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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 577 records · Page 32Linked to original sources

Co-existence of PACAP and nitric oxide synthase in the rat hypothalamus.

The possible co-existence of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and nitric oxide synthase (NOS) in the rat hypothalamus was examined by a combination of PACAP-immunocytochemistry and NADPH-diaphorase histochemistry. Virtually all PACAP-38-immunoreactive neurones in the paraventricular and supraoptic nuclei exhibited NADPH-diaphorase activity. Since NADPH-diaphorase activity was identical to NOS-immunoreactivity in the magnocellular neurosecretory neurones, this finding indicates that the PACAP neurones synthesize NO.

Amino Acid Oxidoreductases↗

U-92032, a T-type Ca2+ channel blocker and antioxidant, reduces neuronal ischemic injuries.

Several diphenylmethylpiperazine derivatives are potential therapeutic agents for prevention of ischemic injuries in the heart and brain, because of their ability to block Ca2+ currents and their antioxidant activity. In this study, the current lead compound, U-92032 ((7-((bis-4-fluorophenyl)methyl)-1-piperazinyl)-2-(2-hydroxyethylamin o)- 4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one), has been compared with flunarizine and nifedipine (well-known T- and L-type Ca2+ channel antagonists, respectively) for their effects on Ca2+ channels in a mouse neuronal cell line, N1E-115 cells, and their ability to preserve the phenomenon of long-term potentiation and to improve neurological symptoms in gerbil ischemic models. U-92032, like flunarizine, blocked transient Ba2+ currents (IBa) through T-type Ca2+ channels with no effect on nifedipine-sensitive non-inactivating currents. Transient IBa was reduced by U-92032 at a constant rate, the magnitude of which depended on the drug concentration, probably because of a time-dependent accumulation of the lipophilic drug in the membrane phase. For instance, the drug at 6 microM reduced IBa by 21% per min and abolished it in less than 5 min, about 3 times faster than flunarizine at the same concentration. Otherwise, U-92032 behaved like flunarizine, showing a use-dependent block without noticeable effects on the current-voltage relationship for transient IBa. Oral administration of U-92032 (1 and 25 mg/kg) or flunarizine (25 mg/kg), but not nifedipine (50 mg/kg), to gerbils 1 h prior to bilateral carotid artery occlusion, preserved long-term potentiation in hippocampal CA1 neurons, which were largely abolished by ischemia without the drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of Rlim, an LIM homeodomain gene, in the rat brain.

We examined the distribution of Rlim, a homologue to Xlim-1, in the rat brain. Rlim, a LIM class homeodomain gene, was isolated from rat brain, and localized in the adult brain by in situ hybridization histochemistry. The expression of Rlim was found in discrete regions, such as the Purkinje cell layer of the cerebellum and several nuclei of the hypothalamus, midbrain and pons. This suggests that Rlim is related to regulation of genes that are specific to some neurons such as Purkinje cells in the adult.

Amino Acid Sequence↗

Asbestos and nonasbestos fiber content in lung tissue of Japanese patients with malignant mesothelioma.

BACKGROUND: Pulmonary fiber content of both asbestos and nonasbestos types were evaluated in Japanese patients with malignant pleural mesotheliomas. METHODS: Pulmonary fiber content was analyzed in 16 patients and 16 case-matched control subjects by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure. RESULTS: The geometric mean content of total asbestos was significantly higher in the patients (22.0 x 10(6) fibers/g dry lung) than in the control subjects (2.24 x 10(6) fibers/g dry lung) (P < 0.01). When the asbestos content was analyzed by fiber type, the geometric means were also consistently and significantly higher among the patients compared with the control subjects (P < 0.01). Results were as follows: (1) amosite: patients 3.94 times 10(6) versus control subjects 0.23 x 10(6); (2) crocidolite: patients 3.56 times 10(6) versus control subjects 0.35 times 10(6); (3) total amphiboles: patients 16.0 times 10(6) versus control subjects 0.77 times 10(6); and (4) chrysotile: patients 3.76 times 10(6) versus control subjects 1.01 times 10(6). However, when individual total asbestos content was considered, 7 of the 16 patients (44%) had levels lower than the highest value noted among the control subjects. Pulmonary fiber content of patients and control subjects also revealed the presence of nonasbestos fibers. The geometric mean of nonasbestos fibers was significantly higher in the patients (87.3 x 10(6)) than in control subjects (33.8 x 10(6)) (P < 0.01). The major type of nonasbestos fibers in both groups was aluminum silicates. The mean of ratios of nonasbestos fiber contents to total asbestos contents in the patients and control subjects was 7.0 and 17.3, respectively. CONCLUSIONS: The results were mainly in agreement with the findings of earlier investigations, but fiber content of both chrysotile and nonasbestos fiber as well as those of amphibole asbestos were significantly higher in the patients than in the control subjects.

Adult↗

Inhibition of the Ca(2+)-activated K(+)-channel by sapecin B, an insect antibacterial protein.

Sapecin is an antibacterial protein of the flesh fly and sapecin B is its homologue structurally similar to charybdotoxin of scorpion venom, which is known to be a K+ channel inhibitor. We found that, like charybdotoxin, sapecin B inhibits part of the voltage pulse-induced K+ currents of rat cerebellar Purkinje cells. We suggest that this effect is due to inhibition of the Ca(+)-activated K+ channel. Probably, sapecin B is a naturally occurring K+ channel inhibitor as well as an antibacterial protein.

Animals↗

Expression of nm23 H-1 RNA levels in human gastric cancer tissues. A negative correlation with nodal metastasis.

BACKGROUND: Gene expression of nm23 has been investigated in number of tumors, including breast cancer, colon cancer, malignant melanoma, and hepatocellular carcinoma. Its down-regulation has been shown to be associated with metastasis or disease progression in some of the tumors. METHODS: nm23 H-1 mRNA levels were investigated in 31 surgically resected specimens of gastric cancer by Northern blot analysis, and association with clinical stages was determined. RESULTS: There was no significant difference in nm23 expression between tumor and matching normal mucosa. There was a significant down-regulation of the nm23 gene in gastric cancer with serosal invasion (T3 and T4 by the TNM classification) and nodal metastasis (pN1 and pN2), although the association of the down-regulation with clinically manifest hepatic or peritoneal metastasis was not significant. The tumors with low nm23 expression were associated with a poor prognosis. CONCLUSIONS: It was suggested that the down-regulation of nm23 gene might have a role in metastasis and invasion in gastric cancer, possibly leading to a poor prognosis.

Cell Line↗

Discrepancy between PNMT presence and relative lack of adrenaline production in extra-adrenal pheochromocytoma.

Among catecholamine synthesizing enzymes, phenylethanolamine-N-methyltransferase (PNMT) exists only in adrenal and extra-adrenal pheochromocytoma has been believed not to produce adrenaline. However, adrenaline production is clinically active in some extra-adrenal cases. To investigate this controversy, the localization of catecholamine synthesizing enzymes was studied by immunohistochemical staining in extra-adrenal and adrenal cases. The results showed that PNMT was expressed not only in many cases of adrenal pheochromocytoma, but also in extra-adrenal pheochromocytoma. It is suspected that little adrenaline production in extra-adrenal cases is attributable to a lack of a good environment for the activation of PNMT by a high concentration of glucocorticoids.

Adrenal Gland Neoplasms↗

Low oxygen tension decreases receptor binding of peptide growth factors in dermal fibroblast cultures.

We have investigated receptor binding of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in cultures of human dermal fibroblasts exposed to low (2%, hypoxia) or standard (20%) oxygen tension. Compared to standard oxygen, the binding of both 125I-TGF-beta and 125I-EGF in low oxygen tension was diminished by a mean of 65 and 62%, respectively (P < 0.02), and was reversed by reexposure of cultures to standard oxygen tension. Low oxygen tension decreased the number of binding sites of both EGF (mean = 44%) and TGF-beta (mean = 33%). Preincubation of the media in the two different oxygen conditions showed that alterations in the redox potential of the medium was not responsible for the changes observed in receptor binding. As shown by Northern analysis, diminished TGF-beta receptor binding in hypoxia was accompanied by up to a 10-fold decrease in mRNA levels of TGF-beta type II receptor. We conclude that low oxygen tension decreases EGF and TGF-beta receptor binding and synthesis.

Adult↗