosynthesis has been studied in the fetal rat lung in vivo and in cultured fetal rat lung cells of varying levels of complexity. Administration of dexamethasone to pregnant rats at 18 days gestation resulted in a significant increase in saturated phosphatidylcholine content in fetal lung 24 h after injection. Dexamethasone administration increased the activity of fetal lung choline-phosphate cytidylyltransferase by 34%. It had no effect on the activities of fetal lung choline kinase and choline phosphotransferase. Exposure of fetal lung type II cells in organotypic cultures (which contain both type II cells and fibroblasts) to cortisol resulted in a 1.6-fold increase in the incorporation of [Me-3H]choline into saturated phosphatidylcholine. The activities of the enzymes in the choline pathway for the de novo biosynthesis of phosphatidylcholine were not significantly altered except for a 105% increase in choline-phosphate cytidylyltransferase activity. Treatment of monolayer cultures of fetal type II cells with cortisol-conditioned medium from fetal lung fibroblasts resulted in a 1.5-fold increase in saturated phosphatidylcholine production. This effect correlated with a doubling of choline-phosphate cytidylyltransferase activity. Additional evidence that this stimulatory action is mediated by fibroblast-pneumonocyte factor, produced by fetal lung fibroblasts in response to cortisol, was obtained. The factor was partially purified from cortisol-conditioned medium of fetal lung fibroblasts by gel filtration and affinity chromatography. Based on biological activity, a 3000-fold purification was obtained. Stimulation of saturated phosphatidylcholine synthesis in type II cells by fibroblast-pneumonocyte factor was maximal within 60 min of incubation. Pulse-chase experiments indicated that the stimulatory effect was correlated with an increased conversion of choline phosphate into CDP choline. Moreover, the enhanced phosphatidylcholine formation by fetal type II cells in response to fibroblast-pneumonocyte factor was accompanied by decreased levels of cellular choline phosphate. These findings further support the concept that glucocorticoid action on surfactant-associated phosphatidylcholine synthesis occurs ultimately at the level of the alveolar type II cell and involves fibroblast-pneumonocyte factor which stimulates the activity of choline-phosphate cytidylyltransferase.

Animals↗
PubMed1986

Reciprocal autocrine and paracrine regulation of growth of mesenchymal and alveolar epithelial cells from fetal lung.

The regulation of DNA synthesis in 19 day rat fetal lung epithelial (alveolar type II) and mesenchymal (fibroblast) cells by protein growth factors has been studied. In each case a single growth factor is capable of stimulating 3H-thymidine incorporation into DNA: platelet-derived growth factor in the case of the alveolar type II cell and epidermal growth factor in the case of the fetal lung fibroblast. We hypothesize that these results indicate that the type II cell endogenously produces progression activities (i.e., epidermal growth factor-like and somatomedin-like activity) while the fibroblast produces competence (i.e., platelet-derived growth factor-like) and progression (i.e., somatomedin-like activity). The latter is in keeping with previous observations with skin fibroblasts. To test the above hypothesis, the effect of fetal lung fibroblast-derived conditioned media upon the growth of fetal alveolar type II cells has been determined. The results indicate that, indeed, such media contain competence activity for this cell type. The mitogenic activity was further characterized as heat-sensitive, trypsin-sensitive, and has an apparent molecular weight of 30,000 Daltons. It is not synthesized by 19 day fetal liver, kidney or skin fibroblasts and its synthesis is higher in lung fibroblasts isolated from 19 day fetuses as compared to those isolated on day 16 or day 22.

Animals↗