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Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 145 records · Page 8Linked to original sources
PubMed1996

Gastric mucus generation in cirrhotic patients with portal hypertension. Effects of tetraprenylacetone.

We have evaluated gastric mucus generation (study 1) and the effects of tetraprenylacetone on gastric mucus generation (study 2) in cirrhotic patients with portal hypertension. Study 1: Included were 50 noncirrhotics (group A), 25 cirrhotics without portal hypertension (group B), and 25 cirrhotics with portal hypertension (group C). The antrum, corpus, and fundus mucus generation was assessed by hexosamine concentration using biopsy specimens. In groups A and B, the antrum hexosamine concentration was significantly higher compared with the corpus (P < 0.01, P < 0.01) and the fundus (P < 0.01). In contrast, the hexosamine concentration at each location was similar in group C. Furthermore, the antrum hexosamine concentration of group C was significantly lower compared with that of group A (P < 0.05). In study 2, a double-blind design, 300 mg of tetraprenylacetone was administered for four weeks in 10 cirrhotics with portal hypertension and placebo in 10. The regional hexosamine concentrations were measured before and after drug administration. Placebo administration did not change hexosamine concentration at each location. In contrast, tetraprenylacetone increased the antrum and corpus hexosamine concentration (P < 0.01, P < 0.05), although the fundus concentration did not change. These data suggest that cirrhotics with portal hypertension have reduced gastric antral mucus generation and tetraprenylacetone normalizes this.

Anti-Ulcer Agents↗
PubMed1996

Differing patterns of mechanical response to direct fetal hormone treatment.

A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age; however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Airway Resistance↗
PubMed1996

Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs.

OBJECTIVE: We hypothesized that fetal betamethasone exposure for < 24 hours would improve postnatal lung function in preterm lambs. STUDY DESIGN: Singleton fetal sheep were randomized to receive by ultrasonographically guided fetal injections of 0.5 mg/kg betamethasone or saline solution either 8 or 15 hours before preterm delivery and postnatal assessment of lung function. RESULTS: After the 15-hour fetal treatment-to-delivery interval, betamethasone-treated lambs had twofold improvement in compliance and lung volumes, a fourfold to fivefold decrease in edema index, and higher blood pressures than saline solution-treated lambs. Postnatal lung function or lung volumes did not improve for the 8-hour treatment-to-delivery interval, although betamethasone decreased the pulmonary edema and increased the postnatal blood pressure. CONCLUSIONS: The minimal interval from fetal exposure to corticosteroids to delivery for improved postnatal lung function was between 8 and 15 hours. Corticosteroid effects on pulmonary edema and blood pressure occurred within 8 hours.

Animals↗
PubMed1996

Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation.

Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate and choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF-deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfactant protein A (SP-A) given by tracheal instillation were cleared rapidly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-deficient mice was normal when tested in preterm surfactant-deficient rabbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Higher lung antioxidant enzyme activity persists after single dose of corticosteroids in preterm lambs.

Although administration of exogenous corticosteroids accelerates the late gestational rise in fetal rat and lamb lung antioxidant enzyme activity, the effect of dosing intervals on these responses remains uncertain. We studied the persistence and efficacy of the antioxidant response in fetal lamb lung to a single fetal dose of corticosteroids injected between 121 and 127 days gestational age. Fetal lambs received 0.5 mg/kg of betamethasone (n = 35) or saline (n = 26) by fetal intramuscular injection 24 h, 48 h, 4 days, or 7 days before preterm delivery at 128 days gestation (term = 150 days). After delivery, the lambs were ventilated for 40 min and killed. Total superoxide dismutase, catalase, glutathione peroxidase activities, and lipid hydroperoxide levels were measured, using homogenized lung. The saline-injected controls were similar at all time points. Lung antioxidant enzyme activity was consistently higher and lipid hydroperoxide presence was lower in the betamethasone-treated groups. We conclude that the positive effect of a single fetal dose of betamethasone on lung antioxidant enzyme activity occurs within 24 h after exposure, persists over a period of 7 days without a major change in the magnitude of the response, and leads to a reduction in lipid hydroperoxide formation during immediate postdelivery oxygen exposure.

Animals↗
PubMed1996

Effect of interval from fetal corticosteriod treatment to delivery on postnatal lung function of preterm lambs.

The effect of altering the interval from treatment to delivery on postnatal lung function of the preterm lamb is unknown. We treated groups of 8-10 singleton fetal sheep with 0.5 mg/kg betamethasone by fetal injection and evaluated postnatal lung function 40 min after preterm delivery at 123 days gestation 2 days after treatment or at 128 days gestation 2, 4, and 7 days after treatment relative to groups of 4-8 saline-injected control animals. At 123 days, betamethasone significantly improved arterial PCO2, dynamic thoracic compliance, and ventilatory efficiency index and doubled lung gas volume relative to a control group. Fetal treatment with betamethasone 2, 4, or 7 days before delivery at 128 days also improved these same indicators of lung function relative to controls, and the magnitude of the improvements was the same for all indicators and independent of treatment-to-delivery interval. Betamethasone suppressed the normal postnatal increase in plasma cortisol after 2 and 4 days of exposure but not after 7 days of exposure. Betamethasone also increased fetal and postnatal triiodothyronine concentrations after 2 days of exposure but not at 4 or 7 days of exposure. Although the hormone effects were transient, postnatal lung functional responses to betamethasone persisted over the 2- to 7-day interval from treatment to delivery.

Adrenal Cortex Hormones↗
PubMed1996

Postnatal lung responses and surfactant function after fetal or maternal corticosteroid treatment.

To evaluate the effect of dose and route of administration of betamethasone on subsequent postnatal lung function, pregnant ewes were randomized at 127 days gestation to receive maternal or fetal intramuscular doses of 0.2 or 0.5 mg/kg body wt betamethasone or saline. At delivery 24 h later, preterm lambs were treated with surfactant and ventilated for 4 h. The lambs exposed to 0.5 mg/kg betamethasone by either the maternal or fetal route had higher Po2 values, lung volumes, dynamic compliances, and ventilatory efficiency indexes, as well as lower ventilatory pressure requirements, than did control animals (P < 0.05). There were no consistent improvements in postnatal lung function for the 0.2 mg/kg dose given to the fetus or ewe. However, measurements of radiolabeled protein in the total lung were decreased in all treatment groups (P < 0.01). Surfactant that was recovered from all groups of lambs and fractionated to isolate the large-aggregate fraction improved lung volumes in preterm rabbits to a greater degree than the surfactant used to treat the lambs (P < 0.05). Surfactant recovered from both groups treated with 0.5 mg/kg betamethasone was less sensitive to inactivation by plasma than was surfactant from the 0.2 mg/kg groups or the controls (P < 0.01). Fetal or maternal treatment with 0.5 mg/kg betamethasone improved postnatal lung function and increased the resistance of surfactant to inactivation.

Adrenal Cortex Hormones↗
PubMed1996

Surfactant inhibition by plasma: gestational age and surfactant treatment effects in preterm lambs.

The preterm infant with respiratory distress syndrome has edematous lungs and small amounts of surfactant that do not function normally. We reported that surfactant recovered from preterm lambs after surfactant treatment can have decreased sensitivity to inhibition of surface tension by plasma. We asked whether this augmented resistance to inhibition was dependent on lung development (gestational age) by testing sensitivity to plasma inhibition of 1) endogenous surfactant from preterm lambs and 2) surfactant from preterm lambs after treatment with an organic solvent-extracted natural sheep surfactant. Surfactant recovered after surfactant treatment of 121- or 128-days-gestation lambs had the same sensitivity to plasma inhibition as did the surfactant used to treat the lambs. Surfactant recovered from 134-days-gestation lambs had decreased sensitivity to inhibition. Lung maturation is a variable influencing surfactant inhibition by plasma.

Animals↗
PubMed1996

Change in properties of exogenous surfactant in injured rabbit lung.

We asked if the function of surfactant could be enhanced after exposure to injured lungs. We also asked if sensitivity to inhibition of the minimal surface-tension-lowering properties of surfactant by plasma could be altered. Lung injury in rabbits was induced with N-nitroso-N-methylurethane (NMU) and 6 of 17 NMU-injured rabbits were treated with 100 mg/kg surfactant. All rabbits were ventilated for 2 h, and large aggregate alveolar surfactant was isolated by centrifugation. In vivo function of the large aggregate surfactant was evaluated by treatment of preterm surfactant-deficient rabbits at 27 d gestation. Surfactant from NMU-injured lungs increased compliance from 0.37 +/- 0.01 in control preterm rabbits to 0.71 +/- 0.05, a value significantly higher than found for the surfactant used for treatment (0.55 +/- 0.04) (p < 0.05). The minimal surface tensions of large aggregate surfactant and the surfactant used for treatment (0.1 mg lipid/ml) were evaluated for inhibition by plasma proteins. Surfactant from NMU-injured and surfactant-treated rabbits was more resistant to inhibition (minimal surface tension, 5.7 +/- 3.9 dyne/cm in the presence of 0.6 mg/ml plasma protein) than the surfactant used for treatment (19.7 +/- 0.8 dyne/cm). These results indicate that after exposure to the injured lung, the function of the surfactant used for treatment was enhanced and made less sensitive to plasma inhibition of the surface-tension-lowering properties of surfactant. These changes probably result from the association of endogenous surfactant components with exogenous surfactant.

Animals↗
PubMed1996

Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm lambs.

To evaluate the efficiency and distribution of ultrasonic nebulized versus instilled surfactant in the treatment of surfactant deficiency at varying degrees of maturation, twin or triplet lamb fetuses were delivered at 125 to 137 d gestational age and received nebulized natural surfactant (Neb Only), instilled surfactant followed by a second instilled dose (Inst/Inst), instilled surfactant followed by nebulized surfactant (Inst/Neb), or no surfactant (Control). The lambs were ventilated for 6 h. Twenty-eight lambs were categorized into two groups (low compliance versus moderate compliance) based on initial physiologic lung characteristics. Efficiency of deposition of nebulized surfactant directly correlated with the compliances and ventilatory efficiency indices measured at 15 min of age. The low-compliance group (Low Comp) had significantly lower efficiency of surfactant deposition (7.6 +/- 1.6%) than did the moderate-compliance group (Mod Comp) (23.4 +/- 2.5%) (p < 0.01). Overall, instilled surfactant had a reasonably homogeneous distribution, whereas nebulized surfactant had a less homogeneous distribution, except for the Low Comp, Inst/Neb group, which had a distribution pattern similar to that for instilled surfactant. The potential for nebulized surfactant therapy for respiratory distress syndrome (RDS) may be limited by the nonhomogeneous nature of ventilation in the preterm lung.

Administration, Inhalation↗
PubMed1996

Alveolar and tissue surfactant pool sizes in humans.

The amounts of surfactant in human lung tissue and in the alveolar pool have not been extensively reported. We used 24 human lungs from persons over the age range of 13 mo to 80 yr to investigate whether the amount of saturated phosphatidylcholine (Sat-PC) in the human lung changed with age. Lung lavages also were obtained from 10 lungs at autopsy for measurements of the alveolar Sat-PC and surfactant protein-A (SP-A) concentrations. We found that (mean +/- SEM) lung Sat-PC/body weight (28.4 +/- 2.2 mumol/kg), Sat-PC/lung protein (0.060 +/- 0.005 mumol/mg), and Sat-PC/lung deoxyribonucleic acid (DNA) (0.23 +/- 0.01 mumol/mg) did not vary significantly with age. The amounts of alveolar Sat-PC (1.9 +/- 0.2 mumol/kg) and SP-A (105 +/- 15 micrograms/kg) were lower than previous estimates in other species. The relatively small surfactant pools in the human may make the lung more susceptible to injuries that interfere with surfactant function.

Adolescent↗
PubMed1996

Increased surface tension of the lung and surfactant in bleomycin-induced pulmonary fibrosis in rats.

The increased elastic recoil of the lung in bleomycin-induced pulmonary fibrosis in the rat is due in part to increased surface forces. This study was designed to determine the role of surface tension in situ and in vitro 21 d after instillation of bleomycin. Using sequentially measured pressure-volume curves generated with air, saline, air after lavage with Tween 20, and saline, surface tension was significantly higher in bleomycin-treated lungs than in untreated lungs (4.7 +/- 1.1 versus 1.8 +/- 0.2 dyne/cm, p < 0.01). Surface tension was determined in vitro with a Wilhelmy balance using bronchoalveolar lavage fluid, surfactant, and organic solvent lipid extracts of surfactant. Bleomycin treatment resulted in elevated minimal surface tensions: BALF (20.7 +/- 0.6 versus 13.6 +/- 3.8 dyne/cm, p < 0.02), isolated surfactant (12.0 +/- 1.3 versus 3.0 +/- 0.5 dyne/cm, p < 0.02), and the organic solvent lipid extracted surfactant (11.0 versus 3.2 dyne/cm). These results indicate that the physical properties of surfactant in lungs of rats treated with bleomycin are abnormal and contribute to the increased elastic recoil in this model of pulmonary fibrosis.

Animals↗
PubMed1996

Single dose fetal betamethasone administration stabilizes postnatal glomerular filtration rate and alters endocrine function in premature lambs.

UNLABELLED: These studies determined the effects of fetal treatment with betamethasone alone, or in combination with thyroid hormone (thyroxine; T4), on postnatal renal and endocrine adaptations in preterm newborn lambs. Ovine fetuses (126 d of gestation; term = 150 d) received single, ultrasound-guided intramuscular injections of saline, 0.5 mg/kg betamethasone (Celestone Soluspan, or 0.5 mg/kg betamethasone plus 60 micrograms/kg T4. After 48 h, lambs were delivered, treated with surfactant (Survanta, 100 mg/kg), and ventilated for 3 h. Due to maintained urine flow in the betamethasone-treated animals and a significant decrease in the saline group, betamethasone versus saline urine flow values (0.11 +/- 0.03 versus 0.03 +/- 0.004 mL.min-1.kg-1) were significantly elevated by the end of studies. GFR (1.5 +/- 0.3 versus 0.8 +/- 0.2 mL.min-1.kg-1) and mean blood pressure (61 +/- 4 versus 42 +/- 3 mm Hg) values also were higher in the betamethasone-treated animals. Although renal blood flow, renal plasma flow, and fractional sodium excretion rates did not differ, betamethasone versus saline values for the filtration fraction (11.9 +/- 1.5 versus 7.4 +/- 1.5%) and total sodium reabsorption (196 +/- 38 versus 81 +/- 16 microEq.min-1.kg-1) were increased. Betamethasone versus saline treatment also was associated with significant reductions in plasma angiotensin II (125 +/- 23 versus 550 +/- 140 pg/mL) and AVP (116 +/- 19 versus 230 +/- 77 pg/mL) levels. Overall, the effects of combined betamethasone + T4 treatment were similar to the effects of betamethasone alone. CONCLUSIONS: 1) fetal betamethasone injection 48 h before delivery stabilizes GFR and significantly alters endocrine function in preterm newborn lambs, and 2) the addition of T4 does not augment betamethasone-induced renal and endocrine responses.

Angiotensin II↗
PubMed1996

Detection of toxic shock syndrome toxin-1 gene in Staphylococcus aureus bovine isolates and bulk milk by the polymerase chain reaction.

Staphylococcus aureus isolates from mastitic cow's milk and farm bulk milk were examined for toxic shock syndrome toxin-1 (TSST-1) gene (tst gene) by the polymerase chain reaction (PCR). The 179 bp band of tst gene was observed in almost all the bovine isolates which showed TSST positive in a latex agglutination, as well as in human strain FRI 1169, but was not observed in bovine isolates of TSST negative. The lowest detectable threshold of the PCR for tst gene was 1.2 x 10(3) cells/ml. When 125 bovine milk samples were cultured selectively for staphylococci and examined by PCR, the tst gene was detected in 10 of the 35 culture fluids, in which staphylococci were recognized by Gram's staining.

Animals↗
PubMed1996

[A case of hemolytic uremic syndrome after cadaveric renal transplantation].

We report a cadaveric renal transplant recipient suffering from hemolytic uremic syndrome (HUS). A 46-year-old woman received a cadaveric renal transplantation on February 16, 1994. From the 20th postoperative day, anemia, thrombocytopenia and deterioration of graft function occurred. Graft biopsy on the 20th postoperative day indicated HUS by microthrombotic arterioglomerulopathy. Plasma exchange and 15-deoxyspergualin improved her graft function. From these clinicopathological findings, we conclude that she had HUS caused by acute humoral rejection.

Cadaver↗
PubMed1996

Surfactant enhances adenovirus-mediated gene expression in rabbit lungs.

The efficiency and localization of gene transfer for gene therapy in the lung will depend on vector selection and technique used to deliver the vector. We hypothesized that surfactant might facilitate gene transfer because of its biophysical properties that enhance spreading of saline suspensions in the airways. We used a replication defective adenovirus directing the expression of the luciferase reporter gene at different virus doses and surfactant concentrations and instilled 4 ml suspensions into the lungs of adult rabbits. Transgene expression measured as luciferase-dependent light units in tissue homogenates 3 days after instillation had similar lobar distributions for surfactant-viral suspensions and for phosphate-buffered saline viral suspensions. However, total light units were four- to six-fold increased for viral doses of < 10(10) plaque forming units in 10 mg/ml or 25 mg/ml surfactant suspensions. The percentage of total transgene expression in the tracheacarina-bronchus decreased from over 50% to about 10% for virus instilled with surfactant concentrations of 2 mg/ml or greater, indicating preferential expression in airway epithelial cells located more distally in the lung. Surfactant did not enhance persistence of transgene expression 7 or 14 days after instillation. Surfactant facilitates adenovirally mediated gene transfer in the peripheral lung and enhances transgene expression.

Adenoviruses, Human↗
PubMed1996

Autoantibodies to bullous pemphigoid and epidermolysis bullosa acquisita antigens in an infant.

We describe a 1-year-old boy with multiple tense blisters on the skin, who showed circulating autoantibodies directed to both bullous pemphigoid and epidermolysis bullosa acquisita antigens. The patient's serum IgG antibodies bound to the 290-kDa epidermolysis bullosa acquisita antigen with immunoblot analysis of human dermal extracts. Immunoblot analysis also demonstrated that the patient's serum autoantibodies were reactive with recombinant NC16a domain of the 180-kDa bullous pemphigoid antigen. This study confirmed the presence of circulating autoantibodies directed to both bullous pemphigoid antigen and epidermolysis bullosa acquisita antigen.

Autoantibodies↗