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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 811 records · Page 45Linked to original sources
PubMed1991

Localization of Mn-superoxide dismutase (Mn-SOD) in cholinergic and somatostatin-containing neurons in the rat neostriatum.

We used rabbit antisera against manganese (Mn)-superoxide dismutase for immunohistochemical studies of localization in the rat neostriatum. Immunostaining was intense in large-sized neurons and several medium-sized neurons, but it was moderate to weak in other cells. Double immunostaining with monoclonal antibody to choline acetyltransferase or somatostatin demonstrated large-sized, Mn-SOD immunoreactive neurons to be cholinergic, and some medium-sized neurons which were intensely immunoreactive for Mn-SOD to contain somatostatinergic.

Animals↗
PubMed1991

Intense immunoreactivity for Mn-superoxide dismutase (Mn-SOD) in cholinergic and non-cholinergic neurons in the rat basal forebrain.

The immunohistochemical localization of manganese (Mn)-superoxide dismutase (Mn-SOD) was studied in the rat basal forebrain using polyclonal antibodies to Mn-SOD. Neurons of the basal forebrain exhibit a high density of Mn-SOD immunoreactivity. Double immunostaining with a monoclonal antibody to choline acetyltransferase demonstrated that both cholinergic and non-cholinergic neurons in the basal forebrain are intensely immunoreactive for Mn-SOD.

Animals↗
PubMed1991

Spiny and aspiny types of neuropeptide Y immunoreactive neurons in the monkey neostriatum.

The present study demonstrates the existence of two types of neurons with neuropeptide Y (NPY) immunoreactivity in the neostriatum of the monkey (Macacus fuscatus) by using the avidin-biotin-immunoperoxidase method. One type, accounted for about 80% of striatal NPY cells, corresponded to the medium-sized aspiny type neurons. The other type resembled the medium-sized, spiny type II neurons. These findings suggest that there are at least two functional subpopulations of NPY neurons in the monkey neostriatum.

Animals↗
PubMed1991

Subrenal capsule assay using nude mice as a predictor of the response of the gastric cancer to chemotherapy.

Feasibility of utilizing human gastric cancers as first transplant generation xenografts in nude mice for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay. A total of 55 human gastric tumors from patients were tested in this assay. Mitomycin-C (MMC) and hexycarbamyl-5-FU (HCFU, 5-FU derivative) were selected for the treatment of these patients after surgery and also for this assay as first transplant. Evaluable rate of MMC in this assay was 92.7% and that of HCFU was 90.9%. Sensitivity of tumors to MMC was 25% and to HCFU was 32%. Correlation between response to chemotherapy of human tumors in patients and in nude mice was 78.6%. These results indicate that this assay could predict effective drugs for patients with gastric cancer.

Adenocarcinoma↗
PubMed1991

A feasibility study of the SDI test for the evaluation of gastrointestinal cancer sensitivity to anticancer drugs.

The succinic dehydrogenase inhibition (SDI) test has been widely used to evaluate the sensitivity of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed; the ability to make formazan has improved with the use of methylthiazol tetrazolium bromide (MTT) instead of triphenyl tetrazolium chloride (TTC) in this assay. Therefore, we modified the SDI test in order to evaluate the drug response to gastrointestinal cancer and applied it in a clinical study. In this assay, the optimal concentration levels of mytomycin-C and Adriamycin for the clinical materials are 10 micrograms/ml, that is, 10 times higher than for the cancer cell line, and that of Cisplatin is 30 micrograms/ml, for Cisplatin is unstable in the culture medium. To evaluate its antitumor effect, it was found necessary to expose the cancer cells to 5-fluorouracil (5-FU) for 3 days. We applied this assay for the clinical materials; the evaluable rate of this assay is 83.3%. The peculiarity of this assay is its high evaluable rate. These results suggest that this test may be useful for clinical application.

Animals↗
PubMed1991

An immunohistochemical study on the effects of cyclosporin on the gut-associated lymphoid tissue of rats.

The effect of Cyclosporin (CS) on the gut-associated lymphoid tissue (GALT) of inbred WKA rats was immunohistochemically studied by the immunoperoxidase method. CS in olive oil was orally administered daily for seven days at the dose of 25, 50 and 100 mg/kg/day. On days 1, 4 and 7 of CS administration, rats were sacrificed under ether anesthesia. By CS administration, the decrease and disappearance of Ia antigen expression were dose-dependently recognized on the epithelial cells and the overlaying cells of Peyer's patches. The reduced cellular population and Ia expression of lymphocytes of the follicle and the disappearance of the germinal center also occurred, and Ia-positive dendritic non-lymphoid cells in Peyer's patches and endothelial cells of capillaries in the lamina propria disappeared on day 7 of CS administration. In addition, a temporary increase of W3/25-positive cells and the appearance of Ia-positive intra-epithelial cells were observed on day 4. Simultaneously, interleukin 2 receptor (IL-2R)-positive cells gradually decreased on day 4, and almost disappeared on day 7. From these results, it is speculated that CS suppresses not only interleukin 2 (IL-2) production as previously reported, but also the expression of Ia antigens and IL-2R. It may well suppress the immune system at the point of recognition and presentation of alloantigen, and the proliferation and differentiation of B cells.

Animals↗
PubMed1991

Mechanism and prevention of ischemia-reperfusion-induced liver injury in rats.

This study was designed to clarify the mechanism of ischemia-reperfusion-induced rat liver injury and to evaluate the effect of long-acting superoxide dismutase (SOD-POE). Liver mitochondrial functional indices, i.e., the respiratory control index (RCI) and the rate of oxygen consumption in State III respiration (St. III O2), were decreased significantly to 1.33 +/- 0.06, mean +/- SD, and 54.4 +/- 3.7 natom/mg protein/min, respectively, after 120 min of ischemia, compared to respective preischemic values (3.94 +/- 0.21 and 80.2 +/- 3.9). These indices did not recover fully following 60 min of reperfusion (RCI, 3.25 +/- 0.17; St. III O2, 69.9 +/- 6.4). Tissue levels of adenosine triphosphate (ATP) were decreased to 2% of preischemic levels after 120 min of ischemia and remained at 39% of preischemic levels following 60 min of reperfusion. Increases in hypoxanthine and xanthine were observed after ischemia. SOD-POE improved the recovery of mitochondrial function (RCI, 3.70 +/- 0.20; St. III O2, 83.3 +/- 7.6) and also accelerated the recovery of ATP (53% of preischemic level). SOD-POE did not affect the decrease in ATP levels or the increase in purine nucleotide levels during ischemia. SOD-POE did not influence changes in tissue blood flow levels throughout the experiments. The leakage of adenine nucleotides immediately after reperfusion was observed (4.2 +/- 2.0 mumole/liter serum), and SOD-POE mitigated this leakage (1.3 +/- 0.5). Purine nucleotides are oxidizable substrates of xanthine oxidase, and an increase in superoxide radical generation by this enzyme might be expected in the ischemia-reperfusion process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1991

Synthesis and mechanism of hydrolysis of estrogen 6-sulfates: model compounds for demonstrating the carcinogenesis of estrogen.

To investigate the carcinogenesis of estrogen with respect to the chemical behavior of estrogen 6-sulfates, two epimeric 6-sulfates, pyridinium 3-methoxyestra-1,3,5(10)-trien-6 alpha-yl (8) and -6 beta-yl (11) sulfates, were synthesized as the model compounds, and their chemical reactivities were examined. These sulfates were shown to be highly reactive: in water, they were readily and quantitatively converted to a common product mixture, composed of 3-methoxyestra-1,3,5(10)-trien-6 alpha-ol (6) and -6 beta-ol (9) in an almost constant product ratio, with a predominant yield of the latter. The hydrolysis of both sulfates 8 and 11 proceeded in first-order kinetics with half-lives of 1.1 and 1.5 minutes, respectively. When the sulfates were hydrolyzed in 18O-water, the heavy-oxygen atom was shown to be incorporated quantitatively into the C-6 position of the products. These results demonstrate that estrogen 6-sulfates generate a highly reactive benzylic (C-6) carbocation in an aqueous solution, suggesting that the sulfates can act as carcinogens.

Chemical Phenomena↗
PubMed1991

Developmental assembly of calcium-mobilizing systems for excitatory amino acids in rat cerebellum.

The postnatal development of calcium-mobilizing systems was studied by both microfluorometric imaging analysis of Ca2+ on living rat cerebellar slices and immunohistochemical labeling of phosphatidylinositol 4,5-bisphosphate (PIP2) and inositol 1,4,5-trisphosphate binding protein (IP3BP) in fixed rat cerebellum. Stimulation with quisqualate (QA) or N-methyl-D-aspartate (NMDA) enhanced the Ca2+ level only diffusely on postnatal day (PND) 3, but more discretely on PNDs 7 and 15. On PND 21, QA-induced responses were localized in the molecular layer especially, but not in the granular layer. By contrast, NMDA mobilized Ca2+ prominently in the granular layer, but only weakly in the molecular layer. Localized expression of PIP2 in the molecular layer paralleled QA-induced Ca2+ mobilization, but IP3BP was expressed more diffusely. The present study offers the first direct evidence that PIP2, but not IP3BP, is essential for QA-induced Ca2+ mobilization in the cerebellar cortex.

Amino Acids↗
PubMed1991

Striatal calcitonin gene-related peptide-like immunoreactive afferents from the regions ventral and medial to the medial geniculate nucleus of rats.

The sources of fibers with immunoreactivity to calcitonin gene-related peptide in the caudal portion of the caudate-putamen were investigated in animals treated by a knife cut, a tracer injection, or an electrolytic lesion of regions ventral and medial to the medial geniculate nucleus. Hemitransection of the brain just caudal to the caudate-putamen decreased ipsilaterally calcitonin gene-related peptide-like immunoreactivity in the caudal portion of the caudate-putamen, suggesting that calcitonin gene-related peptide-like immunoreactive fibers in the caudate-putamen originated from neurons in the area caudal to the caudate-putamen. Some calcitonin gene-related peptide-like immunoreactive neurons in the regions ventral and medial to the medial geniculate nucleus, including the peripeduncular, posterior intralaminar and suprageniculate nuclei, were labeled ipsilaterally with a retrograde tracer after an injection into the caudal portion of the caudate-putamen. In addition, an electrolytic lesion of calcitonin gene-related peptide-like immunoreactive neurons in the regions ventral and medial to the medial geniculate nucleus decreased the number of calcitonin gene-related peptide-like immunoreactive fibers in the ipsilateral caudal portion of the caudate-putamen. These results suggest that some cells containing calcitonin gene-related peptide in several posterior thalamic nuclei project to the caudal caudate-putamen.

Animals↗
PubMed1991

Analgesic effect of L-arginine in patients with persistent pain.

Our previous pharmacological studies using animals indicated that a systemic administration of L-arginine induces an antinociceptive effect and an increase in the brain level of kyotorphin (L-tyrosinyl-L-arginine) which is an endogenous analgesic peptide and a methionine-enkephalin releaser in the brain. The aims of this study were to investigate the analgesic effect of L-arginine, a precursor of kyotorphin, in persistent pain. We selected 12 patients with various kinds of pain of at least 6 months duration. L-Arginine (10% solution, 300 ml (30 g)/patient) was administered by intravenous drip at a rate of 5 ml (0.5 g)/min during a period of 60-70 min. Pain was assessed by the patient using a 10-cm visual analogue scale (VAS), before and after the L-arginine infusion. L-Arginine treatment resulted in slight analgesia at 10-15 min after the onset of infusion and in marked analgesia at 30-40 min after that. This effect lasted for 6-24 h. L-Arginine-induced analgesia was dose-dependent and blocked by intravenous injection of naloxone. In each case, the L-arginine-induced analgesia was statistically significant as compared with the saline-induced effect. Side effects of L-arginine were a slight decrease in mean blood pressure (10-15 mm Hg), and dryness of the month. A suppressive role of a functional link between the L-arginine-kyotorphin system and the enkephalin system of the brain in persistent pain is suggested.

Aged↗
PubMed1991

Comparison of cytochrome P-450 species which catalyze the hydroxylations of the aromatic ring of estradiol and estradiol 17-sulfate.

For identification of microsomal cytochrome P-450 (P-450) enzymes which catalyze 2- or 4-hydroxylations of estrogens in the rat liver, estradiol (E2) and estradiol 17-sulfate (E2-17-S) were selected as the substrates and incubated with various kinds of purified P-450 enzymes: PB-1, PB-2, PB-4 and PB-5 obtained from phenobarbital-treated male rats (Sprague-Dawley); MC-1 and MC-5 from 3-methylcholanthrene-treated male rats; and UT-1, UT-2, UT-4 and UT-5 from untreated animals. The reactions were carried out under the P-450-reconstructed system, and the resulting products were determined by HPLC using electrochemical detection. All the enzymes tested were shown to have varying degrees of catalytic activities for 2-hydroxylation of the two substrates; UT-1 and UT-2 had the highest activity. Of the induced P-450 enzymes, PB-2 and MC-1 showed fairly high catalytic activity for 4-hydroxylation of E2. The P-450 enzymes obtained from the untreated male rats, especially UT-4, showed the highest catalytic activity for 4-hydroxylation of the two substrates. From these results and also from kinetic experiments, the P-450 enzymes which catalyze 2- and 4-hydroxylations of estrogen were considered to be different species. A part of E2 was converted to such metabolites as estrone and those having a hydroxyl group at positions 6 beta, 15 alpha or 16 alpha, each production of which was estimated to be catalyzed by single or multiple P-450s.

Animals↗
PubMed1991

The potential role of postoperative hepatic artery chemotherapy in patients with high-risk hepatomas.

The relationship between operative findings of hepatoma and the postoperative prognosis was studied to clarify indications for adjuvant hepatic arterial chemotherapy after hepatectomy. The results of adjuvant hepatic arterial chemotherapy using 0.4 mg/kg of doxorubicin and 0.12 mg/kg of mitomycin C and infusion of 5-fluorouracil were reported. One hundred sixty patients who had undergone hepatectomy for hepatoma were studied. In the operative findings of hepatoma, with a surgical margin of less than 10 mm, intrahepatic metastasis, tumor embolus in the second or more proximal branch of the portal vein, or lack of capsule formation related to the prognosis were the risk factors for recurrence. In 132 patients with these risk factors the survival rate of 19 patients with adjuvant arterial chemotherapy was significantly higher than for the 113 patients without it. Adjuvant hepatic arterial chemotherapy thus may be an effective therapy and should be studied prospectively in patients undergoing hepatectomy for high-risk hepatoma.

Adult↗
PubMed1991

Aberrant elevation of tyrosine-specific phosphorylation in human gastric cancer cells.

Phosphotyrosine-containing proteins in various human cancer cell lines were studied by immunoblotting with anti-phosphotyrosine antibody. Of 29 cell lines derived from oral epidermoid cancer, esophageal cancer, gastric cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma and malignant melanoma, 3 of the 6 gastric cancer cells showed aberrant elevation of tyrosine-specific phosphorylation. On the other hand, both esophageal cancer cells and colon cancer cells, which were reported to have amplified epidermal growth factor receptor and activated p60v-src kinase, respectively, showed no apparent elevation of tyrosine-specific phosphorylation, and their profiles of phosphorylation were similar to that of normal human fibroblasts. Two gastric cancer cells, NUGC-4 and MKN-45, showed similar profiles of phosphorylation but their responses to growth factors differed from each other. Tyrosine phosphorylation in NUGC-4 was strongly activated by treatment with epidermal growth factor and quickly reduced by the acid treatment which is effective in removing growth factors from cellular surface receptors. On the contrary, phosphorylation in MKN-45 did not respond to either growth factor or acid treatment. These results suggest that NUGC-4 and MKN-45 have tyrosine kinases which are activated by different mechanisms but share similar substrates.

ErbB Receptors↗