Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 127 records · Page 7Linked to original sources

PubMed1991

Augmentation by tumor necrosis factor alpha of the systemic therapeutic effect of lymphokine-activated killer cells in adoptive immunotherapy of murine tumor.

The therapeutic effect of a combined modality of lymphokine-activated killer (LAK) cells and tumor necrosis factor alpha (TNF alpha) on MBL-2 tumor in C57BL/6 mice was studied. Murine LAK cells induced from splenocytes by interleukin 2 (IL2) could lyse MBL-2 target cells in vitro. but no enhancement of the LAK activity was found by the treatment of LAK cells with TNF alpha in vitro. However, the treatment of MBL-2 with TNF alpha enhanced the sensitivity to LAK cells. Moreover, administration of TNF alpha to mice bearing solid MBL-2 tumor led to increased tumor vascular permeability within 1 h, and resulted in the enhanced accumulation of systemically transferred LAK cells in tumor tissue. Based on these results, we treated MBL-2-bearing mice with TNF alpha and then with LAK cells 1 h later. No therapeutic effect was observed when tumor-bearing mice were treated with TNF alpha alone or LAK cells plus IL2. However, adoptive immunotherapy using LAK cells and TNF alpha had therapeutic effects, i.e., growth inhibition of tumor nodules and prolongation of survival. These results indicated that appropriately timed pretreatment of tumor-bearing mice with TNF alpha augmented the anti-tumor efficacy of LAK cells.

Animals↗

PubMed1991

Cytosolic-nuclear tumor promoter-specific binding protein: association with the 90 kDa heat shock protein and translocation into nuclei by treatment with 12-O-tetradecanoylphorbol 13-acetate.

Suspension-cultured HeLa cells possess a cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) which lacks protein kinase C activity. This CN-TPBP existed in cytosol of HeLa cells, but translocated into nuclear fraction of the cells after treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate (TPA). The translocation of CN-TPBP induced by TPA became apparent within 10 min after the treatment with TPA, and was completed within 3 h. CN-TPBP bound TPA with the association constant of 1.4 x 10(10) M-1, and also bound teleocidin B, debromoaplysiatoxin, and thapsigargin in a mutually competitive manner. The binding affinity order of synthetic analogs of teleocidin B correlated with the adhesion-inducing potency order of the compounds toward human leukemia cell line HL-60. The apparent molecular weight of CN-TPBP under non-denaturing conditions was estimated to be 66-68 kDa. CN-TPBP forms a complex with the 90 kDa heat shock protein, and the complex was stabilized by the presence of molybdate. These characteristics of CN-TPBP are similar to those of the nuclear receptors of glucocorticoid and dioxin. These findings suggested that CN-TPBP acts as a nuclear receptor for tumor promoters, and that tumor promoters may exert their biological effects by binding to CN-TPBP.

Carcinogens↗

PubMed1991

Application of colorimetric microdilution plate hybridization for rapid genetic identification of 22 Mycobacterium species.

Quantitative microdilution plate hybridization was used to identify 22 Mycobacterium species. DNAs of clinical strains were rapidly extracted and labeled with photoreactive biotin. Labeled DNAs were distributed into wells of a microdilution plate in which reference DNAs had been immobilized. After 2 h of hybridization, hybridized DNAs were quantitatively detected with peroxidase-conjugated streptavidin and the substrate, tetramethylbenzidine. This method could differentiate among 20 of the 22 Mycobacterium species tested. The type strains of Mycobacterium tuberculosis and M. bovis were genetically highly related and could not be differentiated by this method. Of 194 biochemically identified human clinical strains, 178 (90%) were genetically identified within 3 h of the small-scale DNA extraction.

Aminosalicylic Acid↗

PubMed1991

Retinobenzoic acids and nuclear retinoic acid receptors.

Retinoids (retinoic acid and its analogs) are widely involved in the control of cell proliferation, cell differentiation and embryonic development. A series of potent and novel synthetic retinoids named retinobenzoic acids has been developed. Retinobenzoic acids have proven to be useful tools in the investigation of the molecular mechanisms of retinoidal actions. Retinoids elicit their biological effects by binding to and activating specific nuclear receptors for retinoids (RAR's) which belong to the steroid/thyroid nuclear receptor superfamily. Recent investigations concerning the structure and function of nuclear receptors, namely of RAR's, are reviewed. Three subtypes of RAR (RAR-alpha, RAR-beta and RAR-gamma) have been identified so far. Each RAR is considered to play particular roles in the retinoidal actions. The role of each RAR is discussed in relation to their features and to the structure-activity relationships of retinoids. RAR's act as retinoid-dependent transcription factors which bind to a specific site of the gene and control its expression. Recent progress in the investigation of the interaction of RAR's with the responsive genes and with nuclear co-factors is reviewed. The diversity of retinoidal actions are possibly explained by the diversity of RAR's in their structure and in their spatial and temporal distribution, by the diversity of base sequences which interact with RAR's, by the diversity of cell type-specifically determined hierarchy of gene expression, and by the diversity of the nuclear factors which interact with RAR's.

Animals↗

PubMed1991

Phospholipid-binding properties of calphobindin-II(annexin VI), anticoagulant protein from human placenta.

Calphobindin-II (CPB-II, annexin VI), is a calcium dependent phospholipid binding protein that can be classified as a member of the annexin family. The phospholipid-binding properties of CPB-II were investigated by measuring the binding constants of [125I]-CPB-II using phospholipid vesicles consisting of 80% phosphatidylcholine and 20% phosphatidylserine. A dissociation constant (Kd) of CPB-II with the phospholipid vesicles was determined to be 0.2 to 0.3 nM in the presence of Ca2+ ranging from 0.3 to 30 mM. The number of CPB-II capable of binding to the phospholipid vesicles at 0.3 mM Ca2+ decreased to about 1/2 in the presence of Ca2+ of more than 1 mM. Prothrombin and factor X were effective in competing with the binding of CPB-II to the phospholipid vesicles, although their affinities were lower by two or three orders of magnitude than that of unlabeled CPB-II at 30 nM Ca2+. Competitive effects of CPB-II, calphobindin-I (CPB-I, annexin V) and calphobindin-III (CPB-III, annexin III) on binding of [125I]-CPB-II to phospholipid vesicles, were similarly observed.

Annexin A6↗

PubMed1991

Transport to intestinal lumen and peritoneal cavity of intravenously administered aprinidine in rats.

Transfer of aprindine from the blood into the intestinal lumen or into the peritoneal cavity was examined after intravenous administration of the drug at a dose of 5 mg/kg in rats. The amount of the drug transferred from the blood into the intestinal lumen was much greater than into the peritoneal cavity. The average amounts of aprindine transported into the intestinal lumen and the peritoneal cavity were 0.12 and 0.03% of the dose (5 mg/kg) in 120 min, respectively. Thus, a notable difference in the clearance values of the drug was obtained between the intestinal lumen (14.8 ml/h) and the peritoneal cavity (4.94 ml/h). The net water flux showed that secretion predominated in the peritoneal transport while absorption overbalanced secretion in the intestinal transport. It seems likely that a solvent drag effect by water movement did not contribute much to the transport of aprindine from the blood to the intestinal lumen or the peritoneal cavity. The differences in transport across the two membranes could be due to differences in the surface area and other geometrical factors. Differences could also be due to a difference in the pharmacologic effects of the drug which causes a decrease in tissue splanchnic perfusion.

Animals↗

PubMed1991

Periandradulcins A, B and C: phosphodiesterase inhibitors from Periandra dulcis Mart.

During the course of our screening of bioactive natural products, three new saponins named periandradulcins A (1), B (2) and C (3) were isolated as phosphodiesterase (PDE, EC 3.1.4.17) inhibitors from 80% MeOH extract of the roots of Periandra dulcis Mart. (Leguminosae) by a combination of column chromatography and reversed- and normal-phase high-performance liquid chromatography (HPLC). On the basis of 1H-, 13C- and two-dimensional nuclear magnetic resonance (NMR) spectral data and chemical evidence, their chemical structures were characterized as 3-O-beta-[alpha-L-rhamnopyranosyl(1----2)-beta-D-xylopyranosyl(1----2)-b eta-D- glucuronopyranosyl]-30-hydroxyl-25-formylolean-18-ene-22 beta-O-syringate, 3-O-beta-[alpha-L-rhamnopyranosyl(1----2)-beta-D- xylopyranosyl(1----2)-beta-D-glucuronopyranosyl]-22 beta-hydroxyl-25- formylolean-12-ene and 3-O-beta-[alpha-L-rhamnopyranosyl(1----2)-beta-D- glucopyranosyl(1----2)-beta-D-glucuronopyranosyl]-22 beta-hydroxyl-25-formylolean-18-ene, respectively. The concentrations of periandradulcins A, B and C required to give 50% inhibition (IC50 values) of PDE from bovine heart, were 0.033, 7.6 and 7.7 microM, respectively. Compound 1 was the most potent among the known PDE inhibitors; it inhibited PDE-I (IC50:0.0022 microM) twenty and forty times more effectively than PDE-II and -III, respectively.

Carbohydrate Sequence↗

PubMed1991

Ethacrynic acid-sensitive and ATP-dependent Cl- transport in the rat kidney.

Ouabain- and furosemide-insensitive and ATP-dependent Cl- uptake was demonstrated in rat renal membrane vesicles. Such a Cl- uptake activity was prominent in cortical plasma membrane fractions with high activities of Cl(-)-ATPase and Na+, K(+)-ATPase. The membrane vesicles accumulated Cl- in an osmotically reactive manner with the following sequence of nucleotide specificity: ATP greater than ITP greater than UTP greater than GTP greater than CTP., beta, gamma-Methylene ATP, ADP and AMP had no effect. ATP-dependent Cl- uptake was markedly inhibited by a Cl(-)-ATPase inhibitor, ethacrynic acid (0.3 mM), but not affected by an H(+)-ATPase inhibitor, N,N'-dicyclohexylcarbodiimide (0.1 mM). These findings suggest that an ethacrynic acid-sensitive and ATP-driven

Adenosine Triphosphatases↗

PubMed1991

Early neurobehavioral disorders in the micrencephalic offspring induced by prenatal treatment with N-methyl-N-nitrosourea or methylazoxymethanol in the rat.

Micrencephalic neonatal pups were obtained from pregnant Crj:CD (SD) rats once treated with 5 mg/kg of N-methyl-N-nitrosourea (MNU) or 40 mg/kg of methylazoxymethanol (MAM) on day 12, 13, 14 or 15 of gestation (vaginal plug = day 0). They were reared by their own mothers and were subjected to various neurobehavioral tests during the suckling period, days 0 to 22 after birth. The brain weights in the MNU- and MAM-treated pups on postnatal day 22 were significantly less than those in the control pups. These micrencephalic pups were retarded in neurobehavioral ontogeny. By several tests, each of them showed an impaired performance such as paired limb movement, clumsy locomotion or hyperreflexive reaction. These behavioral disorders appeared different according to the day of treatment, without any substantial difference between the test compounds, MNU and MAM. The findings suggest that the different neurobehavioral characteristics in the micrencephalic pups may reflect their different brain disorders induced by the test compounds given on the different period of the treatment.

Animals↗

PubMed1991

Retinoids and their nuclear receptors.

Retinoids (retinoic acid and its biofunctional analogs) are widely involved in the control of cell proliferation, cell differentiation, and embryogenic development. A series of novel synthetic retinoids (called retinobenzoic acids), which include retinoid antagonists, have been developed and have been shown to be useful tools to investigate retinoidal action molecular mechanisms. Retinoids elicit their biological effects by binding to specific nuclear receptors (RARs) belonging to a steroid/thyroid nuclear receptor superfamily. RARs act as retinoid-dependent transcription factors which bind to a specific gene site and control the gene's expression. The diversity of retinoidal actions can possibly be interpreted by considering the following characteristics, all of which are quite diversified: the structure and spatial/temporal distribution of RARs, the base sequences which interact with RARs, the cell type specifically determined hierarchy of gene expression, and the nuclear coregulators which interact with RARs. Abnormality of an RAR gene which might cause acute promyelocytic leukemia is also discussed.

Animals↗

PubMed1991

[Mouse fetal brain specific protein "GP68" is expressed in human tumor cells].

It is well known that some fetal antigens are expressed in malignant tumor cells. Likewise, brain tumors, especially histologically malignant cases, may have any antigenic relationships with fetal brain. So, we investigated the relationship by immunohistochemical technique, utilizing a polyclonal antibody to mouse fetal stage-specific polypeptide "GP68". We prepared GP68 from homogenate of head part of embryos at the 14th day of gestation mice by RCA-1 agarose column chromatography. And immunized it to Japanese white rabbits and the titer was measured by enzyme-linked immunosorbent assay. We analyzed operatively resected brain tumors and autopsy brain tissues. Frozen tissues were fixed in cold acetone and immunostained with anti-GP68 serum according to biotin-streptavidin peroxidase method. Remained tissues were homogenized in Laemmli's sample buffer and electrophoresed. The proteins were transferred to nitrocellulose membrane and immunostained with anti-GP68. Normal brain tissues were not positively stained, except for capillary endothelium which showed a weak staining. On the other hand, brain tumors of neuroectodermal origin were positively stained in varying degrees, and other tumors were negative. It is especially noteworthy that, in astrocytoma cases, there exists a definite correlation between the intensity of stain and the degree of histological malignancy. Immunoblot studies demonstrated a very weak band at 68 KD in normal brain and meningioma. In contrast, very strong band at the same position was seen in malignant astrocytomas. These results suggested that in brain tumors, especially those of neuroectodermal origin, GP68 antigen is expressed and the degree of expression is related to their histological malignancy. So this fetal antigen may be useful for evaluation of biological malignancy of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[Retinoids and acute promyelocytic leukemia].

Retinoic acid and its analogs, retinoids, have been shown to be useful in the treatment of several types of tumors. Retinoids elicit their biological activities by binding to their specific nuclear receptors, denoted as RAR-alpha, beta and gamma. RAR's have been established to be retinoid-dependent transcription factors which belong to the steroid/thyroid nuclear receptor superfamily. Recently, retinoic acid has been reported to be extremely effective in the treatment of acute promyelocytic leukemia (APL) giving more than 70% complete remission efficiency. APL has been characterized by the specific chromosomal translocation, t(15;17). Analysis of the t(15;17) breaking point revealed that (i) either RAR-alpha on chromosome 17 or the gene named myl on chromosome 15 is abnormal in APL cells, and (ii) the abnormal fused protein myl/RAR-alpha is expressed, which is suspected to cause the APL. Thus, RAR-alpha gene may be now regarded as one of tumor suppressor genes.

Animals↗

PubMed1991

Retinoids and their nuclear receptors.

Amino Acid Sequence↗

PubMed1991

[The effect of oral administration of roxatidine acetate hydrochloride 3 hours prior to the operation on pH and volume of gastric juice].

The effect of roxatidine acetate hydrochloride, administered 3 hours prior to induction of anesthesia, on pH and volume of gastric juice was investigated in preoperative patients. In fifty patients, who were scheduled to undergo elective surgery, 150 mg of roxatidine acetate hydrochloride was administered orally 3 hours before the induction of anesthesia. The volume and pH of gastric juice were measured immediately after the induction of anesthesia. In 46 patients out of fifty, pH of gastric juice was more than 2.5, and its volume was below 25 ml. In another 4 patients, pH of gastric juice was more than 2.5, or its volume below 25 ml. We conclude that, oral administration of 150 mg roxatidine 3 hours preoperatively could be effective for the prevention of an aspiration pneumonitis.

Administration, Oral↗

PubMed1991

[An X-ray study of catheters abnormally placed in the epidural space].

We investigated the roentgenogram of the epidural catheter in 82 patients in whom the injection of local anesthetics had no effect. Contrast medium 0.5 ml was injected through the epidural catheter and antero-posterior roentgenogram was taken. The roentgenograms were categorized into three patterns, according to the relationship of the catheter to the pedicle of lamina, or to the spread of contrast medium. In 43 cases, the catheter passed through the intervertebral foramen. The tip of the catheter was located outside the foramen, and the contrast medium spread outside the vertebra. In 4 cases, the tip of the catheter was located laterally in the vertebral column, and only the catheter itself was contrasted but no spread of medium was observed. The catheter was thought to be misinserted intravascularly. In other 35 cases, catheter ran laterally on the pedicle of lamina, or the spread of medium 2 mins after the injection was indicated by a dumpling-shape even when the tip was in the vertebral column. In these cases, the catheter was thought not to be outside the epidural space.

Anesthesia, Epidural↗

PubMed1991

[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--10. Effects of prostaglandin E1 on the hepatic and renal functions following prolonged surgery under total intravenous anesthesia].

Twenty one patients who underwent prolonged surgical procedures over 10 hours under total intravenous anesthesia with droperidol, fentanyl and ketamine were studied to evaluate post-operative hepatic and renal functions as judged by serum levels of GOT, GPT, BUN and creatinine. They were divided into two groups. Ten patients of the PGE1 group were given PGE1 at a rate of 0.035 micrograms.kg-1.min-1 during anesthesia, and the remaining eleven of the control group were not given PGE1. The two groups were comparable concerning, age, body weight, height, operation time and anesthesia time. In the PGE1 group, significantly more intraoperative fluid was given than in the control group. The blood loss was more but insignificantly in the PGE1 group than in the control group. There was no significant difference in urine output and the amount of blood transfused between the two groups. In both groups, post-operative s-GOT and s-GPT levels were increased significantly compared with pre-operative values, but there was no significant difference between the two groups. Serum BUN levels of the 7-10 the post-operative days were increased significantly in the PGE1 group, but those of the control group were not. These data suggest that our method of total intravenous anesthesia with droperidol, fentanyl and ketamine, when applied even for prolonged surgical procedure over 10 hours, would have beneficial effects on the post-operative hepatic and renal functions.

Alprostadil↗

PubMed1991

[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--12. Effects on plasma complement and immunoglobulin concentrations].

Complements and immunoglobulins in the plasma are the important humoral factors to maintain immunity. As there is no study on immune response to total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK), twelve patients who underwent abdominal, neck dissection, or plastic surgery were studied to determine plasma concentrations of complements and immunoglobulins. In five patients of isoflurane group, anesthesia was induced with intravenous thiopental 5 mg.kg-1 and succinylcholine 0.8-1 mg.kg-1 and maintained with 1-2% isoflurane in nitrous oxide (50%) and oxygen (50%). The remaining seven patients of the DFK group received intravenous droperidol 0.25 mg.kg-1, fentanyl 1-2 micrograms.kg-1, ketamine 1-1.5 mg.kg-1 and succinylcholine 0.8-1 mg.kg-1 for the induction of anesthesia, and then they were given a total dose of fentanyl 5-15 micrograms.kg-1, ketamine 2 mg.kg-1.hr-1 and oxygen (30%) for the maintenance of anesthesia. Vecuronium was given intravenously as needed. Lactated Ringer's solution was used for intraoperative fluid replacement. A total of 40 ml of arterial blood was drawn on four occasions, just before the induction of anesthesia, at the recovery from anesthesia, on the third and tenth post-operative days. Plasma concentrations of complements (C3.C4) and immunoglobulins (IgG.IgA.IgM.IgD) were measured by immuno-turbidimetry. C3 concentrations in the plasma decreased significantly when the patients recovered from anesthesia, but they increased significantly on the third and tenth post-operative days in the isoflurane group. In the DFK group, they increased significantly on the tenth post-operative day only. No significant difference in the C3 concentrations was detected between two groups at any time of measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--13. Application for pediatric patients].

Total intravenous anesthesia with droperidol, fentanyl, and ketamine (FK) was administered to 56 pediatric surgical patients ranging in ages from 5 to 15 years to evaluate their hemodynamics during anesthesia, post-operative hepatic as well as renal functions, and post-operative sedation as well as analgesia. These data were compared with those of the patients who underwent almost the same surgical procedures under enflurane-N2O anesthesia. The post-operative s-GOT, s-GPT, BUN, creatinine levels were not elevated significantly as compared with pre-operative levels in the FK group. As compared with those patients who received enflurane anesthesia, the blood pressure in the FK groups was higher by 15-30 mmHg, but it was stable during anesthesia without any complications. Their post-operative sedation and analgesia were better in the FK group than in the enflurane group and the complications such as nausea and vomiting were observed less frequently in the FK patients than in the patients who received anesthesia with ketamine alone reported in literatures. The data described above suggest that this method of anesthesia deserves further detailed clinical trials for pediatric patients.

Adolescent↗