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Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 91 records · Page 5Linked to original sources
PubMed1999

Positive end-expiratory pressure preserves surfactant function in preterm lambs.

Ventilation style influences lung injury and the amount of large-aggregate biophysically active surfactant in adult lungs. We asked how positive end-expiratory pressures (PEEP) would influence clinical responses and surfactant pools in surfactant-treated preterm lambs ventilated for 7 h with tidal volumes (VT) of 10 ml/kg. The 126-d gestation preterms were delivered and treated with 100 mg/kg recombinant human surfactant protein C (rSP-C) containing surfactant and ventilated with zero, 4, or 7 cm H(2)O of PEEP. A comparison group was treated with natural sheep surfactant and ventilated with zero PEEP. Physiologic measurements were similar for lambs treated with rSP-C surfactant and natural surfactant. PEEP 4 and 7 improved oxygenation and compliance relative to either group of lambs ventilated with PEEP zero. The maximal lung volumes measured at 40 cm H(2)O pressure after 7 h ventilation for the PEEP 4 and 7 groups were more than double those measured for either PEEP zero group. Alveolar surfactant pools were larger for the PEEP 7 group, and the large-aggregate fraction was increased for the PEEP 4 and 7 groups, resulting in large-aggregate pool sizes that were 3-fold higher for the PEEP 4 and 4-fold higher for the PEEP 7 groups relative to the PEEP zero group treated with rSP-C surfactant. All large-aggregate surfactants lowered minimal surface tensions of a captive bubble to less than 5 mN/m. In preterm surfactant-treated lambs PEEP improved lung function and maintained more of an rSP-C surfactant in the biophysically active form.

Adult↗
PubMed1999

Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids.

We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-(13)C]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Palmitic acid in surfactant PC became enriched 27 +/- 2 h after the start of the isotope infusion and was maximally enriched at 100 +/- 4 h. The fractional synthesis rate of PC palmitate in the beta group (1.5 +/- 0.2%/d) was increased by 129% above control (0.7 +/- 0.1%/d) (p < 0.02, Mann- Whitney U test). The absolute synthesis rate of PC in the beta group [1.6 +/- 0.3 micromol/kg/d] was increased by 128% above controls [0.7 +/- 0.2 micromol/kg/d] (p < 0.02). These data show that the synthesis of endogenous surfactant from plasma glucose as precursor is a slow process. It is shown, for the first time in vivo, that prenatal glucocorticosteroids stimulate the synthesis of surfactant PC in the very premature baboon.

Animals↗
PubMed1999

Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A.

Pulmonary surfactant protein-A (SP-A) has been reported to regulate the uptake and secretion of surfactant by alveolar type II cells, to stabilize large surfactant aggregates including tubular myelin, and to protect the surface activity of surfactant from protein inhibitors. In this study we investigated the consequences of overexpression of SP-A on pulmonary homeostasis and surfactant function in transgenic mice. The human SP-C promoter was used to direct synthesis of rat surfactant protein A (rSP-A) in alveolar type II cells and nonciliated bronchiolar cells of the distal respiratory epithelium. Levels of SP-A measured through enzyme-linked immunosorbent assay were 7- to 8-fold higher in lung homogenates and alveolar lavage fluid of the rSP-A mice than in those of transgene-negative littermates. The swimming exercise tolerance and lung compliance of mice bearing the transgene were unchanged. Mean air space sizes seen in randomly selected light-microscopic fields were not significantly different in the transgene-positive and -negative mice by morphometric analysis, but 15% of transgenic animals had scattered foci containing dilated alveoli and alveolar ducts without evidence of inflammation or fibrosis. Some alveolar macrophages contained bar-shaped osmophilic inclusions that had a highly ordered ultrastructure. There were no differences between the transgene-positive and -negative mice in the tissue or alveolar pool sizes of saturated phosphatidylcholine or in the large-aggregate composition of alveolar surfactant. The surface activity of surfactant isolated from the rSP-A mice was similar to that of the controls, but in the presence of protein inhibitors, the surface tension-reducing properties of the rSP-A surfactant were better preserved (P < 0.05). We conclude that overexpression of SP-A does not affect resting surfactant phospholipid levels, but that it enhances the resistance of surfactant to protein inhibition.

Animals↗
PubMed1999

Lung morphometry and collagen and elastin content: changes during normal development and after prenatal hormone exposure in sheep.

This study examined whether the improvement in lung function after prenatal hormone exposure coincided with changes in lung morphometry or in collagen and elastin content. Fetal lambs received a single intramuscular injection of betamethasone (0.5 mg/kg) plus L-thyroxine (T4) (15 micrograms/kg) or vehicle control 48 h before delivery at 121, 128, or 135 d gestational age (d 121, d 128, d 135, term = 150 d). T4 was administered in conjunction with betamethasone in an attempt to enhance the maturational response. The right-upper lobes were instillation fixed at 30 cm H2O by Karnovsky's fixative after a 40-min period of mechanical ventilation. A number of significant changes occurred between d 121 and d 135 in control animals: alveolar airspace volume increased by 270%; despite a 40% reduction in alveolar septal thickness, alveolar septal volume did not change appreciably, suggesting a "redistribution" of septal tissue into the formation of secondary alveolar septa, which doubled in number; and both parenchymal collagen and elastin volume increased significantly, whereas pleural collagen and elastin volume did not change. In contrast to the changes seen in control animals, exposure to betamethasone plus T4 led to alveolar septal thinning at each gestational age without an associated increase in secondary septal number, a 40% decrease in alveolar septal volume, and a proportionate reduction in parenchymal elastin at d 121. Although attenuation of alveolar septa coincides with redistribution of septal tissue into the formation of secondary septa during normal maturation, exposure to betamethasone plus T4 promotes thinning of alveolar septa in the absence of secondary septal formation, which results in a loss of alveolar septal tissue.

Aging↗
PubMed1999

Surfactant protein B corrects oxygen-induced pulmonary dysfunction in heterozygous surfactant protein B-deficient mice.

Surfactant protein B (SP-B) is a 79-amino acid hydrophobic surfactant protein that plays a critical role in postnatal lung function. Homozygous SP-B (-/-)-deficient mice die of respiratory failure at birth, associated with severe pulmonary dysfunction and atelectasis. Heterozygous SP-B (+/-)-deficient mice have 50% less SP-B protein, proprotein, and SP-B mRNA compared with control mice and are highly susceptible to oxygen-induced lung injury. In the current study, we tested whether the susceptibility of SP-B (+/-) mice to hyperoxia was restored by intratracheal administration of exogenous SP-B. After exposure to 95% oxygen for 3 d, opening pressures were increased and maximal lung volumes were significantly decreased in SP-B (+/-) mice compared with SP-B (+/+) mice. SP-B (+/-) mice were administered purified bovine SP-B (2%) with DL-alpha dipalmitoyl phosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-( -glycerol)] (POPG) phospholipids or DPPC and POPG phospholipids intratracheally and exposed to 95% oxygen. SP-B-treated SP-B (+/-) mice survived longer in 95% oxygen. Although decreased lung function in SP-B (+/-) mice exposed to oxygen was not altered by administration of DPPC and POPG, administration of lipids containing 2% purified bovine SP-B restored lung function when assessed after 3 d in oxygen. Abnormalities in pulmonary function in SP-B (+/-) mice after oxygen exposure were associated with increased alveolar capillary leak, which was corrected by administration of SP-B with DPPC and POPG. Likewise, histologic abnormalities caused by oxygen-induced lung injury were improved by administration of SP-B with DPPC and POPG. Administration of phospholipids with the active SP-B peptide was sufficient to restore pulmonary function and prevent alveolar capillary leak after oxygen exposure, demonstrating the protective role of SP-B during oxygen-induced lung injury.

Animals↗
PubMed1999

[Evaluation of blood flow in transplanted kidney by flow profile].

BACKGROUND: The clinical usefulness of color Doppler method with flow profile for examination of blood flow in the transplanted kidney was evaluated. PROCEDURE: We measured blood flow in the transplanted kidney by flow profile in 14 renal recipients. RESULTS: Blood flow in the renal arteries in recipients with graft dysfunction was significantly lower than those in recipients with good graft function. There was significant correlation between blood flow in the renal arteries and graft function. In addition, in the segmental arteries, there was significant correlation between peak flow velocity and blood flow. But there was no significant correlation between index of resistance and blood flow in the transplanted kidney. CONCLUSIONS: Measurement of blood flow by flow profile may improve the examination capability of color Doppler ultrasonography of the transplanted kidney.

Blood Flow Velocity↗
PubMed1998

Surfactant protein metabolism in vivo.

The surfactant components saturated phosphatidylcholine, SP-B and SP-C, are secreted together in lamellar bodies, and at least a part of the de novo synthesized SP-A is secreted independently. The surface film forms from tubular myelin and loose lipid arrays, and it generates unilamellar vesicles that lack surfactant proteins and are thought to represent catabolic forms. The half-life values for the clearance of surfactant proteins from lungs range from 6.5 to 28 h and vary with species. There is minimal information about the associations of the surfactant proteins with lipids or with each other after film formation, although all surfactant components seem to be recycled back into lamellar bodies in type II cells. The relative importance of type II cells or macrophages to the catabolism of the protein components of surfactant remains to be characterized, as do regulators of surfactant homeostasis.

Animals↗
PubMed1998

Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo.

Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (+/-) and SP-D (-/-) mice. Both SP-D (-/-) and SP-D (+/-) mice survived normally in the perinatal and postnatal periods. Whereas no abnormalities were observed in SP-D (+/-) mice, alveolar and tissue phosphatidylcholine pool sizes were markedly increased in SP-D (-/-) mice. Increased numbers of large foamy alveolar macrophages and enlarged alveoli were also observed in SP-D (-/-) mice. Phospholipid composition was unaltered in SP-D (-/-) mice, but surfactant morphology was abnormal, consisting of dense phospholipid membranous arrays with decreased tubular myelin. The pulmonary lipoidosis in the SP-D (-/-) mice was not associated with accumulation of surfactant proteins B or C, or their mRNAs, distinguishing the disorder from alveolar proteinosis syndromes. Surfactant protein A mRNA was reduced and, SP-A protein appeared to be reduced in SP-D (-/-) compared with wild type mice. Targeting of the mouse SP-D gene caused accumulation of surfactant lipid and altered phospholipid structures, demonstrating a previously unsuspected role for SP-D in surfactant lipid homeostasis in vivo.

Animals↗
PubMed1998

Production of toxic shock syndrome toxin by Staphylococcus aureus isolated from mastitic cow's milk and farm bulk milk.

The production of toxic shock syndrome toxin (TSST) by Staphylococcus aureus isolated from mastitic cow's milk and farm bulk milk was examined by a reverse passive latex agglutination method (RPLA). TSST was detected in 25 (58.1%) of 43 isolates from clinical mastitic cow's milk, in 79 (76.7%) of 103 isolates from subclinical mastitic cow's milk, and in 95 (75.4%) of 126 isolates from farm bulk milk, respectively. When the quantity of TSST in the isolates was determined by RPLA, the titers ranged from 5 to 2560. TSST with RPLA titers of 640 to 2,560 was produced by 83 (30.5%) of 272 isolates tested. Almost all of the isolates showing RPLA titers of 640 and over produced enterotoxin C, whereas isolates showing titers of 5 to 320 produced enterotoxin C or both enterotoxin A and C. SDS-polyacrylamide gel electrophoresis and isoelectric focusing with immunoblotting showed that the TSST from bovine isolates had same molecular size (22 kDa) and isoelectric point (7.2) as TSST-1 from human isolates. These findings are consistent with previous reports.

Animals↗
PubMed1998

Breast masses: color Doppler, power Doppler, and spectral analysis findings.

PURPOSE: To determine the diagnostic efficacy of power Doppler sonography (PDS) with spectral analysis for breast diseases, we retrospectively compared PDS and color Doppler sonography (CDS) in patients with breast lesions. METHODS: One hundred thirty-eight women with palpable breast lesions were examined with PDS (65 women) and/or CDS (73 women). We calculated peak velocity, end-diastolic velocity, pulsatility index (PI), and resistance index (RI). RESULTS: On a 4-point subjective visual vascularity scale, PDS demonstrated higher vascularity than did CDS. Although smaller and more subtle vessels could be detected only with PDS, the PI and RI differed significantly between malignant and benign lesions when either PDS or CDS was used. However, logistic regression analysis showed that high PI and RI were associated with malignancy only when CDS was used. When PDS was used, PI was significantly higher in invasive ductal carcinomas with fibrous stroma and ill-defined margins (associated with a poor prognosis) than in invasive ductal carcinomas without fibrous stroma or with well-defined margins. CONCLUSIONS: Doppler spectral analysis of malignant breast lesions using PDS may contribute to the determination of prognosis.

Breast Neoplasms↗
PubMed1998

Complete nucleotide sequence of the genome organization of RNA2 of patchouli mild mosaic virus, a new favavirus.

The complete nucleotide sequence and the genome organization of the RNA 2 of a patchouli mild mosaic virus (PaMMV) was determined. The sequence consists of 3591 nucleotides and contains a single long open reading frame sufficient to code for 118 K protein. Three proteins of 52 K, 44 K and 22 K could be encoded by the PaMMV RNA 2 genome. Our analysis of the N-terminal sequences of two species of coat protein (CP) allowed precise location of the CP cistrons within the polyprotein. 44 K and 22 K proteins are the coat proteins. The positions of the cleavage sites are Gln/Ala between 44 K and 22 K coat proteins and Gln/Gly between 52 K and 44 K proteins. Comparison of PaMMV RNA 2 with comoviral and nepoviral RNA 2 showed no sequence similarity. These results as well as previous serological studies strongly suggest that PaMMV is a member in the genus Fabavirus.

Capsid↗
PubMed1998

Single and repetitive maternal glucocorticoid exposures reduce fetal growth in sheep.

OBJECTIVE: We evaluated the effects of single or three repeated doses of maternal betamethasone on fetal growth at preterm and term delivery in sheep. STUDY DESIGN: Pregnant ewes were randomly assigned to receive one dose of 0.5 mg/kg betamethasone at 104 days' gestational age; three doses of betamethasone at 104, 111, and 118 days' gestational age; or saline for controls. Lambs were delivered at 125 days' (preterm) or at 145 days' (term) gestational age for assessments of fetal growth. RESULTS: The single betamethasone exposure at 104 days' gestational age caused symmetric growth retardation of 11% at 125 days' gestational age and 14% at term. The three-dose exposures decreased body weights by 25% in preterm lambs and by 19% at term. Organ protein and deoxyribonucleic acid per kilogram of body weight were selectively decreased in preterm lambs. At term the decreases in organ weight, protein, and deoxyribonucleic acid were proportionate to the decreased birth weight. CONCLUSION: One or three doses of maternal glucocorticoids begun at an early gestational age caused symmetric growth retardation in lambs delivered prematurely, and the decreased fetal size persisted to term.

Animals↗
PubMed1998

Mechanisms initiating lung injury in the preterm.

Bronchopulmonary dysplasia (BPD)/chronic lung disease occurs primarily in very low birth weight infants (VLBW) often without antecedent severe respiratory distress syndrome. The BPD in these VLBW infants results in less fibrosis than the traditional BPD but the normal process of alveolarization seems to be disrupted. This review develops the thesis that BPD in VLBW infants results from inflammatory mediators interfering with the signaling required for normal late gestational lung development. Proinflammatory mediators may be elevated because of fetal exposure, postnatal infection or by release from preterm lungs ventilated at either low or high lung volumes. The preterm lung is highly susceptible to injury during resuscitation or more chronic mechanical ventilation because the gas volumes/kg body weight of the lungs are small. An understanding of what causes cytokine release and how cytokines influence lung development is necessary to develop targeted therapies to minimize BPD. However, care strategies that minimize inflammation and ventilator-induced lung injury should help decrease BPD.

Bronchopulmonary Dysplasia↗
PubMed1998

Clearance of SP-C and recombinant SP-C in vivo and in vitro.

Surfactant protein (SP) C metabolism was evaluated in vivo by measurements of the clearance of bovine native SP-C (nSP-C) and a recombinant SP-C (rSP-C) in rabbits and mice and in vitro by the uptake into MLE-12 cells. rSP-C is the 34-amino acid human sequence with phenylalanine instead of cysteine in positions 4 and 5 and isoleucine instead of methionine in position 32. Alveolar clearances of iodinated SP-C and rSP-C after tracheal instillation were similar and slower than those for dipalmitoyl phosphatidylcholine (DPC) in the rabbit. nSP-C and rSP-C were cleared from rabbit lungs similarly to DPC, each with a half-life (t1/2) of approximately 11 h. In mice, the clearance of rSP-C from the lungs was slower (t1/2 28 h) than the clearance of DPC (t1/2 12 h). Liposome-associated dinitrophenyl-labeled rSP-C was taken up by MLE-12 cells, and the uptake was inhibited by excess nSP-C. The pattern of inhibition of dinitrophenyl-rSP-C uptake by SP-B, but not by SP-A, was similar to that previously reported for nSP-C. Clearance kinetics of nSP-C were similar to previous measurements of pulmonary clearance of SP-B in rabbits and mice. rSP-C has clearance kinetics and uptake by cells similar to those of nSP-C.

Animals↗
PubMed1998

Characteristics of surfactant from SP-A-deficient mice.

Mice that are surfactant protein (SP) A deficient [SP-A(-/-)] have no apparent abnormalities in lung function. To understand the contributions of SP-A to surfactant, the biophysical properties and functional characteristics of surfactant from normal [SP-A(+/+)] and SP-A(-/-) mice were evaluated. SP-A-deficient surfactant had a lower buoyant density, a lower percentage of large-aggregate forms, an increased rate of conversion from large-aggregate to small-aggregate forms with surface area cycling, increased sensitivity to inhibition of minimum surface tension by plasma protein, and no tubular myelin by electron microscopy. Nevertheless, large-aggregate surfactants from SP-A(-/-) and SP-A(+/+) mice had similar adsorption rates and improved the lung volume of surfactant-deficient preterm rabbits similarly. Pulmonary edema and death caused by N-nitroso-N-methylurethane-induced lung injury were not different in SP-A(-/-) and SP-A(+/+) mice. The clearance of 125I-labeled SP-A from lungs of SP-A(-/-) mice was slightly slower than from SP-A(+/+) mice. Although the absence of SP-A changed the structure and in vitro properties of surfactant, the in vivo function of surfactant in SP-A(-/-) mice was not changed under the conditions of these experiments.

Adsorption↗