[Chronic lung disease of infancy].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D Bader.
Explore the source record for details and available documents.
We report two cases of diffuse neonatal haemangiomatosis. The multiple cutaneous lesions were associated with massive hepatic involvement and congestive heart failure in one, while in the other laryngeal haemangiomas caused stridor and inspiratory distress. A significant regression in vascular lesions was achieved with high dose corticosteroid therapy.
Cardiac myoblast commitment and differentiation were studied in the developing avian embryo. Single cell analysis of isolated cardiogenic cells grown in vitro established that stage 4 (newly gastrulated) mesodermal cells are capable of myocyte differentiation in the absence of intercellular contact or short range cellular interactions. While cardiac myocytes derived from single isolated progenitors expressed muscle-specific myosin heavy chains (MHC), atrial and ventricular MHCs characteristic of in vivo development were not detected. When the same progenitors were grown at high density or in organ cultures, cell-specific, expression of atrial and ventricular MHCs was observed, suggesting a role of cell density-dependent processes for differential MHC expression. Cardiogenic mesoderm (stages 4-8) was treated with the cocarcinogen 12-O-tetradecanoylphorbol-13-acetate (TPA), maintained as organ cultures, and assayed for muscle differentiation in an attempt to identify possible stage-specific variations in cardiac progenitors. TPA irreversibly blocked the differentiation of early (stages 4-7) progenitors. When exposed to TPA, stages 4-7 cardiogenic cells failed to synthesize several muscle-specific proteins as determined by immunochemical analysis of myosin synthesis and two-dimensional gel electrophoresis of 35S-labeled proteins isolated from cardiogenic cultures. In addition, stages 4-7, TPA-treated cells did not differentiate after the withdrawal of TPA. In contrast, TPA had no effect on the expression of several muscle-specific proteins in late (stage 8) cells including the cell-specific expression of atrial and ventricular MHCs.
To determine the incidence of long-term sequelae after meconium aspiration syndrome (MAS), we studied 11 children who had MAS at age 8.2 +/- 0.2 years (mean +/- SD) and nine healthy control subjects with pulmonary function and exercise stress tests. The MAS children had evidence of mild airway obstruction, hyperinflation, and increased closing volumes in comparison with control values. During graded exercise stress tests on a treadmill, MAS children achieved normal maximal oxygen consumption and anaerobic threshold without a significant fall in arterial oxygen saturation or increase in CO2 tension. Exercise-induced bronchospasm occurred in four (36%) MAS subjects but in none of the control subjects. We conclude that children surviving MAS have long-term pulmonary sequelae, including airway obstruction, hyperinflation, elevated closing volumes, and airway hyperreactivity; yet they achieve normal aerobic capacity. These findings are similar, although less severe, than those after prematurity and bronchopulmonary dysplasia.
We have isolated a full length complementary DNA clone (pCTnC1) from a 19-day embryonic chicken heart library corresponding to cardiac troponin C (TnC). Sequence analysis demonstrated varying homologies with TnC complementary DNA clones isolated from developing chick skeletal muscle. Using pCTnC1 as a hybridization probe, we have determined that cardiac TnC is constitutively expressed in both atria and ventricles of the developing and adult heart. These data along with previous immunochemical studies of TnC expression demonstrate that the slow skeletal and cardiac muscle isoform is the only TnC expressed in the heart. In contrast, expression of slow skeletal and cardiac muscle TnC is developmentally regulated in skeletal muscles of the chicken. The tightly controlled expression of slow skeletal and cardiac muscle TnC in the varying myocyte types of the heart suggests a physiologically significant role of this regulatory protein.
Changes in the mechanical properties of pig skin have been studied in vivo, using a dermal extensometer, after irradiation with a single dose of 18 Gy of X rays. There was no significant change in the stiffness of irradiated skin, when compared with unirradiated skin, until 9 weeks after irradiation when the irradiated skin was significantly stiffer. This effect was also found at 12 and 15 weeks after irradiation. When the increase in skin thickness, as a consequence of oedema, was taken into account a significant increase in the unrelaxed elastic modulus of irradiated skin was only seen at 12 and 15 weeks after irradiation. There were no significant changes in force relaxation, after extension of the skin, over this time period. After the resolution of oedema, which was associated with a significant 20% reduction in the thickness of irradiated skin relative to unirradiated skin, the mechanical properties of irradiated skin were not markedly different from those of unirradiated skin. However, between 30 and 39 weeks after irradiation there was a further wave of dermal thinning, resulting in a total reduction in the thickness of irradiated skin relative to unirradiated skin of 26%. This was associated with a rapid rise in the skin stiffness and unrelaxed elastic modulus by approximately 65 and approximately 140%, respectively. It was only at these late times after irradiation that the force relaxation of the skin was modified significantly. At 9 and 12 weeks after irradiation the reduction in skin stiffness and the unrelaxed elastic modulus were dose related. Based on the percentage of fields showing a significant reduction in these biomechanical parameters, ED50 values of between 12 and 14.5 Gy were established. This would appear to be a sensitive method for assessing radiation-induced dermal changes since few gross changes are observed in this dose range.
Explore the source record for details and available documents.
The mechanisms underlying growth failure in infants with bronchopulmonary dysplasia are poorly understood. Thirteen infants with bronchopulmonary dysplasia at 6 months of corrected age and 12 full-term healthy control infants matched for age or size were studied. Resting oxygen consumption was measured during natural sleep, and an estimation of the resting metabolic expenditure by indirect calorimetry was performed. Growth parameters were measured, and a nutritional profile including dietary intake, stool analysis, and serum albumin, cholesterol, glucose, and prealbumin was obtained. Seven of the 13 infants with bronchopulmonary dysplasia had growth failure (defined as length and weight less than the tenth percentile of the Babson growth curves). These infants had lower birth weight, lower gestational age, and a greater number of days spent in supplemental oxygen or on mechanical ventilation. There was no statistical difference between the bronchopulmonary dysplasia-growth failure and bronchopulmonary dysplasia-normal growth infants for dietary intake or stool or serum analyses. However, serum prealbumin showed a significant linear correlation with body weight in infants with bronchopulmonary dysplasia. Resting metabolic expenditure was elevated in infants with bronchopulmonary dysplasia with growth failure and was inversely correlated with body weight in all infants with bronchopulmonary dysplasia. Thus, infants with bronchopulmonary dysplasia and growth failure have increased metabolic demands and decreased prealbumin values suggesting a relative state of protein-calorie malnutrition.
To determine the long-term pulmonary sequelae and effect on exercise tolerance of bronchopulmonary dysplasia (BPD), we studied 10 children at a mean age of 10.4 years, who had been born prematurely, survived respiratory distress syndrome, and subsequently developed BPD, and compared them with eight age-matched normal children born at term. Pulmonary function tests and graded exercise stress tests were performed. Residual volume, the ratio between residual volume and total lung capacity, vital capacity, forced expiratory volume in 1 second, forced expiratory flow between 25% and 75% of vital capacity, and maximal expiratory flows at 80%, 70%, and 60% of total lung capacity were all abnormal (P less than 0.02) in the children with BPD, compared with control values. Pre-exercise transcutaneous CO2 tension was higher (P less than 0.05) in the BPD group than in the control group. At maximal workload, tcPCO2 remained high in patients with BPD compared with control values (P less than 0.05). Arterial oxygen saturation at maximal workload fell below pre-exercise levels in the BPD group (P less than 0.05) but not in control children. There were no differences in maximal oxygen consumption between the BPD group and control children. Exercise-induced bronchospasm occurred in 50% of the BPD group, but not in the control group. We conclude that long-term survivors of BPD have evidence of airway obstruction, hyperinflation, and airway hyperreactivity, compared with a control group. Aerobic fitness was not significantly different in the BPD and control groups, but was achieved in the BPD group at the expense of a fall in SaO2 and a rise in tcPCO2.
In the present study, a monoclonal antibody (McAb), ALD19, generated against myosin of slow tonic muscle, was shown to react with the heavy chain of ventricular myosin in the adult chicken heart. With this antibody, it was possible to detect a ventricular-specific myosin during myocardial differentiation and to show that the epitope recognized by ALD19 was present from the earliest stages of ventricular differentiation and maintained throughout development only in the ventricle. A second McAb, specific for atrial myosin heavy chain (MHC) (Gonzalez-Sanchez, A., and D. Bader, 1984, Dev. Biol., 103:151-158), was used as a control to detect an atrial-specific myosin in the caudal portion of the developing heart at Hamburger-Hamilton stage 15. It was found that the appearance of ventricular MHC predated the expression of atrial MHC by approximately 1 d in ovo and that specific MHCs were always differentially distributed. While a common primordial MHC may be present in the early heart, this study showed the tissue-specific expression of a ventricular MHC during the initial stages of heart development and its differential accumulation throughout development.
We report our experience with coagulase-negative staphylococcal infection over a period of 1 year. The incidence of coagulase-negative staphylococcus septicemia was 4.25% (13 newborn infants) of the 306 admissions to our Neonatal Intensive Care Unit. Ten patients (76.9%) were premature infants. Four infants in our series were less than 48 h of age. Two of these were presumably born with the infection. Six infants had involvement of the lungs. The strains of coagulase-negative staphylococci cultured from all cases of neonatal septicemia were sensitive to cephalothin, but were considerably less sensitive to the currently used antibiotic combinations. Our observations indicate that coagulase-negative staphylococci must be suspected in early or late neonatal sepsis, and that early antibiotic treatment by cephalothin may prevent morbidity.
Explore the source record for details and available documents.
A monoclonal antibody (anterior latissimus dorsi 58 [ALD58]; antimyosin heavy chain, MHC) directed against myosin from slow tonic muscle was found to react specifically with the striated muscle cells of the conductive system in the adult chicken heart. This monoclonal antibody was used to study the expression of myosin in the conductive system of the adult and developing heart. Using immunofluorescence microscopy with ALD58, muscle cells of the conductive system were demonstrated in both the atria and ventricles of the adult heart as previously shown by Sartore et al. (Sartore, S., S. Pierobon-Bormioli, and S. Schiafinno, 1978, Nature (Lond.), 274: 82-83). Radioactive myosin from adult atria and ventricles was precipitated with ALD58 and subjected to limited proteolysis and subsequent peptide mapping. Peptide maps of ALD58 reactive myosin from atria and ventricles were very similar, if not identical, but differed from peptide maps of ordinary atrial and ventricular myosin. The same antibody was used to study cardiac myogenesis in the chick embryo. When ALD58 was reacted with myosin isolated from atria and ventricles at selected stages of development in radioimmunoassays, reactivity was not observed until the last week of embryonic life (greater than 15 d of egg incubation). Thereafter concomitant and progressively increased reactivity was observed in atrial and ventricular preparations. Also, no ALD58 positive cells were observed in immunofluorescence studies of embryonic hearts until 17 d of egg incubation. Primary cell cultures of embryonic hearts also proved to be negative for this antibody. This study demonstrates that an epitope recognized by ALD58 associated with an antimyosin heavy chain of striated muscle cells of the adult heart conductive system is absent or present in only small amounts in the early embryonic heart.
Explore the source record for details and available documents.
Monoclonal antibodies (McAb) against myosin from the pectoralis muscle of the adult chicken have been generated and shown to react specifically with the myosin heavy chain (MHC). The reactivities of two such McAbs with myosin from adult chicken atrial and ventricular myocardium were further analysed by immunoautoradiography, radioimmunoassay, and immunofluorescence microscopy. Monoclonal antibody MF 20 was found to bind both atrial and ventricular MHC and stain all striated muscle cells of the adult chicken heart. In contrast, McAb B1 bound specifically to atrial myocytes in immunofluorescence studies, while immunoautoradiography and radioimmunoassay demonstrated the specificity of this antibody for the atrial MHC. Upon reacting these McAbs with myosin isolated from embryonic hearts where definitive atria and ventricles were present, the same specificity of antibody binding was observed. Immunofluorescence studies demonstrated that all striated muscle cells of the embryonic heart contained MHCs recognized by MF 20, while only atrial muscle cells were bound by B1. When extracts of presumptive atrial and ventricular tissue were reacted with MF 20 and B1, significant reactivity of MF 20 was first observed at stage 10 in the presumptive ventricle and thereafter this McAb reacted with all regions of the developing myocardium. Binding of B1 was detected approximately 1 day later at stage 15 and was confined to atrial-forming tissues. These data demonstrate antigenic similarity between adult and embryonic MHC isolated from atrial myocardium and suggest the expression of an atrial-specific MHC early in the regional differentiation of the heart.
Explore the source record for details and available documents.
Monoclonal antibodies (McAbs) against the myosin heavy chain (MHC) of adult chicken pectoralis muscle have been tested for reactivity with pectoralis myosin at selected stages of chick development in vivo and in vitro. Three such McAbs, MF 20 and MF 14, which bind to light meromyosin, and MF 30, which binds to myosin subfragment two (S2), were used to assay the appearance and accumulation of specific MHC epitopes with: (a) indirect, solid phase radioimmune assay (RIA), (b) immunoautoradiography, (c) immunofluorescence microscopy. McAb MF 20 bound strongly and equivalently to MHC at all stages of embryonic development in vivo. In contrast, the MF 30 epitope was barely detectable at 12 d of incubation but its concentration rose rapidly just before hatching. No detectable binding of MF 14 to pectoralis myosin could be measured during myogenesis in vivo until 1 wk after hatching. Immunofluorescence studies revealed that all three epitopes accumulate in the same myocytes of the developing pectoralis muscle. Since all three McAbs bound with high activity to native and denatured forms of myosin, it is unlikely that differential antibody reactivity can be explained by conformational changes in myosin during development in vivo. When myogenesis in vitro was monitored using the same McAbs, MF 20 bound to the MHC at all stages tested while reactivity of MF 30 and MF 14 with myosin from cultured muscle was never observed. Thus, this study demonstrates three different immunochemical states of the MHC during development in vivo of chick pectoralis muscle and the absence of later occurring immunochemical transitions in the MHC of cultured embryonic muscle.
Explore the source record for details and available documents.