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Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 163 records · Page 9Linked to original sources

Effects of exercise-induced sympathoadrenergic activation on portal blood flow.

We examined the relationship between portal venous blood flow and sympathoadrenergic activation after muscle exercise. For this purpose, we used echo Doppler and measured plasma noradrenaline concentration before and after mild (7 metabolic units, N = 8) and maximal exercise (14 metabolic units, N = 8) in 16 patients without significant disease. Portal venous flow did not change after mild exercise. In contrast, a significant reduction in portal venous flow was observed after maximal exercise (P < 0.01). This was due to reductions in both cross-sectional area of the portal vein (P < 0.01) and portal venous velocity (P < 0.01). Overall, there were significant inverse relationships between the change in plasma noradrenaline concentration and that in cross-sectional area of the portal vein [r = -0.44, P < 0.01 (absolute change); r = -0.47, P < 0.01 (relative change)], that in portal venous velocity (r = -0.63, P < 0.01; r = -0.61, P < 0.01), and that in portal venous flow (r = -0.54, P < 0.01; r = -0.59, P < 0.01). These results suggest that the reduction in portal venous flow after exercise is related to the degree of sympathoadrenergic activation. This reduction may be due mainly to splanchnic vasoconstriction.

Adult↗

Postnatal lung function in preterm lambs: effects of a single exposure to betamethasone and thyroid hormones.

OBJECTIVE: We determined the effect of a single direct fetal injection of corticosteroid and thyroid hormones on postnatal pulmonary function in preterm lambs. STUDY DESIGN: Initially fetal sheep (126 days' gestation) randomly received saline solution, betamethasone (Celestone Soluspan, 0.5 mg/kg), betamethasone plus triiodothyronine (5 micrograms/kg), or betamethasone plus thyroxine (15 micrograms/kg) as a single injection. Forty-eight hours later (128 days' gestation) the fetuses were delivered and ventilated for 50 minutes. In a second protocol fetuses were delivered at 128 days' gestation, after only 24 hours of hormone exposure. RESULTS: Betamethasone treatment improved compliance nearly twofold after 24 or 48 hours of exposure. Efficiency of ventilation also improved after steroid therapy; this effect was augmented 48 hours after thyroxine exposure (but not triiodothyronine). No thyroxine effect was noted after 24 hours of exposure. Maximal lung volume increased by 80% after steroid treatment and doubled in response to combination betamethasone and thyroxine therapy. Alveolar pool sizes of saturated phosphatidylcholine and surfactant protein A were comparable for all groups exposed for 48 hours. CONCLUSIONS: A single fetal exposure to betamethasone improves postnatal pulmonary function after 24 or 48 hours. Addition of thyroxine (but not triiodothyronine) augments this effect at 48 hours.

Animals↗

Omeprazole administration does not impair gastrointestinal mucosal perfusion, oxygenation, and hexosamine generation.

Omeprazole is a potent antisecretory drug that acts by inhibiting the gastric proton pump. In the present study, we have observed the effects of this drug on gastrointestinal mucosal perfusion, oxygenation, and hexosamine generation in humans. Sixteen healthy volunteers were included. Gastrointestinal mucosal perfusion and oxygenation (duodenum, antrum, and corpus) were assessed by laser-Doppler flowmetry and reflectance spectrophotometry. Biopsy specimens were also taken from each location to determine hexosamine content as a quantitative indicator of mucus generation. In addition, serum gastrin level was measured. After baseline data were obtained, subjects were randomly assigned to receive 20 mg of oral omeprazole once daily for 7 days (n = 8) or placebo (n = 8). All measurements were performed again after double-blinded drug administration. No effect was found after placebo administration. In contrast, omeprazole administration significantly increased serum gastrin level (p < .05), suggesting an inhibition of acid secretion. However, this drug did not alter either laser-Doppler signal or oxygen saturation at each location. In addition, no change in mucosal hexosamine content was observed at each location. We conclude that oral omeprazole, despite its well-established antisecretory effect, has no adverse effect on the mucosal defense in humans.

Adult↗

Postnatal renal adaptation in preterm and term lambs.

The present experiments determined if increases in renal reabsorptive capacity during the transition from fetal to neonatal life are gestation dependent. Renal function was studied in chronically-catheterized fetal lambs (133 +/- 1 days; term, 145-150 days). Additionally, renal function was studied in anaesthetized, ventilated, caesarean-delivered preterm lambs (109-139 days gestation) and term lambs (148 days gestation), and in 2-day-old spontaneously-delivered term lambs. Newborns < or = 120 days old received surfactant to facilitate ventilation and maintenance of physiologic blood gases. Two hours after caesarian delivery, urine osmolality, urine flow, glomerular filtration rate (GFR), and fractional sodium excretion (FENa) values were similar for all gestations. Relative to fetal values, caesarean-delivered newborn renal values included lower urine flow rates (0.20 +/- 0.03 v. 0.05 +/- 0.01 mL min-1 kg-1), higher urine osmolalities (118 +/- 15 v. 422 +/- 16 mOsmol kg-1 H2O), and no differences in GFR or FENa. Relative to caesarean-delivered newborns, 2-day newborn renal function included higher values for GFR (0.7 +/- 0.1 v. 3.0 +/- 0.1 mL min-1 kg-1) and urine osmolality (724 +/- 32 mosmol kg-1 H2O), and lower FENa (7.0 +/- 1.5 v. 0.2 +/- 0.02%), and urine flow (0.005 +/- 0.003 mL min-1 kg-1). The 132- and 139-day animals were ventilated for 5 h and 10 h respectively; the only functional change at 10 h was a decrease in FENa (7.0 +/- 1.5 v. 2.8 +/- 0.1%). It is concluded that: (1) relative to fetal animals, renal adaptive responses in anaesthetized, ventilated newborns begin within 2 h following caesarian delivery; (2) initial adaptive responses are not gestation dependent after 109 days; and (3) the combined effects of ventilation and/or anaesthesia delay postnatal renal adaptations for at least 10 h after birth.

Absorption↗

The complete nucleotide sequence of odontoglossum ringspot virus (Cy-1 strain) genomic RNA.

The complete nucleotide sequence of the genomic RNA of odontoglossum ringspot virus Cy-1 strain (ORSV Cy-1) was determined using cloned cDNA. This sequence is 6611 nucleotides long containing four open reading frames, which correspond to 126 K, 183 K, 31 K, and 18 K proteins. Its genomic organization is similar to other tobamoviruses, TMV-V(vulgare), TMV-L (tomato strain), tobacco mild green mosaic virus (TMGMV) and cucumber green mottle mosaic virus (CGMMV). The 5' non-coding regions of ORSV Cy-1 is 62 nucleotides. The ORFs encoded a 126 K polypeptide and a 183 K read-through product in which helicase-sequence and polymerase-sequence motifs are found. The ORFs encoding the 126 K and 183 K proteins have 61% and 63% identities with those of TMV-V. The third ORF encoded a 31 K protein homologous to TMV cell-to-cell movement protein. It has 63% identities with that of TMV-V. The fourth ORF encoded an 18 K coat protein. The 5' non-coding region, which extends from base 1 to 62 has 2 G residues and a ribosome binding site (AUU). The 3' non-coding region, 414 nucleotides in length, is entirely different from that of other tobamoviruses.

Amino Acid Sequence↗

Clearance of surfactant protein B from rabbit lungs.

To characterize the metabolism of surfactant protein B (SP-B) in vivo, we measured the clearance of SP-B from adult rabbit lungs. Purified rabbit SP-B was radiolabeled with 125I by the Bolton-Hunter method. Trace amounts of 125I-labeled SP-B mixed with [14C]dipalmitoylphosphatidylcholine (DPPC) were given intratracheally via a bronchoscope to rabbits 0-16 h before collection of alveolar washes (AW). Macrophages were recovered from AW, and lamellar bodies (LB) were isolated from lung tissue by differential centrifugation. 125I-SP-B was cleared more rapidly from the airspaces and the total lung (half-life 7 h) than was DPPC (half-life 11 h in the total lung). There was an approximately threefold accumulation of SP-B relative to saturated phosphatidylcholine in macrophages at all times. The proportion of 125I and 14C radioactivities in lamellar bodies was similar at 2 and 4 h, but there was 14-fold less 125I-SP-B than [14C]DPPC in lamellar bodies by 16 h. This loss of SP-B from the lamellar body fraction is consistent with less recycling of SP-B. The results demonstrate different clearance kinetics of these two components of surfactant and indicate a significant role of macrophages in the clearance of SP-B.

1,2-Dipalmitoylphosphatidylcholine↗

Surfactant treatment and ventilation effects on surfactant SP-A, SP-B, and SP-C mRNA levels in preterm lamb lungs.

The effects of exogenous surfactant treatment combined with postnatal ventilation on surfactant protein (SP)-A, SP-B, and SP-C steady-state mRNA levels were evaluated in preterm sheep at 120, 132, and 139 days gestation. Three groups were studied at each gestation period: animals ventilated and treated with 100 mg/kg natural sheep surfactant, animals ventilated and not treated with surfactant, and a comparison group of lambs that were neither ventilated nor treated with surfactant. In unventilated lambs, SP-A and SP-C mRNA levels measured by densitometry from Northern blots increased between 120 and 132 days gestation (P < 0.05). At 120 days gestation, no differences in SP-A, SP-B, or SP-C mRNA levels were noted among the three groups. At 132 days gestation, SP-A mRNA levels increased in both ventilated groups (P < 0.01), but no additional surfactant effect on SP-A mRNA expression was detected. There were no changes in SP-B or SP-C mRNA levels among the groups at 132 days gestation. At 139 days gestation, mRNA levels for both SP-A and SP-B increased after ventilation, compared with the unventilated groups (P < 0.05). Furthermore, an additional effect of surfactant treatment to increase SP-A mRNA levels relative to animals undergoing ventilation alone was noted (P < 0.05). We conclude that postnatal changes in mRNA levels for the surfactant proteins are gestationally regulated and protein specific.

Animals↗

Exogenous surfactant function in very preterm lambs with and without fetal corticosteroid treatment.

We have asked whether the function of a bovine source surfactant frequently used clinically (Survanta) could be enhanced after exposure to the very preterm lung when the surfactant was subsequently tested in vivo in preterm surfactant-deficient rabbits. We also evaluated whether there would be effects resulting from fetal treatment with 0.5 mg/kg betamethasone given 48 h before delivery of lambs at 121 days gestational age. The fetal corticosteroid treatment significantly improved gas exchange, increased compliance, increased functional residual capacity, decreased vascular-to-alveolar protein leak, and increased static lung volumes. However, surfactant from both groups of lambs, recovered by alveolar wash and subsequently fractionated to recover the large-aggregate functional surfactant, was equivalent in function to the Survants given to the lambs when tested in preterm surfactant-deficient rabbits. Addition of plasma to Survanta resulted in high minimum surface tensions in vitro, and this inhibition could be prevented by supplementation of the Survanta with 5 or 10% sheep surfactant. No activation occurred with treatment of the very preterm lung, a result consistent with the lung being too immature to contribute components to the surfactant used for treatment. Fetal corticosteroid treatment had no effect on surfactant function at this gestational age.

Adrenal Cortex Hormones↗

Effects of fetal corticosteroid treatments on postnatal surfactant function in preterm lambs.

Effects of prenatal corticosteroid on the properties of surfactant have not previously been evaluated. A single ultrasound-guided fetal injection with 0.5 mg/kg betamethasone 48 h before delivery of preterm lambs at 134- to 135-days gestation improved oxygenation, lowered the ventilatory pressures required to maintain arterial PCO2 between 30 and 40 Torr and decreased the protein leak of albumin from the intravascular to the alveolar space. This dose of glucocorticoid did not alter surfactant-saturated phosphatidylcholine pool sizes in the airspaces of preterm lambs. However, the treatment changed the characteristics of the surfactant recovered from the ventilated preterm lambs. The in vitro conversion from heavy to light subtype surfactant decreased from 59% for the saline-treated lambs to 37% for the corticosteroid-treated lambs after 180 min of surface area cycling (P < 0.02). Surfactant from the corticosteroid-treated lambs also increased the dynamic compliance of preterm surfactant-deficient rabbits more than did surfactant from the saline-treated lambs (P < 0.05). Prenatal treatment of preterm lambs with betamethasone improved the functional characteristics of surfactant without significant effects on the alveolar surfactant pool sizes.

Animals↗

Fetal corticosteroid and T4 treatment effects on lung function of surfactant-treated preterm lambs.

Three groups of sheep fetuses at 125 or 126 d gestational age randomly received a single ultrasound-guided intramuscular injection of saline, 0.5 mg/kg betamethasone, or 0.5 mg/kg betamethasone plus 50 micrograms/kg thyroxine (T4). Forty-eight hours later the fetuses were delivered, treated with a pulmonary surfactant preparation, and ventilated for 3 h. Corticosteroids alone and in combination with T4 increased FRC, compliance, and lung volumes, and decreased the protein leak into the airspace. Saturated phosphatidylcholine pool sizes recovered by alveolar washing were not changed after hormone treatment. To evaluate the function of surfactant recovered from the lambs in vivo, we treated preterm rabbits at 27 d gestational age with the large-aggregate surfactant from alveolar washes. Large-aggregate surfactants and the pulmonary surfactant preparation increased compliances and maximal lung volumes relative to those in untreated preterm rabbits. Large-aggregate surfactants improved compliance more than did the pulmonary surfactant preparation. We conclude that ultrasound-guided single fetal corticosteroid treatment followed by postnatal surfactant improved postnatal lung function in preterm lambs. Addition of T4 did not augment corticosteroid effects. The function of the exogenous surfactant was improved in premature lamb lungs independently of the fetal treatment modality.

Animals↗

Decreased surfactant dose-response after delayed administration to preterm rabbits.

Preterm rabbits from 14 litters were delivered at 27 d gestation, anesthetized, and treated with surfactant at birth, 15 min, or 30 min after the onset of mechanical ventilation. Doses of surfactant ranging from 0 to 100 mg/kg body weight were given intratracheally and the rabbits were ventilated for 45 min after birth. Pressure-volume curves and dynamic compliances demonstrated that the dose response to surfactant progressively decreased with delayed treatment. Following surfactant treatments of 50 mg/kg at birth, 15 min, and 30 min, peak lung volumes at 35 cm H2O were increased by 49, 30, and 8.4%, respectively over those of untreated controls. Lung lavages from rabbits receiving surfactant at 30 min had significantly higher protein contents and minimum surface tensions on the Wilhelmy balance than those from rabbits treated at birth (23.1 +/- 1.1 versus 16.0 +/- 2.7 dynes/cm), and lung sections from rabbits treated at 30 min had a significantly less uniform distribution of surfactant than those from rabbits treated at birth. While increasing phospholipid concentrations may reverse the inhibition of surfactant by serum proteins in vitro, there was a progressive inability of exogenous surfactant to overcome this inhibition in vivo following delayed administration to very immature rabbits. This inability to overcome inhibition with increasing surfactant dose was associated with a less uniform distribution of surfactant following its delayed administration.

Animals↗

Postnatal lung function in lambs after fetal hormone treatment. Effects of gestational age.

We previously found that a single dose of betamethasone in combination with thyroxine given by intramuscular injection to fetal sheep 48 h before preterm delivery at 128 d gestation improved postnatal lung function. We have now asked how the combination of 0.5 mg/kg betamethasone and 15 micrograms/kg T4 given by a single fetal intramuscular injection changes lung response 48 h after treatment at 121 and 135 d gestation. At 121 d gestation the fetal hormone treatment significantly improved postnatal lung function. Compliance increased by 55%, arterial PO2 increased from 39 to 215 mm Hg, PCO2 decreased from 109 to 79 mm Hg, and maximal lung volumes increased by 112%. The hormone treatment decreased the severity of the respiratory failure, although these very preterm lambs still had severe respiratory failure. At 135 d gestation, the fetal hormone treatment decreased the ventilatory pressure requirements that were needed to normalize PCO2 values from 30 to 21 cm H2O. Compliance increased by 40%, and maximal lung volumes increased by 33%. Alveolar or lung tissue, saturated phosphatidylcholine, or alveolar SP-A pool sizes did not change with hormone treatment at 135 d gestation. We conclude that fetal hormone treatment significantly improved postnatal lung function at both gestational ages, although the characteristics of the responses were different.

Animals↗

Clearance of surfactant protein A from rabbit lungs.

Surfactant protein A (SP-A) is a major surfactant protein with multiple biophysical, metabolic, and host defense functions. To further characterize its metabolism in vivo, we measured clearance of SP-A from adult rabbit lungs. Trace amounts of [125I]SP-A radiolabeled by the Bolton-Hunter method and mixed with [3H]dipalmitoylphosphatidylcholine (DPPC) were given intratracheally via a bronchoscope to rabbits. Groups of five to six animals were studied 10 min to 16 h after labeled surfactant administration. After collection of alveolar washes, lamellar bodies were isolated from lung tissue. Macrophages also were isolated from alveolar washes. [125I]SP-A was cleared more rapidly than DPPC from the airspaces. Both [125I]SP-A and [3H]DPPC were lost exponentially from the total lungs, with half-life values of 6.5 h for SP-A and 12 h for DPPC (P < 0.01). In macrophages, the highest radioactivities for SP-A and DPPC were at 10 to 45 min and the radiolabels subsequently disappeared similarly. In lamellar bodies, 125I and 3H radioactivities per mumol saturated phosphatidylcholine (Sat PC) increased in parallel and were highest at 2 h. Whereas radiolabeled lipids were recovered in lamellar bodies for up to 16 h, iodinated SP-A was lost, indicating less recycling of SP-A than DPPC. We previously showed independent pathways of SP-A and Sat PC secretion in rabbits. These results demonstrate the different clearance kinetics of these two principle components of surfactant.

1,2-Dipalmitoylphosphatidylcholine↗

Surfactant protein-B supplementation improves in vivo function of a modified natural surfactant.

The effect of the addition of surfactant protein (SP)-B or SP-B plus SP-C (SP-BC) to a surfactant made from bovine lung (Survanta) was evaluated in 27-d-gestation preterm rabbits. The animals were treated with Survanta, Survanta + 2% SP-B, Survanta + 3% SP-BC, or sheep surfactant. They were then ventilated with 3 cm H2O positive end-expiratory pressure and tidal volumes of 8 mL/kg. Survanta + 2% SP-B was prepared by adding SP-B in water to Survanta or by adding SP-B in chloroform [SP-B(Chl)] to lipid-extracted Survanta. Dynamic compliances of the Survanta + 2% SP-B(Chl)- and Survanta + 3% SP-BC-treated rabbits were greater (p < 0.05) than those treated with Survanta or Survanta + 2% SP-B in water and were comparable to sheep surfactant. Postventilation pressure-volume curves for the groups treated with Survanta supplemented with SP-B had significantly larger retained volumes on deflation compared with those treated only with Survanta (p < 0.01). The effects of ventilation style on the responses were assessed by ventilating other groups of rabbits treated with Survanta, Survanta + 0.5% SP-B(Chl), Survanta + 2% SP-B(Chl), or sheep surfactant with tidal volumes of 10 mL/kg and 0 cm H2O positive end-expiratory pressure. SP-B (2%) augmented the in vivo function of Survanta without positive end-expiratory pressure, and 0.5% SP-B had no effect. Infasurf, a surfactant with more SP-B, was more effective than Survanta when tested in the preterm rabbits. SP-B is a critical factor for optimum immediate surfactant function.

Animals↗

Postnatal cardiovascular and metabolic responses to a single intramuscular dose of betamethasone in fetal sheep born prematurely by cesarean section.

Although the benefits of antenatal hormone treatment are well accepted, most studies have reported only pulmonary effects. There is evidence of beneficial cardiovascular and metabolic effects in studies using chronically catheterized animals; however because of the route of administration, the results are not directly applicable to clinical strategies. We previously demonstrated significant pulmonary effects in animals treated antenatally with a single, direct fetal, intramuscular injection of glucocorticoids. This study was performed to determine the effects of a single fetal injection of betamethasone (BETA) alone or in combination with thyroxine (T4) on cardiovascular and metabolic responses after preterm birth. Hemodynamic and metabolic responses at birth were determined in fetuses (126-d gestation; term = 150 d) treated with ultrasound-guided intramuscular injections of 0.5 mg/kg BETA (n = 7), BETA plus 60 g/kg T4 (n = 7), or saline (SAL, n = 9). After 48 h, lambs were delivered by cesarean section and studied for 3 h. BETA treatment increased mean arterial blood pressure [56 +/- 6 (SEM) versus 42 +/- 3 mm Hg], heart rate (152 +/- 5 versus 123 +/- 4 beats/min), and cardiac output (467 +/- 17 versus 349 +/- 36 mL/min/kg) versus SAL. Responses of BETA+T4-treated animals were not different from animals treated with BETA alone. Glucose and FFA were similar among all groups. The increase in catecholamine levels normally seen at birth was significantly attenuated in both the BETA and BETA+T4-treated animals. A single, intramuscular injection of glucocorticoids 48 h before delivery improves cardiovascular responses to preterm birth. This effect is not augmented by concomitant administration of T4.

Animals↗

[Renal transplant calculi in a renal allograft treated with extracorporeal shock wave lithotripsy in a patient with persistent hyperparathyroidism: a case report].

Between 1984 and 1991, six of 105 renal transplant recipients at our institution formed urinary tract calculi after transplantation (5.7%). In these 6 patients, one case of nephrolithiasis in a transplanted kidney was treated with extracorporeal shock wave lithotripsy (ESWL). A 37-year-old woman underwent cadaveric renal transplantation twenty months before, and her renal function remained stable. However calculi in the transplanted kidney and bladder were formed and ESWL was used for the treatment of the renal calculus in the transplanted kidney. She was discharged from the hospital two weeks postoperatively while passing small gravel in the urine after successful fragmentation of the calculus without any major complications. As follow-up KUB film two weeks later demonstrated that all stone fragments had been passed, but she was treated again by ESWL four months later because IVP films four weeks later revealed recurrent calculi in the transplanted kidney. The stones were fragmented successfully and spontaneously passed with voiding. Moreover we performed total parathyroidectomy with autotransplantation for persistent hyperparathyroidism, with subsequent good clinical results.

Adult↗

[Tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in transplanted kidneys].

We have studied the involvement of fibrinolysis in acute rejection after kidney transplantation by analyzing changes in urinary levels of substances such as FDP, D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Fibrinolytic activity was found to be low (that is, PAI is dominant) during acute rejection, and it was elevated (that is, PA became dominant) as acute rejection subsided. It appears that the dominance of PA leads to an increase in the products of fibrinolysis and an elevation in the D-dimer/FDP ratio, resulting in disappearance of the acute rejection. Based on these findings, we thought it necessary to administer t-PA to kidney recipients so that PA becomes dominant earlier and the acute rejection can be reduced. It is necessary for us to directly study the phenomena within the kidneys. Therefore, we recently conducted a histochemical study of the distribution of t-PA, Urokinase type PA (u-PA) and PAI in transplanted kidneys. Transplanted kidney, which functioned well or showed signs of acute or chronic rejection, were biopsied. These renal samples as well as control samples (biopsied from normal nongrafted kidney) were examined as to distribution of t-PA, u-PA and PAI by the indirect enzyme complement method. In conclusion, t-PA, u-PA and PAI were detected in the glomeruli, arterioles, tubule and interstices of the control kidneys, well functioning grafts, acutely rejected grafts chronically rejected grafts. All samples showed intense chromatic responses in the arterioles and part of the tubules. On the whole, the chromatic response tended to be more intense in the acute rejection group than in the other group.

Fibrinolysis↗

[The phenotypic expressions of AFP producing gastric carcinoma].

The phenotypic expressions of AFP producing gastric carcinomas were investigated by histological, immunohistochemical, mucinhistochemical and biochemical studies. Intramucosal histology was well differentiated adenocarcinoma in fifteen out of seventeen cases. In the invasive area, papillary or papillary and solid structure of the cancer cells with clear cytoplasms were in fourteen cases, but there were only three cases that showed hepatoid structure. In the mucinhistochemistry, thirteen cases (76%) showed intestinal type mucin. And in the lectin binding property of serum AFP, five of seven cases showed yolk sac tumor like pattern and the other two cases showed hepatic pattern. These results suggests that most of the AFP producing gastric carcinomas derive from intramucosal intestinal type well differentiated adenocarcinoma, that retrodifferentiated to fetal intestine in the invasive area and produce fetal intestinal type AFP.

Adenocarcinoma↗