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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 757 records · Page 42Linked to original sources

[Intraoperative radiation therapy of carcinoma of the pancreas].

From May 1978 to December 1989, 54 patients with pancreatic carcinoma underwent electron beam intraoperative radiotherapy (IORT). Three died of preoperative complications within a month. In 19 patients, liver metastasis and/or peritoneal dissemination became obvious at laparotomy. They therefore underwent IORT with palliative intent. Relief of pain was obtained in 12 of the 14 patients with pain (85.7%), although three of them were treated in combination with splanchnic nerve block. Thirty-two patients with localized carcinoma underwent IORT with curative intent (total tumor resection in 6, partial resection in 6, and no tumor resection in 20). With additional IORT treatment, their survival was significantly (p less than 0.05 during the 18th month) longer than that of 40 patients without IORT (total tumor resection in 13, partial resection in 9, and no tumor resection in 18). Among the patients without tumor resection, the 20 patients who underwent IORT survived significantly (p less than 0.05 during the 7th month) longer than the 18 patients who did not. Twelve patients who underwent total pancreatectomy died earlier than the 23 patients treated with IORT in combination with partial tumor resection or no tumor resection (not significant). In 26 patients with partial tumor resection or no tumor resection, either additional external irradiation or IORT using a small field within a large field significantly (p less than 0.05 during the 7th and 8th month) improved survival compared with IORT using a single field. Of the 20 patients without tumor resection, relief from pain was obtained in 18 of 19 patients with pain (94.7%), although two of them were treated in combination with splanchnic nerve block. In terms of adverse effects possibly caused by IORT in 26 patients who survived longer than 6 months, gastrointestinal problems were serious in several (gastric ulcer in 2, duodenal stenosis in 1, gastric ulcer and duodenal stenosis in 1, and duodenal perforation and duodenal ulcer in 1). In conclusion, our experience suggests that IORT can relieve patients of serious pain and improve survival in patients with localized pancreatic carcinoma.

Adult↗

Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells.

Proteasomes and ubiquitin (Ub) are essential components of the energy-dependent, nonlysosomal proteolytic pathway. To clarify the physiological role of this proteasome/Ub-dependent pathway, we meaured the levels of expressions of proteasomes and Ub in human renal cancers by Northern blot and immunochemical analyses. The mRNAs for two of the multiple subunits of proteasomes, C2 and C9, were expressed at abnormally high levels in most neoplastic lesions of patients with various primary renal cell carcinomas and in all renal cancer cell lines examined. However, no significant difference was found by enzyme immunoassay in the proteasomal contents of cancerous and normal parts of the kidney. The levels of mRNAs for the subunits of proteasomes were high in rapidly proliferating renal cells and appeared to be correlated with the activities of these cells for proteasome synthesis, but the cellular contents of proteasomes in these cells were normal, suggesting rapid turnover of proteasomes in rapidly proliferating cancer cells. Consistent with the increased expressions of proteasomal mRNAs, the expressions of three Ub genes, mono-UbA80, mono-UbA52, and poly-UbC, were found to be greatly increased in these renal cancer cells. Immunohistochemical staining of normal kidney showed that the levels of both proteasomes and Ub were high in cells of renal tubules and collecting ducts, but low in the glomerulus. The levels of both proteins appeared to be considerably increased in the nuclei of granular and clear carcinoma cells of the kidney. Moreover, the profiles of cellular proteins conjugated with Ub in normal kidney tissues were different from those in cancerous parts of the kidney and in established renal cancer cells. These results suggest that the proteasome- and ubiquitin-mediated system is functionally involved in the cancerous state in human kidney.

Adult↗

Amphetamine-antagonistic properties of 4-phenyl-1,2,3,4- tetrahydroisoquinoline: inhibition of spinal reflex-enhancing effects of methamphetamine, phenylethylamine and nomifensine.

The antagonistic effects of 4-phenyl-1,2,3,4-tetrahydroisoquinoline (4PTIQ) against S(+)-methamphetamine, phenylethylamine and nomifensine were studied by measurement of spinal monosynaptic reflex potential (MSR). S(+)-Methamphetamine, phenylethylamine and nomifensine enhanced the amplitude of MSR in C1-spinalized rats through release of noradrenaline from the terminals of descending fibers and consequent activation of alpha 1-adrenoceptors. Although 4PTIQ alone did not change the amplitude of the MSR, 4PTIQ inhibited the enhancement of MSR induced by S(+)-methamphetamine and related compounds. The MSR of rats with an intact spinal cord was enhanced by conditioning stimulation of the ipsilateral locus ceruleus. The MSR enhancement produced by the stimulation was blocked by prazosin but unaffected by 4PTIQ, showing that 4PTIQ does not have an alpha 1-blocking action. These results suggest that the antagonistic effects of 4PTIQ on MSR enhancement by S(+)-methamphetamine, phenylethylamine and nomifensine are due to its blocking of noradrenaline release produced by these amphetamine-like agents.

Amphetamine↗

Changes in glycolipids in human renal-cell carcinoma and their clinical significance.

The expression patterns of glycolipids of human renal-cell carcinoma were studied in primary tumors from 23 cases and 5 metastatic lesions from 4 cases using HPTLC (high-performance thin-layer chromatography). The expression pattern of glycolipids in primary tumors was characteristic of the histological cell type. In granular-cell carcinoma, lactosylceramide (CDH), GM3 and the longer-chain gangliosides (gangliosides migrating more slowly than GM3) increased, although in clear-cell carcinoma, CDH and other glycolipids tended to decrease. Globoside decreased in all cases but one, irrespective of cell type. In metastatic lesions of the clear-cell type, the prominent increase in longer-chain gangliosides was characteristic. Furthermore, the same expression pattern as that of metastastatic lesions was shown in 3 of 14 patients with primary clear-cell carcinoma, all of whom developed metastases soon after radical nephrectomy. These studies indicate that the increased expression of the longer-chain gangliosides in primary tumor is one of the factors associated with high metastatic potential, and also predict early post-operative development of metastasis.

Aged↗

Molecular cloning, nucleotide sequence and expression of the tufB gene encoding elongation factor Tu from Thermus thermophilus HB8.

The tufB gene encoding elongation factor Tu (EF-Tu) of Thermus thermophilus HB8 was cloned and expressed. Compared with the known tufA gene of T. thermophilus, nucleotide differences were found at 10 positions out of 1221 nucleotides, and amino acid substitutions were found at 4 positions out of 406 amino acids. The tufB product was 70.9% homologous to the corresponding sequence of the tufB product of E. coli. The G+C content of the third base of the codon in the tufB gene was 84.8% and G was especially preferred in this position.

Amino Acid Sequence↗

A facilitatory role of endogenous somatostatin in long-term potentiation of the mossy fiber-CA3 system in guinea-pig hippocampus.

To estimate the functional role of endogenous somatostatin in the production of long-term potentiation (LTP) in mossy fiber-CA3 system, an influence of depletion of somatostatin on the magnitude of it was examined in guinea-pig hippocampal slices. Administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin, to guinea-pigs 13 h prior to preparing slices resulted in a significant decrease in the magnitude of LTP of population spikes in mossy fiber-CA3 system, being associated with a significant depletion of the content of somatostatin in the hippocampus. Furthermore, bath-applied somatostatin (1-14) at a concentration, at which the substance did not influence LTP in slices prepared from saline-treated animals, significantly augmented LTP in slices from cysteamine-treated animals. Cyclo-somatostatin (0.32 and 3.2 microM), a putative antagonist of somatostatin receptors, failed to affect the magnitude of LTP of mossy fiber-CA3 system when applied alone; however, the combined application of cyclo-somatostatin with somatostatin (0.32 microM) significantly inhibited the augmenting action of somatostatin on LTP. From these observations, it is suggested that endogenous somatostatin plays a facilitatory role in the production of LTP in mossy fiber-CA3 system in guinea-pig hippocampus.

Animals↗

Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices.

The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK-602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner. LTP in slices of the hippocampus obtained from animals given 6-hydroxydopamine (6-OHDA) intraventricularly was significantly lower than that in non-treated animals. However, both TRH and CNK-602A (10(-6) M) augmented LTP in slices from 6-OHDA-treated animals. These findings suggest that TRH and CNK-602A augment LTP in the mossy fiber-CA3 pathway without activating noradrenergic and/or dopaminergic fibers.

Animals↗

Somatostatin augments long-term potentiation of the mossy fiber-CA3 system in guinea-pig hippocampal slices.

The effect of exogenously applied somatostatin (1-14), which is one of the candidates of neuromodulators in the hippocampus, on long-term potentiation (LTP) was investigated in the CA1 and CA3 subfields of guinea-pig hippocampal slices. In the mossy fiber-CA3 pyramidal cell system, the magnitude of LTP of both population excitatory postsynaptic potential (pEPSP) and population spike was significantly augmented by somatostatin (10(-7)-10(-6) M) perfused before and during tetanic stimulation which never affected basal amplitude of population spikes before tetanus. The enhancement of LTP by somatostatin lasted for at least one hour after washout. On the other hand, somatostatin at the most effective concentration (3.2 x 10(-7) M) in the above described system failed to affect the magnitude of the LTP of population spikes in Schaffer collateral-CA1 pathway. The enhancing effect of somatostatin on LTP in the mossy fiber CA3 system was inhibited either by a muscarinic antagonist, scopolamine (10(-6) M), or a beta-adrenoceptor antagonist, timolol (10(-6) M). These results suggest that somatostatin enhances the production of LTP in the mossy fiber-CA3 pathway of the guinea-pig hippocampus through the intervention of cholinergic and noradrenergic neurons.

Animals↗

Cadmium directly acts on endothelin receptor and inhibits endothelin binding activity.

The binding of endothelin (ET) to human placenta ET receptor was strongly inhibited by cadmium ions (Cd2+) (IC50 = 2 x 10(-5) M). Experiments with affinity cross-linking showed that the major 40 kDa receptor was inhibited to form a [125I]ET-1/receptor complex. The mode of inhibition was noncompetitive with respect to ET-1. The inhibitory effect of Cd2+ on solubilized ET receptor was partially reversed by the chelating agent, ethylenediaminetetraacetic acid (EDTA), whereas the effect was irreversible for the membrane-associated receptor. The rat aorta contractions by ET were prevented by pretreatment or addition of Cd2+.

Animals↗

Methamphetamine-induced expression of interleukin-1 beta mRNA in the rat hypothalamus.

The effect of methamphetamine on the expression of interleukin-1 beta (IL-1 beta) mRNA in the rat brain was investigated with Northern blot analysis. Methamphetamine (2-15 mg/kg, i.p.) caused a marked induction of IL-1 beta mRNA in the hypothalamus among the 8 brain regions examined, in a dose-dependent manner. The level of IL-1 beta mRNA reached a maximum at 1 h and rapidly declined within 2 h after the injection of 15 mg/kg. These results provide the first evidence that methamphetamine induces the expression of IL-1 beta mRNA in the hypothalamus, which may be partly involved in the production of central actions of this drug.

Animals↗

Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding.

The effects of several cerebroprotective and nootropic drugs on the function of excitatory amino acid (EAA) receptor subtypes expressed in Xenopus oocytes after injection of rodent brain poly(A)+ mRNA were investigated. The oocyte response to N-methyl-D-aspartate (NMDA) in the presence of glycine (Gly) was inhibited dose-dependently by bifemelane, indeloxazine, vinpocetine and vincamine while no effect was observed by idebenone, Ca hopantenate, aniracetam or piracetam. Bifemelane, indeloxazine and vinpocetine suppressed the maximum response of NMDA and Gly without affecting their EC50 values. Unlike Mg2+, they did not affect the current-voltage relationship of the NMDA response below 0 mV. On the non-NMDA-type responses of the injected oocytes to kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate (QA), no significant effects were observed by these drugs at 100 microM. On the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine. The dissociation rate of [3H]MK-801 was significantly slowed by Zn2+ and vinpocetine, but not affected by bifemelane or indeloxazine. The Kd value for [3H]MK-801 binding was increased by bifemelane and indeloxazine while Bmax was unchanged. These results suggest that the inhibition of NMDA channels by vinpocetine shows a similarity to the action of Zn2+ which closes the gate of the NMDA channel. In contrast, bifemelane and indeloxazine may affect the phencyclidine (PCP)-site in the open channels and inhibit NMDA function.

Animals↗

Phosphorylation of the stress protein hsp27 is an early event in murine myelomonocytic leukemic cell differentiation induced by leukemia inhibitory factor/D-factor.

Leukemia inhibitory factor/D-factor, a potent differentiation-inducing glycoprotein for murine myelomonocytic leukemic M1 cells, rapidly stimulated the phosphorylation of a 27 kDa protein with an isoelectric point of 5.6 in a LIF-sensitive M1-T22 cell line but not in a LIF-resistant M1-D(-) cell line. The increase in phosphorylation was detectable 5 min after LIF treatment and was maximal at 10 min. Heat shock treatment at 44.5 degrees C for 30 min also induced the phosphorylation of the same 27 kDa protein. Although this 27 kDa protein did not become labeled with [35S]-methionine, metabolic labeling experiments using [35S]-cysteine or [3H]-leucine clearly demonstrated that the synthesis of this protein was enhanced after heat shock. These results suggest that the phosphorylated 27 kDa protein is a low molecular weight stress protein and that the protein may play a role at an early stage in the LIF signaling pathway probably linked to macrophagic differentiation.

Animals↗

Effects of kainic acid on messenger RNA levels of IL-1 beta, IL-6, TNF alpha and LIF in the rat brain.

We examined the kainic acid-induced changes of mRNA levels of several cytokines such as IL-1 beta, IL-6, TNF alpha and LIF in the rat brain regions using semiquantitative RT-PCR method. IL-1 beta mRNA was markedly increased in the cerebral cortex (CC), thalamus (THL) and hypothalamus (HT) 2 h after the injection of kainic acid in a convulsive dose (12 mg/kg i.p.), and tended to decrease 4 h after the injection. IL-6 mRNA was weakly induced in the hippocampus (HPP) 2 h after the injection of kainic acid and was markedly increased in the CC, HPP, THL, and HT at 4 h. The level of TNF alpha mRNA was highly elevated in the CC, HPP, striatum (STR), THL and HT at 2 and 4 h after the injection. LIF mRNA apparently expressed in the CC and HPP of control rats and was increased in the CC, HPP and HT by the treatment with kainic acid. These results indicate that mRNAs of several cytokines are increased in various brain regions with different time-courses by kainic acid.

Animals↗

Identification of the ATP-binding heat-inducible protein of MR = 37,000 as glyceraldehyde-3-phosphate dehydrogenase.

We previously found a novel ATP-binding heat-inducible protein of Mr = 37,000 in BALB/c 3T3 cells. Here, we found that the peptide mapping of this 37-kDa protein was similar to that of rabbit glyceraldehyde-3-phosphate dehydrogenase. Therefore, we biochemically compared the 37-kDa protein with a product translated from mRNA which was hybrid-selected using a cDNA for encoding chick glyceraldehyde-3-phosphate dehydrogenase and found that these two proteins were very similar. Northern blotting analysis using its cDNA as a probe revealed that glyceraldehyde-3-phosphate dehydrogenase was a heat-inducible protein in BALB/c 3T3 cells and that it was induced by stresses including treatment with alpha, alpha'-dipyridyl.

Adenosine Triphosphate↗

Immobilization stress induces interleukin-1 beta mRNA in the rat hypothalamus.

Immobilization stress induced interleukin-1 beta (IL-1 beta) mRNA in the rat hypothalamus. IL-1 beta mRNA was induced at 30 min after the start of immobilization, reached a maximum at 60 min and then was still detected with a decreased level at 120 min. However, 240 min after the start of the immobilization, IL-1 beta mRNA became hardly detectable despite the continuance of immobilization. Distinct expression of IL-1 beta mRNA was not detected in any other brain region examined at 30 and 60 min after the start of immobilization. These results demonstrate that the immobilization stress induces the expression of IL-1 beta mRNA solely in the hypothalamus and suggest that IL-1 beta is involved in the response to stress there.

Animals↗

Fibrinogen date: congenital hypodysfibrinogenemia associated with decreased binding of tissue-plasminogen activator.

A new case of congenital hypodysfibrinogenemia associated with a thrombotic tendency (thrombosis of the peroneal artery, the pulmonary artery and the deep veins of the lower extremities), is reported. Clotting time using Reptilase was significantly prolonged. The low levels of plasma fibrinogen were demonstrated using both thrombin time (Clauss) method (45.0 mg/ml) and radial immunodiffusion technique (106.1 mg/ml). The fibrinogen is also characterized by a defective polymerization of fibrin monomers. Furthermore, the important functional property of this fibrinogen is that the patient's fibrin adsorbs approximately 31-38% of added tissue-plasminogen activator (t-PA) at the time of fibrin formation, whereas control fibrin can adsorb about 79% of added t-PA. This result could provide an explanation for the thrombotic tendency in this patient. This variant fibrinogen appears to have unique characteristics and has been designated as "Fibrinogen Date," according to the city where the proband has lived.

Afibrinogenemia↗