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Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 865 records · Page 48Linked to original sources

Effects of a stable prostacyclin analog on experimental ischemic acute renal failure.

The effect of OP-41483, a stable prostacyclin (PGI2) analog, on ischemic acute renal failure (ARF) was investigated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creatinine levels remained relatively low during postoperative days 1-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histologic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed extensive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical setting.

Acute Kidney Injury↗

A monoclonal antibody, KM10 reactive with human gastrointestinal cancer and its application for immunotherapy.

A monoclonal antibody, KM10 (IgG1) was produced by fusing spleen cells from a human gastric cancer cell (MKN45)-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastrointestinal carcinoma. Sections of the malignant and benign tissues were tested with immunoperoxidase. All of 10 (100%) large intestinal cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and all of 3 (100%) ampullary cancers reacted positively. Moderate or weak reactivity was observed with normal human tissues, hepatoma and carcinomas of mammary, thyroid and adrenal glands. According to a study of the distribution of 125I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole body autoradiography also supported such a selective distribution. Destruction of antigenic properties by pronase digestion demonstrated its protein nature and by Western blot analysis, it was identified as a protein with an Mr of 180-200 kd. KM10-adriamycin (ADM) conjugate was prepared via an oxidized dextran bridge and this immunoconjugate retained the binding activity against human gastric cancer. MKN45 cells were inoculated subcutaneously into athymic mice and intravenous treatment was begun when the tumor became measurable. A dose-dependent antitumor activity was observed in vivo with KM10-ADM conjugate, while this conjugate was less toxic than free ADM.

Animals↗

Alteration of amino acid content of cerebrospinal fluid from patients with epilepsy.

The alteration of amino acids content in cerebrospinal fluids (CSF) from 31 cases of epilepsy and 10 cases of headache (as control) was studied using high performance liquid chromatography (HPLC). In patients with epilepsy, it was found that the CSF levels of GABA and aspartic acid had a tendency to decrease, but these changes were not statistically significant. In simple partial seizures, the CSF levels of glutamic acid and glycine also showed a tendency to decrease. The decrease of CSF GABA found in epileptics had a tendency to normalize following treatment with valproic acid. At the same time, administration of valproic acid induced a decrease of aspartic acid in the CSF of epileptics. These results suggest that administration of valproic acid may induce an increase in GABA and a decrease in aspartic acid in the CSF of epileptics.

Adult↗

Differential mechanism for differentiation into immunoglobulin-secreting cells in human resting B lymphocyte subsets isolated on the basis of cell density.

We have investigated differential mechanism for differentiation of human peripheral blood resting B cells to Ig-secreting cells. Purified resting B cells were further fractionated into subsets by discontinuous density gradients of Percoll, and proliferation and differentiation responses to Staphylococcus aureus Cowan I (SAC) and/or T cell-derived soluble factors were studied. High density resting B cells were stimulated to proliferate vigorously in response to SAC, but were poorly differentiated by SAC in presence of T cell factors. In contrast, low density resting B cells failed to proliferate in response to SAC and/or T cell factors; these cells could, however, be induced by stimulation with SAC plus T cell factors to become cells actively secreting Ig. These results indicate that there may exist heterogeneity in the human resting B cells: one subset of resting B cells (B cells with low density) can differentiate directly into Ig-secreting cells without the need for proliferation, and another subset (B cells with high density) can proliferate actively without subsequent differentiation into Ig-secreting cells. To address whether these resting B cell subsets belong to the same lineage, only high density B cells recovered from circulating resting B cells were first stimulated for 7 d with SAC, refractionated on Percoll gradients, and differentiation response of the refractionated B cells to SAC and T cell factors was examined. B cells shifting toward low density fraction were located in the resting status and could differentiate in response to SAC plus T cell factors. These results indicate that some of B cells with high density belong to the same cell lineage as those with low density and they must first proliferate before differentiation.

Antibody-Producing Cells↗

Comparison of the facilitative roles of insulin and insulin-like growth factor I in the functional differentiation of granulosa cells: in vitro studies with the porcine model.

The facilitative effects of insulin and IGF-I were compared in vitro with regard to induction of differentiated functions of porcine granulosa cells. The monolayers were maintained under serum-free conditions in the absence or presence of porcine FSH (20 micrograms/l), with or without graded doses of insulin or IGF-I. Concurrent treatment with IGF-I and FSH produced morphological differentiation and augmented LH/hCG receptor binding together with an enhancement in progesterone and estradiol secretion relative to treatment with FSH alone. IGF-I alone was incapable of exhibiting these effects. Insulin synergized with FSH to facilitate the granulosa cell functions except estradiol secretion. Maximal effective dose of IGF-I was 100 micrograms/l which is within the physiological concentration in vivo, whereas that of insulin was 1.0 mg/l, which is 1000-fold higher than the physiological level. Although the maximal effective doses of IGF-I and insulin produced a comparable increment in progesterone secretion and LH/hCG receptor induction, combined treatment with IGF-I and insulin did not prove additive. [125I]IGF-I binding revealed that specific IGF-I receptors with two classes of binding sites are present on porcine granulosa cells. No distinct differences were detected between IGF-I receptors of granulosa cells from small, medium and large follicles. Insulin was approximately 100-fold less active than IGF-I in competing for [125I]IGF-I binding. These findings suggest that porcine granulosa cells possess specific IGF-I binding sites which may mediate the cytodifferentiative actions of insulin-like peptides. Since IGF-I is more potent than insulin in amplifying the actions of FSH and maximally exerts the cytodifferentiative effects at the physiological concentration, it is likely that IGF-I plays the more important role in granulosa cell differentiation in synergy with FSH.

Animals↗

Oxygenation effect of fluosol-DA on hypoxic tumor tissue and retention of PFCs in the tumor-bearing rats.

An i.v. injection of Fluosol-DA 20% without hydroxy-ethylstarch in combination with carbogen (95% Oz and 5% COz) elevated dose-dependently the tumor POz in AH-109A tumor-bearing rats. The elevation of the tumor PO2 by the treatment of Fluosol-DA injection and carbogen breathing was significantly high at the period when the elevated tumor blood flow declined to the original level and lasted for 3 hours following Fluosol injection. Saline injection with carbogen induced a small increase in the tumor PO2. These results suggest that the oxygenation effect of Fluosol was primarily attributed to the oxygen carrying effect of Fluosol itself. The tumor PO2 increased almost linearly with the arterial PO2. The enhancement in tumor growth delay was observed on the 1 hour post 60CO -ray irradiation with carbogen following Fluosol injection in the Lewis lung tumor-bearing BDF; mice, but not with the 1 day-post irradiation. No significant differences were observed in perfluorochemical retention from the blood circulation and in organ distribution between the tumor bearing rats and normal rats.

Animals↗

Effect of FK506 in experimental organ transplantation.

FK506 is the most potent immunosuppressive agent known. Its toxicity is substantial in dogs, minor in rats, and unknown in subhuman primates. In small doses that are nontoxic even in dogs, it can be used in synergistic combination with cyclosporine, steroids, and presumably in other drugs.

Animals↗

Immunosuppression of canine, monkey, and baboon allografts by FK 506: with special reference to synergism with other drugs and to tolerance induction.

In dogs the most effective oral dose of FK 506 for prevention of renal homograft rejection was 1.5 mg/kg/day. With maximum credit allowed at 90 days, survival was increased to 61.0 +/- 33.6 (SD) days compared with 13.0 +/- 4.1 in untreated control animals. Higher doses were toxic. The smallest dose that was used (0.5 mg/kg/day) prolonged survival after renal transplantation to 33.7 +/- 23.9 (SD) days. When the small dose of FK 506 was combined with 5 mg/kg/day of cyclosporine and 5 mg of prednisone, five of six canine kidney recipients lived for 90 days. These results were degraded by omission of any of the constituent drugs or reduction by half of the triple drug doses. Thirteen of the dogs treated with various drug regimens lived for 90 days, after which time treatment was stopped; 10 of the dogs eventually rejected the grafts, but three had continued graft function for 6 months or longer and may be permanently tolerant. Moreover, in dogs when 1 mg/kg of intramuscular FK was given to 19 kidney and seven liver recipients for 3 days on postoperative days 1 to 3, 4 to 6, or 7 to 9, the animals survived subsequently for 11 to more than 160 days. All but four of the grafts were eventually rejected, but the prolonged effect of a short course of delayed therapy suggests the possibility of tolerance induction. In cynomolgus monkeys and baboons, FK as a single drug was found to be immunosuppressive after kidney transplantation. Correlation in the dogs and primates between immunosuppression, toxicity, and FK blood levels was not possible because of presently imperfect standardization of assay and monitoring techniques. FK had serious side effects in dogs, but not so obviously in monkeys and not at all in baboons.

Animals↗

Long-term results of aortic valvuloplasty for aortic regurgitation associated with ventricular septal defect.

Long-term results in 64 patients who underwent aortic valvuloplasty for aortic regurgitation associated with ventricular septal defect are presented. The average age of the patients was 10.2 years and the average cardiothoracic ratio was 0.57 at the time of operation. The average degree of aortic regurgitation, as classified by Sellers, was 2.7. The type of ventricular septal defect was subpulmonic in 31 patients, perimembranous in 20, and was a total conal defect in five patients. Valvuloplasty was performed at one end of an aortic cusp in 23 patients, at two ends in 33, at three ends in six, and at four ends in two patients. There was one operative death (1.6%). The follow-up period was 447.7 patient-years, and there were no late deaths. The actuarial survival rate was 98.3% at 5, 10, and 15 years. Postoperative cardiac catheterization was performed in 40 patients. Valvuloplasty failure was defined as the presence of a cardiothoracic ratio greater than 0.6, a loud regurgitant murmur (Levine grade 3/6 or greater), moderate or severe aortic regurgitation (Sellers grade 3 or 4), or the necessity of reoperation. There were 17 patients whose valvuloplasty failed. The freedom from valvuloplasty failure was 74.2% at 5 and 10 years and 55.3% at 15 years. Eight patients underwent reoperation because of residual aortic regurgitation, and all survived. The freedom from reoperation was 90.1% at 5 years, 80.5% at 10 years, and 63.7% at 15 years. Multiple regression analysis revealed that older age, a greater cardiothoracic ratio, perimembranous ventricular septal defect, and multiple valvuloplasties were significant contributing factors for residual regurgitation after aortic valvuloplasty.

Actuarial Analysis↗