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Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 253 records · Page 14Linked to original sources

[Studies on the multiple-drug induction immunosuppressive therapies with cyclosporine after renal transplantation].

Our induction immunosuppressive therapies were carried out on patients split into three groups. The first group of 25 recipients were treated with regimen I [cyclosporin (CsA); 12 mg/kg/day and prednisolone (Pred)]. The second group of 16 recipients were treated with regimen II [CsA; 6 mg/kg/day, Pred and mizoribine (MIZ) or azathioprine (AZA)]. The third group of 14 recipients were treated with regimen III [CsA; 10 mg/kg/day, Pred and MIZ or AZA]. There was no significant difference among the three groups in renal function three months after renal transplantation. The frequency and grade of rejection were significantly higher in Group II than in the other groups. One of group I had CsA nephrotoxicity and none of group III had liver dysfunction three months after renal transplantation. Group I had a higher incidence of posttransplant hypertension. Hypertension of group I was very severe. We concluded that the triple-drug therapy on group III was the best induction immunosuppressive therapy after renal transplantation of the above three.

Adult↗

[Experimental studies on the mode of action of cyclosporine and FK506 assessed by proliferation response of human cloned T lymphocytes].

We applied cloned human T lymphocytes established in our laboratory to evaluate the mode of action of Cyclosporine (CsA) and FK506. Phenotypic and functional analysis led us to conclude that HTL403 was a helper T cell clone and HTL805 a cytotoxic one. Susceptibility of HTL-403 to the immunosuppressants demonstrated that alloantigen-driven proliferative response can recover to the rIL2-driven level by the addition of rIL2 at higher concentration of the agents. Although full recovery was not observed in FK506, this finding indicated that FK506 as well as CsA inhibit IL2 secretion from HTL403. FK506 showed remarkable suppressive effect on the proliferative response of HTL-805 even at a considerably low concentration, while CsA suppressed such a response dose-dependently. We concluded that FK506 can be used to reverse ongoing acute rejection as well as to prevent acute rejection.

Cell Division↗

[Patent urachus associated with abdominal abscess: report of a case].

A case of the patent urachus associated with abdominal abscess was reported. A 44-year-old woman was consulted to our clinic with the complaints of bladder irritability and discharge from the navel on October 27, 1987. A fist-sized tumor around the umbilicus was pointed out and the cystography from the umbilicus demonstrated that the contrast medium reached to the urinary bladder. The cystoscopy showed the protruded lesion on the dome of the bladder. The pre-operative diagnosis was patent urachus. She received resection of the urachus on November 11, 1987. The pathological finding was pyogenic granuloma of the urachus due to chronic inflammation.

Abdominal Muscles↗

Dose response of thyrotropin-releasing hormone on pulmonary maturation in corticosteroid-treated preterm rabbits.

The dose-response effect of thyrotropin-releasing hormone in enhancing pulmonary maturation was investigated with six dosing regimens. Pregnant does received thyrotropin-releasing hormone (5, 10, or 50 micrograms/kg every 12 hours for four doses or one dose of 20 micrograms/kg) in conjunction with betamethasone beginning on day 25 of gestation, with betamethasone alone or saline solution used as comparison treatment groups. Half of the newborn rabbits received supplemental surfactant therapy after delivery on day 27, and all were ventilated on a ventilator plethysmography system for 30 minutes. There were no differences among the four thyrotropin-releasing hormone doses in surfactant pool sizes, compliances, or proteins leak into or out of the air spaces. The groups that received multiple doses of thyrotropin-releasing hormone had significantly higher perinatal loss rates than the single-dose group. The lungs of the group treated with thyrotropin-releasing hormone plus steroid and the rabbits treated only with steroid were more compliant than the controls without surfactant therapy, and showed significant improvements in protein leak. The addition of thyrotropin-releasing hormone to betamethasone improved several of the protein leak measurements compared with use of betamethasone alone. These results question the necessity of multiple doses of thyrotropin-releasing hormone to induce pulmonary maturation, especially when the higher perinatal mortality and the theoretical long-term effects of fetal hyperthyroidism on thyroid axis function are considered.

Animals↗

Antenatal betamethasone dose effects in preterm rabbits studied at 27 days gestation.

Pregnant rabbits received bethamethasone (0.05, 0.2, 0.4, or 0.5 mg.kg-1.day-1) or vehicle control for 2 days before delivery of fetuses at 27 days gestation to evaluate dose-related effects on surfactant pool sizes with and without ventilation, pressure-volume measurements, lung protein leaks, and precursor incorporation into lung saturated phosphatidylcholine (PC). Alveolar wash-saturated PC pool sizes in betamethasone-exposed fetuses were less than in controls (P less than 0.01). At higher doses, total lung saturated PC also decreased (P less than 0.01). Maximal lung volumes on pressure-volume loops were larger than controls only at the 0.4 mg.kg-1.day-1 dose (P less than 0.05). The larger maximal volumes, despite decreased saturated PC pools, indicated increased responsiveness of the steroid-treated lungs to the smaller saturated PC pool sizes. Vascular-to-alveolar iodinated albumin leak decreased with steroid treatment independently of dose (P less than 0.01). No consistent pattern of increased precursor incorporation into saturated PC by lung slices was seen. Our results indicate that, in preterm rabbits exposed to a range of maternal corticosteroid doses, the beneficial lung maturational effect of structural alterations with increased responses to endogenous saturated PC pools was maximal even at the lowest dose.

Animals↗

Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs.

The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radio-labeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

1,2-Dipalmitoylphosphatidylcholine↗

Intrapulmonary catabolism of surfactant-saturated phosphatidylcholine in rabbits.

Intrapulmonary surfactant catabolism was investigated by use of a phospholipase A1- and A2-resistant analogue of dipalmitoylphosphatidylcholine (DPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPC ether). [14C]DPC ether, made into liposomes with [3H]DPC and associated with 32P-labeled rabbit surfactant, was given intratracheally to 1-kg rabbits, which were killed at preset times to 48 h. Recoveries of radiolabel as saturated phosphatidylcholine (Sat PC) isolated from alveolar wash (AW), postlavage lung homogenate (LH), and alveolar macrophages were measured. All groups had similar AW and LH Sat PC pool sizes, indicating no perturbation of endogenous Sat PC pools. Despite a nearly fivefold accumulation of [14C]DPC ether in the lung by 48 h (P less than 0.01), the three probes had similar alveolar clearance curves. Furthermore, the Sat PC reutilization efficiency (41.6%) and turnover time (5.9 h) calculated for DPC ether were not different from values for the DPC and rabbit surfactant. Of the DPC ether (0.7%) and DPC (9%) labels recovered as PC in organs outside the lung, greater than 85% was unsaturated, indicating de novo synthesis using precursors from degraded PC. DPC ether was a useful probe of intrapulmonary DPC catabolism, and after alveolar uptake there was no direct reentry of intact DPC from the catabolic compartment(s) into the secretory pathway.

1,2-Dipalmitoylphosphatidylcholine↗

Altered surfactant function and metabolism in rabbits with acute lung injury.

Lung injury was induced in rabbits with N-nitroso-N-methylurethane (NNNMU), and saturated phosphatidylcholine (Sat PC) pool sizes and phospholipid compositions were measured in alveolar wash subfractions isolated by differential centrifugation (large and small surfactant aggregates). Surfactant metabolism also was studied using intravascular and intratracheal radiolabels. Protein permeability, gas exchange, and compliance were significantly abnormal as lung injury progressed. At peak injury, there was a decrease in the large aggregate Sat PC pool size in alveolar wash accompanied by increased uptake of Sat PC from the air space and increased specific activity of both intravascular and intratracheal radiolabels in lamellar bodies. This was followed by a marked rise in the small aggregate pool size in the alveolar wash and increased secretion of Sat PC into the air spaces. Phospholipid compositions, total phospholipid-to-protein ratios, and in vivo functional studies using a preterm ventilated rabbit model were abnormal for both large and small aggregate surfactant fractions from the lung-injured rabbits. These studies characterize quantitative, qualitative, and functional changes of alveolar wash surfactant subfractions in NNNMU-injured lungs.

Animals↗

Physical mapping and molecular cloning of mung bean yellow mosaic virus DNA.

Viral single-stranded DNA of mung bean yellow mosaic virus (MYMV) was converted to the double-stranded state in vitro, and physical mapping was carried out. The genome of MYMV was found to consist of two major components (designated as DNA 1 and DNA 2). In addition, some minor components were detected. Molecular cloning of the major components was carried out, using in vitro double-stranded DNA and replicative intermediate DNAs. DNA 1 is about 2.72 and DNA 2 about 2.67 kilobase pairs. No similarities were observed when the two restriction maps of DNA 1 and 2 were compared.

Cloning, Molecular↗

Effects of surfactant protein-A on surfactant function in preterm ventilated rabbits.

Surfactant protein-A (SP-A) isolated from cow surfactant was added to organic solvent extracts of natural bovine surfactant or of Survanta (Abbott Laboratories), and dynamic compliances and pressure-volume curves were measured in rabbits with a gestational age of 27 days. Organic solvent extracts of natural surfactant and Survanta significantly improved dynamic compliances and lung volumes compared with those in control rabbits, but the effects were less than for natural surfactant. Adding 1 to 10% by weight SP-A to organic solvent extracts of natural surfactant increased dynamic compliances and maximal lung volumes on pressure-volume curves to values comparable with natural surfactant. Lung volumes at 10 cm H2O on deflation curves increased in a dose-dependent fashion at concentrations of SP-A between 0.5 and 5% by weight with no further improvement at 10% SP-A, although the volumes were significantly lower than for natural surfactant. Five percent by weight SP-A did not improve any measurements for Survanta. These results indicated that SP-A favorably improved organic solvent extracted natural surfactant function in vivo. However, the responses could not be generalized to another surfactant.

Animals↗

Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals.

Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

Animals↗

Effects of surfactant subfractions on preterm rabbit lung function.

Surfactant isolated from adult rabbits was separated into large aggregate forms (LA) and small aggregate forms (SA) by centrifugation at 40,000 x g. LA contain SP-A and the surfactant lipophilic proteins SP-B and SP-C and are surface-active in vitro, whereas SA lack the surfactant proteins and have poor surface properties. Premature rabbits were treated with LA or SA and ventilated to evaluate the effects of LA and SA in vivo. There were dose-response effects of LA at doses between 10 and 50 mg total lipid/kg: dynamic compliances increased from 0.4 to 0.8 mL/cm H2O/kg and pressure-volume curves improved significantly, whereas SA did not improve any of the measurements at any dose. Organic solvent extracts of SA made up into LA also did not improve in vivo function. When 1.5% SP-B and SP-C isolated from calf surfactant was added to organic solvent extracts of SA, the surfactant had good in vitro surface properties and increased maximum lung volumes. However, this surfactant did not improve dynamic compliances or lung stability on pressure-volume curves. Because the lipids from SA seemed to limit the compliance response, we tried to identify differences in lipids from LA and SA. Phospholipids from SA reconstituted with SP-BC did not function well in vivo, whereas phospholipids from LA with SP-BC were similar to LA surfactant. The neutral lipid fractions from LA or SA did not contribute very much to or inhibit function. Fatty acid composition of the phospholipids and phosphatidylcholine from LA and SA were not remarkably different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Urinary FDP D-dimer and E fragments in renal transplantation].

Both D-dimer and E fragments in urinary FDP were determined in renal transplantation patients. Urinary D-dimer fragments increased in 14 out of 20 acute rejections (70.0%) and in 6 out of 18 chronic rejections (33.3%). Urinary E fragments increased in 8 out of 9 acute rejections (88.9%) and in 4 out of 5 chronic rejections (80.0%). It is suggested that urinary FDP-E fragment is a better indicator to detect or predict rejection than the whole Urinary FDP. The appearance of D-dimer in the urine indicates intravascular coagulation in glomeruli followed by a secondary fibrinolysis in the course of the rejection reaction. The urinary D-dimer/FDP ratio which was used as the indicator of fibrinolytic activity in glomeruli was obtained in various conditions of renal transplants. The ratios were relatively high in the urines from well functioning grafts. This ratio deteriorated at the onset of rejection crisis and tended to go upward during the course of the recovery when the rejection was reversible. In the cases of irreversible acute rejection and chronic rejection, these ratios remained at a low level. D-dimer/FDP ratio might be useful indicator to predict the reversibility of rejection and the prognosis of renal allograft. Furthermore, these findings suggest that fibrinolytic and thrombolytic therapy by the tissue-type plasminogen activator (t-PA) along with immunosuppressive drugs might be more effective for the treatment of these rejections.

Fibrin Fibrinogen Degradation Products↗

[Management of hypertension after renal transplantation].

We report the clinical result of our management for post-transplant hypertension in 47 renal allograft recipients who were followed up for more than one year after transplantation. Hypertension developed in 4 (26.7%) out of 15 cases who were treated with conventional immunosuppressive therapy (Group I) and 18 (56.3%) out of 32 cases treated with CsA (Group II). In group I, all the 6 patients who had been nephrectomized their original kidney at the time of transplantation did not develop hypertension. And the blood pressure before transplantation had a marked effect on post-transplant blood pressure. In group II, there were many recipients who had become hypertensive after transplantation though most of them became normotensive with dose reduction of immunosuppressants. Ten normotensive patients before transplantation who had not developed hypertension retained their normal blood pressure throughout the course without any antihypertensive medication. We could find no correlation between graft function and blood pressure, although recipients with poor graft function had a tendency to be hypertensive. A satisfactory fall in blood pressure in the patients treated with CsA was observed when the immunosuppressive regimen was changed to triple therapy to reduce the dose of CsA. The recorded blood pressure were 174.0 +/- 19.0/105.2 +/- 16.5 mmHg after transplantation and 145.2 +/- 15.7/78.4 +/- 17.1 mmHg at the latest follow-up. We performed original nephrectomy in 6 patients whose blood pressure could not have been controlled by the antihypertensive medication. All the venous sampling studies showed that increased renin secretion was confined to original kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The effects of thromboxane A2 synthetase inhibitor on chronic rejection of kidney transplantation].

There has been no useful treatments for chronic vascular rejection (CVR) after kidney transplantation until now. Recently, however, some reports have suggested that the thromboxane A2 synthetase inhibitor, OKY-046, is useful in reducing proteinuria in nephrotic syndrome and preventing progression of CVR. Five patients with CVR (serum creatinine range: 1.7-2.6 mg/dl) were treated with OKY-046 for over one year and the effect of OKY-046 was evaluated. One patient developed acute rejection and another renal hypertension during this study. Except for the cases of acute rejection and renal hypertension, serum creatinine slightly decreased in 1 case and remained unchanged in 2 cases. Urinary excretion of protein and thromboxane B2 decreased significantly but prostaglandin E2 did not change in the treatment of the deterioration with OKY-046. We concluded that OKY-046 was effective in preventing graft function and decreasing urinary protein excretion in kidney transplant recipients with CVR.

Acrylates↗

[Detection of antigenic determinants of autoantibodies in idiopathic thrombocytopenic purpura using anti-platelet monoclonal antibodies and flow cytometry in whole blood].

To detect antigenic sites of platelet-bound autoantibodies in chronic ITP, whole blood or platelet-rich plasma from patients was stained with monoclonal antibodies (MoAbs) directed against platelet membrane glycoproteins (GPs) and with FITC-conjugated anti-mice IgG in an unwashed system followed by flow cytometric analysis. Platelets were identified by light-scattering profile and the amount of anti GP MoAb bound to platelets was measured and expressed as mean fluorescence intensity. This system enabled to quantitate the amount of intact GPs on platelet surface, regardless of activation of platelet. As a result, decreased amount of platelet-bound anti GPIIb/IIIa MoAb was noted in 5 of 22 patients with chronic ITP comparing to those with normal subjects. On the contrary, none of these patients revealed any demonstrable decrease in the amount of anti GPIb MoAb binding. From these observations, we suggest that the decreased MoAb binding to platelets in these five patients indicates the binding of autoantibody directed toward antigenic determinants, which are on or close to the epitope of this MoAb.

Adolescent↗