Search PubMed⌕ Search

Biomedical subjects

T Teramoto

Publications and source records attributed to T Teramoto.

At least 181 records · Page 10Linked to original sources

Regression of coronary atherosclerosis by combined LDL-apheresis and lipid-lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study. The LARS Investigators.

The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events.

Adult↗

Redundant nerve roots of the cauda equina caused by lumbar spinal canal stenosis.

To investigate pathogenesis of redundant nerve roots of the cauda equina, which were concomitant with severe lumbar spinal canal stenosis, six cadavers were examined anatomically and histopathologically, and quantitative analysis of nerve fibers was performed. In this anatomic study, it was observed that all the redundant nerve roots passed through the constriction of the spinal canal. No significant pathologic change was detected in the spinal ganglia and in the spinal cords except for the posterior column, in which dorsal redundant roots were entering. Redundant nerve roots of unequal length also were observed in the anatomic study. The spatial distribution of redundant nerve roots and the extent of degeneration of nerve fibers in them were established by these histopathologic and quantitative studies. These facts indicated a close causal relationship between redundant nerve roots and constriction of the spinal canal, and that the pathogenesis of redundant nerve roots was a squeezing force acting on the nerve roots at the area of spinal canal constriction.

Cauda Equina↗

Production of human immunoglobulin G reactive against human cancer in tumor-bearing mice with severe combined immunodeficiency reconstituted with human splenic tissues.

Splenic tissues derived from patients with gastric cancer were implanted into mice with severe combined immunodeficiency (SCID) and then the mice were challenged with COLO-205, a human colon cancer cell line. Production of human immunoglobulin G (IgG) reactive against the COLO-205 cells was detected by enzyme-linked immunosorbent assay in sera from the reconstituted and tumor-bearing SCID mice. The titers of the reactive IgG relative to total IgG in the sera of SCID mice began to increase from one week after implantation of the tumor cells, and became 10- to 100-fold higher than that in the donor's serum by 3-4 weeks. This model using implantation of human cancer cells in SCID mice reconstituted with human splenic tissues would facilitate further studies of human cancer immunology.

Animals↗

Inhibitory effects of bis(2-aminohexyl)disulfide and its analogues on polymorphonuclear leukocyte functions in vitro.

Water soluble analogues of the anti-inflammatory compound, bis(2-aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III), benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were synthesized, and their effects on the functions of cells related to inflammation were studied in vitro. Compounds II, III and IV showed much higher inhibitory activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O2(-)-generation of polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed the strongest activity among the compounds (IC50 values: 2.6 microM). The inhibition of O2(-)-generation of PMNs by compd. II was the most effective when FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187 and opsonized zymosan were used. However, compd. II was not an O2(-)-scavenger. Compounds II, III and IV significantly inhibited a series of activation processes in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging from 10 to 100 microM. Under these doses, compds II, III and IV did not affect the histamine release from mast cells or the hemolysis of erythrocytes. These results strongly suggest that the anti-inflammatory action caused by compd. II and its analogues was at least partly due to inhibition of several functions of PMNs and platelets.

Amines↗

Preparation of biologically active and site specifically radioiodinated recombinant human insulin-like growth factor-I.

Recombinant human insulin-like growth factor-I (rhIGF-I) was iodinated using a lactoperoxidase-catalyzed labeling method. The labeled products were separated into more than five fractions by ion-paired reverse-phase high performance liquid chromatography (HPLC). A fraction (peak 1), which showed the highest yield and radioactivity, was found to be biologically active in the BALB/c 3T3 cell proliferating system. The site of the iodination was investigated by S-pyridylethylation followed by trypsinization and separation with HPLC using reverse phase columns. From the amino acid analysis of the peaks which were radioactive, the iodination site of peak 1 was revealed to be Tyr-24 and Tyr-60. This is the first report of the biological activity of radioactive peptide hormone with a defined labeled site.

3T3 Cells↗

[Sharp decline in plasma CEA and reduction of liver metastasis after UFT administration in a patient with recurrent gastric cancer].

Carcinoembryonic antigen (CEA) in plasma is useful for the detection of recurrent colonic or gastric cancer and the monitoring of plasma in patients with recurrent cancer displaying therapeutic effect. We report a sharp decline of CEA in a patient with recurrent gastric cancer by 6 months oral administration of UFT. The patient was an 81-year-old male who had undergone gastrectomy for advanced gastric cancer. Eight months post-operatively, the plasma CEA began to rise logarithmically, and recurrent tumor in the remnant stomach and liver metastasis were detected by fibergastroscope (FGS) and abdominal CT. After administration of UFT at a dose of 300 mg per day, CEA abruptly declined logarithmically and normalized in 6 months. Presently marked reduction of recurrent foci and metastases were found by FGS and abdominal CT. Therefore sequential changes in plasma CEA in this patient can be considered to reflect the effect of therapy for recurrent gastric cancer by UFT.

Adenocarcinoma↗

Inhibition of platelet function by high-density lipoprotein from a patient with apolipoprotein E deficiency.

Apolipoprotein E-(apoE-) rich high-density lipoprotein (HDL) of normal subjects showed marked inhibitory effects on platelet aggregation and ATP release as compared with apoE-poor HDL, suggesting that apoE has inhibitory effects on platelet function (Desai et al. J. Lipid Res. 30:831, 1989; Higashihara et al. FEBS Lett. 282:82, 1991). A patient with apoE deficiency showed evidence of decreased platelet aggregability in platelet-rich plasma, but normal aggregability in washed platelets. Both patient's plasma and HDL fraction inhibited platelet aggregation of normal subjects. Patient's HDL reconstituted with recombinant apoE showed further inhibitory effects on platelet function. These results suggest that apoE is a potent, but not unique, inhibitory factor for HDL.

Adenosine Diphosphate↗

Potent and preferential inhibition of Ca2+/calmodulin-dependent protein kinase II by K252a and its derivative, KT5926.

Effects of protein kinase inhibitors, K252a and its derivative KT5926, on Ca2+/calmodulin-dependent protein kinase II were examined. Both compounds potently inhibited Ca2+/calmodulin-dependent protein kinase II. Kinetic analyses indicated that the inhibitory effect of K252a and KT5926 was competitive with respect to ATP (Ki: 1.8 and 4.4 nM, respectively) and noncompetitive with respect to the substrates. Taken together with a previous report (Nakanishi et al. Mol. Pharmacol. 37, 482, 1990) concerning the Ki values of these compounds for ATP with various protein kinases, the results suggest that K252a and KT5926 are potent and preferential inhibitors of Ca2+/calmodulin-dependent protein kinase II.

Alkaloids↗

Characterization of partially purified prostaglandin E2 receptor from the canine renal medulla: evidence for physical association of the receptor protein with the inhibitory guanine nucleotide-binding protein.

Prostaglandin (PG) E2 binding protein, a putative PGE2 receptor, was purified 26-fold with 0.4% recovery from canine renal outer medullary membranes solubilized with 12% digitonin with the sequential use of a Superose 12, Wheat Germ Agglutinin (WGA) Affigel 10, DEAE-5PW and Ampholine column chromatographies. The final preparation retained the binding activity specific for PGE2, but lost most of the sensitivity to guanosine-5'-(gamma-thio)triphosphate (GTP gamma S). An antibody against alpha subunit of the inhibitory guanine nucleotide-binding protein (alpha Gi)1 and alpha Gi2 or that against common sequences of alpha subunit of guanine nucleotide-binding proteins (alpha G(common)) reacted at 41 kDa protein in the sample of each step of purification, but failed to do so in the final preparation. An antibody against alpha Gi3 or alpha Go had no effect. In fact, peaks of the binding activity and immunoreactivity for alpha Gi1,2 were chromatographically separated by isoelectric focusing. Moreover, antibodies against alpha G(common) or alpha Gi1,2, but not that against alpha Gi3 and alpha Go, precipitated PGE2 binding activity in the active fractions of WGA-Affigel 10 column chromatography. These results suggest that the PGE2 receptor is an acidic glycoprotein and that Gi1 or Gi2 is physically associated with the PGE2 receptor and dissociates from the receptor protein during purification procedures.

Animals↗

The role of apoE in inhibitory effects of apoE-rich HDL on platelet function.

Apolipoprotein E- (ApoE-) rich high-density lipoprotein (HDL), which was prepared from the bound fraction of normolipemic volunteers on heparin-Sepharose and from a hyperalphalipoproteinemic patient, potently inhibited aggregation of human platelets in a dose-dependent fashion. Dimyristoyl phosphatidylcholine liposome with apoE (apoE.DMPC) also inhibited platelet aggregation, and incubation of washed platelets with apoE.DMPC resulted in the release of cholesterol into the supernatant in a time- and dose-dependent manner. These results suggest that apoE plays a major role in the inhibitory effect of apoE-rich HDL in platelet function, presumably due to the release of cholesterol from the plasma membrane.

Adenosine Triphosphate↗

Apolipoprotein E deficiency with a depressed mRNA of normal size.

We studied a 39-year-old man who had palmar xanthomas complicated with marked hyperlipidemia. His serum cholesterol and triglyceride were 2000 and 6300 mg/dl, respectively. Serum apolipoprotein E (apo E) was undetectable in the patient by the methods of single radial immunodiffusion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and radioimmunoassay. Serum apo E concentrations of his father and sister were low. This evidence is consistent with a diagnosis of familial apo E deficiency. We studied the synthesis of apo E in cultures of peripheral blood monocyte macrophages (M-M cultures) obtained from the patient, and detected no secretion of apo E in the culture medium and no newly synthesized apo E in the cell lysate. There were only trace amounts of apo E mRNA of the M-M cultures and the size of the mRNA appeared the same as normal apo E mRNA, indicating a different mutation of the gene from that of the case reported by Zannis et al. (J. Biol. Chem., 260 (1985) 12891).

Adult↗

Deficiency of apolipoprotein B synthesis in Suncus murinus.

We reported previously that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food. In this study, we focused on lipoprotein and apolipoprotein secretion from the liver. The study of lipoproteins from this animal revealed that small amounts of lipoproteins with apolipoprotein (apo) E but without apo B were observed in the fraction of density less than 1.08 g/ml. In order to learn whether apo B is synthesized by the liver or not, isolated suncus livers were perfused with an addition of [35S]methionine. Small amounts of radioactivity were observed in apo E of VLDL, and fairly large amounts in apo E and A-I in the fraction of LDL + HDL, suggesting that VLDL was secreted with apo E but not with apo B from the liver. Northern blot analysis with use of rat apo B cDNA revealed a weak signal of hybridized rat apo B cDNA between 15 kb and 9 kb in the suncus liver and intestinal mucosa; this is almost the same size as rat apo B mRNA. This finding suggests the presence of apo B mRNA in the suncus. In conclusion, apo B is not secreted from the suncus liver, owing to a defect in intracellular post-transcriptional processing or to ineffective transcription. This might be one of the reasons for fatty deposits in the suncus liver. Suncus may be a candidate for an animal model of abetalipoproteinemia as well as fatty liver due to a defect of apo B synthesis.

Animals↗

[T-serotype distribution of group A hemolytic streptococci in a rapidly expanding residential area in Sanda City, Hyogo Prefecture, with reference to an outbreak of serotype T-28 in autumn, 1988].

In the fall of 1988, an outbreak of streptococcal infections was observed at 2 pediatric clinics in Sanda City, Hyogo prefecture. The 2 clinics were independent of each other; one (clinic A) was located in the down town area, in the older part of the city, where there is little population turn over, while the other (clinic B) was in a newly developed-fast growing residential district. The strains and the distribution of T-serotypes isolated at each location are as follows: clinic A; 58 strains (34.5% serotype T-4, 31.0% serotype T-12, 10.3% serotype T-1, and 23.3% serotype T-28), clinic B; 43 strains (48.8% serotype T-28, 23.3% serotype T-12, 11.6% serotype T-4 and 7.0% serotype T-1). According to the data from Kobe City infectious disease surveillance center, there were a total of 102 group A hemolytic streptococci strains isolated in 1988, the T-serotypes distribution of which was as follows: 47.0% serotype T-4, 15.7% serotype the T-12, 10.8% serotype T-1 and 9.8% serotype T-28. Serotype T-4 was dominant here, as it was in location A of Sanda City. The epidemic proportion of serotype T-28 found at location B is considered to be due to the fact that location B has very little social interaction with location A and other areas. No difference was observed among the different serotypes on the drug susceptibility test: all strains showed a sensitivity to ampicillin and penicillin G, but were resistant to tetracycline and chloramphenicol.

Adolescent↗

Isolation of a new antitumor substance from Bacillus stearothermophilus.

A new antitumor substance, BS-1, was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563 by ethylacetate extraction and HPLC. BS-1 inhibited the proliferation of mouse macrophage-like cells, P388-D1 (IC50: 4 micrograms/ml) and mouse mastocytoma, P-815 (IC50: 0.6 microgram/ml), but not that of Balb/c 3T3.

Animals↗

[Immunoscintigraphy of colorectal cancer with 111In labeled anti-CEA monoclonal antibody (ZCE-025)].

Clinical trials with 111In labeled anti-CEA monoclonal antibody (ZCE-025) was initiated. Five patients with colorectal cancer suspected were given an intravenous injection of 1 mg of 111In labeled ZCE-025. Planar and SPECT images were obtained 24 and 72 hours after injection. Surgical operation was performed on all patients between 7 and 10 days post injection. Of 4 primary sites, all were clearly visualized. Intrahepatic metastasis was visualized as higher activity than normal liver in one of two patients. In one patient whose imaging was negative, no residual cancer was found at surgery. Persistent accumulation of 111In in the lymph nodes was also observed in one patient. Surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon cancer. No side effects were encountered, although HAMA were detected in all 5 patients by 4 weeks after the administration of ZCE-025. Immunoscintigraphy appears useful in distinguishing recurrent tumor from postoperative granuloma. Further investigation directed to the causes of 111In accumulation in tumor-free lymph nodes is required.

Aged↗

Induction of fatty liver by fasting in suncus.

We found that a fatty liver was easily induced in a novel experimental animal, Suncus murinus (suncus), by withholding food. Hepatic triglyceride content increased linearly for up to 24 h after fasting in these animals. Serum levels of neutral lipids are very low in the fed state compared with those in rats, and decreased significantly after 24 h fasting. On the other hand, serum free fatty acids, which are at the same level in fed animals as in rats, increased threefold in the fasting suncus. In order to learn whether the fatty liver induced by fasting is an unusual physiological state or a pathological on-going state in suncus, they were refed after 24 h fasting. Refeeding resulted in a decrease in hepatic triglyceride content to the level of fed animals. Serum lipid levels, which decreased with fasting, returned to those of fed animals. This evidence indicates that hepatic lipid secretion is impaired even in a physiological state to some extent and that starvation causes increasing influx of free fatty acid to the liver, which might be followed by esterification and result in triglyceride accumulation in the liver. In conclusion, hepatic lipid and lipoprotein metabolism is unique to the suncus, which is a useful animal model for the study of intra-hepatic lipid transport.

Animals↗

Characterization of the guinea pig lung membrane leukotriene D4 receptor solubilized in an active form. Association and dissociation with an islet-activating protein-sensitive guanine nucleotide-binding protein.

Membrane fractions from the guinea pig lung had high- and low-affinity binding sites for LTD4 with Kd values of 0.016 and 9.1 nM, respectively. In the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or by prior treatment of the membrane with islet-activating protein (IAP), the high-affinity site shifted to a low-affinity state. Consistently, a 41-kDa protein was ADP-ribosylated by treatment of the lung membranes with IAP, and this event was inhibited by the addition of GTP gamma S. We solubilized the LTD4 receptor from the lung membranes in an active form with 5 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and 10% glycerol. On a gel filtration column, the binding activity was eluted at the volume corresponding to a Mr of 70,000 or over 500,000 in the presence or absence of Mg2+ (5-20 mM), respectively, in solubilizing buffers. The Kd value of [3H]LTD4 binding to the 70-kDa protein was similar to the low-affinity binding constant of the membrane and was insensitive to GTP gamma S. The preparation solubilized in the absence of Mg2+ showed both high- and low-affinity binding sites for LTD4, and the addition of GTP gamma S shifted the high-affinity site to a low-affinity one. Thus, 1) the LTD4 receptor is coupled to an IAP-sensitive GTP-binding protein, 2) this GTP-binding protein is dissociable from the receptor by solubilizing the lung membrane with CHAPS and Mg2+, and 3) the receptor associated to or dissociated from a GTP-binding protein exhibited a high- or low-affinity state, respectively. These data provide an insight into the molecular mechanism of regulation of the LTD4 receptor signaling process by association and dissociation with an IAP-sensitive GTP-binding protein.

Animals↗