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Biomedical subjects

Y Suda

Publications and source records attributed to Y Suda.

At least 91 records · Page 5Linked to original sources
PubMed1993

Chemical and biological degradation of 5-fluorouracil prodrugs having high serum albumin binding potencies.

In order to understand the fundamental structural features which yield both high serum albumin binding potency and desired property as a prodrug, the derivatization was performed at N-1 or N-3 position in 5-fluorouracil. The N-3 derivatives were more stable than N-1 derivatives in vitro, whereas they were metabolized quickly in vivo. It is suggested that N-1 position should be blocked to avoid fast metabolism in vivo.

Animals↗
PubMed1993

The synthesis and in vitro and in vivo stability of 5-fluorouracil prodrugs which possess serum albumin binding potency.

For a new drug delivery system of 5-fluorouracil, we prepared prodrugs possessing certain desired properties. The prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil and 1-(N-2,4-dichlorophenyl-N-methylcarbamoyl)-5-fluorouracil, contain high serum albumin binding potency and a comparably long half life in the bloodstream in vivo to Tegafur. These two prodrugs are expected to be retained in the bloodstream as a polymeric complex with albumin and to circulate in the body for a long time, like a polymeric prodrug.

Animals↗
PubMed1993

Enhanced proliferative potential in culture of cells from p53-deficient mice.

Normal somatic cells are endowed with limited doubling potential in culture, and the process of immortalization is an inevitable step in neoplastic transformation of the cells. To examine the roles of p53 in this process, the cells of p53-deficient mice were examined for doubling potential. Fibroblast-like cells from a variety of tissues of these mice proliferated continuously without showing aging or crisis. The aneuploid cells overcome the population with passage, but cloning experiment indicated that chromosomal changes were not essential to this process. The enhanced proliferative potential in culture of cells from the p53-deficient mice was also observed in epithelial cells of lens, mammary glands and seminal vesicles and in neural precursor cells. Proliferation of bone marrow cells in response to stem cell factor was enhanced in long term culture, but not in in vitro colony assay; no permanent cell lines could be obtained. No effects of p53-deficiency were found in proliferation of cardiac muscle cells or hepatocytes.

Aneuploidy↗
PubMed1993

[Pulmonary artery reconstruction for extreme tetralogy of Fallot and similar complex heart diseases before cardiopulmonary bypass].

It is sometimes difficult to repair the pulmonary artery in extreme tetralogy of Fallot and other similar complex heart diseases, such as pulmonary atresia with major aorto-pulmonary collateral arteries, because of their complexity. Therefore, cardiopulmonary bypass takes longer in these patients than in those with usual tetralogy of Fallot. We undertook reconstruction of the pulmonary artery in 4 cases of extreme tetralogy of Fallot and other similar complex heart diseases before cardiopulmonary bypass. We investigated the cardiopulmonary bypass time in these patients and compared it with that in patients with usual tetralogy of Fallot. There was no significant difference in cardiopulmonary bypass time between the two groups. In the 4 extreme cases, the postoperative course was uneventful. We conclude that this attempt reduced the cardiopulmonary bypass time and facilitated the surgical correction.

Adolescent↗
PubMed1993

MDS-like experimental myelodysplasia: multilineage abnormal hematopoiesis in transgenic mice harboring the SV40 large T antigen under an immunoglobulin enhancer.

The SV40 large T gene under the control of immunoglobulin enhancer induced hyperproliferation of multilineage hematopoiesis in transgenic mice. Huge splenomegaly was the major gross abnormality; mice were rather anemic, and neither leukoerythroblastosis nor invasion into tissues such as liver, kidneys or lymph nodes was common. In the latter phases of the disease, the proliferating cell type tended to shift to a variety of single-lineage hematopoiesis, but the majority of mice still showed the presence of multilineage hematopoiesis; such cells were somewhat dysplastic but low in neoplastic potential. A long-term observation by transplantation of the hematopoietic cells into lethally irradiated C57BL/6 mice resulted in a variety of neoplastic growths in the recipients; not only was myelodysplastic hypercellularity seen, but also single-lineage hematopoietic malignancies such as B cell lymphomas/leukemias, histiocytic malignancies and even myeloid leukemias. The disease bore the proliferative feature solely in the spleen and bone marrow, and the transition from multilineage myelodysplasia into single-lineage hematopoiesis at some frequency is reminiscent of myelodysplastic syndromes (MDS) in humans. The results that the SV40 large T antigen was expressed in every proliferating cell, and that there was no apparent increase in any colony-stimulating cytokine(s), together with the results of the transplantation assays, suggested that the hyperproliferation of the hematopoietic cells was a direct consequence of the expression of SV40 large T antigen in these cells themselves.

Animals↗
PubMed1992

Influence of oophorectomy on serum levels of sex steroids and bone metabolism and assessment of bone mineral density in lumbar trabecular bone by QCT-C value.

The present cross-sectional study was carried out to determine the influence of oophorectomy (OPX) on serum levels of sex steroids and bone metabolism, as well as bone mineral density (BMD), in OPX subjects in comparison with age- and body size-matched controls. Quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) demonstrated a remarkable reduction in BMD in OPX subjects. In particular, the QCT of the centrum of vertebral bone (QCT-C) in these subjects was no more than 69.33 +/- 3.40% (X +/- SEM) of the control value, and this parameter was much lower than the QCT integral (QCT-I) value of total lumbar vertebrae. This means that BMD decreases specifically in spongy portions after OPX. The serum level of estrone (E1) was significantly lower in OPX subjects than in controls. The hormonal action of E1 on target organs has been thought to be only one-third of that of estradiol (E2), but the marked reduction in serum E1 level seemed to be a significant cause of the reduction in BMD. The serum level of androstenedione (delta 4) significantly decreased in OPX subjects and appeared to affect bone metabolism negatively. Both bone formation and bone resorption were found to be stimulated following OPX, but the rate of bone resorption was found to be higher than that of bone formation: there was an imbalance between bone formation and bone resorption in OPX subjects. However, it was not possible to prove a relationship between Ca regulating hormone and this phenomenon. In conclusion, the QCT-C value reflects the changes in spongy vertebral BMD more sensitively than the QCT-I value or DPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1992

Which is more osteoporosis-inducing, menopause or oophorectomy?

The present study was designed to investigate in a comparative manner whether menopause or oophorectomy (OPX) would be a more osteoporosis-inducing factor with regard to sex steroids, bone metabolism and bone mineral density (BMD), including postmenopausal subjects, OPX subjects and age- and body-size-matched premenopausal controls. Serum levels of estradiol (E2), testosterone (TS) and dehydroepiandrosterone (DHEA) were found to decrease in both the postmenopausal and OPX subjects without any significant difference between them, while serum levels of estrone (E1) and androstenedione (delta 4), which have been reported to be related to bone metabolism, were significantly lower in the OPX subjects than in the postmenopausal subjects. According to the indices representing bone formation and bone resorption, as well as the changes in serum levels of Ca-regulating hormones, bone metabolic balance seemed to be slightly more negative in the former than in the latter. However, there was no difference between these two groups of subjects with regard to BMD in lumbar vertebral spongy portion which sensitively reflects the changes in total lumbar BMD and bone metabolism and in which compressive fracture is apt to occur. This fact suggests that these two groups of subjects may be managed in the same way in clinical practice. In other terms, the menopause, a natural event in women, influences BMD as much as OPX, which is the greatest risk factor in osteoporosis, does.

Androgens↗
PubMed1992

Airway epithelial cells enhance eosinophil survival.

Guinea pig and human eosinophils were co-cultured with or without epithelial cells (controls). Eosinophil survival was enhanced in the presence of the cultured epithelial cells in a number-dependent fashion. Further, supernatants from cultured epithelial cells also enhanced eosinophil survival. Both a monoclonal antibody to GM-CSF and indomethacin inhibited these epithelial-cell-mediated effects, and GM-CSF and PGE2 were shown to prolong eosinophil survival. These findings indicate that airway epithelial cells can enhance eosinophil survival. It is suggested that the mechanism may involve GM-CSF and PGE2 generation.

Animals↗
PubMed1992

[Mitral valve surgery using combined superior-transseptal approach to the left atrium].

Although various approaches to the mitral valve surgery have been tried in the past, it still may be difficult to obtain a good surgical field, particularly in cases of small left atrium or reoperation. We performed mitral valve surgery in 6 patients using the combined superior-transseptal approach to the left atrium proposed by Berreklouw. Exposure of the mitral valve was excellent and the operative procedure was simple in all cases. There were no differences in bleeding volume, length of operation or complication of arrhythmia between patients treated with this new approach and a group treated with conventional approach in our institute.

Adult↗
PubMed1992

[Blood concentrations of futraful, uracil and 5-fluorouracil (5-FU) after UFT administration in the various reconstructions after gastrectomy. Saitama UFT Research Group].

The study was undertaken in the total of 58 gastric cancer patients among which 17 of Billroth (BI), 14 of Billroth II (B II) anastomosis after subtotal gastrectomy, and 7 of jejunal interposition, 9 of double tract and 11 of Roux en Y anastomosis after total gastrectomy were included. Blood samples were taken before 200 mg of per oral UFT administration and after 1, 2, 3, 5 and 7hrs. consecutively. The blood Futraful (FT) level in the total gastrectomy groups reached peak concentration within 1hr and kept in relatively high level during the observation period of 7hrs. The time to maximum FT concentration delayed in almost of B I and a few of B II patients. The concentration curves of uracil (URA) and 5-FU were similar in shape, revealing steep increase and decrease except B I anastomosis which showed gentle course. The plotted maximum concentrations of URA and 5-FU in the every type of reconstruction showed a significant correlation in the regression line. In the analysis of AUC, URA/FT was under 10%, suggesting the longer retention of the unmetabolite type of FT and early disappearance of URA. The ratio of 5-FU/FT was indifferent in each reconstruction. 5-FU/URA was higher in subtotal rather than total gastrectomy groups. From the data obtained, blood concentration of 5-FU after UFT administration was considered to depend on the emptying status in the gastrectomies. And moreover, it depended on blood URA level, since FT from which 5-FU was derived, was kept still sufficiently remained during observation period.

Anastomosis, Roux-en-Y↗
PubMed1992

[Intraoperative radiotherapy for local recurrence of intrapelvic malignancies].

From 1986 to 1992, seventeen patients with recurrent intrapelvic malignancies have been treated with intraoperative radiotherapy (IOR) in Saitama Cancer Center. They were 8 males and 9 females. The age ranged 44 to 83 (mean:61.6). The primary organs involved were rectum in 7, urinary bladder in 5, uterine cervix in 3 and ovary in 2. Invasion of recurrent disease into bony pelvis was noted in all but one patient. A total of 27 IORs were done on 18 occasions for 17 patients. The mean radiation dose was 25.6 Gy (range: 12-30). The cones used were 4 to 7 (mean: 5.4) cm in diameter. Debulking surgery was performed in 13 patients just before IOR. Chemotherapy and/or external radiotherapy were done in addition to IOR in most of the cases. As of May 1992, 14 patients had died with a mean survival time of 10 months (range:0.5-29.8). IOR seems to be useful in controlling the intrapelvic recurrent disease and may warrant further investigation.

Adult↗
PubMed1992

Hemopoietic neoplasms in lethally irradiated mice repopulated with bone marrow cells carrying the human c-myc oncogene: a repopulation assay.

Bone marrow (BM) cells from two transgenic mice carrying the human c-myc oncogene were separately harvested, and each sample was injected into 25 lethally irradiated mice. We observed the contribution of the myc gene to the occurrence of hemopoietic neoplasms in the BM-repopulated mice, establishing a new experimental system for analyzing oncogene expression in the hemopoietic system in vivo. The hybrid gene that was transferred into the original transgenic mice was a combination of the human c-myc gene with a regulatory unit consisting of a murine immunoglobulin-heavy chain with an SV40 early-T promoter gene (Ig/Tp-myc). Among the transgenic lines, the tested BM cells were chosen from two lines that had been low-prone in leukemia; in these lines hemopoietic neoplasms did not appear for greater than or equal 200 days after birth. Lethally irradiated controls received BM cells from litters of transgenic mice that did not carry c-myc. The lifetime incidence of hemopoietic neoplasms was 94% and 91% in the two groups of mice repopulated with myc+ BM. By contrast, only 15% of control mice with myc- BM developed hemopoietic lesions. The incidence of hemopoietic malignancies combined with nonthymic lymphomas and myeloma cases (88% and 65%) was higher in the repopulated mice than the incidence of pre-B cell lymphomas in the original transgenic lines (56%). Thirty-two of the 40 myc+ mice that were examined showed the presence of the transferred gene in either the normal hemopoietic tissue or in the hemopoietic neoplasm. Furthermore, 18 of 22 hemopoietic neoplasms studied by Northern hybridization expressed mRNA from the transgenic gene; in other four neoplasms, expression was weak or absent.

Animals↗
PubMed1991

[Effects of preoperative local administration of BRM on cellular immunity and prognosis of patients with esophageal cancer].

We studied the effects of OK-432 administered preoperatively on the cellular immunity and prognosis of patients with esophageal cancer. The preoperative injection of OK-432 was effective to preserve the NK activity in the peripheral blood. Especially the local priming and eliciting with OK-432 seemed to contribute to the activation of NK cells in the regional lymph nodes and to the improved prognosis of the patients.

Esophageal Neoplasms↗
PubMed1991

[Immunohistochemical Study of 3-methylcholanthrene inducible cytochrome P-450 in the stomach and liver--a guide of postoperative chemotherapy in gastric cancer].

Immunohistochemical determination of 3-methylcholanthrene (MC) inducible cytochrome P-450 (MC-P-450) was investigated in rat and human tissue, and its clinical availability was discussed. Induced by MC, MC-P-450 in rat liver and stomach was well stained immunohistochemically, showing clear contrast against control without induction. The staining intensity in the tissue was correlated with the amount of tissue MC-P-450 which was determined previously by electrophoretical and biochemical technics. By the same immunohistochemical method MC-P-450 in human liver and stomach was also detectable. The staining grade of MC-P-450 in human liver and stomach was different from each person. However, its intensities in liver and stomach in the same individual showed clear correlation with p less than 0.02. Since MC-P-450 in liver plays a major role in drug metabolism, the proof of correlation between staining degree of the resected stomach and hepatic tissue would provide useful clue in gastric cancer for postoperative administration of masked compounds activated by MC-P-450.

Animals↗
PubMed1991

[Influences of menopause and oophorectomy on bone metabolism and spinal bone mineral content].

The present study was performed on bone metabolism and spinal bone mineral content (BMC) in 3 groups of age- and body size-matched subjects: Thirty-three postmenopausal subjects, 37 oophorectomized (OPX) subjects and 22 premenopausal subjects. Serum levels of Alp and osteocalcin (OC) as indices of bone formation, U-Ca/cr and U-hydroxyproline (Hpr)/cr as indices of bone resorption, and Ca-regulating hormones, M-PTH, calcitonin (CT) and 1,25(OH)2D; were measured and spinal BMC was determined by QCT. Alp and OC levels were slightly higher in the postmenopausal group than in the OPX group and, in contrast, U-Ca/cr and U-Hpr/cr were slightly higher in the latter. The M-PTH level was slightly higher in the latter, and the CT level in the former. There was no difference in the 1,25(OH)2D level between two groups. For BMC, there was no difference between the two groups. The above results corresponded to the previously reported significant reductions in sex steroids. OPX seemed to affect bone metabolism more than menopause, there was no specific influence of OPX on spinal BMC as compared with QCT findings in postmenopausal subjects. Our previous study and the present study demonstrated that, at an interval of about 3 years after menopause or OPX, the endocrine system and bone metabolism tended to be more affected by OPX. However, BMC did not reflect any influence of OPX, or of menopause. There was no clear clinical difference between postmenopausal subjects and the OPX subjects with regard to the osteoporotic condition.

Alkaline Phosphatase↗
PubMed1990

Effect of aspartame on N-methyl-D-aspartate-sensitive L-[3H]glutamate binding sites in rat brain synaptic membranes.

Aspartame (L-aspartyl-L-phenylalanine methyl ester), an artificial low-calorie sweetener, was shown to dose-dependently inhibit L-[3H]glutamate binding to its N-methyl-D-aspartate-specific receptors. L-Aspartic acid, a major endogenous metabolite of aspartame, inhibited the binding more stronger than aspartame, while the other metabolites, L-phenylalanine and methanol, had no effect at the same concentration. Aspartame caused a significant change in the affinities of L-[3H]glutamate binding without altering the Vmax values of the binding, suggesting the inhibition is competitive. These in vitro findings suggested that aspartame may act directly on the N-methyl-D-aspartate-sensitive glutamate recognition sites in the brain synaptic membranes.

Animals↗