[Cyclic thrombocytopenia treated by high-dose intravenous immunoglobulin with a favorable response].
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Child, Preschool↗
Biomedical subjects
M Ikegami
Publications and source records attributed to M Ikegami.
Total nucleotide sequences of the infectious cloned DNAs of bean golden mosaic virus.
Complete nucleotide sequences of the infectious cloned DNA components (DNA A and B) of bean bolden mosaic virus were determined. The DNA A (2585 nucleotides) and DNA B (2647 nucleotides) have little sequence homology with each other, but both A and B contain a common region of 205 nucleotides. A possible large hairpin structure is detected in the common region. Nucleotide sequences of DNAs A and B revealed the presence of 8 potential coding regions for proteins (m.w. greater than 10,000). Among them, four open reading frames (ORFs 1-4) encode proteins of m.w. 30,000 or greater, and are individually coded in virion DNA A and B senses (+) and their complementary senses (-), respectively. The other four ORFs 5-8 are in virion DNA B(+) and its complementary sense (-). All of the ORFs 1-4 have regulatory signals for RNA synthesis (TATAA/T) in the region 5' upstream from a potential start codon ATG.
Base Sequence↗
Effects of maternal treatment with corticosteroids, T3, TRH, and their combinations on lung function of ventilated preterm rabbits with and without surfactant treatments.
Pregnant does were treated with betamethasone, T3, TRH, or combinations of betamethasone plus T3 or TRH using doses of each agent known to effect lung maturation. Preterm rabbits were then delivered at 27 days gestational age, half of each group was treated with Surfactant TA, and the rabbits were ventilated in a ventilator-plethysmograph system such that tidal volumes were regulated to mean values of 12 to 13 ml/kg. At 30 min of age when mean PCO2 values for the study groups were between 33 and 42 mm Hg, lung function of each rabbit was evaluated by the peak inspiratory pressure needed to achieve the desired tidal volume, by compliance, and by the ventilation efficiency index. These measures of lung function showed no benefit of corticosteroids or T3 in the absence of surfactant, whereas TRH significantly improved lung function. Although surfactant treatment improved lung function in all groups, the best effect after a single hormone treatment was with corticosteroids. The combined use of corticosteroids and TRH in surfactant-treated animals resulted in the best overall responses. The leak of protein into and out of the lungs was measured with radiolabeled albumins. The leak decreased as peak ventilatory pressures decreased in all groups and decreased with surfactant treatments of all groups. Corticosteroids decreased the protein leak into the airways more than could be accounted for by the effects of corticosteroids on ventilatory pressures alone (p less than 0.01). None of the hormone treatments significantly increased the saturated phosphatidylcholine pool sizes from the low values noted in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Surfactant for the treatment of respiratory distress syndrome.
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Animals↗
Effects of distention of the preterm fetal lamb lung on lung function with ventilation.
Constant distending pressure when applied to the immature fetal lamb lung was reported to improve compliance and prevent the subsequent development of the respiratory distress syndrome after delivery. These experiments were designed to repeat those observations and identify the mechanism(s) responsible for the effects of constant distending pressure on subsequent lung function. The compliance of the lungs of exteriorized fetal lambs at 130 to 133 days gestational age increased 2.5-fold after 1 h of 15 cm of distending pressure. However, subsequent ventilation of the lambs exposed to distending pressure and control lambs resulted in comparable sequential compliance and blood gas and pH measurements. Severity of lung disease as reflected by the peak inspiratory pressure needed to normalize Pco2 values decreased as surfactant-saturated phosphatidylcholine pool sizes increased (r values greater than 0.90) and minimum surface tensions of alveolar washes decreased, but the distention procedure did not change these relationships. Distention of the fetal lung did result in an apparent increase in pulmonary blood flow in the fetus and an increased leak of labeled albumin from the vascular space to the lung interstitium and airways during the 1-h period of ventilation after delivery. However, the leak of protein into the lungs exposed to the distending pressures was not increased during the period of exteriorization and distention, suggesting that distention sensitized the preterm lung to leak protein with subsequent mechanical ventilation. The leak of labeled albumin out of the airways was not changed by distention, and total lung water was not changed.(ABSTRACT TRUNCATED AT 250 WORDS)
Albumins↗
Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.
Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.
Adrenal Cortex Hormones↗
Effect of fetal adrenalectomy on catecholamine release and physiologic adaptation at birth in sheep.
Plasma catecholamine levels increase dramatically at birth. To determine the contribution of adrenal catecholamine secretion to the surge in catecholamines at birth and the role in newborn adaptation, we performed surgical adrenalectomy or sham operation on near-term ovine fetuses. After recovery in utero, the animals were delivered and supported by mechanical ventilation. Plasma catecholamine levels, heart rate, blood pressure, cardiac output, pulmonary function, surfactant secretion, and release of free fatty acids (FFA) and glucose were compared in control and adrenalectomized animals. Plasma epinephrine increased rapidly at birth in controls but was undetectable in adrenalectomized animals. Norepinephrine levels were not statistically different. Heart rate, blood pressure, cardiac output and contractility increased abruptly after cord cutting in controls but did not increase in adrenalectomized animals. Lung compliance, pulmonary function, surfactant pool size, glucose and FFA levels were significantly decreased in adrenalectomized animals. These results suggest that adrenal epinephrine secretion is vital to many of the adaptive events at birth.
Adaptation, Physiological↗
A pathological study on colorectal cancer. From de novo carcinoma to advanced carcinoma.
The development and progression of colorectal cancer were studied by examining the mode of proliferation of cancer and adenoma in 806 cases (857 lesions) of colorectal cancers and 12 cases of familial polyposis coli. Colorectal cancer was classified into two groups: those accompanied by intramucosal growth or with polypoid growth and those without polypoid growth. Early cancer in the group without polypoid growth was considered to originate from de novo carcinoma of about 5 mm, showing vascular invasion when reaching the size of about 10 mm and then exhibiting massive submucosal invasion. Their cut-surface closely simulated cancer of ulcerative type without polypoid growth which occupied the greater portion of advanced cancer of the large bowel. In other words, ulcerative type cancer without polypoid growth is considered to arise from de novo carcinoma and this type occupies 70-90% of all colorectal cancers. Since the lesions originating from de novo carcinoma develops from an extremely small intramucosal carcinoma and then leads to a massive submucosal growth, immediate partial resection is recommended.
Adenoma↗
Comparison of four surfactants: in vitro surface properties and responses of preterm lambs to treatment at birth.
Natural sheep surfactant, rabbit surfactant, human surfactant, and surfactant TA were compared for in vitro surface properties and for responses of preterm lambs to treatment. Equivalent amounts of sheep, rabbit, and human surfactants were needed to lower the surface tension to less than 10 dynes/cm, whereas four times less surfactant TA similarly lowered the surface tension. Surface-spreading rates were similar for the surfactants. The surface adsorption of the batch of human surfactant tested was much slower than was adsorption of the other surfactants. Ventilation was significantly improved in all surfactant-treated lambs relative to the control lambs, indicating the general efficacy of the surfactant treatments. Overall, surfactant TA had the best in vitro characteristics, yet the preterm lambs treated at birth with surfactant TA had lower PO2 values and higher ventilatory requirements than did the sheep surfactant-treated lambs. The in vivo responses to rabbit surfactant were intermediate between the responses to sheep surfactant and to surfactant TA. Human surfactant resulted in the least effective clinical response. More of the phosphatidylcholine associated with human surfactant and surfactant TA was lost from the alveoli and lung tissue after four hours of ventilation than was lost from sheep or rabbit surfactant-treated lambs. More intravascular radiolabeled albumin leaked into the alveoli of the surfactant TA-treated lambs than sheep or rabbit surfactant-treated lambs. The four surfactants also had different sensitivities to the effects on minimum surface tensions of the soluble proteins present in alveolar washes. The study demonstrates that the range of clinical responses was not predictable based on the in vitro surface properties that we measured.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Gene transfer into intact plant cells by electroinjection through cell walls and membranes.
Tobacco mosaic virus (TMV) RNA was introduced directly into mesophyll cells of Nicotiana tabacum var. Samsun using electric-field pulses (electroinjection). The injected gene was successfully expressed in the recipient cells as judged by the assay for the virus coat protein using immunofluorescence and by the virus infectivity assay of the homogenate of the electroinjected cells for local lesions on tobacco leaves. As much as 50% of the cells that survived 24 days after electroinjection showed immunofluorescent specks.
Capsid↗
Respiratory distress and surfactant inhibition following vagotomy in rabbits.
We used the model of bilateral cervical vagotomy of adult rabbits to cause respiratory failure characterized by pulmonary edema, decreased lung compliance, and atelectasis. We documented an 18-fold increase in radiolabeled albumin leak from the vascular space into alveolar washes of vagotomy vs. sham-operated rabbits (P less than 0.01). Despite a twofold increase in percent of prelabeled saturated phosphatidylcholine secreted (P less than 0.01), the alveolar wash saturated phosphatidylcholine pool sizes were not different. The minimum surface tensions were 19.6 +/- 2.5 vs. 9.4 +/- 2.2 dyn/cm for alveolar washes from vagotomy and control rabbits, respectively (P less than 0.01). The soluble proteins from alveolar washes inhibited the surface tension lowering properties of natural surfactant, whereas those from the control rabbits did not (P less than 0.01). When vagotomy rabbits in respiratory failure were treated with 50 mg natural surfactant lipid per kilogram arterial blood gas values and compliances improved relative to control rabbits. Vagotomy results in alveolar pulmonary edema, and surfactant dysfunction despite normal surfactant pool sizes and respiratory failure. A surfactant treatment can improve the respiratory failure.
Animals↗
Hemodynamic effects of high frequency ventilation in surfactant-treated preterm lambs.
We compared the hemodynamic status and left ventricular (LV) performance in 7 twin pairs of preterm lambs delivered at 124 days gestational age (83% of term gestation) and ventilated by either conventional ventilation (CV) or high frequency ventilation (HFV) at 15 Hz. The lambs were treated with suspensions of natural sheep surfactant to permit ventilation and survival, and ventilatory settings were adjusted to maintain physiologic blood gas values. The ductus arteriosus was occluded with a balloon catheter at 40-45 min of age to eliminate the variable of a left to right ductal shunt. Cineangiocardiographic, pressure, and blood flow measurements were made 1 and 2 h after ductal occlusion. At the same mean airway pressures, the heart rates, LV end-diastolic volumes, and mean arterial pressures were similar in both groups. LV stroke volumes, ejection fractions, LV outputs, and organ blood flows also did not differ between the two groups. When compared with CV, HFV provides comparable ventilation with no apparent deleterious hemodynamic effects in preterm surfactant-treated lambs with occluded ductus arteriosus.
Acid-Base Equilibrium↗
A protein that inhibits surfactant in respiratory distress syndrome.
A protein that interferes with surfactant function is present in the airways and alveoli of infants with respiratory distress syndrome (RDS). This inhibitor is also found in serum and amniotic fluid and presumably appears in the alveoli because of the abnormal protein leak present in the lungs of infants with RDS. This protein has a molecular weight of about 110,000 and is resistant to boiling or lipid extraction. As measured by radioimmunoassay, the ratio of inhibitor to phosphatidylcholine decreased from 8.1 +/- 2.3 early in the course of RDS to 0.7 +/- 0.1 on the day of extubation. The value at extubation was the same as that measured for preterm infants without RDS. The inhibitor to phosphatidylcholine ratio in airway samples from infants with RDS correlated significantly with simultaneously recorded pO2/FiO2 ratios and the peak inspiratory pressures used to normalized pCO2 values. These results are consistent with the concept that the inhibitor contributes to surfactant dysfunction and thus the respiratory failure characteristic of RDS.
Amniotic Fluid↗
Left ventricular performance and contractility before and after volume infusion: a comparative study of preterm and full-term newborn lambs.
We studied left ventricular performance and contractility after volume loading in lambs at 122 days (group I, n = 9) and 139 days gestational age (group II, n = 9) and in 8-day-old full-term lambs (group III, n = 7). All were mechanically ventilated; each preterm lamb was treated with surfactant to stabilize pulmonary function and the ductus arteriosus was occluded with an inflated catheter balloon. Cineangiograms, left ventricular and vascular pressures, and the isovolumetric index of contractility, first derivative of left ventricular pressure (dP/dt), were recorded before and after three successive whole blood volume infusions of 10 ml/kg (total 30 ml/kg). The left ventricular end-diastolic volume per kilogram and stroke volume per kilogram increased significantly in all groups after volume infusion; these measurements and heart rate and systemic vascular resistance did not differ significantly between the groups either before or after the infusions. The left ventricular peak dP/dt did not change significantly within the groups during the volume infusions. The left ventricular stroke work was greatest in full-term animals and increased significantly in all groups after volume infusion. Thus, the left ventricles of the preterm and full-term lambs had quantitatively similar Frank-Starling responses and there was no increase in contractility during the infusions of whole blood. However, the left ventricle of the full-term lamb is capable of generating greater stroke work than that of the preterm lamb. These findings may contribute to the understanding of development aspects of postnatal circulatory adaptation.
Animals↗
Clearance of natural surfactant phosphatidylcholine from 3-day-old rabbit lungs: effects of dose and species.
Surfactants were labeled in vivo with [3H] choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 +/- 1.8% per 24 h (mean +/- SE) of the injected doses of surfactant that contained from 0.41 to 10.2 mumol phosphatidylcholine. At all times following injection, approximately 50% of the labeled phosphatidylcholine remaining within the lungs was recovered in the alveolar wash and 50% with the lung tissue. The percent clearances for sheep, cat, and pig surfactant phosphatidylcholine in rabbits were 12.5, 16.6, and 16.3% per 24 h, respectively, values not different from that measured for rabbit surfactant. The results documented a slow clearance of exogenously administered surfactant phosphatidylcholine as a fixed percent of the injected dose that was unchanged by species source of the surfactant.
Animals↗
Reutilization of surfactant phosphatidylcholine in adult rabbits.
32P-saturated phosphatidylcholine was added to [3H]choline-labeled natural surfactant and the mixture was injected intratracheally into 87 adult rabbits. The rabbits were also given [14C]palmitate intravenously at the same time. Rabbits were killed in groups from 10 min to 72 h after injection. In each rabbit we measured the total recovered [3H]phosphatidylcholine (PC) in the alveolar wash, the ratio of [3H]PC to [32P]PC in the alveolar wash, and the specific activity of [14C]PC in the alveolar wash and lamellar bodies. Values were averaged for all rabbits killed at the same times and smooth curves were fit to the data by computer. From the intravenous [14C]palmitate data we calculated a turnover time for alveolar PC of 6.0 h. From the intratracheal labeling data, we calculated a turnover time for alveolar PC of 5.7 h and determined that alveolar PC was reutilized at an efficiency of only 23%. We also concluded that this reutilization occurred as intact molecules.
Animals↗
Liposomes of dipalmitoylphosphatidylcholine associate with natural surfactant.
Unilamellar liposomes of an average diameter of 0.05 micron formed by sonication of dipalmitoylphosphatidylcholine associate in vitro with the large aggregate forms of natural surfactant. The liposomal-surfactant aggregates are stable and previously associated liposomes are not released from the aggregates by the addition of more liposomes. Radiolabeled liposomes, surfactant, and preformed liposomal-surfactant aggregates were injected at a dose of 8-10 mg lipid (about 2-times the endogenous surfactant pool size) into the airways of 3-day-old rabbits. Following airway injection, labeled phosphatidylcholine from the liposomal-surfactant aggregates were recovered in approximately equal amounts by alveolar wash and in the residual lung tissue fractions. This recovery pattern and the clearance kinetics were equivalent for 48 h after airway injection to those measured with radiolabeled surfactant alone. In contrast, following the injection of liposomes alone, labeled phosphatidylcholine from the liposomes was recovered primarily by alveolar wash at 3 and 24 h. The overall clearance of the liposomal-derived phosphatidylcholine from the lung was more rapid than was the clearance of the phosphatidylcholine from the surfactant or liposome-surfactant complexes. Liposomes can interact with surfactant in vitro, and the liposomes associated with the surfactant aggregate have a metabolic fate in vivo similar to surfactant and different from liposomes alone.
Animals↗
Reutilization of phosphatidylglycerol and phosphatidylethanolamine by the pulmonary surfactant system in 3-day-old rabbits.
Developing rabbits reutilize the phosphatidylcholine of surfactant with an efficiency of about 95%. The efficiency of reutilization of other components of surfactant have not been determined. 3-day-old rabbits were injected intratracheally with [3H]dipalmitoylphosphatidylcholine (DPPC) mixed with unlabeled natural surfactant and either disaturated [32P]phosphatidylglycerol (DSPG) or [14C]dipalmitoylphosphatidyl-ethanolamine (DPPE). The recovery of [3H]DPPC, [14C]DPPE, and [32P]DSPG in the alveolar wash was measured at different times after injection. By plotting the ratio of [32P]DSPG to [3H]DPPC or [14C]DPPE to [3H]DPPC counts/min in the alveolar wash vs. time after injection we showed that these two phospholipids are reutilized less efficiently than phosphatidylcholine. Based on other studies, several assumptions were made about the kinetics of surfactant phosphatidylethanolamine and phosphatidylglycerol. From the slopes of the semilog plots of total [14C]DPPE and total [32P]DSPG counts/min in the alveolar wash vs. time and these assumptions, we determined that these two phospholipids were reutilized at an efficiency of only 79%.
Age Factors↗