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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 181 records · Page 10Linked to original sources

[Experimental study of percutaneous hot ethanol injection therapy (PHEIT) by continuous heating device for hepatocellular carcinoma].

Percutaneous ethanol injection therapy (PEIT) is widely used as a local treatment for hepatocellular carcinoma (HCC). However, because only a small amount of ethanol can be used in one PEIT session and because the antitumor effect is limited, this modality is indicated only when there are three or fewer tumors and when the tumor diameter is < or = 3 cm. To obtain a more potent and certain antitumor effect, we have devised a new treatment called percutaneous hot ethanol injection therapy (PHEIT), and developed a Continuous Heating Device with which ethanol can be heated and locally injected at a specified temperature. The continuous Heating Device is composed of three major components: a syringe heater, a needle thermocontroller, and a needle tip thermosensor. A disposable syringe filled with liquid is inserted into the syringe heater, which heats the liquid to a desired temperature by adjusting the voltage. The needle thermocontroller is a puncture guide needle to which a heating device has been attached. The needle-tip thermosensor constantly measures, displays and records the temperature of the liquid at the needle tip during injection. Also, because the Continuous Heating Device is a closed-circuit system, there is no risk of accidental a fire, which ensures procedural safety. It is also possible to use this device to safely heat and inject a variety of other liquids, such as physiological saline and anticancer agents and thus contribute to the widespread development of ultrasound-guided injection therapy.

Animals↗

In vitro effects of various neuropharmacological agents on the motility of adult Clonorchis sinensis.

Stimulatory effects were observed in vitro when 5-HT was applied to whole worm preparations of Clonorchis sinensis. The stimulatory action of 5-HT was antagonized by tryptophol, clomipramine and imipramine. Strychnine remarkably stimulated motility. The action of strychnine was enhanced by 5-HT but inhibited by tryptophol. GABA, Phenylephrine, isoproterenol, dibenamine and phentolamine showed little influence on motility. Inhibitory effects were caused by eserine, arecoline, carbachol, DMPP and hemicholinium-3, but not by ACh, pilocarpine and McN-A-343. The inhibitory actions of eserine or carbachol were not antagonized by d-tubocurarine, hexamethonium or atropine. These results suggest that in regulating the motility of C. sinensis ACh may function as an inhibitory neurotransmitter and 5-HT as an excitatory transmitter in a manner similar to that already established for other trematodes such as Fasciola hepatica and Schistosoma mansoni.

Adrenergic Agents↗

[New molecular prognostic markers in gastric carcinoma].

Many molecular events have been reported as prognostic factors in gastric cancer. Amplifications of K-sam and c-met genes are often associated with poorly differentiated adenocarcinoma, while ERBB2 genes are amplified in well--differentiated adenocarcinomas of the stomach. Alterations of tumor suppressor regulators confer progression of gastric cancer. On the other hand, multi autocrine loops of growth factors/receptors in gastric cancer cells play a key role in the progression and metastasis of cancer cells. The overexpression of K-sam gene, occurs in 31.9% of gastric cancers, and the prognosis of patients with overexpression of K-sam gene is poorer than those without it. Multivariate analysis reveals that the overexpression of K-sam gene is an important factor for prognosis, lymphnode metastasis and the depth of tumor invasion of gastric carcinomas.

Female↗

[An autopsy case of poisoning by neuropsychopharmaceuticals including zopiclone].

We report here a suicide case involving neuropsychopharmaceuticals. The deceased was a 30-year-old housewife, 151 cm in height and 46.0 kg in weight. Macroscopically, slight lung congestion and edema and slight brain edema were noted. The stomach contained approximately 200 ml of a greenish-brown material with many solid granules. Toxicological analysis demonstrated 44.9 micrograms/ml of zopiclone (ZP), 12.8 micrograms/ml of phenobarbital (PB), 10.9 micrograms/ml of chlorpromazine (CPZ), and 4.8 micrograms/ml of promethazine (PM) in the gastric contents; 0.5 microgram/ml of ZP, 8.6 micrograms/ml of PB, 0.2 microgram/ml of CPZ, and 0.3 microgram/ml of PM in the serum; and 43.0 micrograms/ml of ZP, 8.1 micrograms/ml of PB, 1.3 micrograms/ml of CPZ, and 1.3 micrograms/ml of PM in the urine. On the basis of these findings, the cause of death was considered to be neuropsychopharmaceutical poisoning; ZP was most probably responsible for her death.

Adult↗

Growth regulation of human prostate cancer cells by bone morphogenetic protein-2.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGF-beta) family and have been identified as factors that stimulate bone formation in vivo. They turned out to be multifunctional molecules regulating the growth, differentiation, and apoptosis in various target cells. Some BMPs and their receptors (BMPRs) are expressed on prostate cancer cells. We have reported previously that BMPR-IB mRNA expression is highest in the prostate, a characteristic that is not shared by the other BMPRs, BMPR-IA and BMPR-II. However, the amounts of BMPR-IB mRNA were significantly low in prostate tissues after androgen withdrawal therapy. They were also low in prostate cancer cell lines. Semiquantitative RT-PCR showed that BMPR-IB mRNA was induced by androgen in the androgen-sensitive human prostatic cancer cell line LNCaP, whereas the expression of BMPR-IA and BMPR-II mRNAs was not affected by androgen. When the recombinant human BMP-2 was added to the LNCaP cells in the presence of androgen, cell growth was inhibited. In contrast, the growth rate was increased by the addition of the same ligand when the cells were cultured in the absence of androgen; under this condition, the amounts of BMPR-IB mRNA were decreased significantly. These observations showed that the amounts of BMPR-IB, but not those of BMPR-IA, were regulated by androgen and further suggest that BMPR-IA and BMPR-IB differentially modulate prostate cancer cell growth in response to BMP under different hormonal conditions; BMPR-IA elicits growth stimulation, and BMPR-IB conveys a negative regulatory signal in response to BMP-2.

Bone Morphogenetic Protein 2↗

Urgent living-related liver transplantation using a graft with multiple intrahepatic arterioportal fistulae.

BACKGROUND: We describe the case of a man with intrahepatic arterioportal fistulae located in the left lobe, whose left lateral segment was transplanted into his son who was suffering from severe acute hepatitis B. METHODS: A male infant with severe acute hepatitis B was considered to be a candidate for liver transplantation. The father was willing to be the donor. Preoperative evaluation of the donor revealed intrahepatic arterioportal fistulae, however, duplex ultrasonography showed normograde portal blood flow. A living-related liver transplantation was performed. RESULTS: The postoperative course for both the donor and recipient was uneventful. The recipient is free of recurrent hepatitis B and has normograde portal blood flow. CONCLUSIONS: The present case suggests that there may be a symptomless population with intrahepatic arterioportal fistulae, which cause various degrees of disruption of the portal blood flow. Duplex ultrasonography might be helpful in the evaluation of candidates for liver donation.

Adult↗

cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line.

Members of the ATP binding cassette (ABC) superfamily are involved in the energy-dependent transport of a wide variety of substrates including anticancer agents across the membranes. We have cloned a cDNA fragment including a novel ABC sequence from a cisplatin-resistant human lung adenocarcinoma cell line, PC-14/CDDP, by reverse transcription polymerase chain reaction (RT-PCR) using degenerate primers and screened a cDNA library using the cDNA fragment as a probe. A full-length cDNA clone, BM4.8, was obtained. Sequence analysis showed that the cDNA encoded a short type of multidrug resistance protein homologue, SMRP, by computed homology search. SMRP was composed of 946 amino acids and had two ABCs with walker A and B motifs. This gene was mapped on chromosome 3 at band q27 by fluorescence in situ hybridization (FISH) analysis and was found to be expressed in various tissues by Northern blot analysis.

ATP-Binding Cassette Transporters↗

Isolation of a candidate gene, CAB1, for cholesterol transport to mitochondria from the c-ERBB-2 amplicon by a modified cDNA selection method.

An improved cDNA selection method was established to isolate expressed genes efficiently from an amplified chromosome region in human cancer. Biotinylated yeast artificial chromosome DNA containing c-ERBB-2 was hybridized in solution with PCR-amplifiable cDNAs of an esophageal cancer cell line bearing the c-ERBB-2 amplification. After capturing the hybrids on avidin-coated magnetic beads, the cDNAs were amplified by PCR. Four new genes (A39, C51, CAB1, and GRB-7) coamplified with c-ERBB-2 were isolated from the enriched cDNA library. CAB1, GRB-7, and c-ERBB-2 were overexpressed in gastric and esophageal cancer cells in correspondence with the amplification. The deduced amino acid sequence of the CAB1 gene had significant homology to the recently discovered steroidogenic acute regulatory protein, StAR, which plays an essential role in cholesterol transport to mitochondria. It was established that multiple overexpressed genes are frequently present in a single amplicon.

Amino Acid Sequence↗

Oncology.

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Acid Anhydride Hydrolases↗

MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase.

c-Jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs) are mitogen-activated protein kinase (MAPK)-related protein kinases that are involved in several cellular events, including growth, differentiation, and apoptosis. Mixed lineage kinases (MLKs) form a family of protein kinases sharing two leucine zipper-like motifs and a kinase domain whose primary structure is similar to both the tyrosine-specific and the serine/threonine-specific kinase classes. We have reported that a member of the MLK family, MUK/DLK/ZPK, can activate JNK/SAPK in vivo, and here we show that another member of the MLK family, MST/MLK2, activates JNK/SAPK. Both MUK/DLK/ZPK and MST/MLK2 cause a slight activation of p38/Mpk2 when overexpressed in COS-1 cells, whereas MST/MLK2, but not MUK/DLK/ZPK, activates extracellular response kinase (ERK) to a certain degree. The activity of SEK1/MKK4/JNKK, a MAPK kinase class protein kinase designated as a direct activator of JNK/SAPK, is also induced by MUK/DLK/ZPK or MST/MLK2 overexpression. Furthermore, recombinant MST/MLK2 produced in bacteria directly phosphorylates and activates SEK1/MKK4/JNKK in vitro, showing that MST/MLK2 acts like a MAPK kinase kinase. Taken together, these results suggest that MLK family members are MAPK kinase kinases preferentially acting on the JNK/SAPK pathway.

Animals↗

Gene therapy for peritoneal dissemination of pancreatic cancer by liposome-mediated transfer of herpes simplex virus thymidine kinase gene.

Peritoneal dissemination is one of the most common complications of the malignancies of the digestive system, such as gastric or pancreatic cancers. Yet, no effective therapy has been established so far to alleviate this devastating and often fatal end-stage condition. Here we describe a novel approach of intraperitoneal (i.p.) lipofection of a suicidal gene to the pancreatic cancer cells in a mouse peritoneal dissemination model. A human pancreatic cancer cell line, PSN-1, was inoculated into the peritoneal cavity of nude mice. Eight days later, a herpes simplex virus thymidine kinase (HSV-TK) gene expression plasmid under a potent hybrid promoter CAG was injected as a DNA-lipopolyamine complex. Ganciclovir (GCV) was then administered for 8 days, and the mice were examined for tumor development at the 24th day after the tumor inoculation. Although all 24 control mice showed macroscopic peritoneal dissemination and solid tumors on the pancreas, 8 of the 14 mice treated with HSV-TK and GCV were free of tumors, and only a few small tumors were observed in the remaining 6 mice. Treatment-related toxicity was not observed. The semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis suggested that the HSV-TK transgene was expressed in about 10% of tumor cells but not in the normal pancreas or in the small intestine. When the lacZ gene was transduced in place of the HSV-TK gene, the blue-stained cells were identified only in tumor nodules and not in normal organs. This preclinical study suggests the therapeutic feasibility of the i.p. lipofection-based suicidal gene/prodrug strategy for peritoneal dissemination of pancreatic cancer.

Animals↗

Forensic analysis of eleven cyclic antidepressants in human biological samples using a new reversed-phase chromatographic column of 2 microm porous microspherical silica gel.

A high-performance liquid chromatographic method has been developed for the forensic analysis of eleven frequently used cyclic antidepressant drugs (ADSs) (amitriptyline, amoxapine, clomipramine, desipramine, dosulepine, doxepin, imipramine, maprotiline, melitracen, mianserine and nortriptyline) using a recently developed reversed-phase column with 2 microm particles for the analysis of biological samples. The separation was carried out using two different C8 reversed-phase columns (column 1: 100 mm X 4.6 mm I.D., particle size 2 microm, TSK gel Super-Octyl; column 2: 100 mm X 4.6 mm I.D., particle size 5 microm, Hypersil MOS-C8) for comparison. The mobile phase was composed of methanol-20 mM KH2PO4 (pH 7) (60:40, v/v) and the flow-rate was 0.6 ml/min for both columns. The absorbance of the eluent was monitored at 254 nm. When the eleven drugs were determined, the sensitivity with the 2 microm particles was about five times greater than with the 5 microm particles. Retention times on column 1 were shorter than those on column 2. These results show that the new ODS column packing with a particle size of 2 microm gives higher sensitivity and a shorter analysis time than the conventional ODS column packing when applied to the analysis of biological samples.

Antidepressive Agents, Tricyclic↗

Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs.

Bone metastasis is a common event in prostate cancer, and it is known that some of the bone morphogenetic proteins (BMPs) are expressed in prostate cancer cells, while no study on the expression of their receptors, BMPRs, has been reported. Here we report cloning and sequence analysis of the human BMPR-IB cDNA. We also analysed the expression of transcripts of three types of the BMPR genes in human tissues and prostate cancer cell lines. The BMPR-IB mRNA was present in various organs, but the highest level was found in the prostate. Moreover, the amount of BMPR-IB mRNA was significantly low in prostate cancer tissues after androgen withdrawal and was also low in prostate cancer cell lines. RT-PCR analysis showed that the BMPR-IB message was upregulated by androgen stimulation in the LNCaP cell line which expresses the androgen receptor. By contrast, the mRNA levels of BMPR-IA and BMPR-II were not significantly different among non-cancerous and cancerous prostate tissues. It was also suggested that human BMPR-IA and BMPR-IB might have different biological functions in the prostate, although their sequences were 85.3% identical in the serine-threonine kinase domain.

Amino Acid Sequence↗

Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer.

Many amplified-chromosome regions in human cancers have been identified, while there are only a limited number of reports for amplified genes in a single amplicon. We recently isolated four cDNA clones, A39, B47, C51, and CAB1, from 500 kilobases of yeast artificial chromosome DNA containing the c-ERBB-2 gene. B47 consisted of 615 base pairs and had about 85% homology with the corresponding sequence of mouse Grb-7. We report here the structure of human GRB-7 cDNA, and we report that the amounts of mRNA for c-ERBB-2, CAB1, and GRB-7 were elevated in concordance with the amplification.

Amino Acid Sequence↗

Forensic analysis of 10 barbiturates in human biological samples using a new reversed-phase chromatographic column packed with 2-micrometre porous microspherical silica-gel.

A high-performance liquid chromatographic method has been developed for the forensic analysis of 10 frequently used barbiturates (BARs) (allobarbital, amobarbital, barbital, cyclobarbital, hexobarbital, metharbital, pentobarbital, phenobarbital, secobarbital and thiopental) using a recently developed reversed-phase column packed with 2-micron particles. The results show that the new ODS column packing gives higher sensitivity and a shorter analysis time than the conventional ODS column packing when applied to the analysis of biological samples.

Autopsy↗

Cardioprotective effect against ischemia-reperfusion injury of AHC-52, a dihydropyridine compound with inhibitory effect on Cl- but not Ca2+ current.

We examined the effects of a dihydropyridine compound, AHC-52, on guinea pig myocardium. In ventricular cardiomyocytes, AHC-52 (1 microM) had no effect on the basal peak inward and steady state currents, but inhibited the isoprenaline-induced time independent Cl- current. In coronary perfused right ventricular preparations, no-flow ischemia induced decreases in developed tension which recovered only to about 50% of initial values after reperfusion. AHC-52 (0.1 microM) had no effect on developed tension under normal conditions and during ischemia, but significantly improved the recovery of developed tension after reperfusion to about 80% of preischemic values. Thus, AHC-52 inhibits Cl- channels in cardiac muscle and may have protective effects against ischemia-reperfusion injury.

Animals↗

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain.

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 +/- 0.38, 2.12 +/- 0.37, and 1.38 +/- 0.24 (micrograms/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50% more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus.. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus.

Basal Ganglia↗

Influence of PF1022A on the motility of Angiostrongylus cantonensis in vitro.

Our previous in vivo studies on angiostrongyliasis showed that PF1022A had stronger killing effects against female adults than against males. No killing effects were observed against young adult worms in the central nervous system. To characterize the former in vivo action of PF1022A, in vitro effects of PF1022A on the motility of Angiostrongylus cantonensis were studied directly. Few differences in the efficacy were observed between male and female worms, but dose- and time-dependent inhibition was observed in adults treated with PF1022A at 10(-7)-10(-11) g/ml. PF1022A was slightly less effect we against young-adult worms than against adult worms. Minor effects of PF1022A were observed on the third-stage larvae. These results suggest that selectivity against adult females in vivo could be attributable to non-neuropharmacological mechanisms and that PF1022A does not pass through the blood-brain barrier in host animals.

Angiostrongylus cantonensis↗